FlowMotion Multiparametric PET Suite

White Paper FlowMotion Multiparametric PET Suite The Patlak Model Anne M. Smith, PhD, Bruce Spottiswoode, PhD, Vijay Shah, PhD, Jicun Hu, PhD, Carl von Gall, MD Siemens Healthineers Molecular Imaging SIEMENS Healthineers siemens.com/mi White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite Contents ADMIRE: Advanced Modeled Iterative Reconstruction Introduction 3 Glossary of terms 4 SUV and its limitations by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, 5 Patlak modeling and Rainer Raupach, PhD 6 Overview: fully-automated multiparametric PET acquisition protocol 8 Input function CB(t) 9 Fully-automated CB(t) estimation 9 Automatic identification of blood pool region Introduction: Evolution of Siemens CT image reconstruction technologies 9 Time activity curves from dynamic PET Series 10 Input function modeling Image reconstruction is an essential technology that every computed tomography (CT) scanner requires for operation. The function of CT image reconstruction is to translate 10 Possible issues for automated CB(t) estimation all of the acquired X-ray data (raw data) into a meaningful three-dimensional 11 User-entered data for CB(t) representation of the patient. The most well-known method of image reconstruction 12 is commonly referred to as filtered back projection (FBP), in which measured X-ray Methods for measuring blood time activity samples for estimating CB(t) 12 Estimating CB(t) from user input CSV data projections are directly translated into images. In most modern scanners, it is likely that not all measured data can be used for image reconstruction with FBP,1 i.e., not 13 Possible issues for user-entered CB(t) estimation all radiation dose applied to the patient is actually used for image reconstruction. To 15 Reconstruction of parametric volumes of MRFDG and DVFDG address this, Siemens Healthineers CT scanners offer an improved three-dimensional 16 FBP, called weighted filtered back projection (WFBP).2 More efficient workflow due to faster parametric volume formation 17 A common characteristic of both FBP and WFBP is that they do not consider statistical Synchronization of blood input function and CBM sinogram 17 Direct parametric volume reconstruction properties of measured X-ray projections. What this means is that all CT projections 18 Units of parametric images collected in the detectors are weighted the same, regardless of their quality. With the increased focus in dose reduction, the lack of inclusion of statistical properties 19 Factory default parametric PET Patlak workflows of conventional FBP or WFBP become an important barrier that prevents further 21 Automated Workflow radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art 20 Standard Workflow CT scanners have been developed with more advanced technology, known as iterative 23 Retrospective QC reconstruction (IR). Not surprisingly, among the key advantages of IR is that the statistical properties of measured CT projection data can be readily incorporated into 23 TrueD Tools the CT image reconstruction process. This would allow, for example, low-quality (noisy) 24 Use cases projections to carry less weight than high-quality projections. 26 Enabling multiparametric PET in a clinical setting There has been an expanding utilization of IR in clinical practice in recent years, 26 primarily due to the increased focus on radiation dose optimization. Of note, Siemens Using the automated workflow to optimize the standard workflow 26 Deeper understanding of factors that affect SUV Healthineers has been placing emphasis on devising technical solutions that can help 26 Augment diagnostic information in addition to SUV to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As 26 Research testing of new tracers and non-Patlak kinetic models Reasonably Achievable” to deliver diagnostic image quality. 27 Practical considerations 27 Viewing and analysis of the parametric volumes 28 Differences between SUV and 18F FDG Patlak 28 Sensitivity of multiparametric PET 29 Conclusion 31 References 32 Appendix A – User Defined Input Function CSV File Format Specifications 35 2 2 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Introduction Advanced Modeled Iterative Anne M. Smith, PhD, Bruce Spottiswoode, PhD, Reconstruction Vijay Shah, PhD, Jicun Hu, PhD and Carl von Gall, MD Positron Emission Tomography (PET) is a naturally quantitative imaging modality1–4. Historically, the first prototypes and commercial PET scanners were used as sophisticated scientific measurement devices to measure dynamic in vivo physiological processes such by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, as 18F fluorodeoxyglucose (18F FDG)* metabolism (MRFDG), blood perfusion, oxygen and Rainer Raupach, PhD consumption, cell proliferation, and receptor density5,6. MRFDG was used to infer the glucose metabolic rate (MRGlu) with corrections for metabolic differences between 18F FDG and glucose. Measuring MRFDG, in particular, filled a large unmet need in the clinic to both stage and monitor cancer treatments7–9. However, the manual effort needed to perform the MRFDG measurement was prohibitive given the clinical constraints, and hence a Introduction: Evolution of Siemens CT image reconstruction technologies simplified surrogate was developed instead: static images after a specified uptake time Development of IR methods and the now familiar Standard Uptake Value or SUV10–16. Siemens Healthineers latest Image reconstruction is an essential technology that every computed tomography (CT) innovation no longer requires the intense manual effort and takes PET “back to the It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate future” of its original roots—a fully-automated implementation of the Patlak model to in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional estimate MRFDG and 18F FDG distribution volume (DVFDG). These measures are estimated The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction directly into multiparametric volumes in addition to the standard reconstructed tracer Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray activity volume (e.g. Bq/ml) used for SUV measures. This new feature will greatly image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely accelerate the accumulation of data needed to determine the impact of this extra that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 information in the clinic. Potential clinical advantages of Patlak modeling may be better However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To visualization of low uptake 18F FDG tumors, lesions in high background regions (e.g. the in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional liver), and early identification and changes in MRFDG and DVFDG. Although testing focused with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 on 18F FDG data, it can also be used with other tracer data that conform to the Patlak technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative A common characteristic of both FBP and WFBP is that they do not consider statistical model. Finally, this feature supports retrospective quality control checks and the creation Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections of dynamic DICOM time series, which can be exported to off-line modeling tools for first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With non-Patlak (e.g. multi-compartmental models) parametric volume formation. “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported *Fludeoxyglucose F 18 5-10 mCi IMPORTANT SAFETY INFORMATION reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in as an IV Injection Radiation Risk: Radiation-emitting • applications ranging from routine to specialized body and neuro CT – in both adults Dosage Forms and Strengths: Multiple-dose • statistical properties of measured CT projection data can be readily incorporated into INDICATIONS AND USAGE 30 mL and 50 mL glass vial containing 0.74 the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 products, including Fludeoxyglucose F 18 Fludeoxyglucose F 18 Injection (18F FDG) is Injection, may increase the risk for cancer, to 7.40 GBq/mL (20 to 200 mCi/mL) of projections to carry less weight than high-quality projections. indicated for positron emission tomography especially in pediatric patients. Use the Fludeoxyglucose F 18 injection and 4.5 mg smallest dose necessary for imaging and of sodium chloride with 0.1 to 0.5% w/w There has been an expanding utilization of IR in clinical practice in recent years, (PET) imaging in the following settings: Oncology: For assessment of abnormal ensure safe handling to protect the patient ethanolas a stabilizer (approximately 15 • primarily due to the increased focus on radiation dose optimization. Of note, Siemens and health care worker. glucose metabolism to assist in the to 50 mL volume) for intravenous • Healthineers has been placing emphasis on devising technical solutions that can help evaluation of malignancy in patients with Blood Glucose Abnormalities: In the administration. to consistently achieve the right dose, for the right diagnostic task, for every patient. known or suspected abnormalities found oncology and neurology setting, suboptimal See page 38 for full prescribing information by other testing modalities, or in patients imaging may occur in patients with for Fludeoxyglucose F 18 Injection. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. with an existing diagnosis of cancer. inadequately regulated blood glucose Cardiology: For the identification of left levels. In these patients, consider medical Fludeoxyglucose F 18 injection is therapy and laboratory testing to assure manufactured by Siemens’ PETNET Solutions, • ventricular myocardium with residual 810 Innovation Drive, Knoxville, TN 39732 glucose metabolism and reversible loss of at least two days of normoglycemia prior systolic function in patients with coronary to Fludeoxyglucose F 18 Injection In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical artery disease and left ventricular administration. * • dysfunction, when used together with Adverse Reactions: Hypersensitivity location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the myocardial perfusion imaging. reactions with pruritus, edema and rash appropriate dose to obtain diagnostic image quality for the particular clinical task. ** Neurology: For the identification of regions have been reported; have emergency In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical • resuscitation equipment and personnel location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the of abnormal glucose metabolism appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to associated with foci of epileptic seizures. immediately available. determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 3 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: Advanced Modeled Iterative Glossary of Terms Reconstruction Term Definition ALPHA Automated learning and parsing of human anatomy CBM Continuous bed motion PET acquisition by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, CB(t) Concentration of 18F FDG in arterial whole blood as a function of time and Rainer Raupach, PhD CT(t) Concentration of 18F FDG in tissue as a function of time CSV Comma separated values (file format) Introduction: Evolution of Siemens CT image reconstruction technologies DVFDG or Patlak intercept Apparent tracer distribution volume of the Patlak model Image reconstruction is an essential technology that every computed tomography (CT) IDIF scanner requires for operation. The function of CT image reconstruction is to translate Image-derived input function all of the acquired X-ray data (raw data) into a meaningful three-dimensional Ki or Patlak slope representation of the patient. The most well-known method of image reconstruction Rate of tracer uptake in the trapped compartment of the Patlak model is commonly referred to as filtered back projection (FBP), in which measured X-ray LC projections are directly translated into images. In most modern scanners, it is likely Lumped constant (converts MRFDG to MRGlu) that not all measured data can be used for image reconstruction with FBP,1 i.e., not LV all radiation dose applied to the patient is actually used for image reconstruction. To address this, Siemens Healthineers CT scanners offer an improved three-dimensional Left ventricle MRFDG FBP, called weighted filtered back projection (WFBP).2 Metabolic rate of 18F FDG A common characteristic of both FBP and WFBP is that they do not consider statistical MRGlu properties of measured X-ray projections. What this means is that all CT projections Metabolic rate of glucose collected in the detectors are weighted the same, regardless of their quality. With Multiparametric A model that is defined by more than one parameter (e.g. MRFDG and DVFDG in the case the increased focus in dose reduction, the lack of inclusion of statistical properties of Patlak modeling of 18F FDG) of conventional FBP or WFBP become an important barrier that prevents further Parametric volume radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art An image whose voxel values represent a model parameter such as MRFDG or DVFDG CT scanners have been developed with more advanced technology, known as iterative p.i. reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Post-injection time of the radiotracer statistical properties of measured CT projection data can be readily incorporated into S&S the CT image reconstruction process. This would allow, for example, low-quality (noisy) Step and shoot PET acquisition projections to carry less weight than high-quality projections. SUV Standard uptake value There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens t* Uptake time of 18F FDG where the non-metabolized tissue concentration is considered Healthineers has been placing emphasis on devising technical solutions that can help to be in equilibrium with the blood concentration to consistently achieve the right dose, for the right diagnostic task, for every patient. t0 This was in line with the ALARA principle, that is to use a dose that is “As Low As Injection time of PET tracer Reasonably Achievable” to deliver diagnostic image quality. tWB Start of dynamic whole-body PET CBM acquisition VOI Volume of interest WB Whole body 2 4 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Advanced Modeled Iterative SUV and its limitations Reconstruction SUV and its limitations For whole- body PET 18F FDG imaging for in clinical oncology applications, the current For whole-body PET 18F FDG imaging in clinical oncology applications, the current state-of-the- state-of-the-art quantitative measure is the SUVbw, calculated as follows: art quantitative measure is the SUVbw, calculated as follows: SUV$% = '()*+*), ./0(10)23)*/0 ( 567 89 ) ;0<1()1= >/?1 (@67) by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, 6/=, A1*Bℎ) (5B) In the equation above, the normalization was done to subject body weight (bw), but body and Rainer Raupach, PhD In the equation above, the normalization was done to subject body weight (bw) but body surface area (bsa) or lean body mass (lbm) can also be used. The sources which limit the surface area (bsa) or lean body mass (lbm) can also be used. The sources which limit the quantitative value of SUV are well known 10–17 . Some of which are listed below: quantitative value of SUV are well known 10–17 , some of which are listed below: subject size and body composition • Introduction: Evolution of Siemens CT image reconstruction technologies Subject size and body composition body fat has a lower 18F FDG uptake compared to other tissues • o Development of IR methods Body fat has a lower 18F FDG uptake compared to other tissues liver SUV can vary by 50% for patient weights of 50 to 110 kg18 – o uptake time of 18F FDG Image reconstruction is an essential technology that every computed tomography (CT) Liver SUV can vary by 50% for patient weights of 50 to 110 kg18 It is well known that the degradation in image quality, most notably an increase – • scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. a lung tumor SUV can increase by 40% from 30 to 50 min p.i.12 o Uptake time of 18F FDG • The first IR technology commercially developed by Siemens Healthineers was Iterative • accurate calibration of the dose calibrator to the PET scanner all of the acquired X-ray data (raw data) into a meaningful three-dimensional – representation of the patient. The most well-known method of image reconstruction A lung tumor SUV can increase by 40% from 30 to 50 min p.i.12 Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased o makes comparing SUVs across scanners and sites challenging the type of SUV measured (e.g. SUVmax, SUVpeak, SUVbw, SUVlbm, etc.) and the is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 Calibration of the dose calibrator to the PET scanner IRIS is a scientifically validated technology • • projections are directly translated into images. In most modern scanners, it is likely algorithmic details of how calculation was made17dependent on the reconstruction that is effective in reducing image noise in a variety of clinical applications.4, 5 Makes comparing SUVs across scanners and sites challenging – algorithm used to create the Bq/ml image volume that not all measured data can be used for image reconstruction with FBP,1 i.e., not However, it is expected that IR technologies not only aid in noise reduction but also The type of SUV measured (e.g. SUVmax, SUVpeak, SUVbw, SUVlbm, etc.) dependence on plasma glucose level, since hyper-glycemia causes significant reduction all radiation dose applied to the patient is actually used for image reconstruction. To • • in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional in tissue 18F FDG update and the algorithmic details of how calculation was made17 with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 physical activity of subject during uptake time (ideally, a patient should rest quietly with • technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative Injection infiltration which will incorrectly lower the SUV • A common characteristic of both FBP and WFBP is that they do not consider statistical eyes closed) Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ Dependence on the reconstruction algorithm used to create the Bq/ml image volume • first IR technology that integrated a correction loop in the raw-data domain (a.k.a. Using Patlak modeling may overcome many if not all of the limitations listed above. In addition, properties of measured X-ray projections. What this means is that all CT projections “sinogram”) and added a model of the CT system geometry during the data forward the clinical benefits of 18F FDG Patlak modeling may be: collected in the detectors are weighted the same, regardless of their quality. With Dependence on plasma glucose level, since hyper-glycemia may cause significant • projection. This correction loop that operates through to the raw-data domain is reduction in 18F FDG uptake in tissue of interest of conventional FBP or WFBP become an important barrier that prevents further improved separation of non-metabolized and metabolized 18F FD17 the increased focus in dose reduction, the lack of inclusion of statistical properties • particularly helpful for reducing spiral artifacts. A second correction loop in image • radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art o Physical activity of subject during uptake time (ideally, a patient should rest quietly increased contrast, especially in regions of high baseline uptake (e.g. non- space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative metabolized 18F FDG) with eyes closed) since its introduction, and a wealth of scientific literature has consistently supported o reconstruction (IR). Not surprisingly, among the key advantages of IR is that the improved assessment of response in low-FDG-uptake tumors the capabilities of SAFIRE to reduce dose while maintaining high image quality in Using Patlak modeling may overcome many, if not all, of the limitations listed above. § smaller tumors may be more visible statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults In addition, the impact of this modeling in the clinic may be: o differentiation of inflammation versus malignant tumors and pediatrics.7-10 improved quantification the CT image reconstruction process. This would allow, for example, low-quality (noisy) • projections to carry less weight than high-quality projections. Providing parametric images of non-metabolized and metabolized 18F FDG17 • • improved reproducibility Increasing contrast especially in regions of high baseline uptake – There has been an expanding utilization of IR in clinical practice in recent years, (e.g. non-metabolized 18F FDG) primarily due to the increased focus on radiation dose optimization. Of note, Siemens Improving assessment of response in low- FDG- uptake tumors – Healthineers has been placing emphasis on devising technical solutions that can help Smaller tumors may be more visible • to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Improving quantification • Confidential 4 Reasonably Achievable” to deliver diagnostic image quality. Especially in the case of injection infiltration since the actual input function – can be measured in vivo for each patient Improving reproducibility • * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 5 Patlak modeling White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite Using Patlak modeling is one way to use the dynamic nature of PET to estimate dynamic physiological processes19–22. Unlike the standard SUV acquisition protocol, where the subject is injected in an uptake room and waits a set amount of time before the PET acquisition starts, the subject is injected on the bed at the same time as the PET acquisition is started. Therefore, the injected activity can be followed from injection, to first pass circulation, to tissue uptake and finally to tissue washout, providing more information that may be useful for a more accurate diagnosis23. ADMIRE: Patlak is one of many graphical modeling techniques that can be applied to dynamic data. It Patlak modeling assumes that there is a single input function (CB(t) in Figure 1 below) and that the tracer of Advanced Modeled Iterative Using Patlak modeling is one way to use the dynamic nature of PET to estimate interest (in this case 18F FDG) can enter and leave any number of compartments, but there must dynamic physiological processes19–22. Unlike the standard SUV acquisition protocol, Reconstruction be at least one compartment where it remains trapped (Figure 1). Therefore, a Patlak model where the subject is injected in an uptake room and waits a set amount of time before may not be optimal for all PET tracers or all anatomical regions17. the PET acquisition starts, the subject is either injected on the bed at the same time as the PET acquisition is started or the initial bolus concentration in the blood is estimated using non-imaging techniques. Therefore, the injected activity can be followed from injection, to first pass circulation, to tissue uptake and finally to tissue washout, providing more information that may be useful to physicians by allowing them to provide a more accurate diagnosis23. by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD Patlak is one of many graphical modeling techniques that can be applied to dynamic Blood Plasma K1 Exchangeable Trapped Figure 1. Compartmental model repre- data. It assumes that there is a single input function (CB(t) in Figure 1 below) and 18F FDG] sentation of 18F FDG distribution in the that the tracer of interest (in this case 18F FDG) can enter and leave any number of [ [ 18F FDG] k3 [ 18F FDG-6-P] body, with rate constants denoting the compartments, but there must be at least one compartment where it remains trapped exchange rate (units of ml/min/cm3 but (Figure 1). Therefore, a Patlak model may not be optimal for all PET tracers or all Introduction: Evolution of Siemens CT image reconstruction technologies CB(t) k2 C1(t) C2(t) often simplified to inverse time) between the compartments19–22. The anatomical regions17. Image reconstruction is an essential technology that every computed tomography (CT) model assumes that once 18F FDG enters the trapped compartment, it scanner requires for operation. The function of CT image reconstruction is to translate Tissue CT(t) [18F] cannot exit because it is metabolized to all of the acquired X-ray data (raw data) into a meaningful three-dimensional 18F Fluorodeoxyglucose-6-phosphate representation of the patient. The most well-known method of image reconstruction (18F FDG-6-P). Note that 18F FDG is commonly referred to as filtered back projection (FBP), in which measured X-ray K1 exchanges quickly between red blood projections are directly translated into images. In most modern scanners, it is likely Figure 1. Compartmental model representation of 18F FDG distribution in the body, with rate Blood Plasma Exchangeable k3 Trapped cells (RBCs) and plasma such that the that not all measured data can be used for image reconstruction with FBP,1 [ 18F FDG] k2 [ 18F FDG] [ 18F FDG-6-P] 18F FDG concentration in RBCs is equiv- constants denoting the exchange rate (units of inverse time) between the compartments19– CB(t) C1 (t) i.e., not alent to blood plasma24. Therefore, no all radiation dose applied to the patient is actually used for image reconstruction. To C2 (t) 22 The model assumes that once 18F FDG enters the trapped compartment, it cannot exit . correction for hematocrit is needed and address this, Siemens Healthineers CT scanners offer an improved three-dimensional and is metabolized to 18F Fluorodeoxyglucose-6-phosphate (18F FDG-6-P). Note that 18F FDG both plasma and whole-blood input FBP, called weighted filtered back projection (WFBP).2 functions can be used, which is a exchanges quickly between red blood cells (RBCs) and plasma, such that the 18F FDG unique feature of 18F FDG. A common characteristic of both FBP and WFBP is that they do not consider statistical concentration in RBCs is equivalent to 19–22blood plasma24. Therefore, no correction for properties of measured X-ray projections. What this means is that all CT projections Tissue CT (t) [18F] hematocrit is needed, and both plasma and whole-blood input functions can be used, which collected in the detectors are weighted the same, regardless of their quality. With is a unique feature of 18F FDG. the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further Mathematically, the concentration of 18F FDG in the tissue compartment as a function of time Mathematically, the concentration of 18F FDG in the tissue compartment as a function radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art of time can be written as: can be written as: CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the !" # = !% # ⊗ . - )*+)- 0 + '()- statistical properties of measured CT projection data can be readily incorporated into '()* (1) '()* )*+ )- Deleted: !" # = !% # ⊗ . - )*+)- 0 + '()- , the CT image reconstruction process. This would allow, for example, low-quality (noisy) )*+ )- (1) )*+ )- )*+ )- projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, where U is the convolution operation. When the above equation is solved and the where Ä is the convolution operation. When the above equation is solved, and the Patlak Confidential 5 primarily due to the increased focus on radiation dose optimization. Of note, Siemens Patlak transformation is applied, the result can be written as a familiar linear equation where Ä is the convolution operation. When the above equation is solved, and the Patlak transformation is applied, the result can be written as a familiar linear equation (i.e. y = mx + b): Healthineers has been placing emphasis on devising technical solutions that can help transformation is applied, the result can be written as a familiar linear equation (i.e. y = mx + b): to consistently achieve the right dose, for the right diagnostic task, for every patient. (i.e. y = mx + b): - ( ( 2 ) This was in line with the ALARA principle, that is to use a dose that is “As Low As , !"($) *& + .+ .+ , !&($) = () - *& + !"($) , Reasonably Achievable” to deliver diagnostic image quality. !"($) !&($) *& + + 01, (2) .+ , Deleted: - !&($) (2) !&($) = () - + 01 !&($) = () + 01, (2) !&($) = () *& + .+ - !&($) + 01 !&($) !"($) Deleted: where the slope is !" = $%&' where the slope is !" = $%&' &()&' and the y-intercept is DV. Figure 2 shows the Patlak Deleted: !" = $%&' where the slope is and the y-intercept is DVFDG. and the y-intercept is DV. Figure 2 shows the Patlak &()&' Deleted: !" = $%&' &()&' &()&' K1 is the rate of 18F FDG entry into the tissue, while k3/(k2+k3) represents how much 18F FDG is metabolized or trapped. Figure 2 shows the Patlak transformation in the more familiar graphical form. 6 2 t* t* An important point to remember is that the Patlak transformation is only valid after the tracer has reached equilibrium between the blood and tissue compartments. Graphically, this is the time The slope Ki of the Patlak transformation can be converted to MRGlu and MRFDG units via the (see Figure 2). For 18F FDG, t* is typically in the range of 20 – 60 min p.i., depending on the physiological properties of the tissue21,22. following equations: after which the transformed data points become linear. This time is traditionally labeled as t*, The slope Ki of the Patlak transformation can be converted to MRGlu and MRFDG units via the following equations: (see Figure 2). For 18F FDG, t* is typically in the range of 20 – 60 min p.i., depending on the Figure 2. Patlak plot of hypothetical 18F FDG tumor data where original Bq/ml PET physiological properties of the tissue21,22. data (dark red dotted line) were transformed using equation 2. The blue line shows the fit of the transformed blue symbols after time t*=34 min (note that t* denotes time after 18F FDG injection shown on upper x-axis, not Patlak transformation time which is shown on the lower x-axis). The slope of the blue line is Ki and the y-intercept is DV. shown on the lower x-axis). The slope of the blue line is Ki and the y-intercept is DV. after 18F FDG injection shown on upper x-axis, not Patlak transformation time which is the fit of the transformed blue symbols after time t*=34 min (note that t* denotes time data (dark red dotted line) were transformed using equation 2. The blue line shows An important point to remember is that the Patlak transformation is only valid after the tracer has Figure 2. Patlak plot of hypothetical 18F FDG tumor data where original Bq/ml PET reached equilibrium between the blood and tissue compartments. Graphically, this is the time after which the transformed data points become linear. This time is traditionally labeled as t*, DV DV t* t* % $ '"()) !" # $ % !" # '"()) &# slope = Ki (min) slope = Ki &# (min) Confidential 6 Confidential 6 % $ !" # Deleted: Deleted: !" # $ % &# '"()) &# '"()) White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Patlak transformation Patlak fit Tumor activity Advanced Modeled Iterative Time after injection (T) Reconstruction 0 25 50 75 2.0 5 4 1.5 by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD 3 CT (t)/CB(t) (ml/ml) 1.0 2 Figure 2. Patlak plot of 18F FDG lung PET SUV tumor data where original SUV PET Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods 0.5 data (dark red dotted line) were trans- formed using equation 2. The orange Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase line shows the fit of the transformed scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. orange symbols after time t*≈30 min all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative 0 0 (note that t* denotes time after 18F FDG representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased injection shown on upper x-axis, not 0 50 100 150 Patlak transformation time, which is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology is shown on the lower x-axis). The projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 ∫t CB(s)ds slope of the orange line is Ki and the o i.e., not that not all measured data can be used for image reconstruction with FBP,1 However, it is expected that IR technologies not only aid in noise reduction but also (min) in reducing spiral artifacts, which can be exacerbated when using CT acquisitions CB(t) y-intercept is DVFDG. Data courtesy of all radiation dose applied to the patient is actually used for image reconstruction. To Yale University. address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections An important point to remember is that the Patlak transformation is only valid first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With after the non-metabolized tracer has reached equilibrium between the blood and tissue “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties compartments. Graphically, this is the time after which the transformed data points projection. This correction loop that operates through to the raw-data domain is of conventional FBP or WFBP become an important barrier that prevents further become linear. This time is traditionally labeled as t* (see Figure 2). For 18F FDG, t* particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art is typically in the range of 20 – 60 min p.i., depending on the physiological properties space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative of the tissue21,22. since its introduction, and a wealth of scientific literature has consistently supported reconstruction (IR). Not surprisingly, among the key advantages of IR is that the The slope Ki the capabilities of SAFIRE to reduce dose while maintaining high image quality in of the Patlak transformation can be converted to MRGlu and MRFDG units statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults via the following equations: the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, MRGlu = Ki × Subject Blood Glucose (3) Lumped Constant primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. MRFDG = Ki × Subject Blood Glucose (4) This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. The lumped constant (LC) is a unit-less physical constant that converts MRFDG to MRGlu 21,22 . The LC varies by tissue type and pathology. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 7 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: The rate constant Ki (slope) physiologically represents the net uptake rate in the trapped compartment20 in Figure 1 (e.g. MRFDG). Note that the traditional PET image with units of Advanced Modeled Iterative Bq/ml will appear similar to the MRFDG parametric image, but represents physiologically Reconstruction something quite different–the distribution of 18F activity, with no differentiation between 18F FDG and 18F FDG-6-P. Therefore, the MRFDG parametric image essentially removes the non-metabolized 18F FDG signal leaving only the metabolized 18F FDG-6-P signal, which is effectively removing background activity from the signal of interest when a parametric image of MRFDG is desired. This may allow low grade tumors in regions with high non- metabolized 18F FDG to be more visible, for example (see Viewing and analysis of parametric volumes section). by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, The parameter DVFDG physiologically represents the apparent distribution volume and Rainer Raupach, PhD because it equals the volume of blood that contains the same non-metabolized activity as 1 ml of tissue20. For example, a DVFDG=200% means that the non-metabolized tracer in the region of interest has twice the concentration as that in blood or, said differently, that 2 ml of blood has the same quantity of radioactivity as 1 ml of tissue. By definition, Introduction: Evolution of Siemens CT image reconstruction technologies DVFDG is heavily influenced by the activity distribution at time t* (see Figure 2). Therefore this parametric image will heavily reflect the distribution of activity at this time, and Image reconstruction is an essential technology that every computed tomography (CT) motion artifacts will be more apparent in this volume as compared to the MRFDG or scanner requires for operation. The function of CT image reconstruction is to translate Bq/ml volumes which weight evenly each dynamic pass (see Viewing and analysis all of the acquired X-ray data (raw data) into a meaningful three-dimensional of parametric volumes section). representation of the patient. The most well-known method of image reconstruction is commonly referred to as filtered back projection (FBP), in which measured X-ray projections are directly translated into images. In most modern scanners, it is likely Overview: fully-automated multiparametric PET acquisition protocol that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To A fully-automated parametric PET acquisition protocol that contains all needed address this, Siemens Healthineers CT scanners offer an improved three-dimensional information for Patlak analysis is depicted in Figure 3. Note that there are two PET FBP, called weighted filtered back projection (WFBP).2 acquisitions, with the first being a single-bed position, listmode acquisition centered over the cardiac region and starting at time t0 and the second being a dynamic WB CBM A common characteristic of both FBP and WFBP is that they do not consider statistical scan starting at tWB. The patient is injected with 18F FDG on the bed at time t0. The same CT properties of measured X-ray projections. What this means is that all CT projections can be used to correct the PET data from both acquisitions and should have the same collected in the detectors are weighted the same, regardless of their quality. With axial coverage as the dynamic WB CBM acquisition. The first single-bed, listmode the increased focus in dose reduction, the lack of inclusion of statistical properties acquisition will have sufficient temporal coverage to sample the initial bolus of conventional FBP or WFBP become an important barrier that prevents further Figure 3. Acquisition planning for the of the injected 18F FDG while the second acquisition has both sufficient temporal and radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art two different axial field of view (FOV) spatial coverage to sample the kinetics at later time points of 18F FDG and the clinical CT scanners have been developed with more advanced technology, known as iterative coverages for an automated (i.e. regions of interest for a given patient, respectively. reconstruction (IR). Not surprisingly, among the key advantages of IR is that the needed information is fully contained in data) image-based parametric statistical properties of measured CT projection data can be readily incorporated into acquisition. The orange lines depict a the CT image reconstruction process. This would allow, for example, low-quality (noisy) typical CT and whole-body, dynamic Input Function CB(t) projections to carry less weight than high-quality projections. PET axial FOV, and the red lines denote the single-bed position PET acquisition Quantitatively accurate values of MRFDG and DVFDG depend on an accurate estimation of the There has been an expanding utilization of IR in clinical practice in recent years, centered over the subject’s heart. The blood input function CB(t) (see Figure 1). The input function can be estimated in two ways: primarily due to the increased focus on radiation dose optimization. Of note, Siemens red axial FOV must be fully contained Healthineers has been placing emphasis on devising technical solutions that can help 1) Fully-automated CB(t) estimation: a completely automated approach that uses CT and within the orange axial coverage. Note to consistently achieve the right dose, for the right diagnostic task, for every patient. that single organ regions (e.g. brain, PET images to generate the input function (see Figure 3). This was in line with the ALARA principle, that is to use a dose that is “As Low As prostate, etc.) can still be acquired with Reasonably Achievable” to deliver diagnostic image quality. 2) User-entered data for CB(t): this approach obtains the input function from data this workflow. Using variable-speed, FlowMotion regions when setting up imported by the user (see Appendix A for details of the expected format). For this the whole-body dynamic PET acquisi- approach, the PET injection can occur in an uptake room or on the bed at the start tions can help maximize the acquisition of the acquisition. of counts from the organ of interest (e.g. use slower speeds in the brain region and quickly move back and forth in the cardiac region to sample the input function). Data courtesy of Erlanger Health System, Chattanooga, Tennessee, USA 2 8 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Fully-automated CB(t) Estimation Advanced Modeled Iterative This is a fully automated approach, which uses the CT and dynamic PET data to generate an image-derived input function (IDIF). Reconstruction Automatic identification of blood pool region Siemens Healthineers has developed a way to automatically find anatomical landmarks on CT images, known as automated learning and parsing of human anatomy (ALPHA)25. CB(t) can be automatically generated from both the left ventricular blood pool (LV) and by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, proximal descending aorta using ALPHA. and Rainer Raupach, PhD The CT reconstruction that is used for the PET attenuation correction (AC_CT by default) is used to find these landmarks. An internal analysis on 110 WB AC_CTs showed a success rate of >95%. Potential reasons for failure are incomplete CT scan coverage over the heart and descending aorta regions, or if the algorithm reports low confidence in the location of the landmark. If an input function VOI is not found automatically, the user will be Introduction: Evolution of Siemens CT image reconstruction technologies required to generate one manually in TrueD, export the time activity curve, and reload it Development of IR methods Image reconstruction is an essential technology that every computed tomography (CT) into the scanner user interface (see Retrospective QC section). It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 that not all measured data can be used for image reconstruction with FBP,1 i.e., not However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR Figure 4A. Example of automatically generated reference regions for the left FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative ventricular blood pool (left), descend- A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ ing aorta (middle), and liver (right). properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. A A Data courtesy of University of Geneva, Geneva, Switzerland collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively The following VOIs are generated, centered on the ALPHA landmarks: a sphere of CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported radius 12 mm (volume 7.2 cm3 ) for the LV and a cylinder of length 20 mm and radius reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in 5 mm (volume 1.6 cm3 ) for the aorta. A liver reference VOI (radius 15 mm) will also be statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults created if the liver is in the field of view. These VOIs are stored automatically in the patient the CT image reconstruction process. This would allow, for example, low-quality (noisy) database, and can be loaded into TrueD along with the CT and the dynamic PET series and pediatrics.7-10 projections to carry less weight than high-quality projections. (Figure 4A). Further details about this are in the Retrospective QC section below. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 9 External Dynamic Images External Images Dynamic Fully-automated CB(t) Estimation section. Figure 5b shows the example of CSV data input from the user, automatically-generated, blood ,time-activity samples from PET images, which are passed to input function modeling to generate the input function. Dynamic Images IF IF Activity Bq/ml 6 5 4 3 2 1 0 7 x 10⁴ Blood Time Activity Samples from PET Image Blood Time Activity Samples from CSB File Input Function Modeling Modeling Function Figure 5b. Samples from CSV file shown in black that need to be scaled to PET images shown in White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction External FlowMotion Multiparametric PET Suite 0 1000 2000 3000 4000 5000 6000 red circles. Figure 5b. Samples from CSV file shown in black that need to be scaled to PET images shown in Times(s) red circles. A scaling factor is determined based on the area under the curve (AUC) of the A scaling factor is determined based on the area under the curve (AUC) of the overlapping region on the PET-derived input function and the CSV data input function as overlapping region on the PET-derived input function and the CSV data shown in Figure 6. Note that this option can generate up to two input functions as two ADMIRE: shown in Figure 6. Note that this option can generate up to two input functions as two blood regions are identified on the PET images (aorta and LV), and both are used to Whole body x 10⁴ blood regions are identified on the PET images (aorta and LV), and both are used to Advanced Modeled Iterative scale the input function. The new input functions are stored in the database (see 7 Retrospective QC section below) with the naming convention in the database being: scale the input function. The new input functions are stored in the database (see 6 Reconstruction IF__IF_AORTA_ Retrospective QC section below) with the naming convention in the database being: • 5 IF__IF_LV_ • IF__IF_AORTA_ 4 Input Function • Modeling 3 IF__IF_LV_ Activity Bq/ml • 2 by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, 1 and Rainer Raupach, PhD 0 00:08:20 00:25:00 00:41:40 00:58:20 01:15:00 01:31:40 TT 00:16:40 00:33:20 00:50:00 01:06:40 01:23:20 to tWB T Introduction: Evolution of Siemens CT image reconstruction technologies Time (hh:mm:ss) tend Image reconstruction is an essential technology that every computed tomography (CT) Figure 4B. Time activity samples gener- scanner requires for operation. The function of CT image reconstruction is to translate Time activity curves from dynamic PET Series ated from PET images, where injection all of the acquired X-ray data (raw data) into a meaningful three-dimensional must occur while the patient is on the The LV and aorta VOIs are used to automatically generate whole-blood, time-activity representation of the patient. The most well-known method of image reconstruction scanner bed. Input function modeling curves using the dynamic PET series. In the case of injection done on the patient bed and is commonly referred to as filtered back projection (FBP), in which measured X-ray helps to generate the image-derived the PET scan starting at the same time, the time-activity samples (both bolus and tail) input function. Here the t0 is injection projections are directly translated into images. In most modern scanners, it is likely can be generated automatically (as shown in Figure 4B). time, twb is the time when the whole- that not all measured data can be used for image reconstruction with FBP,1 i.e., not body scan started, and tend is the end all radiation dose applied to the patient is actually used for image reconstruction. To Input function modeling time of the whole-body scan. address this, Siemens Healthineers CT scanners offer an improved three-dimensional FBP, called weighted filtered back projection (WFBP).2 Time-activity samples are converted to the input function, which is then interpolated to a temporal resolution of 1 second for the required duration using following operations: A common characteristic of both FBP and WFBP is that they do not consider statistical properties of measured X-ray projections. What this means is that all CT projections 1. For time t < 25 minute p.i., interpolation is performed using a piece-wise linear fit. collected in the detectors are weighted the same, regardless of their quality. With If the frame-duration of the consecutive frames is unequal, the piece-wise linear the increased focus in dose reduction, the lack of inclusion of statistical properties constant interpolation is performed between the frames to preserve the area under of conventional FBP or WFBP become an important barrier that prevents further the curve (AUC) as shown in Figure 4C. radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative 1. Measure difference in frame duration reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Frame statistical properties of measured CT projection data can be readily incorporated into duration between consecutive frames the CT image reconstruction process. This would allow, for example, low-quality (noisy) Interpolated line 2. If frame duration is not equal, adjust projections to carry less weight than high-quality projections. area used for the slope calculation Bq/ml There has been an expanding utilization of IR in clinical practice in recent years, Preserves AUC 3. Preserve area under the curve for total duration during interpolation primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. Does not preserve AUC Figure 4C. Interpolation performed preserves the area under the curve (AUC). The dashed red line corresponds to a piece-wise linear fit where the AUC isn’t preserved. The orange line is 05 15 30 55 Time obtained with a custom interpolation method to preserve the AUC when frame duration is not equal. Frame Reference Time (FRT) 10 2 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: 2. For 18F FDG, if there are 3 samples beyond 25 min p.i., exponential fitting (A·e-tλ ), where Advanced Modeled Iterative λ is rate constant of the exponential and A is the intercept at zero time is performed on the tail portion (t ≥ 25 min p.i.) of the input function. For non-FDG tracers, interpolation Reconstruction is performed using a piece-wise linear fit. 3. For 18F FDG, extrapolation of the input function to the end of the dynamic acquisition is performed using an exponential fitting model as shown in Figure 4D. Exponential fit post 25 min p.i Sample-IF by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD Activity vs. time x 10⁴ 7 14000 12000 Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods 6 10000 Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. 5 8000 all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative 6000 representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased 4 Activity Bq/ml is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 4000 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 that not all measured data can be used for image reconstruction with FBP,1 i.e., not However, it is expected that IR technologies not only aid in noise reduction but also 3 2000 Activity (Bq/ml) all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions 0 address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR 2 00:25:00 00:41:40 00:58:20 01:15:00 01:31:40 FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative 00:33:20 00:50:00 01:06:40 01:23:20 A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. Time (hh:mm:ss) 1 collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is 0 Figure 4D. Typical input function of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image space is applied iteratively to reduce image noise. SAFIRE has been used extensively generated after passing through 00:08:20 00:25:00 00:41:40 00:58:20 01:15:00 01:31:40 radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art input-function modeling. The magnified since its introduction, and a wealth of scientific literature has consistently supported 00:16:40 00:33:20 00:50:00 01:06:40 01:23:20 CT scanners have been developed with more advanced technology, known as iterative view shows the data points beyond reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in applications ranging from routine to specialized body and neuro CT – in both adults Time (hh:mm:ss) 25 minutes, where the exponential statistical properties of measured CT projection data can be readily incorporated into fit is applied. the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, Possible issues for CB(t) estimation primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help The following conditions will result in an error message to the user, and the input function to consistently achieve the right dose, for the right diagnostic task, for every patient. will not be processed further: This was in line with the ALARA principle, that is to use a dose that is “As Low As No blood input function landmark location found on the CT images. • Reasonably Achievable” to deliver diagnostic image quality. If the blood, time-activity samples have a negative value after the bolus peak. • For 18F FDG, if the input function modeling returns a negative rate constant (λ) in the • exponential fit, i.e. increasing tail points. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 11 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: User-entered data for CB(t) Advanced Modeled Iterative Data from external sources can be imported by the user with the comma-separated values (CSV) file format (see Appendix A for details of the expected format) as shown Reconstruction in Figure 5A. For this approach, the PET injection can occur in an uptake room or on the bed at the start of the acquisition. Figure 5A. User interface (UI) dialog for user-entered input file. Scaling of Import Input Function from CSV X the data to the PET image activity is enabled by default, as well as fitting and extrapolation (if needed). If data CSV File D:\PATLAK\Pat21_ArterialPlasma_IF.csv by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, is scaled to the PET image activity, there will be two input functions: one and Rainer Raupach, PhD scaled to LV and the other to the aorta Use PET Images to scale Bq/ml VOI. The resulting input functions will be stored in the patient database, and Fit to end of PET scan later, can be chosen as an input for a Patlak reconstruction (see below). For Introduction: Evolution of Siemens CT image reconstruction technologies details of the required CSV format, Import Cancel please see Appendix A. Image reconstruction is an essential technology that every computed tomography (CT) scanner requires for operation. The function of CT image reconstruction is to translate all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction is commonly referred to as filtered back projection (FBP), in which measured X-ray Methods for measuring blood time activity samples for estimating CB(t) projections are directly translated into images. In most modern scanners, it is likely Some techniques for measuring CB(t) are: that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To Arterial or venous blood draws counted in a gamma counter26 • address this, Siemens Healthineers CT scanners offer an improved three-dimensional Population-based average27–29 FBP, called weighted filtered back projection (WFBP).2 • Image-based by drawing a VOI inside a blood pool (similar to the fully-automated A common characteristic of both FBP and WFBP is that they do not consider statistical • approach above except the VOI was drawn manually)29–31 properties of measured X-ray projections. What this means is that all CT projections collected in the detectors are weighted the same, regardless of their quality. With Time activity samples for input functions can also be generated by saving TACs the increased focus in dose reduction, the lack of inclusion of statistical properties • in CSV files in TrueD or syngo.via MM oncology, allowing the user to draw the input of conventional FBP or WFBP become an important barrier that prevents further region on any suitable vessel radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative The format of these CSV files is readable by the Navigator UI - reconstruction (IR). Not surprisingly, among the key advantages of IR is that the If multiple TACs are present in the CSV file, then each TAC will be saved statistical properties of measured CT projection data can be readily incorporated into - as an individual input function in the database the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. Radiation detection probe placed over an artery during injection27 • There has been an expanding utilization of IR in clinical practice in recent years, The software will optionally allow the user to scale the data to the PET image and primarily due to the increased focus on radiation dose optimization. Of note, Siemens interpolate and extrapolate these data until the end of PET scan (see more details below). Healthineers has been placing emphasis on devising technical solutions that can help Note that the software will not perform decay correction, metabolite correction, and to consistently achieve the right dose, for the right diagnostic task, for every patient. dispersion correction (estimation of time delay or dispersion that occurs between where This was in line with the ALARA principle, that is to use a dose that is “As Low As the input function was measured, e.g. radial artery and the LV or aorta). Users desiring Reasonably Achievable” to deliver diagnostic image quality. to make such corrections will have to implement these effects offline and enter the new input function as a CSV file in the workflow (see Appendix A for the expected format). 2 12 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Estimating CB(t) from user input CSV data Advanced Modeled Iterative The user has the option to select which tasks he/she would like to perform on the external data supplied for the input function (Figure 5A). The software allows the user to scale the Reconstruction data to the PET image activity and interpolate and extrapolate the data until the end of the PET scan. However, in total there are four possible scenarios, based on the selections performed by the user 1. Both options are selected This is the default. The external data supplied by CSV is interpolated and extrapolated by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, using the approach described previously in the Input function modeling section. Blood- and Rainer Raupach, PhD time activity samples for both LV and aorta regions from the PET images are generated automatically using the approach described previously in the Fully-automated CB(t) estimation section. Figure 5B shows a CSV file from the user and, blood, time-activity samples from PET images, which are scaled to generate the input function. Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods Image reconstruction is an essential technology that every computed tomography (CT) Fully-automated CB(t) Estimation section. Figure 5b shows the example of CSV data Dynamic Images Blood time activity samples from CSV file It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate input from the user, automatically-generated, blood ,time-activity samples from PET in image noise, is the standard tradeoff for achieving a substantial dose reduction. Blood time activity samples from PET image all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative images, which are passed to input function modeling to generate the input function. x 10⁴ representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased 7 is commonly referred to as filtered back projection (FBP), in which measured X-ray projections are directly translated into images. In most modern scanners, it is likely Dynamic image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology that is effective in reducing image noise in a variety of clinical applications.4, 5 6 that not all measured data can be used for image reconstruction with FBP,1 i.e., not However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions 5 address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 Dynamic Images technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative 4 Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ Input Function A common characteristic of both FBP and WFBP is that they do not consider statistical first IR technology that integrated a correction loop in the raw-data domain (a.k.a. 3 Modeling properties of measured X-ray projections. What this means is that all CT projections Function collected in the detectors are weighted the same, regardless of their quality. With External “sinogram”) and added a model of the CT system geometry during the data forward projection. This correction loop that operates through to the raw-data domain is IF Modeling Activity Bq/ml 2 the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further External particularly helpful for reducing spiral artifacts. A second correction loop in image IF 1 radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in 0 statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults External IF Figure 5b. Samples from CSV file shown in black that need to be scaled to PET images shown in the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 00:00:00 00:16:40 00:33:20 00:50:00 01:06:40 01:23:20 01:40:00 red circles. projections to carry less weight than high-quality projections. Figure 5b. Samples from CSV file shown in black that need to be scaled to PET images shown in Times (hh:mm:ss) There has been an expanding utilization of IR in clinical practice in recent years, red circles. primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help Figure 5B. Samples from CSV file to consistently achieve the right dose, for the right diagnostic task, for every patient. shown in orange that need to be scaled to PET images shown in red circles. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 13 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: A scaling factor is determined based on the area under the curve (AUC) of the overlapping region of the PET-derived data and the CSV data as shown in Figure 6. Note that this Advanced Modeled Iterative option can generate multiple input functions as two blood regions are identified on the Reconstruction PET images (aorta and LV) and both are used to scale the input functions. The new input functions are stored in the database (see the Retrospective QC section below) with the naming convention in the database being: Blood time activity samples from CSV file IF__IF_AORTA_ Input function from CSV file • Blood time activity samples from PET image PET image input function IF__IF_LV_ • by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, x 10⁴ 7 and Rainer Raupach, PhD Blood time activity samples from CSV file Input function from CSV file 6 Blood time activity samples from PET image PET image input function 5 x 10⁴ 7 Introduction: Evolution of Siemens CT image reconstruction technologies 4 Image reconstruction is an essential technology that every computed tomography (CT) 6 3 scanner requires for operation. The function of CT image reconstruction is to translate Activity Bq/ml 5 2 all of the acquired X-ray data (raw data) into a meaningful three-dimensional t1 t2 representation of the patient. The most well-known method of image reconstruction 4 1 is commonly referred to as filtered back projection (FBP), in which measured X-ray projections are directly translated into images. In most modern scanners, it is likely 3 0 that not all measured data can be used for image reconstruction with FBP,1 Activity Bq/ml 2 00:00:00 00:16:40 00:33:20 00:50:00 01:06:40 01:23:20 01:40:00 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To t1 t2 address this, Siemens Healthineers CT scanners offer an improved three-dimensional 1 Time (hh:mm:ss) FBP, called weighted filtered back projection (WFBP).2 0 A common characteristic of both FBP and WFBP is that they do not consider statistical properties of measured X-ray projections. What this means is that all CT projections 00:00:00 00:16:40 00:33:20 00:50:00 01:06:40 01:23:20 01:40:00 collected in the detectors are weighted the same, regardless of their quality. With the increased focus in dose reduction, the lack of inclusion of statistical properties Time (hh:mm:ss) of conventional FBP or WFBP become an important barrier that prevents further radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative Figure 6. The top graph shows reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the blood, time-activity samples from Blood time activity samples from CSV file Unscaled input function from CSV-file data the CSV file (orange circles) and the statistical properties of measured CT projection data can be readily incorporated into resampled and fit input function shown the CT image reconstruction process. This would allow, for example, low-quality (noisy) x 10⁴ CSV-file input function scaled to PET images with the solid orange line. The blood, projections to carry less weight than high-quality projections. 7 time-activity samples from the whole- body dynamic PET scan are shown There has been an expanding utilization of IR in clinical practice in recent years, 6 as red circles with the associated primarily due to the increased focus on radiation dose optimization. Of note, Siemens Blood time activity samples from CSV file Unscaled input function from CSV-file data exponential fit as a red line, and the Healthineers has been placing emphasis on devising technical solutions that can help 5 shaded portion from time t1 to t2 x 10⁴ CSV-file input function scaled to PET images to consistently achieve the right dose, for the right diagnostic task, for every patient. represents the common time points This was in line with the ALARA principle, that is to use a dose that is “As Low As 7 4 of the CSV and PET input functions. Reasonably Achievable” to deliver diagnostic image quality. The scaling factor is the ratio of the 6 3 area under curve (AUC) of PET input Activity Bq/ml 5 function (red line passing through 2 red circles) to area under curve (AUC) 4 of input function from CSV file (orange 1 line) for time t1 to t2. The bottom 3 graph shows the scaled CSV input 0 function by making the AUCs equiva- Activity Bq/ml 2 00:00:00 00:16:40 00:33:20 00:50:00 01:06:40 01:23:20 01:40:00 lent (red curve). The orange curve is the fitted unscaled CSV input function, 1 Time (hh:mm:ss) shown for comparison. 0 ..... 00:00:00 00:16:40 00:33:20 00:50:00 01:06:40 01:23:20 01:40:00 2 14 Time (hh:mm:ss) White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: 2. Both options are unselected Advanced Modeled Iterative This option is for advanced users. In this scenario, no modifications will be performed on the user-defined input function, and this option is effectively a “pass-through” Reconstruction mode. In this case, the user will be expected to provide samples starting at t=0 p.i., with each sample having a frame duration of either 1 second or samples every second. The input function must include the entire length of the PET data acquisition and can extend beyond this time as well. Users will also need to perform scaling or other corrections offline. by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, 3. Option ‘Use PET images to scale Bq/ml’ is selected This option is for advanced users. In this scenario, the software will perform the and Rainer Raupach, PhD scaling of the user-provided input function using the PET images and will generate up to two input functions that will be stored in the database (see option 1 above for more details). In this case, the user will be expected to provide samples starting at t=0 p.i., with each sample having a frame duration of 1 second and complete time coverage until end of the PET acquisition or longer. Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods 4. Option ‘Fit to end of PET scan’ is selected Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase The user may want to use this option when the CSV data is derived from PET images scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. using external software such as TrueD or syngo.via MM Oncology, or if an activity all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative cross-calibration was performed between the PET scanner and the device used to representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased measure the external input function. In this scenario, the software will generate the is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology input function CB(t) using operations described previously in the Input function projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 modeling section. i.e., not that not all measured data can be used for image reconstruction with FBP,1 However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To Possible issues for user-entered CB(t) estimation in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 The following conditions will result in an error message to the user, and the input function technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative will not be further processed: A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ Incorrect formatting of CSV file (see Appendix A for formatting) • properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward Samples in the CSV file should be in the ascending order of acquisition time or • the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is frame reference time. of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively If the blood time-activity samples have negative values after the bolus peak • CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported If the option of ‘Use PET images to scale Bq/ml’ is selected, but the PET image • reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in does not include the landmark location found by CT images statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) For 18F FDG, if the option of ‘Use PET images to scale Bq/ml’ or ‘Fit to end of PET scan’ and pediatrics.7-10 • projections to carry less weight than high-quality projections. is selected, and the input function modeling returns a positive slope from the There has been an expanding utilization of IR in clinical practice in recent years, exponential fit primarily due to the increased focus on radiation dose optimization. Of note, Siemens For the “pass-through” mode, if the frame duration is not 1 second or consecutive • Healthineers has been placing emphasis on devising technical solutions that can help samples are not separated by a 1-second intervals to consistently achieve the right dose, for the right diagnostic task, for every patient. For the “pass-through” mode, if the input function does not cover the entire range • This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. of the injection time t = 0 to the end of the PET scan * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 15 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: a Advanced Modeled Iterative Max: 9.16 SUV-bw Mean: 5.84 SUV-bw Reconstruction by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD b Mean: c 1.86 mg/min/100ml Mean: 114.02% Introduction: Evolution of Siemens CT image reconstruction technologies Image reconstruction is an essential technology that every computed tomography (CT) scanner requires for operation. The function of CT image reconstruction is to translate all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction is commonly referred to as filtered back projection (FBP), in which measured X-ray projections are directly translated into images. In most modern scanners, it is likely Figure 7. Example MIP coronal that not all measured data can be used for image reconstruction with FBP,1 i.e., not images from a patient with small all radiation dose applied to the patient is actually used for image reconstruction. To cell lung cancer. (a) SUV, (b) MRFDG address this, Siemens Healthineers CT scanners offer an improved three-dimensional d e (mg/min/100ml) and (c) DVFDG (%) from direct reconstruction, while (d) FBP, called weighted filtered back projection (WFBP).2 and (e) are the respective MRFDG and A common characteristic of both FBP and WFBP is that they do not consider statistical DVFDG parametric images from an indi- properties of measured X-ray projections. What this means is that all CT projections rect image-based formation. Note the difference in the noise characteristics collected in the detectors are weighted the same, regardless of their quality. With and image quality with the Patlak the increased focus in dose reduction, the lack of inclusion of statistical properties transformation during reconstruction of conventional FBP or WFBP become an important barrier that prevents further appearing less noisy. A suspicious radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art lesion has been segmented to CT scanners have been developed with more advanced technology, known as iterative “illustrate the measurement units. reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Data courtesy of Yale University. statistical properties of measured CT projection data can be readily incorporated into the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. Reconstruction of parametric volumes of MRFDG and DVFDG There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens A major technical innovation of this feature is to perform the Patlak transformation Healthineers has been placing emphasis on devising technical solutions that can help during the reconstruction process and directly form two parametric volumes: MRFDG and to consistently achieve the right dose, for the right diagnostic task, for every patient. DVFDG27,32–36 using the blood input function CB(t) and dynamic emission sinograms as inputs. This was in line with the ALARA principle, that is to use a dose that is “As Low As Traditionally, the Patlak transformation was done on a series of dynamic PET images on Reasonably Achievable” to deliver diagnostic image quality. a voxel-by-voxel basis in image space. Performing the Patlak transformation during reconstruction has the following advantages (see Figure 7): Improved noise characteristics • Better delineation of organs and tumors • 16 2 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: More efficient workflow due to faster parametric volume formation Advanced Modeled Iterative Synchronization of blood input function and CBM sinogram Reconstruction FlowMotion continuous bed motion acquisition offers great flexibility to acquire dynamic data for parametric imaging in terms of scan range, scan direction, and scan speed compared to step and shoot acquisition. Accurate imaging time information is needed for the correct quantification of parametric PET kinetic parameters such as metabolism rate. Therefore, in order for a PET system to perform parametric imaging, the time information must be tracked accurately during the dynamic scan procedure by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and synchronized to the blood input function and dynamic PET data. Unlike in S&S and Rainer Raupach, PhD acquisitions, CBM time information is slice- rather than acquisition-frame dependent as illustrated in Figure 8. Each slice in the CBM volume corresponds to a different time point in the blood input function. To track the CBM scan, we record multiple finely-sampled bed tag pairs. In each bed Introduction: Evolution of Siemens CT image reconstruction technologies tag, we record the time and position information. By using these bed tags, we are able to Development of IR methods accurately calculate the time information for each slice. This also allows us to do flexible Image reconstruction is an essential technology that every computed tomography (CT) scans with CBM. Bi-directional and sequential, same-direction scan modes are supported It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate in the current release. in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative CBM scan direction A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections CB(t) first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is t1 tn of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported Figure 8. Example where, after the first reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in ~6 minute list mode acquisition over statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults the heart, a whole body CBM scan is and pediatrics.7-10 performed from head-to-foot. Each the CT image reconstruction process. This would allow, for example, low-quality (noisy) image slice corresponds to a different projections to carry less weight than high-quality projections. Time time point in the blood input function. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 17 CB(t) CB(t) CB(t) CB(t) White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: Figure 8. Each image slice corresponds to a different time point in blood input function. Figure 8. Each image slice corresponds to a different time point in blood input function. Direct parametric volume reconstruction Advanced Modeled Iterative Direct parametric volume reconstruction Input dynamic CBM sinograms and blood input function Direct parametric volume reconstruction We implemented direct parametric reconstruction methods for CBM data to form Figure 8. Each image slice corresponds to a different time point in blood input function. the parametric images. Both the value for each time point and the integral of blood Figure 8. Each image slice corresponds to a different time point in blood input function. Reconstruction We implemented direct parametric reconstruction methods for CBM data to form the parametric We implemented direct parametric reconstruction methods for CBM data to form the parametric input function are calculated for every dynamic frame and axial slice. Each axial slice Direct parametric volume reconstruction images. Both the value for each time point and the integral of blood input function are calculated images. Both the value for each time point and the integral of blood input function are calculated corresponds to specific time points and can be calculated from bed tags. After t*, the Direct parametric volume reconstruction Caluclate CB(t) and integral of CB(t) for each frame for We implemented direct parametric reconstruction methods for CBM data to form the parametric for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and each axial slice based on bed tags tracer activity at each voxel over time xj (t) can be modeled as follows according to for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and We implemented direct parametric reconstruction methods for CBM data to form the parametric images. Both the value for each time point and the integral of blood input function are calculated can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be the Patlak model (see Figures 1 and 2). can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be images. Both the value for each time point and the integral of blood input function are calculated for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and modeled as follows according to the Patlak model (see Figures 1 and 2). modeled as follows according to the Patlak model (see Figures 1 and 2). for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and Initialize parametric images Ki and DV can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be modeled as follows according to the Patlak model (see Figures 1 and 2). ! 𝑡𝑡 > 𝑡𝑡∗ 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , and Rainer Raupach, PhD ( ) (5) (5) ! 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , ( ) modeled as follows according to the Patlak model (see Figures 1 and 2). ! 𝑡𝑡 > 𝑡𝑡∗ (5) ! where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! ! 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , 𝑡𝑡 > 𝑡𝑡∗ Calculate frame emission images with Patlak equation where j is the index of image voxel, Ki (5) ! where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! ! 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , is the net influx rate and DVFDG 𝑡𝑡 > 𝑡𝑡∗ (5) using Ki and DV from previous iteration is the distribution volume. ! The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. Introduction: Evolution of Siemens CT image reconstruction technologies The expected value of dynamic raw CBM PET data can be modeled as follows. ! Update frame images with EM based on estimation The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. 𝑦𝑦!(𝑡𝑡) = Image reconstruction is an essential technology that every computed tomography (CT) 𝑦𝑦!(𝑡𝑡) = !!! 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) (6) from previous step ! The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. !!! scanner requires for operation. The function of CT image reconstruction is to translate - where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) (6) all of the acquired X-ray data (raw data) into a meaningful three-dimensional 𝑦𝑦!(𝑡𝑡) = ! !!! ( ) 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) (6) (6) of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, ! where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value representation of the patient. The most well-known method of image reconstruction 𝑦𝑦!(𝑡𝑡) = !!! 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) (6) M No where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value and 𝑠𝑠 is the expected value for scatter events. is commonly referred to as filtered back projection (FBP), in which measured X-ray of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, Update Ki and DV based on linear fitting with where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value where t is the frame index for dynamic sinograms, p is the system matrix, r is the expected of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, projections are directly translated into images. In most modern scanners, it is likely frame emission images No and 𝑠𝑠 is the expected value for scatter events. Parametric images can be reconstructed by maximizing the following Poisson log likelihood value of random events, i is the sinogram bin index, j is the voxel index, N is the number of of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, that not all measured data can be used for image reconstruction with FBP,1 and 𝑠𝑠 is the expected value for scatter events. i.e., not voxels, and s is the expected value for scatter events. all radiation dose applied to the patient is actually used for image reconstruction. To function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity and 𝑠𝑠 is the expected value for scatter events. Parametric images can be reconstructed by maximizing the following Poisson log likelihood address this, Siemens Healthineers CT scanners offer an improved three-dimensional constraint. Parametric images can be reconstructed by maximizing the following Poisson log likelihood Number of nested Parametric images can be reconstructed by maximizing the following Poisson log iterations reached? FBP, called weighted filtered back projection (WFBP).2 Parametric images can be reconstructed by maximizing the following Poisson log likelihood function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity likelihood function from measured dynamic data y(t) with respect to Ki and DVFDG Nested Loop constraint. function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity under a non-negativity constraint. 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝐷𝐷 = constraint. !! !! 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) A common characteristic of both FBP and WFBP is that they do not consider statistical (7) !!! !!! Yes properties of measured X-ray projections. What this means is that all CT projections constraint. 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝐷𝐷 = collected in the detectors are weighted the same, regardless of their quality. With 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝐷𝐷 = !! !! 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) !! !! Confidential 18 the increased focus in dose reduction, the lack of inclusion of statistical properties 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝑉𝑉FDG = !!! !!! !!! !! !!! !! () - ) 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) - (7) (7) Number of main (7) (7) iterations reached? of conventional FBP or WFBP become an important barrier that prevents further !!! !!! Main Loop M M radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art Confidential 18 Confidential 18 Confidential 18 Yes CT scanners have been developed with more advanced technology, known as iterative Where t is frame index, i is the sinogram bin index, Nt is the number of dynamic frames, and Ni Where 𝑡𝑡 is frame index, 𝑖𝑖 is the sinogram bin index, 𝑁𝑁! is the number of dynamic frames, and reconstruction (IR). Not surprisingly, among the key advantages of IR is that the is the number of sinogram bins for each frame. Convert Ki image to MRFDG 𝑁𝑁! is the number of sinogram bins for each frame. statistical properties of measured CT projection data can be readily incorporated into Mathematically, the reconstruction of Ki and DVFDG can be formulated as follows. the CT image reconstruction process. This would allow, for example, low-quality (noisy) Mathematically, the reconstruction of 𝐾𝐾! and DV can be formulated as follows. projections to carry less weight than high-quality projections. Output parametric images MRFDG and DV There has been an expanding utilization of IR in clinical practice in recent years, 𝐾𝐾!, 𝐷𝐷𝑉𝑉FDG = arg max!!!!,!"!!𝐿𝐿(𝑦𝑦(𝑡𝑡)|𝐾𝐾!, 𝐷𝐷𝐷𝐷FDG) primarily due to the increased focus on radiation dose optimization. Of note, Siemens (8) (8) Healthineers has been placing emphasis on devising technical solutions that can help Using an optimization transfer, a nested Expectation Maximization (EM) update algorithm can to consistently achieve the right dose, for the right diagnostic task, for every patient. be derived for the parametric images32. In the main loop, we updated the emission images using Using an optimization transfer, a nested Expectation Maximization (EM) update This was in line with the ALARA principle, that is to use a dose that is “As Low As algorithm can be derived for the parametric images32. In the main loop, we updated the Reasonably Achievable” to deliver diagnostic image quality. sinogram data and emission images estimated from parametric images in the previous loop. emission images using sinogram data and emission images estimated from parametric After emission images are estimated in the main loop for each frame, the parametric images 𝐾𝐾! images in the previous loop. After emission images are estimated in the main loop for and DV are updated based on the Patlak linear equation using an iterative procedure in the each frame, the parametric images Ki and DVFDG are updated based on the Patlak linear nested loop. 𝐾𝐾! can be converted into MRFDG according to user inputs. We adopted an ordered equation using an iterative procedure in the nested loop. Ki can be converted into MRFDG according to user inputs. We adopted an ordered subset version of the EM algorithm subset version of the EM algorithm to speed up the convergence. The typical number of main to speed up the convergence. The typical number of main loops (iterations), subsets, loops (iterations), subsets, and nested loops are 3, 21 and 20, respectively. and nested loops are 3, 21 and 20, respectively. A diagram of the algorithm is shown in Figure 9. A diagram of the algorithm is shown in Figure 9. 18 2 Confidential 19 CB(t) CB(t) CB(t) CB(t) White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper Figure 8. Each image slice corresponds to a different time point in blood input function. Direct parametric volume reconstruction Figure 8. Each image slice corresponds to a different time point in blood input function. ADMIRE: Advanced Modeled Iterative Input dynamic CBM sinograms and blood input function We implemented direct parametric reconstruction methods for CBM data to form Direct parametric volume reconstruction Direct parametric volume reconstruction Figure 8. Each image slice corresponds to a different time point in blood input function. the parametric images. Both the value for each time point and the integral of blood We implemented direct parametric reconstruction methods for CBM data to form the parametric input function are calculated for every dynamic frame and axial slice. Each axial slice Reconstruction Direct parametric volume reconstruction We implemented direct parametric reconstruction methods for CBM data to form the parametric Figure 8. Each image slice corresponds to a different time point in blood input function. Direct parametric volume reconstruction corresponds to specific time points and can be calculated from bed tags. After t*, the images. Both the value for each time point and the integral of blood input function are calculated images. Both the value for each time point and the integral of blood input function are calculated Caluclate CB(t) and integral of CB(t) for each frame for We implemented direct parametric reconstruction methods for CBM data to form the parametric for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and each axial slice based on bed tags tracer activity at each voxel over time xj (t) can be modeled as follows according to for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be the Patlak model (see Figures 1 and 2). We implemented direct parametric reconstruction methods for CBM data to form the parametric images. Both the value for each time point and the integral of blood input function are calculated modeled as follows according to the Patlak model (see Figures 1 and 2). for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and modeled as follows according to the Patlak model (see Figures 1 and 2). images. Both the value for each time point and the integral of blood input function are calculated for every dynamic frame and axial slice. Each axial slice corresponds to specific time points and and DV can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be Initialize parametric images Ki modeled as follows according to the Patlak model (see Figures 1 and 2). 𝑡𝑡 > 𝑡𝑡∗ by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , ! can be calculated from bed tags. After t*, the tracer activity at each voxel over time 𝑥𝑥! 𝑡𝑡 can be (5) ! and Rainer Raupach, PhD (5) 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! (5) ! 𝑡𝑡 > 𝑡𝑡∗ modeled as follows according to the Patlak model (see Figures 1 and 2). ! where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , ! 𝑡𝑡 > 𝑡𝑡∗ (5) Calculate frame emission images with Patlak equation ! (5) 𝑡𝑡 > 𝑡𝑡∗ where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. is the net influx rate and DVFDG where j is the index of image voxel, Ki 𝑐𝑐! 𝜏𝜏 𝑑𝑑𝑑𝑑 + 𝐷𝐷𝐷𝐷!𝑐𝑐! 𝑡𝑡 , 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! 𝑥𝑥! 𝑡𝑡 = 𝐾𝐾!! ! using Ki and DV from previous iteration where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. is the distribution volume. ! The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. Introduction: Evolution of Siemens CT image reconstruction technologies The expected value of dynamic raw CBM PET data can be modeled as follows. The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. where 𝑗𝑗 is the index of image voxel, 𝐾𝐾! is the net influx rate and DV is the distribution volume. Development of IR methods 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. 𝑦𝑦!(𝑡𝑡) = + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) (6) ! Update frame images with EM based on estimation !!! Image reconstruction is an essential technology that every computed tomography (CT) from previous step scanner requires for operation. The function of CT image reconstruction is to translate (6) The expected value of dynamic raw CBM PET data 𝑦𝑦 can be modeled as follows. 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 ! 𝑦𝑦!(𝑡𝑡) = It is well known that the degradation in image quality, most notably an increase + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) !!! + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) (6) ! 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 𝑦𝑦!(𝑡𝑡) = where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value !!! in image noise, is the standard tradeoff for achieving a substantial dose reduction. (6) of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, 𝑦𝑦!(𝑡𝑡) = 𝑝𝑝!"𝑥𝑥! 𝑡𝑡 ! + 𝑟𝑟!(𝑡𝑡) + 𝑠𝑠!(𝑡𝑡) all of the acquired X-ray data (raw data) into a meaningful three-dimensional (6) The first IR technology commercially developed by Siemens Healthineers was Iterative !!! where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value representation of the patient. The most well-known method of image reconstruction where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased No of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, is commonly referred to as filtered back projection (FBP), in which measured X-ray and 𝑠𝑠 is the expected value for scatter events. Update Ki and DV based on linear fitting with where t is the frame index for dynamic sinograms, p is the system matrix, r is the expected where 𝑡𝑡 is the frame index for dynamic sinograms, 𝑝𝑝 is the system matrix, 𝑟𝑟 is theexpected value image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology No and 𝑠𝑠 is the expected value for scatter events. of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, projections are directly translated into images. In most modern scanners, it is likely frame emission images that is effective in reducing image noise in a variety of clinical applications.4, 5 Parametric images can be reconstructed by maximizing the following Poisson log likelihood and 𝑠𝑠 is the expected value for scatter events. that not all measured data can be used for image reconstruction with FBP,1 i.e., not of random events, 𝑖𝑖 is the sinogram bin index, j is the voxel index, N is the number of voxels, value of random events, i is the sinogram bin index, j is the voxel index, N is the number of However, it is expected that IR technologies not only aid in noise reduction but also and 𝑠𝑠 is the expected value for scatter events. voxels, and s is the expected value for scatter events. all radiation dose applied to the patient is actually used for image reconstruction. To function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity Parametric images can be reconstructed by maximizing the following Poisson log likelihood in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional constraint. Parametric images can be reconstructed by maximizing the following Poisson log likelihood with reduced dose or fast acquisition techniques. In response to this, the next IR Number of nested Parametric images can be reconstructed by maximizing the following Poisson log iterations reached? Parametric images can be reconstructed by maximizing the following Poisson log likelihood function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity and DVFDG FBP, called weighted filtered back projection (WFBP).2 likelihood function from measured dynamic data y(t) with respect to Ki technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative Nested Loop function from measured dynamic data 𝑦𝑦 𝑡𝑡 with respect to 𝐾𝐾! and DV under a non-negativity under a non-negativity constraint. 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) !! !! 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝐷𝐷 = constraint. constraint. (7) A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ !!! !!! first IR technology that integrated a correction loop in the raw-data domain (a.k.a. Yes properties of measured X-ray projections. What this means is that all CT projections constraint. 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝐷𝐷 = 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) !! !! !! (7) Confidential 18 !! 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) (7) 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝐷𝐷 = collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward Number of main 𝑦𝑦! 𝑡𝑡 log (𝑦𝑦! 𝑡𝑡 ) − 𝑦𝑦!(𝑡𝑡) !! (7) (7) !!! !!! 𝐿𝐿 𝑦𝑦 𝑡𝑡 𝐾𝐾!, 𝐷𝐷𝑉𝑉FDG = !! the increased focus in dose reduction, the lack of inclusion of statistical properties !!! !!! projection. This correction loop that operates through to the raw-data domain is !!! !!! particularly helpful for reducing spiral artifacts. A second correction loop in image Main Loop iterations reached? Confidential 18 Confidential 18 of conventional FBP or WFBP become an important barrier that prevents further space is applied iteratively to reduce image noise. SAFIRE has been used extensively Confidential 18 radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art Where t is frame index, i is the sinogram bin index, Nt is the number of dynamic frames, CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported Yes Where 𝑡𝑡 is frame index, 𝑖𝑖 is the sinogram bin index, 𝑁𝑁! is the number of dynamic frames, and reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in statistical properties of measured CT projection data can be readily incorporated into 𝑁𝑁! is the number of sinogram bins for each frame. and Ni is the number of sinogram bins for each frame. applications ranging from routine to specialized body and neuro CT – in both adults Convert Ki image to MRFDG the CT image reconstruction process. This would allow, for example, low-quality (noisy) Mathematically, the reconstruction of Ki and DVFDG can be formulated as follows. and pediatrics.7-10 Figure 9. Diagram of direct Mathematically, the reconstruction of 𝐾𝐾! and DV can be formulated as follows. projections to carry less weight than high-quality projections. Output parametric images MRFDG and DV parametric reconstruction with nested EM algorithm. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens 𝐾𝐾!, 𝐷𝐷𝑉𝑉FDG = arg max!!!!,!"!!𝐿𝐿(𝑦𝑦(𝑡𝑡)|𝐾𝐾!, 𝐷𝐷𝐷𝐷FDG) (8) (8) Healthineers has been placing emphasis on devising technical solutions that can help Using an optimization transfer, a nested Expectation Maximization (EM) update algorithm can As seen previously, Figure 7 shows the advantages of direct parametric formation over Using an optimization transfer, a nested Expectation Maximization (EM) update be derived for the parametric images32. In the main loop, we updated the emission images using to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As indirect parametric reconstruction with respect to image quality. Overall, the indirect sinogram data and emission images estimated from parametric images in the previous loop. Reasonably Achievable” to deliver diagnostic image quality. algorithm can be derived for the parametric images32. In the main loop, we updated the parametric formation is noisier than direct methods, and the direct parametric images After emission images are estimated in the main loop for each frame, the parametric images 𝐾𝐾! emission images using sinogram data and emission images estimated from parametric show better delineation of the organs and tumors. each frame, the parametric images Ki and DVFDG are updated based on the Patlak linear and DV are updated based on the Patlak linear equation using an iterative procedure in the images in the previous loop. After emission images are estimated in the main loop for equation using an iterative procedure in the nested loop. Ki can be converted into MRFDG nested loop. 𝐾𝐾! can be converted into MRFDG according to user inputs. We adopted an ordered * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical subset version of the EM algorithm to speed up the convergence. The typical number of main according to user inputs. We adopted an ordered subset version of the EM algorithm location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the to speed up the convergence. The typical number of main loops (iterations), subsets, appropriate dose to obtain diagnostic image quality for the particular clinical task. loops (iterations), subsets, and nested loops are 3, 21 and 20, respectively. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical and nested loops are 3, 21 and 20, respectively. location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to A diagram of the algorithm is shown in Figure 9. A diagram of the algorithm is shown in Figure 9. determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 19 Confidential 19 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: Units of parametric images Advanced Modeled Iterative If the LC is set to 1.0 (default), then the Ki parametric image represents MRFDG rather than MRGlu . The units of MRFDG can be either Reconstruction mg of 18F FDG of tissue) or μmol of 18F FDG min (cm3 min (cm3 of tissue) , depending on the unit used to measure the subject’s plasma glucose (e.g. mg/dL or by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, mmol/L, respectively), where 1 mg of 18F FDG = 5.52 μmol. The DVFDG parametric volume is and Rainer Raupach, PhD expressed in units of percentage, and as noted above, can have values greater than 100%. Factory default parametric PET Patlak workflows Introduction: Evolution of Siemens CT image reconstruction technologies The FlowMotion Multiparametric PET Suite Patlak feature has two basic acquisition protocols, denoted as automated and standard. Please see Figures 3 and 10 for more Image reconstruction is an essential technology that every computed tomography (CT) details about these protocols. scanner requires for operation. The function of CT image reconstruction is to translate all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction is commonly referred to as filtered back projection (FBP), in which measured X-ray Standard acquisition protocol projections are directly translated into images. In most modern scanners, it is likely that not all measured data can be used for image reconstruction with FBP,1 Patient rests quietly i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To with eyes closed address this, Siemens Healthineers CT scanners offer an improved three-dimensional FBP, called weighted filtered back projection (WFBP).2 A common characteristic of both FBP and WFBP is that they do not consider statistical WB dynamic properties of measured X-ray projections. What this means is that all CT projections collected in the detectors are weighted the same, regardless of their quality. With t0 tWB tend the increased focus in dose reduction, the lack of inclusion of statistical properties FDG injection in Multi-pass dynamic WB CBM (10-30 min) of conventional FBP or WFBP become an important barrier that prevents further radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art uptake room Figure 10. Pictorial representation CT scanners have been developed with more advanced technology, known as iterative of the two different acquisition reconstruction (IR). Not surprisingly, among the key advantages of IR is that the protocols that can be used to acquire statistical properties of measured CT projection data can be readily incorporated into Patlak parametric PET data. Note that Fully-automated acquisition protocol the CT image reconstruction process. This would allow, for example, low-quality (noisy) the automated protocol (bottom) is automated from the start of the PET projections to carry less weight than high-quality projections. scan to the images appearing in the Single bed listmode There has been an expanding utilization of IR in clinical practice in recent years, database. In the standard protocol primarily due to the increased focus on radiation dose optimization. Of note, Siemens acq over heart (top), the PET data are not self- (≈ 6 min) contained. The bolus part of the input Healthineers has been placing emphasis on devising technical solutions that can help function was not imaged by the PET to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Heart WB dynamic scanner, and the user must enter this missing information as a CSV file Reasonably Achievable” to deliver diagnostic image quality. t0 tWB tend (see Figure 5A). An input function from a CSV file can also be entered offline in the automated protocol in order FDG injection on Multi-pass dynamic WB CBM (30-50 min) to validate the automated image- bed at start of derived input function. acquisition 2 20 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Automated Workflow WholebodyDynamicCBM_Patlak (Adult) Advanced Modeled Iterative In the automated workflow the 18F FDG is injected on the bed at time t0, and the PET Topogram acquisition is started at the same time or just before. A factory default Patlak workflow Reconstruction is present when a valid Patlak license is present and is called “WholebodyDynamicCBM_ CT WB RT Patlak.” The Parametric PET feature is only available for FlowMotion acquisitions and is Pause not available for step and shoot acquisitions. PET Input Rgn The acquisition chronicle is very similar to a whole-body dynamic FlowMotion acquisition; Pause it just contains an extra single-bed position PET scan after the CT (see Figure 11). PET WB Dyn 0000 by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD Figure 11. The acquisition chronicle A typical acquisition planning is shown in Figure 3. The same CT is used for both for a WholebodyDynamicCBM_ PET acquisitions to perform attenuation and scatter corrections. Patlak protocol. The defaults for the two PET acquisitions and reconstructions are outlined below. Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods 1. Single-bed PET acquisition centered over subject’s heart Image reconstruction is an essential technology that every computed tomography (CT) a. 6-minute acquisition duration It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate b. Reconstruction in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional i. Dynamic and used to generate the bolus part of the input function The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction 12 frames x 5s, 6 frames x 10s, 8 frames x 30s • Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray ii. decay correction is set to injection time image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 2. Whole-body dynamic PET acquisition that not all measured data can be used for image reconstruction with FBP,1 i.e., not However, it is expected that IR technologies not only aid in noise reduction but also a. 74-minute acquisition duration all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions b. Figure 2 shows t* at 50 minutes address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR c. 18 total passes FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative i. 8 passes x 3 min A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 ii. 10 passes x 5 min SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. Best practice is to keep the duration of the passes the same regardless • collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward of subject height, so bed speed should be faster for taller subjects the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is d. 1st reconstruction is the online whole-body dynamic reconstructions of each pass of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image i. decay correction is set to injection time t0 radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively e. 2nd reconstruction CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported i. Dynamic reconstruction with the same axial FOV and reconstruction parameters reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in as the single-bed cardiac region reconstruction 1.b above statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults ii. These input region “tail” dynamic images will be merged with the bolus input the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 region images from 1.b above (see Figure 12), and this dynamic DICOM series projections to carry less weight than high-quality projections. will be stored in the database iii. Decay correction is set to injection time t0 There has been an expanding utilization of IR in clinical practice in recent years, f. 3rd reconstruction primarily due to the increased focus on radiation dose optimization. Of note, Siemens i. Creates the image volume where SUVs can be calculated by summing the Healthineers has been placing emphasis on devising technical solutions that can help last six dynamic frames (50-80 minutes p.i.) to consistently achieve the right dose, for the right diagnostic task, for every patient. g. 4th reconstruction This was in line with the ALARA principle, that is to use a dose that is “As Low As i. Patlak reconstruction Reasonably Achievable” to deliver diagnostic image quality. Passes the last six sinograms to the Patlak reconstruction algorithm • (50-80 minutes p.i., so t*=50 min, see Figure 2 above) Note: minimum number of sinograms for a Patlak reconstruction is 3 – and the maximum is 6 * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical Uses the aorta input function by default location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the • The MRFDG and DVFDG Patlak Parametric Volumes will be stored in the database appropriate dose to obtain diagnostic image quality for the particular clinical task. • ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical If the tracer was not 18F FDG or the subject’s blood glucose was not entered, – location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the then the slope parametric volume will have units of ml/min/ml appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 21 3 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: Figure 12. The reconstruction The user can choose a different input function in the Patlak sub-taskcard, which appears sub-taskcard for the 2nd reconstruction when a Patlak reconstruction has been selected (see Figure 13). Advanced Modeled Iterative of the whole-body dynamic data from the Patlak protocol. The Input Region Reconstruction field showing a reconstruction protocol Recon job 1 2 3 4 5 6 7 8 Series description INPUT REGION MERGED means that the current reconstruction is linked back to the PET input region Pass 1 19 Range Custom -296.5 -75.5 Attenuation correction CT bolus dynamic reconstruction (1.b in Output Image type Corrected AC CT WB_1 (1-1) the outline above), which fixes most of Scatter Correction the PET reconstruction parameters to Recon method TrueX+TOF (ultraHD-PET) Relative the same ones that were used for PET by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Iterations 2 Subsets 21 Registration Matrices input region bolus dynamic reconstruc- and Rainer Raupach, PhD Default tion (values that are gray cannot be edited), including using the same axial Image size 200 v Zoom 1.0 Input Region FOV as shown in the custom range INPUT REGION BOLUS (2-2 fields. The dynamic image volumes of Filter Gaussian FWHM (mm) 5.0 this reconstruction will be merged with those from bolus dynamic cardiac Introduction: Evolution of Siemens CT image reconstruction technologies Offset (mm) × 0 =Y 0 Additional Settings reconstruction and stored in the data- base using the “Series description” field Image reconstruction is an essential technology that every computed tomography (CT) Comments in the figure, which lists the name as scanner requires for operation. The function of CT image reconstruction is to translate “INPUT REGION MERGED”. all of the acquired X-ray data (raw data) into a meaningful three-dimensional Routine Scan Recon Auto Tasking representation of the patient. The most well-known method of image reconstruction is commonly referred to as filtered back projection (FBP), in which measured X-ray Figure 13. The Patlak sub-taskcard projections are directly translated into images. In most modern scanners, it is likely allows the user to select the input that not all measured data can be used for image reconstruction with FBP,1 i.e., not function, change the LC and verify all radiation dose applied to the patient is actually used for image reconstruction. To the subject’s blood glucose value. The address this, Siemens Healthineers CT scanners offer an improved three-dimensional selected input function is shown in the FBP, called weighted filtered back projection (WFBP).2 graph, where the symbols represent the original measured value and A common characteristic of both FBP and WFBP is that they do not consider statistical the line shows the fitted values used properties of measured X-ray projections. What this means is that all CT projections during the Patlak reconstruction. The Recon job 1 2 3 4 5 6 1 Series description PET WB Dynamic collected in the detectors are weighted the same, regardless of their quality. With LC is set to 1.0 by default (range is 0.5- Figure 13. The Patlak sub-taskcard allows the user to select the input function, change the LC the increased focus in dose reduction, the lack of inclusion of statistical properties 2.0 inclusive) and the user-entered and verify the subject’s blood glucose value. The selected input function is shown in the graph, Lumped Constant 1.0 Blood Glucose 0.00 of conventional FBP or WFBP become an important barrier that prevents further mmol/L Display SUV blood glucose plasma from the dose where the symbols represent the original measured value and the line shows the fitted values used during the Patlak reconstruction. The LC is set to 1.0 by default (range is 0.5-2.0 inclusive) sub-taskcard is shown. The y-axis units radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art and the user-entered blood glucose plasma from the dose sub-taskcard is shown. The y-axis can be toggled between SUV (shown) CT scanners have been developed with more advanced technology, known as iterative and Bq/ml. The button will save reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Input Function IF_AORTA_20170808_140205 units can be toggled between SUV (shown) and Bq/ml. The button will save two CSV files to two CSV files to the directory H:\Site- statistical properties of measured CT projection data can be readily incorporated into the directory H:\SiteData\PETIF—the original input function data points and the actual fitted input Data\PETIF—the original input func- function that was used during the Patlak reconstruction (contains “resampled” in the CSV the CT image reconstruction process. This would allow, for example, low-quality (noisy) 34.4 tion data points and the actual fitted filename). The x-axis and y-axis scales can be modified by moving the horizontal and vertical projections to carry less weight than high-quality projections. 27.1 input function that was used during the sliders on the left, and clicking the blue circular arrow button will reset the scaling. Patlak reconstruction (contains There has been an expanding utilization of IR in clinical practice in recent years, SUV 12.5 “resampled” in the CSV filename). primarily due to the increased focus on radiation dose optimization. Of note, Siemens 5.2 - Standard Workflow The x-axis and y-axis scales can be Healthineers has been placing emphasis on devising technical solutions that can help -2.1 modified by moving the horizontal and The standard workflow is identical to the standard clinical 18F FDG workflow used in the clinic to consistently achieve the right dose, for the right diagnostic task, for every patient. 00:00:00 00:10:25 00:20:50 DD:31:15 00:41:40 00:52:05 01:02:30 vertical sliders on the left, and clicking Time (hh:mm:ss) today, with two exceptions: the whole-body acquisition needs to be dynamic, with at least 3 This was in line with the ALARA principle, that is to use a dose that is “As Low As the blue circular arrow button will passes, and an input function needs to be estimated and entered by the user. The same reset the scaling. Reasonably Achievable” to deliver diagnostic image quality. acquisition chronicle in Figure 11 can be used except that the first PET input region acquisition Routine Scan Recon Auto Tasking Patlak will not be present. When setting up a dynamic, whole-body reconstruction, the “Input Region” of Figure 12 should be set to “Advanced User (CSV)”. The UI in Figure 5a will appear, and the user should select a valid CSV file that contains the measured input function. This input function may come from several sources as noted in the Input function user-entered CB(t) section above. 2 22 Confidential 25 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Standard Workflow Advanced Modeled Iterative The standard workflow is identical to the standard clinical 18F FDG workflow used in the clinic today, with two exceptions: the whole-body acquisition needs to be dynamic, Reconstruction with at least 3 passes, and an input function needs to be estimated and entered by the user. The same acquisition chronicle in Figure 11 can be used except that the first PET input region acquisition will not be present. When setting up a dynamic, whole-body reconstruction, the “Input Region” of Figure 12 should be set to “Advanced User (CSV)”. The UI in Figure 5A will appear, and the user by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, should select a valid CSV file that contains the measured input function. This input and Rainer Raupach, PhD function may come from several sources as noted in the Input function user-entered CB(t) section. Retrospective QC Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods The aorta, LV, and liver VOIs, which were found automatically on the acquisition Image reconstruction is an essential technology that every computed tomography (CT) workplace are stored in the database as shown in Figure 14. It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional Patient Browser Patient Applications The first IR technology commercially developed by Siemens Healthineers was Iterative Transfer Edit PET View Filter Evaluation Sort Options Help representation of the patient. The most well-known method of image reconstruction PET 3 6 Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 AT693 i.e., not that not all measured data can be used for image reconstruction with FBP,1 However, it is expected that IR technologies not only aid in noise reduction but also R///11 : ER323 all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR geneveHBdynvariableCBMv JA266 FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative [1] 3D Application Data R// / / / / 11111 1 Local Database patient15 PET FDGWBdynamiqu [7] PET TAC Data A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ first IR technology that integrated a correction loop in the raw-data domain (a.k.a. Scheduler PH192 [4] PET Statistics R// / / / / 11111 : properties of measured X-ray projections. What this means is that all CT projections [603] INPUT REGION BOLUS Sinograms collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward projection. This correction loop that operates through to the raw-data domain is [3] INPUT REGION BOLUS the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image [6] INPUT REGION MERGED [602] PET Raw Data R/// / / / radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively [2] AC CT WB-CBM 5.0 HD_FoV since its introduction, and a wealth of scientific literature has consistently supported R/// / / / CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in [1] Topogram 0.6 T80f R/// // / statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 projections to carry less weight than high-quality projections. Patient name patient15 Date of birth 01-Jan-1973 Patient ID Anonymous Study description PET FDGWBdynamique (Adult) Study date 23-Dec-2015 Modality PT Figure 14. The automatically- Instanc ... Instance Type |Instance Date and ... Instance Comm ... There has been an expanding utilization of IR in clinical practice in recent years, 2 [ORIGINAL] [PI 12-Feb-2018 16:29:53 IF LV generated LV and aorta VOIs are stored 1 [ORIGINAL] [PI 12-Feb-2018 16:29:52 IF AORTA primarily due to the increased focus on radiation dose optimization. Of note, Siemens under the “3D Application Data” series name. The input functions are stored Healthineers has been placing emphasis on devising technical solutions that can help under the “PET TAC Data” series name to consistently achieve the right dose, for the right diagnostic task, for every patient. in the database. The entries can be This was in line with the ALARA principle, that is to use a dose that is “As Low As selected as input functions for a Patlak Reasonably Achievable” to deliver diagnostic image quality. Current Filter. Off reconstruction (see Figure 13). * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 23 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: TrueD Tools Advanced Modeled Iterative TrueD on the acquisition workplace console can be used to check for correct anatomical VOI placement, assess subject motion, and move VOIs as needed to account for subject Reconstruction motion and can be used to generate new input functions (see Figures 15 and 16). Another Patlak reconstruction can be done choosing this new motion-corrected input function. Patient Transfer Edit View Image Orientation VRT Type Quantification Tools Reports Options Help patient5 CT, Friday, July 03, 2015 PT AC, Friday, July 03, 2015 by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD Intervention -O- Avg: 1231 8 BgAnL Viewing Baseline Introduction: Evolution of Siemens CT image reconstruction technologies 50 % PET 50 % CT 3 PT 3D Max. 19838 Ecimg Volume Registration Image reconstruction is an essential technology that every computed tomography (CT) Visualization Max 18808 Bq/ML Volume : 14.14 cm MIP 3D scanner requires for operation. The function of CT image reconstruction is to translate Quantification rueD: Cine Control X Quantification Tools Reports Options Help all of the acquired X-ray data (raw data) into a meaningful three-dimensional Properties O representation of the patient. The most well-known method of image reconstruction Choose Color. IM Advanced Fis Cine Ctrl+B is commonly referred to as filtered back projection (FBP), in which measured X-ray 4 Copy to previous slice All Segments projections are directly translated into images. In most modern scanners, it is likely rueD Copy to next slice Ctrl+F Show Max Vol displacement Group VOI Copy VOI for Comparison that not all measured data can be used for image reconstruction with FBP,1 i.e., not Copy Iso-Contour Area for Comparison all radiation dose applied to the patient is actually used for image reconstruction. To VOI Analysis. Shift+F3 address this, Siemens Healthineers CT scanners offer an improved three-dimensional Iso-Contour Threshold FBP, called weighted filtered back projection (WFBP).2 3 Save active time-point VOIs (RT) CT Save all VOls (RT) Hide VOI Graphics Ctrl+F11 A common characteristic of both FBP and WFBP is that they do not consider statistical 78 HU.1983 39 Am Hide Bounding box properties of measured X-ray projections. What this means is that all CT projections V Hide Selected VOI Details Delete Selected VOI A Del collected in the detectors are weighted the same, regardless of their quality. With Report Delete All VOI(s) Ctrl+Delete the increased focus in dose reduction, the lack of inclusion of statistical properties Load AUTO VOI(s) of conventional FBP or WFBP become an important barrier that prevents further 25-Aug-2017 11:30:21 (a) (b) radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the statistical properties of measured CT projection data can be readily incorporated into Figure 15. (a) After loading the dynamic, merged, input-function images with the associated CT images in TrueD, the aorta, LV, and liver VOIs the CT image reconstruction process. This would allow, for example, low-quality (noisy) can be loaded by selecting “Load AUTO VOI(s)”. (b) The VOIs are displayed and copied across the dynamic volumes. A dynamic cine can be played to assess patient motion, and the VOIs can be moved on a volume basis to account for motion, with all VOIs on succeeding volumes moved in the projections to carry less weight than high-quality projections. same manner. Tip: if VOIs were moved and a new input function was saved to the database (see Figure 16B), it is helpful to add a label to the moved There has been an expanding utilization of IR in clinical practice in recent years, VOIs by clicking on the “Report” taskcard (bottom left of 15b), filling in the “Label” field and pressing return when done. This label will appear primarily due to the increased focus on radiation dose optimization. Of note, Siemens in the “Input Function” drop down list shown in Figure 13. Data courtesy of University of Geneva, Geneva, Switzerland. Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. 2 24 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Advanced Modeled Iterative The exact input function that was used for the Patlak reconstruction can be exported as a CSV file (see Figure 13). Reconstruction TrueD: VOI Analysis X Presets Default Quality Control TAC Trending Conditional Formatting Show on Graph All VOIS Time Unit second by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Time Slice LinkSet Metrics Plot On Graph Time Slice 1 Time Slice 2 Time Slice 3 Time Slice 4 Time Slice 5 Time Slice 6 Tim and Rainer Raupach, PhD VOI:1 Time (second) 5.00 15.00 25.00 35.00 45.00 55.00 Min (Bq/mL) 1 455 39343 81909 56565 36133 Max (Bq/mL) ** 2298 5864 84936 161797 160929 91244 Average (Bq/mL) 144 1570 57482 128432 114758 70572 Total Activity (Ba) 2480 90822 202922 19, 17 228 111503 Introduction: Evolution of Siemens CT image reconstruction technologies Standard Deviation (Bq/mL) Development of IR methods 359 785 8702 12356 17974 8511 Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. 1.54e5. all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative 1.23e5 representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased 9.25e4 is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 6.16e4 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 3.08e4 that not all measured data can be used for image reconstruction with FBP,1 i.e., not However, it is expected that IR technologies not only aid in noise reduction but also Metrics (Bq/mL) 0.00 all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions 300 600 900 1200 1500 1800 2100 2400 700 3000' 3300 3600 ALL VOIS address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR Time (second) FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative Add to Report Export to CSV Save As 3673 X-Min X-Max A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 OK SAFIRE was Siemens Healthineers’ Help (a) properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward TrueD: TAC Save As the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is X of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image space is applied iteratively to reduce image noise. SAFIRE has been used extensively · Input Function radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art Figure 16. (a) TrueD on the acquisition CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported Secondary Capture workplace can save TACs as input reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in applications ranging from routine to specialized body and neuro CT – in both adults . BMP File Name functions into the database. Simply statistical properties of measured CT projection data can be readily incorporated into click on the “Save As” button, and the the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 Folder Name |H.\SiteData\TrueD bottom screenshot appears as shown in (b). Select “Input Function”, and a projections to carry less weight than high-quality projections. new input function will be stored in There has been an expanding utilization of IR in clinical practice in recent years, OK Cancel the database. This input function will then be available for selection as primarily due to the increased focus on radiation dose optimization. Of note, Siemens (b) shown in Figure 13. Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 25 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: Use cases Advanced Modeled Iterative Initially, the main use cases of this feature are: Reconstruction •Enabling multiparametric PET in a clinical setting •Using the automated workflow to optimize the standard workflow •Deeper understanding of factors that affect SUV •Augmenting diagnostic information in addition to SUV by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, •Research testing of new PET tracers and/or kinetic models in a clinical setting and Rainer Raupach, PhD The use cases are anticipated to evolve depending on the conclusions of the scientific evaluations of this feature Enabling multiparametric PET in a clinical setting Historically, trained staff and researchers were needed to perform multiparametric Introduction: Evolution of Siemens CT image reconstruction technologies PET, which relegated its use to the clinical research realm. Due to the novel automation Image reconstruction is an essential technology that every computed tomography (CT) innovations of this feature, multiparametric PET can now be performed in the clinic using scanner requires for operation. The function of CT image reconstruction is to translate the same staffing as standard PET/CT imaging. When the automated workflow is run, the all of the acquired X-ray data (raw data) into a meaningful three-dimensional technician simply starts the PET acquisition just before tracer injection on the patient bed, representation of the patient. The most well-known method of image reconstruction and the scanner and console will automatically acquire and process the data. The MRFDG, is commonly referred to as filtered back projection (FBP), in which measured X-ray DVFDG and SUV multiparametric volumes will be automatically stored in the patient projections are directly translated into images. In most modern scanners, it is likely database and shared with e.g. syngo.via MM Oncology for further reading.[a] that not all measured data can be used for image reconstruction with FBP,1 i.e., not Using the automated workflow to optimize the standard workflow all radiation dose applied to the patient is actually used for image reconstruction. To address this, Siemens Healthineers CT scanners offer an improved three-dimensional The automated workflow can be considered as the “super data set” since the data FBP, called weighted filtered back projection (WFBP).2 acquired from a standard workflow is a subset of these data. As noted above, the standard workflow requires an external input function be supplied in the form of a A common characteristic of both FBP and WFBP is that they do not consider statistical CSV file. Therefore, the parametric images created using the automated workflow can properties of measured X-ray projections. What this means is that all CT projections be compared to those created using the standard workflow where an external input collected in the detectors are weighted the same, regardless of their quality. With function was used (e.g. population-based) and any significant differences noted. the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further Deeper understanding of factors that affect SUV radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art As noted above, the SUV is a composite estimate of all activity in a region, which in CT scanners have been developed with more advanced technology, known as iterative the case of 18F FDG, is a combination of both non-metabolized and metabolized 18F FDG. reconstruction (IR). Not surprisingly, among the key advantages of IR is that the The MRFDG estimates only the metabolized component while the DVFDG estimates the statistical properties of measured CT projection data can be readily incorporated into non-metabolized 18F FDG distribution. This physiologically meaningful way of separating the CT image reconstruction process. This would allow, for example, low-quality (noisy) the components of an SUV image may lead to a deeper understanding of the SUV. projections to carry less weight than high-quality projections. With designated layouts for this data, windowing presets and clinically feasible scaling There has been an expanding utilization of IR in clinical practice in recent years, of the additional units besides SUV, syngo.via MM Oncology can help support gathering primarily due to the increased focus on radiation dose optimization. Of note, Siemens those insights. Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. Augment diagnostic information in addition to SUV This was in line with the ALARA principle, that is to use a dose that is “As Low As In addition to the standard SUV diagnostic volume, two parametric volumes can Reasonably Achievable” to deliver diagnostic image quality. now be created representing MRFDG and DVFDG. Sites can build experience with these new parametric volumes to determine their usefulness for clinical diagnosis and patient follow-up after treatment. 26 2 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Research testing of new tracers and non-Patlak kinetic models Advanced Modeled Iterative While this feature has only been tested with 18F FDG data acquired according to the recommended factory protocol, it can be used for other suitable tracers that meet the Reconstruction Patlak assumptions (see Patlak modeling section), but a warning to the user will be issued. For tracers where the Patlak assumptions are not met, the acquisition protocol from the automated workflow can still be used to acquire the data, but a Patlak reconstruction to form the parametric images will not be suitable. The dynamic whole- body series, merged, input-region dynamic series, auto-created VOIs, and auto-created by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, input function can all be exported from the database and imported into offline kinetic modeling analysis tools. All of the PET dynamic data are decay corrected to the injection and Rainer Raupach, PhD time of the radiopharmaceutical so no modifications of the DICOM information is needed, and the data can be imported “as is”. Offline kinetic modeling allows for many different types of models to be fitted to the dynamic image data, which can assist in fast and efficient new PET tracer and therapeutic drug development. Note that non-Patlak models such as compartmental models can be fit to 18F FDG data so the early uptake can be Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods modeled appropriately (i.e. use of the data acquired before time t*, which is a Patlak Image reconstruction is an essential technology that every computed tomography (CT) model constraint, see above). It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction Practical considerations Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology Due to the length of scan time for the automated workflow, note that: projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 1. Subjects may not tolerate scanning with arms up However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To a. If arms down is needed, ask subjects to keep arms close to their torso or on in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional top of their torso so they fit into the measured central 50 cm transverse CT FOV, with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 to minimize CT truncation artifacts technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative A common characteristic of both FBP and WFBP is that they do not consider statistical b. Arms down may be required for blood sampling access Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. 2. Precautions should be taken to minimize subject movement collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward a. Comfortable constraints the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is b. Relaxing atmosphere (dim lights, soothing music, etc.) of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image c. Coaching subject before and during the acquisition radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative 3. Performing the automated workflow on the first patient of the day may be optimum since its introduction, and a wealth of scientific literature has consistently supported reconstruction (IR). Not surprisingly, among the key advantages of IR is that the a. Logistically this does not affect the clinical scheduling since no PET/CT scanning the capabilities of SAFIRE to reduce dose while maintaining high image quality in statistical properties of measured CT projection data can be readily incorporated into is done during uptake of first patient applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) b. Check that the PET SUV diagnostic read from the summed image is eligible and pediatrics.7-10 projections to carry less weight than high-quality projections. for reimbursement i. Note that the WB dynamic passes chosen to form the summed image should There has been an expanding utilization of IR in clinical practice in recent years, be the standard timing used for static WB acquisitions (e.g. sum the passes primarily due to the increased focus on radiation dose optimization. Of note, Siemens between 60 – 75 min p.i.). Healthineers has been placing emphasis on devising technical solutions that can help c. As noted above, keep the acquisition time (e.g. 5 minute whole-body scan time) to consistently achieve the right dose, for the right diagnostic task, for every patient. of the dynamic passes the same for all patients, regardless of patient size This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. 4. Single organ regions (e.g. brain, liver, etc.) can also take advantage of the automated workflow by using the automatically generated input functions from the aorta and LV, thereby removing the need to find a suitable artery near the organ of interest (e.g. carotid). In this case, using a variable-speed CBM acquisition can help maximize * acquiring counts from the organ of interest by using slow bed speeds, with faster speeds In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the used to quickly move back to the input cardiac region for sampling the tail points of appropriate dose to obtain diagnostic image quality for the particular clinical task. the input function (see Figure 3). The initial cardiac region listmode acquisition is still ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical used for fast temporal sampling of the bolus portion of the input function. location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 27 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: Since the reconstruction of the Patlak parametric images is completely automated in this Advanced Modeled Iterative workflow, it is very important that the following acquisition and patient specific parameters are entered correctly either before or after the first PET acquisition: Reconstruction Patient weight • Patient height • Blood glucose • • by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Isotope Radiopharmaceutical and Rainer Raupach, PhD • Injection time and dose • Residual dose and time • Not entering some of these parameters may change the units and quantification Introduction: Evolution of Siemens CT image reconstruction technologies of the multiparametric images. Image reconstruction is an essential technology that every computed tomography (CT) If the dose related information cannot be entered before the first scan, then a good scanner requires for operation. The function of CT image reconstruction is to translate alternative is to enter it after the first acquisition and before the start of the WB dynamic all of the acquired X-ray data (raw data) into a meaningful three-dimensional acquisition. As long as the WB acquisition has not started, all dose information will be representation of the patient. The most well-known method of image reconstruction copied automatically. The first PET acquisition reconstructions should be manually is commonly referred to as filtered back projection (FBP), in which measured X-ray started after all dose information has been entered, but all of the WB reconstructions projections are directly translated into images. In most modern scanners, it is likely can be set to start automatically. that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To address this, Siemens Healthineers CT scanners offer an improved three-dimensional Viewing and analysis of the parametric volumes FBP, called weighted filtered back projection (WFBP).2 The MRFDG and DVFDG parametric volumes can be loaded into syngo TrueD and syngo.via A common characteristic of both FBP and WFBP is that they do not consider statistical MM Oncology, along with the CT volume and standard Bq/ml volume used for calculating properties of measured X-ray projections. What this means is that all CT projections SUV values. syngo.via MM Oncology offers a designated layout for fast visualization of collected in the detectors are weighted the same, regardless of their quality. With the three data sets. Windowing presets as well as scaled MRFDG units make the image the increased focus in dose reduction, the lack of inclusion of statistical properties series accessible in a daily setting. of conventional FBP or WFBP become an important barrier that prevents further radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art The same tools used to analyze and view the Bq/ml, or SUV volume, respectively, can be CT scanners have been developed with more advanced technology, known as iterative used to view and analyze the parametric volumes (e.g. VOI reporting, lesion segmentation, reconstruction (IR). Not surprisingly, among the key advantages of IR is that the MIP images, fusion with the CT volume, etc.) The analysis results are included in the same statistical properties of measured CT projection data can be readily incorporated into report as the CT and SUV report, with the correct units specified. the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. Differences between SUV and 18F FDG Patlak There has been an expanding utilization of IR in clinical practice in recent years, Besides the more technical parameters influencing SUV on the acquisition level (see primarily due to the increased focus on radiation dose optimization. Of note, Siemens Section SUV and its limitations), other factors such as perfusion, 18F FDG transport, and Healthineers has been placing emphasis on devising technical solutions that can help 18F FDG-6-P trapping also affect the SUV. These factors can be influenced by alterations of to consistently achieve the right dose, for the right diagnostic task, for every patient. the tissue on a cellular level, such as over-expression or silencing of driver genes for This was in line with the ALARA principle, that is to use a dose that is “As Low As perfusion, neovascularization, receptor-expression, enzymatic activity etc., to gather more Reasonably Achievable” to deliver diagnostic image quality. nutrition and promote growth of the neoplastic tissue, all with the aim to improve survival. This is true for initial evaluation and can change dramatically during treatment depending on the drugs used and signal pathways that were targeted37–40. Among these alterations, a change in blood perfusion can have one of the largest impacts on SUV. Therefore, the activity from increased perfusion or vascularization in a VOI can mimic or overwhelm the physiological process of interest, which in this case is MRFDG or MRGlu. Using the Patlak approach may provide extra information, which may help the physician in clinical decision making, especially when SUV alone has low specificity, sensitivity or both. 2 28 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Sensitivity of multiparametric PET Advanced Modeled Iterative Historically, image-based Patlak parametric volumes in general were not optimized for visual reading due to the low signal-to-noise ratios. With direct Patlak reconstruction Reconstruction approaches as developed for this feature, visualization makes clinical sense and combines the advantages of quantification and visual orientation for improved reading. Due to the noise reduction as mentioned above, more subtle changes might surface and be accessible to the reader. In particular, low 18F FDG uptake tumors in the liver may become visible since the liver often has high activity, and separating the activity into metabolized and by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, non-metabolized 18F FDG may help the physicians be more confident in their diagnosis. and Rainer Raupach, PhD Figure 17 demonstrates a patient scan with the SUV, the DVFDG, and the MRFDG volumes. The SUV appears as the reader would expect—very similar to a conventional static image from an 18F FDG scan. The MRFDG image nicely visualizes the metabolized and trapped tracer while the DVFDG demonstrates the activity that was not trapped and therefore, not metabolized. In the middle, for example, the MRFDG image shows the bone marrow but Introduction: Evolution of Siemens CT image reconstruction technologies almost no tracer in the mediastinum, while the DVFDG image shows almost no tracer in the Development of IR methods bones but clearly demonstrates activity in the mediastinum. In fact, as we have stated as Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase one of the use cases of this feature above, this approach helps improve the understanding scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. of the different factors contributing to SUV and can now be visualized as well as all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative measured. Note the second left hilar lung nodule almost disappears in the Ki image. representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 However, it is expected that IR technologies not only aid in noise reduction but also Figure 17. Example MIP images all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions demonstrating the different uptake address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR steps over time, visualized by (A) FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative SUV, (B) the MRFDG (μmol/min/100ml). Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ and (C) DVFDG (%) Note the different A common characteristic of both FBP and WFBP is that they do not consider statistical first IR technology that integrated a correction loop in the raw-data domain (a.k.a. visualization of the mediastinum, properties of measured X-ray projections. What this means is that all CT projections the lung nodules in the left hilar region collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward or the bladder filling, representing the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is different weighting of the time for of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image DVFDG and MRFDG data. Data courtesy radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively of Yale University, New Haven, since its introduction, and a wealth of scientific literature has consistently supported Connecticut, USA CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, A B C primarily due to the increased focus on radiation dose optimization. Of note, Siemens Summed SUV Healthineers has been placing emphasis on devising technical solutions that can help Patlak Slope Patlak Intercept frames 14-19 (MRFDG) image (DVFDG) image to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 29 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: SUV Nodule/lung Advanced Modeled Iterative Ki Nodule/lung 50.0 Reconstruction 40.0 Figure 18. Comparison SUV and Ki 30.0 nodule/lung ratios (a metric for contrast to background) for 6 lung 20.0 cancer patients and 9 nodules. Note Ratio Value that the Ki ratios were always larger 10.0 than the corresponding SUV ratios. by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, 0 Data courtesy of Yale University and Rainer Raupach, PhD A-1 B-1 C-1 D-1 D-2 D-3 E-1 F-1 F-2 A comparison of some preliminary clinical data from Yale University is shown in Figure 18, and demonstrates the differences between SUV and Ki The data were acquired Introduction: Evolution of Siemens CT image reconstruction technologies . from a 90-minute acquisition of lung lesions from different patients using a single bed Image reconstruction is an essential technology that every computed tomography (CT) position centered on a lesion. Although scanning for 90 minutes is not clinically feasible, scanner requires for operation. The function of CT image reconstruction is to translate this effort was chosen to take a closer look into the characteristics of the Patlak dynamics all of the acquired X-ray data (raw data) into a meaningful three-dimensional and to gain knowledge about the behavior of SUV and Ki The graph indicates how Ki . representation of the patient. The most well-known method of image reconstruction might contribute differently than the SUV in different lesions and tissues. Notice the is commonly referred to as filtered back projection (FBP), in which measured X-ray second and third nodule comparing SUV and Ki and the different pattern among the projections are directly translated into images. In most modern scanners, it is likely overall examples. that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To address this, Siemens Healthineers CT scanners offer an improved three-dimensional FBP, called weighted filtered back projection (WFBP).2 A common characteristic of both FBP and WFBP is that they do not consider statistical properties of measured X-ray projections. What this means is that all CT projections collected in the detectors are weighted the same, regardless of their quality. With the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the statistical properties of measured CT projection data can be readily incorporated into the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. 2 30 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Conclusion Advanced Modeled Iterative As mentioned in the Introduction, PET was and is inherently about biological Reconstruction characterization of tissue, especially malignantly altered tissue. With the introduction of WB PET/CT, there was a clear need to make the acquisition and reading of PET data as efficient and CT-like as possible. This led to the introduction of SUV and development of guidelines to define the start time of a single time point acquisition to be around 60 minutes post injection. This simple approach of facilitated acquisition and reading came at the price of ignoring dynamic information that could be useful for diagnostic decisions. by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Historically, this type of analysis was limited to research-focused institutions because of and Rainer Raupach, PhD its complexity. With the introduction of this fully-automated FlowMotion Multiparametric PET Suite feature, we are enabling our clinicians and researchers to take a closer look into molecular changes that go beyond SUV and static imaging. By offering an easy-to- reproduce workflow, automated input function estimation, integrated state-of-the-art Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods reconstruction, and an environment to read the clinical SUV data side by side with the Image reconstruction is an essential technology that every computed tomography (CT) parametric data using syngo.MM Oncology, FlowMotion Multiparametric PET Suite is a It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate complete feature set to expand the use and understanding of dynamic PET. in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 31 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: References 1 Ter-Pogossian, MM, Phelps, ME & Advanced Modeled Iterative 7 Dimitrakopoulou-Strauss, A., Pan, L. & Hoffman, EJ. A Positron-Emission Strauss, L. Quantitative approaches of Transaxial Tomograph for Nuclear dynamic FDG-PET and PET/CT studies Reconstruction Imaging (PETT) 1. Radiology (1975). (dPET/CT) for the evaluation of doi:10.1148/114.1.89 oncological patients. Cancer Imaging 12, 2 Hoffmann, E. J., Phelps, M. E., Mullani, N. 283–289 A., Higgins, C. S. & Ter-Pogossian, M. M. 8 Kramer et al. Repeatability of Design and performance characteristics Quantitative Whole-Body 18F-FDG PET/ of a whole-body positron transaxial CT Uptake Measures as Function of by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, tomograph. J. Nucl. Med. 17, 493–502 and Rainer Raupach, PhD Uptake Interval and Lesion Selection in (1976). Non-Small Cell Lung Cancer Patients. 3 Hoop, B. et al. Techniques for positron Journal of Nuclear Medicine 57, 1343– scintigraphy of the brain. J. Nucl. Med. 17, 1349 (2016). 473–9 (1976). 9 Wahl, Jacene, Kasamon & Lodge. Introduction: Evolution of Siemens CT image reconstruction technologies 4 Sokoloff, L., Reivich, M. & Kennedy, C. The From RECIST to PERCIST: Evolving Image reconstruction is an essential technology that every computed tomography (CT) [14C] deoxyglucose method for the Considerations for PET Response Criteria scanner requires for operation. The function of CT image reconstruction is to translate measurement of local cerebral glucose in Solid Tumors. Journal of Nuclear all of the acquired X-ray data (raw data) into a meaningful three-dimensional utilization: theory, procedure, and normal Medicine 50, 122S–150S (2009). representation of the patient. The most well-known method of image reconstruction values in the conscious and anesthetized 10 Hamberg, L. M. et al. The dose uptake is commonly referred to as filtered back projection (FBP), in which measured X-ray Journal of Neurochemistry 28, (1977). ratio as an index of glucose metabolism: …. projections are directly translated into images. In most modern scanners, it is likely 5 Phelps, M., Huang, S., Hoffman, E. & useful parameter or oversimplification? that not all measured data can be used for image reconstruction with FBP,1 Selin, C. Tomographic measurement of J. Nucl. Med. 35, 1308–12 (1994). i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To local cerebral glucose metabolic rate in 11 Boellaard, R., Krak, N. & Hoekstra, O. address this, Siemens Healthineers CT scanners offer an improved three-dimensional humans with (F-18) 2-fluoro-2-deoxy-D- FBP, called weighted filtered back projection (WFBP).2 Effects of noise, image resolution, and glucose: validation of method. Ann ROI definition on the accuracy of A common characteristic of both FBP and WFBP is that they do not consider statistical Neurol (1979). doi:10.1002/ standard uptake values: a simulation properties of measured X-ray projections. What this means is that all CT projections ana.410060502 study. J Nucl Med (2004). collected in the detectors are weighted the same, regardless of their quality. With 6 Huang, S. C. et al. Noninvasive 12 Keyes, J. SUV: standard uptake or silly the increased focus in dose reduction, the lack of inclusion of statistical properties determination of local cerebral metabolic useless value? J Nucl Med (1995). of conventional FBP or WFBP become an important barrier that prevents further rate of glucose in man. Am. J. Physiol. radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art 238, E69–82 (1980). 13 Huang, S. Anatomy of SUV. J Nucl Med CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Biol (2000). statistical properties of measured CT projection data can be readily incorporated into the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. 2 32 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Advanced Modeled Iterative 14 Thie, J. Understanding the standardized 24 Gjedde, A. Modulation of substrate uptake value, its methods, and transport to the brain. Acta Neurol Scand implications for usage. J Nucl Med 67, 3–25 (1983). Reconstruction (2004). 25 Tao, Y., Peng, Z., Krishnan, A. & Zhou, X. 15 Adams, M., Turkington, T., Wilson, J. & Robust Learning-Based Parsing and Wong, T. A Systematic Review of the Annotation of Medical Radiographs. IEEE Factors Affecting Accuracy of SUV Transactions on Medical Imaging 30, Measurements. American Journal of 338–350 (2011). by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Roentgenology 195, 310–320 (2010). 26 Muzi, M. et al. Quantitative assessment and Rainer Raupach, PhD 16 Lodge, M. Repeatability of Standardized of dynamic PET imaging data in cancer Uptake Value in Oncologic 18F-FDG PET. imaging. Magnetic Resonance Imaging Journal of nuclear medicine: official 30, 1203–1215 (2012). publication, Society of Nuclear Medicine 58, 523–532 (2017). 27 Karakatsanis, N., Zhou, Y. & Lodge, M. Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods Clinical Whole-body PET Patlak imaging Image reconstruction is an essential technology that every computed tomography (CT) 17 Keramida, G., Anagnostopoulos, C. & 60-90min post-injection employing a It is well known that the degradation in image quality, most notably an increase Peters, M. The extent to which scanner requires for operation. The function of CT image reconstruction is to translate population-based input function. in in image noise, is the standard tradeoff for achieving a substantial dose reduction. standardized uptake values reflect FDG (2015). all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction phosphorylation in the liver and spleen as functions of time after injection of 28 Zanotti-Fregonara, P. et al. Population- Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions. 18F-fluorodeoxyglucose. EJNMMI 3 based input function and image-derived IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely Research 7, 13 (2017). input function for [11C](R)-rolipram PET that is effective in reducing image noise in a variety of clinical applications.4, 5 that not all measured data can be used for image reconstruction with FBP, i.e., not 1 imaging: Methodology, validation and However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To 18 Zasadny, K. R. & Wahl, R. L. Standarized application to the study of major in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional Uptake Value of Normal Tissues at PET depressive disorder. NeuroImage 63, with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP). 2 with 2-[Fluorine-18]-Fluoro-2-deoxy-D- 1532–1541 (2012). technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative glucose: Variations with Body Weigth and Reconstruction (SAFIRE**), launched in 2010. 6 A common characteristic of both FBP and WFBP is that they do not consider statistical SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections a Method for Correction. Radiology 189, 29 Vriens, de Geus-Oei, L.-F., Oyen, J. G. & first IR technology that integrated a correction loop in the raw-data domain (a.k.a. 847–850 (1993). Visser. A Curve-Fitting Approach to collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward Estimate the Arterial Plasma Input the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is 19 Patlak, C. S. & Blasberg, R. G. Graphical Function for the Assessment of Glucose of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image evaluation of blood-to-brain transfer Metabolic Rate and Response to radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively constants from multiple-time uptake Treatment. Journal of Nuclear Medicine CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported data. Generalizations. J. Cereb. Blood 50, 1933–1939 (2009). reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in Flow Metab. 5, 584–90 (1985). statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults 30 Zanotti-Fregonara, P., Chen, K., Liow, the CT image reconstruction process. This would allow, for example, low-quality (noisy) 20 Patlak, C. S., Blasberg, R. G. & and pediatrics.7-10 J.-S., Fujita, M. & Innis, R. Image-Derived projections to carry less weight than high-quality projections. Fenstermacher, J. D. Graphical Input Function for Brain PET Studies: evaluation of blood-to-brain transfer Many Challenges and Few Opportunities. There has been an expanding utilization of IR in clinical practice in recent years, constants from multiple-time uptake Journal of Cerebral Blood Flow & primarily due to the increased focus on radiation dose optimization. Of note, Siemens data. J. Cereb. Blood Flow Metab. 3, 1–7 Metabolism 31, 1986–1998 (2011). Healthineers has been placing emphasis on devising technical solutions that can help (1983). to consistently achieve the right dose, for the right diagnostic task, for every patient. 31 Su, Y. et al. Noninvasive Estimation of the This was in line with the ALARA principle, that is to use a dose that is “As Low As 21 Carson, R. in 2, 127–159 (2005). Arterial Input Function in Positron Reasonably Achievable” to deliver diagnostic image quality. 22 Morris, E. D. et al. Chapter 23 Kinetic Emission Tomography Imaging of Modeling in Positron Emission Cerebral Blood Flow. Journal of Cerebral Tomography. 499–540 (2004). Blood Flow & Metabolism 33, 115–121 doi:10.1016/B978-012744482-6.50026-0 (2013). * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the 23 Kotasidis, F., Tsoumpas, C. & Rahmim, A. 32 Wang, G. & Qi, J. Direct Estimation of appropriate dose to obtain diagnostic image quality for the particular clinical task. Advanced kinetic modelling strategies: Kinetic Parametric Images for Dynamic ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical PET. Theranostics 3, 802–815 (2013). location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the towards adoption in clinical PET appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to imaging. Clinical and Translational determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, Imaging 2, 219–237 (2014). low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 33 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: 33 Yan, J., Planeta-Wilson, Gallezot, J.-D. & Advanced Modeled Iterative 38 Strauss, L. et al. Impact of Cell- Carson, R. E. Initial evaluation of direct Proliferation-Associated Gene Expression Reconstruction 4D parametric reconstruction with on 2-Deoxy-2-[18F]fluoro-d-Glucose human PET data. 2503–2506 (2009). (FDG) Kinetics as Measured by Dynamic doi:10.1109/NSSMIC.2009.5402049 Positron Emission Tomography (dPET) in 34 Karakatsanis, N. et al. Generalized Colorectal Tumors. Molecular Imaging whole-body Patlak parametric imaging and Biology 13, 1290–1300 (2011). for enhanced quantification in clinical 39 Bretschi, M. et al. Cilengitide affects by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, PET. Physics in Medicine and Biology 60, tumor compartment, vascularization 8643–8673 (2015). and Rainer Raupach, PhD and microenvironment in experimental 35 Karakatsanis, N. et al. Dynamic whole- bone metastases as shown by body PET parametric imaging: I. Concept, longitudinal 18F-FDG PET and gene acquisition protocol optimization and expression analysis. J Cancer Res Clin clinical application. Physics in Medicine 139, 573–583 (2013). Introduction: Evolution of Siemens CT image reconstruction technologies and Biology 58, 7391–7418 (2013). 40 Lubberink, M. et al. 15O-Water PET Study Image reconstruction is an essential technology that every computed tomography (CT) 36 Panin, VY et al. Whole body parametric of the Effect of Imatinib, a Selective scanner requires for operation. The function of CT image reconstruction is to translate imaging on clinical scanner: Direct 4D Platelet-Derived Growth Factor Receptor all of the acquired X-ray data (raw data) into a meaningful three-dimensional reconstruction with simultaneous Inhibitor, Versus Anakinra, an IL-1R representation of the patient. The most well-known method of image reconstruction Antagonist, on Water-Perfusable Tissue attenuation estimation and time- is commonly referred to as filtered back projection (FBP), in which measured X-ray dependent normalization. 1–7 (2015). at Fraction in Colorectal Cancer projections are directly translated into images. In most modern scanners, it is likely 56, 1144–1149 (2015). all radiation dose applied to the patient is actually used for image reconstruction. To address this, Siemens Healthineers CT scanners offer an improved three-dimensional 37 Breki, C.-M. et al. Fractal and FBP, called weighted filtered back projection (WFBP).2 multifractal analysis of PET/CT images of metastatic melanoma before and after A common characteristic of both FBP and WFBP is that they do not consider statistical treatment with ipilimumab. EJNMMI properties of measured X-ray projections. What this means is that all CT projections Research 6, 61 (2016). collected in the detectors are weighted the same, regardless of their quality. With the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the statistical properties of measured CT projection data can be readily incorporated into the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. 2 34 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Advanced Modeled Iterative Appendix A Reconstruction User-defined input function CSV file format specifications by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Design principles and Rainer Raupach, PhD The design of this format follows these principles: The user defined input function file should contain all information needed to estimate • the dynamics of a PET tracer input function such that it is a reasonable representation of the actual input function. The CSV format is the same as the format used by commercial spreadsheet programs • Introduction: Evolution of Siemens CT image reconstruction technologies such as Excel. Development of IR methods Both the MS-DOS and Apple/Macintosh CSV formats are supported. The only • Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase difference between the two is that the Apple/Macintosh format does not put a scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. after a line of values. all of the acquired X-ray data (raw data) into a meaningful three-dimensional Assumptions The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray The activity time 0.000 s must always represent the injection time of the PET tracer. For image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely example, if the injection time was at the clock time 13:52:41 (HH:MM:SS), then 0 s that is effective in reducing image noise in a variety of clinical applications.4, 5 that not all measured data can be used for image reconstruction with FBP,1 i.e., not represents this clock time. The start and end sampling times also use this time frame of However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To reference. The activity needs to be decay corrected for the PET isotope (e.g. 18-F) using the in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional tracer injection time as the reference. Blank lines will always be ignored. with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 Limitations technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ At least four sampling time and activity data point pairs must be contained in this file. properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With CSV syntax “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties The CSV is an ASCII format and consists of comma separated values. In the case where projection. This correction loop that operates through to the raw-data domain is of conventional FBP or WFBP become an important barrier that prevents further there are actually commas in the value, then these values should be enclosed in quotes. particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively CSV syntax has two key words: CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported Comment – any values following this key word until a will be ignored • reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in DATA – when this key word is encountered, the next line below is expected to be the • statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults data column titles, and the line below that the start of the actual input function data the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 projections to carry less weight than high-quality projections. Comments Any number of comments may be added above the DATA keyword, and some examples There has been an expanding utilization of IR in clinical practice in recent years, are shown below. primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help Comment,Required CSV format for user-entered input function, to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Comment,”Data may come from arterial blood draws, detector probe over an artery, Reasonably Achievable” to deliver diagnostic image quality. population-based, etc.”, * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 35 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite ADMIRE: DATA keyword and data The DATA keyword should be on a line by itself, with the column titles immediately below Advanced Modeled Iterative this line. The actual data will then be below the column titles, in ascending time order. Reconstruction Note that the Activity time has units of seconds, and Activity the units of Bq/ml. All numerical values will be treated as floats in the format of F12.3. There can be multiple input function data sets in a single CSV file, with the input functions grouped by the Input function name. Therefore, each input function data point must have the same Input function name if it is to be grouped properly. DATA,,,,,, by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD Input function name,Activity time (s) [F12.3],Activity (Bq/ml) [F12.3],Sample start(s) [F12.3],Sample end(s) [F12.3],, Arterial blood sample,5.000,23.000,5.000,5.000,, Arterial blood sample,10.000,100.000,10.000,10.000,, Introduction: Evolution of Siemens CT image reconstruction technologies Arterial blood sample,15.000,400.000,15.000,15.000,, Image reconstruction is an essential technology that every computed tomography (CT) scanner requires for operation. The function of CT image reconstruction is to translate Arterial blood sample,20.000,800.000,20.000,20.000,, all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction ... is commonly referred to as filtered back projection (FBP), in which measured X-ray Carotid probe,5.000,230.000,0.000,10.000,, projections are directly translated into images. In most modern scanners, it is likely Carotid probe,10.000,1000.000,5.000,15.000,, that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To Carotid probe,15.000,4000.000,10.000,20.000,, address this, Siemens Healthineers CT scanners offer an improved three-dimensional FBP, called weighted filtered back projection (WFBP).2 Carotid probe,20.000,8000.000,15.000,25.000,, A common characteristic of both FBP and WFBP is that they do not consider statistical Checks performed on CSV file properties of measured X-ray projections. What this means is that all CT projections The following checks will be performed to ensure that the user-entered CSV file is valid: collected in the detectors are weighted the same, regardless of their quality. With the file is readable as a CSV file the increased focus in dose reduction, the lack of inclusion of statistical properties • of conventional FBP or WFBP become an important barrier that prevents further keyword DATA is present on a line by itself • radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art at least 4 data points are present per input function CT scanners have been developed with more advanced technology, known as iterative • reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the data points are sorted by ascending time order • statistical properties of measured CT projection data can be readily incorporated into the CT image reconstruction process. This would allow, for example, low-quality (noisy) after peak bolus activity value, there are no negative activity values • projections to carry less weight than high-quality projections. Generation of CSV file - recommendations There has been an expanding utilization of IR in clinical practice in recent years, The most typical way users will generate the CSV file is by using a commercial primarily due to the increased focus on radiation dose optimization. Of note, Siemens spreadsheet program such as Excel. Below is how an example CSV file looks when viewed Healthineers has been placing emphasis on devising technical solutions that can help by Excel. Note that this file contains two input functions: “Arterial blood sample” and to consistently achieve the right dose, for the right diagnostic task, for every patient. “Carotid probe”, which are also known as the “finding names” and will be a part of the This was in line with the ALARA principle, that is to use a dose that is “As Low As input function filename stored in the database (see Figure 13). Reasonably Achievable” to deliver diagnostic image quality. 36 2 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper ADMIRE: Advanced Modeled Iterative DATA Reconstruction Input function name Activity time(s) Activity (Bq/ml) Sample start(s) Sample end(s) [F12.3] [F12.3] [F12.3] [F12.3] Arterial blood sample 5.000 23.000 5.000 5.000 Arterial blood sample 10.000 100.000 10.000 10.000 by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Arterial blood sample 15.000 400.000 15.000 15.000 and Rainer Raupach, PhD Arterial blood sample 20.000 800.000 20.000 20.000 Arterial blood sample 25.000 1000.000 25.000 25.000 Arterial blood sample 30.000 900.000 30.000 30.000 Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods Arterial blood sample 40.000 600.000 40.000 40.000 Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate Arterial blood sample in image noise, is the standard tradeoff for achieving a substantial dose reduction. 50.000 300.000 50.000 50.000 all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative 60.000 320.000 60.000 60.000 representation of the patient. The most well-known method of image reconstruction Arterial blood sample Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray Arterial blood sample image noise in reduced dose acquisitions.3 4000.00 IRIS is a scientifically validated technology 60.267 4000.000 4000.000 projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 Arterial blood sample However, it is expected that IR technologies not only aid in noise reduction but also 5000.00 36.554 5000.000 5000.000 all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions 5.000 230.000 0.000 10.000 address this, Siemens Healthineers CT scanners offer an improved three-dimensional Carotid probe with reduced dose or fast acquisition techniques. In response to this, the next IR FBP, called weighted filtered back projection (WFBP).2 Carotid probe technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative 10.000 1000.000 5.000 15.000 A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ Carotid probe first IR technology that integrated a correction loop in the raw-data domain (a.k.a. 15.000 4000.000 10.000 20.000 properties of measured X-ray projections. What this means is that all CT projections collected in the detectors are weighted the same, regardless of their quality. With Carotid probe “sinogram”) and added a model of the CT system geometry during the data forward projection. This correction loop that operates through to the raw-data domain is 20.000 8000.000 15.000 25.000 the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further Carotid probe particularly helpful for reducing spiral artifacts. A second correction loop in image 25.000 10000.000 20.000 30.000 radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative Carotid probe since its introduction, and a wealth of scientific literature has consistently supported 30.000 9000.000 25.000 35.000 reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Carotid probe the capabilities of SAFIRE to reduce dose while maintaining high image quality in 35.000 6000.000 30.000 40.000 statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 Carotid probe 40.000 3000.000 35.000 45.000 projections to carry less weight than high-quality projections. Carotid probe 45.000 3200.000 40.000 50.000 There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Carotid probe 50.000 3300.000 45.000 55.000 Healthineers has been placing emphasis on devising technical solutions that can help 55.000 3400.000 50.000 60.000 to consistently achieve the right dose, for the right diagnostic task, for every patient. Carotid probe This was in line with the ALARA principle, that is to use a dose that is “As Low As Carotid probe 60.000 3500.000 3.000 90.000 Reasonably Achievable” to deliver diagnostic image quality. Carotid probe 90.000 3400.000 60.000 120.000 Carotid probe 120.000 3350.000 90.000 150.000 * Carotid probe In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the 150.000 3200.000 120.000 180.000 appropriate dose to obtain diagnostic image quality for the particular clinical task. Carotid probe In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical 180.000 3100.000 150.000 210.000 ** location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the Carotid probe appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to 210.000 3050.000 170.00 250.000 determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, Carotid probe low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed 250.000 3000.000 200.00 300.000 with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 37 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite FLUDEOXYGLUCOSE F 18- fludeoxyglucos e f-18 injection, solution PETNET Solutions, Inc. ADMIRE: ---------- Advanced Modeled Iterative HIGHLIGHTS OF PRESCRIBING INFORMATION Reconstruction These highlights do not include all the information needed to use Fludeoxyglucose F 18 Injection safely and effectively. See full prescribing information for Fludeoxyglucose F 18 Injection. Fludeoxyglucose F 18 Injection, USP For intravenous use Initial U.S. Approval: 2005 RECENT MAJOR CHANGES by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Warnings and Precautions (5.1, 5.2) 7/2010 Adverse Reactions (6) 7/2010 and Rainer Raupach, PhD INDICATIONS AND USAGE Fludeoxyglucose F18 Injection is indicated for positron emission tomography (PET) imaging in the following settings: Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer. Introduction: Evolution of Siemens CT image reconstruction technologies Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging. Image reconstruction is an essential technology that every computed tomography (CT) scanner requires for operation. The function of CT image reconstruction is to translate Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures (1). all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction is commonly referred to as filtered back projection (FBP), in which measured X-ray DOSAGE AND ADMINISTRATION projections are directly translated into images. In most modern scanners, it is likely Fludeoxyglucose F18 Injection emits radiation. Use procedures to minimize radiation exposure. Screen for blood glucose abnormalities. that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To In the oncology and neurology settings, instruct patients to fast for 4 to 6 hours prior to the drug’s injection. Consider address this, Siemens Healthineers CT scanners offer an improved three-dimensional medical therapy and laboratory testing to assure at least two days of normoglycemia prior to the drug’s administration (5.2). FBP, called weighted filtered back projection (WFBP).2 In the cardiology setting, administration of glucose-containing food or liquids (e.g., 50 to 75 grams) prior to the drug’s injection facilitates localization of cardiac ischemia (2.3). A common characteristic of both FBP and WFBP is that they do not consider statistical properties of measured X-ray projections. What this means is that all CT projections collected in the detectors are weighted the same, regardless of their quality. With Aseptically withdraw Fludeoxyglucose F18 Injection from its container and administer by intravenous injection (2). The recommended dose: the increased focus in dose reduction, the lack of inclusion of statistical properties for adults is 5 to 10 mCi (185 to 370 MBq), in all indicated clinicalsettings (2.1). of conventional FBP or WFBP become an important barrier that prevents further for pediatric patients is 2.6 mCi in the neurology setting (2.2). radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative Initiate imaging within 40 minutes following drug injection; acquire static emission images 30 to 100 minutes from time of injection (2). reconstruction (IR). Not surprisingly, among the key advantages of IR is that the statistical properties of measured CT projection data can be readily incorporated into DOSAGE FORMS AND STRENGTHS the CT image reconstruction process. This would allow, for example, low-quality (noisy) Multi-dose 30mL and 50mL glass vial containing 0.74 to7.40 GBq/mL (20 to 200 mCi/mL) Fludeoxyglucose F18 Injection projections to carry less weight than high-quality projections. and 4.5mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a stabilizer (approximately 15 to 50 mL volume) for intravenous administration (3). There has been an expanding utilization of IR in clinical practice in recent years, CONTRAINDICATIONS primarily due to the increased focus on radiation dose optimization. Of note, Siemens None (4) Healthineers has been placing emphasis on devising technical solutions that can help WARNINGS AND PRECAUTIONS to consistently achieve the right dose, for the right diagnostic task, for every patient. Radiation risks: use smallest dose necessary for imaging (5.1). This was in line with the ALARA principle, that is to use a dose that is “As Low As Blood glucose abnormalities: may cause suboptimal imaging (5.2). Reasonably Achievable” to deliver diagnostic image quality. ADVERSE REACTIONS Hypersensitivity reactions have occurred; have emergency resuscitation equipment and personnel immediately available (6). To report SUSPECTED ADVERSE REACTIONS, contact PETNET Solutions, Inc. at 877-473-8638 or FDA at 1- 800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS Pregnancy Category C: No human or animal data. Consider alternative diagnostics; use only if clearly needed (8.1). 38 2 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper Nursing mothers: Use alternatives to breast feeding (e.g., stored breast milk or infant formula) for at least 10 half-lives of radioactive decay, if Fludeoxyglucose F 18 Injection is administered to a woman who is breast-feeding (8.3). Pediatric Use: Safety and effectiveness in pediatric patients have not been established in the oncology and cardiology ADMIRE: settings (8.4). Advanced Modeled Iterative See 17 for PATIENT COUNSELING INFORMATION. Revised: 1/2016 Reconstruction by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE and Rainer Raupach, PhD 1.1 Oncology 1.2 Cardiology 1.3 Neurology 2 DOSAGE AND ADMINISTRATION Introduction: Evolution of Siemens CT image reconstruction technologies 2.1 Recommended Dos e for Adults Development of IR methods 2.2 Recommended Dose for Pediatric Patients Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate 2.3 Patient Preparation in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional 2.4 Radiation Dosimetry The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction 2.5 Radiation Safety – Drug Handling Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray 2.6 Drug Preparation and Administration image noise in reduced dose acquisitions.3 2.7 Imaging Guidelines IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 3 DOSAGE FORMS AND STRENGTHS However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To 4 CONTRAINDICATIONS in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional 5 with reduced dose or fast acquisition techniques. In response to this, the next IR WARNINGS AND PRECAUTIONS FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative 5.1 Radiation Risks A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 5.2 Blood Glucos e Abnormalities SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections 6 first IR technology that integrated a correction loop in the raw-data domain (a.k.a. ADVERSE REACTIONS collected in the detectors are weighted the same, regardless of their quality. With 7 “sinogram”) and added a model of the CT system geometry during the data forward DRUG INTERACTIONS the increased focus in dose reduction, the lack of inclusion of statistical properties 8 projection. This correction loop that operates through to the raw-data domain is USE IN SPECIFIC POPULATIONS of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image 8.1 Pregnancy radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively 8.3 Nursing Mothers CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported reconstruction (IR). Not surprisingly, among the key advantages of IR is that the 8.4 Pediatric Use the capabilities of SAFIRE to reduce dose while maintaining high image quality in statistical properties of measured CT projection data can be readily incorporated into 11 DESCRIPTION applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 11.1 Chemical Characteristics projections to carry less weight than high-quality projections. 11.2 Physical Characteristics 12 CLINICAL PHARMACOLOGY There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens 12.1 Mechanism of Action Healthineers has been placing emphasis on devising technical solutions that can help 12.2 Pharmacodynamics to consistently achieve the right dose, for the right diagnostic task, for every patient. 12.3 Pharmacokinetics This was in line with the ALARA principle, that is to use a dose that is “As Low As 13 NONCLINICAL TOXICOLOGY Reasonably Achievable” to deliver diagnostic image quality. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 14.1 Oncology 14.2 Cardiology * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical 14.3 Neurology location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the 15 REFERENCES appropriate dose to obtain diagnostic image quality for the particular clinical task. ** 16 In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical HOW SUPPLIED/STORAGE AND DRUG HANDLING location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the 17 PATIENT COUNSELING INFORMATION appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to * determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, Sections or subsections omitted from the full prescribing information are not listed. low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 39 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite FULL PRESCRIBING INFORMATION ADMIRE: 1 INDICATIONS AND USAGE Advanced Modeled Iterative Fludeoxyglucose F18 Injection is indicated for positron emission tomography (PET) imaging in the following settings: Reconstruction 1.1 Oncology For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis o f cancer. by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, 1.2 Cardiology and Rainer Raupach, PhD For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging. 1.3 Neurology Introduction: Evolution of Siemens CT image reconstruction technologies Image reconstruction is an essential technology that every computed tomography (CT) For the identification of regions of abnormal glucose metabolism associated with foci of epileptic scanner requires for operation. The function of CT image reconstruction is to translate seizures. all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction 2 DOSAGE AND ADMINISTRATION is commonly referred to as filtered back projection (FBP), in which measured X-ray projections are directly translated into images. In most modern scanners, it is likely that not all measured data can be used for image reconstruction with FBP,1 Fludeoxyglucose F18 Injection emits radiation. Use procedures to minimize radiation exposure. i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To Calculate the final dose from the end of synthesis (EOS) time using proper radioactive decay factors. address this, Siemens Healthineers CT scanners offer an improved three-dimensional Assay the final dose in a properly calibrated dose calibrator before administration to the patient [see Description (11.2)]. FBP, called weighted filtered back projection (WFBP).2 A common characteristic of both FBP and WFBP is that they do not consider statistical 2.1 Recommended Dose for Adults properties of measured X-ray projections. What this means is that all CT projections collected in the detectors are weighted the same, regardless of their quality. With Within the oncolog y, cardiology and neurology settings, the recommended dose for adults is 5 to 10 mCi (185 to 370 MBq) as an intravenous injection. the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further 2.2 Recommended Dos e for Pediatric Patients radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Within the neurology setting, the recommended dose for pediatric patients is 2.6 mCi, as an intravenous statistical properties of measured CT projection data can be readily incorporated into injection. The optimal dose adjustment on the basis of body size or weight has not been determined [see Use in Special Populations (8.4)]. the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. 2.3 Patient Preparation There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens To minimize the radiation absorbed dose to the bladder, encourage adequate hydration. Encourage Healthineers has been placing emphasis on devising technical solutions that can help the patient to drink water or other fluids (as tolerated) in the 4 hours before their PET study. to consistently achieve the right dose, for the right diagnostic task, for every patient. Encourage the patient to void as soon as the imaging study is completed and as often as possible thereafter for at least one hour. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. Screen patients for clinically significant blood glucose abnormalities by obtaining a history and/or laboratory tests [see Warnings and Precautions (5.2)]. Prior to Fludeoxyglucose F 18 PET imaging in the oncology and neurology settings, instruct patient to fast for 4 to 6 hours prior to the drug’s injection. In the cardiology setting, administration of glucose-containing food or liquids (e.g., 50 to 75 grams) prior to Fludeoxyglucose F 18 Injection facilitates localization of cardiac ischemia 2 40 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper 2.4 Radiation Dosimetry The estimated human absorbed radiation doses (rem/mCi) to a newborn (3.4 kg), 1-year old (9.8 kg), 5- ADMIRE: year old (19 kg), 10-year old (32 kg), 15-year old (57 kg), and adult (70 kg) from intravenous administration of Fludeoxyglucose F 18 Injection are shown in Table 1. These estimates were Advanced Modeled Iterative calculated based on human data and using the data published by the International Commission on 2 Radiological Protection for Fludeoxyglucose 4 18 F. The dosimetry data show that there are slight Reconstruction variations in absorbed radiation dose for various organs in each of the age groups. These dissimilarities in absorbed radiation dose are due to developmental age variations (e.g., organ size, location, and overall metabolic rate for each age group). The identified critical organs (in descending order) across all age groups evaluated are the urinary bladder, heart, pancreas, spleen, and lungs. by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Table 1. Estimated Absorbed Radiation Dos es (rem/mCi) After Intravenous and Rainer Raupach, PhD Administration of Fludeoxyglucose F 18 Injection a Organ Newborn 1-year old 5-year old 10-year old 15-year old Adult (3.4 kg) (9.8 kg) (19 kg) (32 kg) (57 kg) (70 kg) Bladder wall b 4.3 1.7 0.93 0.60 0.40 0.32 Introduction: Evolution of Siemens CT image reconstruction technologies Development of IR methods Heart wall 2.4 1.2 0.70 0.44 0.29 0.22 Image reconstruction is an essential technology that every computed tomography (CT) Pancreas It is well known that the degradation in image quality, most notably an increase 2.2 0.68 0.33 0.25 0.13 0.096 scanner requires for operation. The function of CT image reconstruction is to translate Spleen in image noise, is the standard tradeoff for achieving a substantial dose reduction. 2.2 0.84 0.46 0.29 0.19 0.14 all of the acquired X-ray data (raw data) into a meaningful three-dimensional Lungs The first IR technology commercially developed by Siemens Healthineers was Iterative Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased 0.96 0.38 0.20 0.13 0.092 0.064 representation of the patient. The most well-known method of image reconstruction is commonly referred to as filtered back projection (FBP), in which measured X-ray Kidneys image noise in reduced dose acquisitions.3 0.81 0.34 IRIS is a scientifically validated technology 0.19 0.13 0.089 0.074 projections are directly translated into images. In most modern scanners, it is likely Ovaries that is effective in reducing image noise in a variety of clinical applications.4, 5 0.80 0.8 0.19 0.11 0.058 0.053 that not all measured data can be used for image reconstruction with FBP,1 i.e., not Uterus However, it is expected that IR technologies not only aid in noise reduction but also 0.79 0.35 0.19 0.12 0.076 0.062 all radiation dose applied to the patient is actually used for image reconstruction. To LLI wall * in reducing spiral artifacts, which can be exacerbated when using CT acquisitions 0.69 0.28 0.15 0.097 0.060 0.051 address this, Siemens Healthineers CT scanners offer an improved three-dimensional FBP, called weighted filtered back projection (WFBP).2 Liver with reduced dose or fast acquisition techniques. In response to this, the next IR technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative 0.69 0.31 0.17 0.11 0.076 0.058 Gallbladder wall Reconstruction (SAFIRE**), launched in 2010.6 0.69 0.26 SAFIRE was Siemens Healthineers’ 0.14 0.093 0.059 0.049 A common characteristic of both FBP and WFBP is that they do not consider statistical Small intestine properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. 0.68 0.29 0.15 0.096 0.060 0.047 collected in the detectors are weighted the same, regardless of their quality. With ULI wall ** “sinogram”) and added a model of the CT system geometry during the data forward 0.67 0.27 0.15 0.090 0.057 0.046 the increased focus in dose reduction, the lack of inclusion of statistical properties Stomach wall projection. This correction loop that operates through to the raw-data domain is 0.65 0.27 0.14 0.089 0.057 0.047 of conventional FBP or WFBP become an important barrier that prevents further Adre nals particularly helpful for reducing spiral artifacts. A second correction loop in image space is applied iteratively to reduce image noise. SAFIRE has been used extensively 0.65 0.28 0.15 0.095 0.061 0.048 radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art Testes since its introduction, and a wealth of scientific literature has consistently supported 0.64 0.27 0.14 0.085 0.052 0.041 CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Red marrow the capabilities of SAFIRE to reduce dose while maintaining high image quality in 0.62 0.26 0.14 0.089 0.057 0.047 statistical properties of measured CT projection data can be readily incorporated into Thymus applications ranging from routine to specialized body and neuro CT – in both adults 0.61 0.26 0.14 0.086 0.056 0.044 the CT image reconstruction process. This would allow, for example, low-quality (noisy) and pediatrics.7-10 Thyroid 0.61 0.26 0.13 0.080 0.049 0.039 projections to carry less weight than high-quality projections. Muscle 0.58 0.25 0.13 0.078 0.049 0.039 There has been an expanding utilization of IR in clinical practice in recent years, Bone surface 0.57 0.24 0.12 0.079 0.052 0.041 primarily due to the increased focus on radiation dose optimization. Of note, Siemens Breast 0.54 0.22 0.11 0.068 0.043 0.034 Healthineers has been placing emphasis on devising technical solutions that can help Skin 0.49 0.20 0.10 0.060 0.037 0.030 to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Brain 0.29 0.13 0.09 0.078 0.072 0.070 Reasonably Achievable” to deliver diagnostic image quality. Other tissues 0.59 0.25 0.13 0.083 0.052 0.042 a MIRDOSE 2 software was used to calculate the radiation absorbed dose. Assumptions on the biodistribution based on data from Gallagher et al. and Jones et al. 1 2 * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical b location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the The dynamic bladder model with a uniform voiding frequency of 1.5 hours was used. *LLI = lower appropriate dose to obtain diagnostic image quality for the particular clinical task. large intestine; **ULI = upper large intestine ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to 2.5 Radiation Safety – Drug Handling determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed Use waterproof gloves, effective radiation shielding, and appropriate safety measures when with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 41 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite handling Fludeoxyglucose F18 Injection to avoid unnecessary radiation exposure to the patient, occupational workers, clinical personnel and other persons. ADMIRE: Radiopharmaceuticals should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate governmental agency authorized to Advanced Modeled Iterative license the use of radionuclides. Calculate the final dose from the end of synthesis (EOS) time using proper radioactive decay Reconstruction factors. Assay the final dose in a properly calibrated dose calibrator before administration to the patient [see Description (11.2)]. The dose of Fludeoxyglucose F18 used in a given patient should be minimized consistent with the objectives of the procedure, and the nature of the radiation detection devices employed. 2.6 Drug Preparation and Administration by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD Calculate the necessary volume to administer based on calibration time and dose. Aseptically withdraw Fludeoxyglucose F18 Injection from its container. Inspect Fludeoxyglucose F18 Injection visually for particulate matter and discoloration before administration, whenever solution and container permit. Introduction: Evolution of Siemens CT image reconstruction technologies Do not administer the drug if it contains particulate matter or discoloration; dispose of these unacceptable or unused preparations in a safe manner, in compliance with applicable regulations. Image reconstruction is an essential technology that every computed tomography (CT) Use Fludeoxyglucose F 18 Injection within 12 hours from the EOS. scanner requires for operation. The function of CT image reconstruction is to translate 2.7 Imaging Guidelines all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction Initiate imaging within 40 minutes following Fludeoxyglucose F 18 Injection administration. is commonly referred to as filtered back projection (FBP), in which measured X-ray projections are directly translated into images. In most modern scanners, it is likely Acquire static emission images 30 to 100 minutes from the time of injection. that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To 3 DOSAGE FORMS AND STRENGTHS address this, Siemens Healthineers CT scanners offer an improved three-dimensional FBP, called weighted filtered back projection (WFBP).2 Multiple-dose 30mL and 50mL glass vial containing 0.74 to 7.40 GBq/mL (20 to 200 mCi/mL) of A common characteristic of both FBP and WFBP is that they do not consider statistical Fludeoxyglucose F 18 Injection and 4.5 mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a properties of measured X-ray projections. What this means is that all CT projections stabilizer (approximately 15 to 50 mL volume) for intravenous administration. collected in the detectors are weighted the same, regardless of their quality. With the increased focus in dose reduction, the lack of inclusion of statistical properties 4 CONTRAINDICATIONS of conventional FBP or WFBP become an important barrier that prevents further None radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the 5 WARNINGS AND PRECAUTIONS statistical properties of measured CT projection data can be readily incorporated into the CT image reconstruction process. This would allow, for example, low-quality (noisy) 5.1 Radiation Risks projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, Radiation-emitting products, including Fludeoxyglucose F 18 Injection, may increase the risk for primarily due to the increased focus on radiation dose optimization. Of note, Siemens cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe Healthineers has been placing emphasis on devising technical solutions that can help handling to protect the patient and health care worker [see Dosage and Administration (2.5)]. to consistently achieve the right dose, for the right diagnostic task, for every patient. 5.2 Blood Glucos e Abnormalities This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. In the oncology and ne urology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to assure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration. 6 ADVERSE REACTIONS Hypersensitivity reactions with pruritus, edema and rash have been reported in the post-marketing setting. Have emergency resuscitation equipment and personnel immediately available. 2 42 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper 7 DRUG INTERACTIONS ADMIRE: The possibility of interactions of Fludeoxyglucose F 18 Injection with other drugs taken by patients undergoing PET imaging has not been studied. Advanced Modeled Iterative Reconstruction 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with Fludeoxyglucose F 18 Injection. It is also by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, not known whether Fludeoxyglucose F 18 Injection can cause fetal harm when administered to a and Rainer Raupach, PhD pregnant woman or can affect reproduction capacity. Consider alternative diagnostic tests in a pregnant woman; administer Fludeoxyglucose F 18 Injection only if clearly needed. 8.3 Nursing Mothers Introduction: Evolution of Siemens CT image reconstruction technologies It is not known whether Fludeoxyglucose F 18 Injection is excreted in human milk. Consider alternative Development of IR methods diagnostic tests in women who are breast-feeding. Use alternatives to breast feeding (e.g., stored breast Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase milk or infant formula) for at least 10 half-lives of radioactive decay, if Fludeoxyglucose F 18 Injection scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. is administered to a woman who is breast-feeding. all of the acquired X-ray data (raw data) into a meaningful three-dimensional The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased 8.4 Pediatric Us e is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely The safety and effectiveness of Fludeoxyglucose F 18 Injection in pediatric patients with epilepsy is that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 established on the basis of studies in adult and pediatric patients. In pediatric patients with epilepsy, the However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To recommended dose is 2.6 mCi. The optimal dose adjustment on the basis of body size or weight has not in reducing spiral artifacts, which can be exacerbated when using CT acquisitions address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR been determined. In the oncology or cardiology settings, the safety and effectiveness of FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative Fludeoxyglucose F 18 Injection have not been established in pediatric patients. A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With 11 “sinogram”) and added a model of the CT system geometry during the data forward DESCRIPTION the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is of conventional FBP or WFBP become an important barrier that prevents further 11.1 Chemical Characteristics particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively Fludeoxyglucose F 18 Injection is a positron emitting radiopharmaceutical that is used for diagnostic CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported purposes in conjunction with positron emission tomography (PET) imaging. The active ingredient 2- reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in 18 18 statistical properties of measured CT projection data can be readily incorporated into deoxy-2-[ F]fluoro-D-glucose has the molecular formula of C6H11 FO5 with a molecular weight of applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) 181.26, and has the following chemical structure: and pediatrics.7-10 projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, CH2OH primarily due to the increased focus on radiation dose optimization. Of note, Siemens H Healthineers has been placing emphasis on devising technical solutions that can help OH H OHY OH to consistently achieve the right dose, for the right diagnostic task, for every patient. H 18F This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. Fludeoxyglucose F 18 Injection is provided as a ready to use sterile, pyrogen free, clear, colorless solution. Each mL contains between 0.740 to 7.40GBq (20.0 to 200 mCi) of 2-deoxy-2-[ F]fluoro-D- 18 glucose at the EOS, 4.5 mg of sodium chloride and 0.1 to 0.5% w/w ethanol as a stabilizer. The pH of the solution is between 4.5 and 7.5. The solution is packaged in a multiple-dose glass vial and does not * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the c ontain any preservative. appropriate dose to obtain diagnostic image quality for the particular clinical task. ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical 11.2 Physical Characteristics location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, Fluorine F 18 decays by emitting positron to Oxygen O 16 (stable) and has a physical half-life of 109.7 low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed minutes. The principal photons useful for imaging are the dual 511 keV gamma photons, that are with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 43 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite produced and emitted simultaneously in opposite direction when the positron interacts with an electron (Table 2). ADMIRE: Table 2. Principal Radiation Emission Data for Fluorine F 18 Radiation/Emission Advanced Modeled Iterative % Per Disintegration Mean Energy Positron(β+) Gamma(±)* Reconstruction 96.73 249.8 keV 193.46 511.0 keV *Produced by positron annihilation From: Kocher, D.C. Radioactive Decay Tables DOE/TIC-I 1026, 89 (1981) by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, The specific gamma ray co nstant (point source air kerma coefficient) for fluorine F 18 is 5.7 R/hr/mCi and Rainer Raupach, PhD (1.35 x 10 Gy/hr/kBq) at 1 cm. The half-value layer (HVL) for the 511 keV photons is 4 mm lead (Pb). -6 The range of attenuation coefficients for this radionuclide as a function of lead shield thickness is shown in Table 3. For example, the interposition of an 8 mm thickness of Pb, with a coefficient of attenuation of 0.25, will decrease the external radiation by 75%. Introduction: Evolution of Siemens CT image reconstruction technologies Table 3. Radiation Attenuation of 511 Image reconstruction is an essential technology that every computed tomography (CT) keV Photons by lead (Pb) shielding scanner requires for operation. The function of CT image reconstruction is to translate all of the acquired X-ray data (raw data) into a meaningful three-dimensional Shield thickness Coefficient of representation of the patient. The most well-known method of image reconstruction (Pb) mm attenuation is commonly referred to as filtered back projection (FBP), in which measured X-ray 0 0.00 projections are directly translated into images. In most modern scanners, it is likely 4 0.50 that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To 8 0.25 address this, Siemens Healthineers CT scanners offer an improved three-dimensional 13 0.10 FBP, called weighted filtered back projection (WFBP).2 26 0.01 A common characteristic of both FBP and WFBP is that they do not consider statistical 39 0.001 properties of measured X-ray projections. What this means is that all CT projections 52 0.0001 collected in the detectors are weighted the same, regardless of their quality. With the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further For use in correcting for physical decay of this radionuclide, the fractions remaining at selected intervals after calibration are shown in Table 4. radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the Table 4. Physical Decay Chart for statistical properties of measured CT projection data can be readily incorporated into Fluorine F 18 the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. Minutes Fraction Remaining 0* 1.000 There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens 15 0.909 Healthineers has been placing emphasis on devising technical solutions that can help 30 0.826 to consistently achieve the right dose, for the right diagnostic task, for every patient. 60 0.683 This was in line with the ALARA principle, that is to use a dose that is “As Low As 110 0.500 Reasonably Achievable” to deliver diagnostic image quality. 220 0.250 *calibration time 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 2 44 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper Fludeoxyglucose F 18 is a glucose analog that concentrates in cells that rely upon glucose as an energy source, or in cells whose dependence on glucose increases under pathophysiological conditions. ADMIRE: Fludeoxyglucose F 18 is transported through the cell membrane by facilitative glucose transporter proteins and is phosphorylated within the cell to [ F] FDG-6-phosphate by the enzyme hexokinase. 18 Advanced Modeled Iterative Once phosphorylated it cannot exit until it is dephosphorylated by glucose-6-phosphatase. Therefore, within a given tissue or pathophysiological process, the retention and clearance of Fludeoxyglucose F Reconstruction 18 reflect a balance involving glucose transporter, hexokinase and glucose-6-phosphatase activities. When allowance is made for the kinetic differences between glucose and Fludeoxyglucose F 18 transport and phosphorylation (expressed as the ''lumped constant'' ratio), Fludeoxyglucose F 18 is used to assess glucose metabolism. In comparison to background activity of the specific organ or tissue type, regions of decreased or by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, absent uptake of Fludeoxyglucose F 18 reflect the decrease or absence of glucose metabolism. and Rainer Raupach, PhD Regions of increased uptake of Fludeoxyglucose F 18 reflect greater than normal rates of glucose metabolism. 12.2 Pharmacodynamics Introduction: Evolution of Siemens CT image reconstruction technologies Fludeoxyglucose F 18 Injection is rapidly distributed to all organs of the body after intravenous Development of IR methods administration. After background clearance of Fludeoxyglucose F 18 Injection, optimal PET imaging is Image reconstruction is an essential technology that every computed tomography (CT) generally achieved between 30 to 40 minutes after administration. It is well known that the degradation in image quality, most notably an increase scanner requires for operation. The function of CT image reconstruction is to translate in image noise, is the standard tradeoff for achieving a substantial dose reduction. all of the acquired X-ray data (raw data) into a meaningful three-dimensional In cancer, the cells are generally characterized by enhanced glucose metabolism partially due to (1) an The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction increase in activity of glucose transporters, (2) an increased rate of phosphorylation activity, (3) a Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray reduction of phosphatase activity or, (4) a dynamic alteration in the balance among all these processes. image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely However, glucose metabolism of cancer as reflected by Fludeoxyglucose F 18 accumulation shows that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 considerable variability. Depending on tumor type, stage, and location, Fludeoxyglucose F 18 However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions accumulatio n may be increased, normal, or decreased. Also, inflammatory cells can have the same address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR variability of uptake of Fludeoxyglucose F 18. FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative A common characteristic of both FBP and WFBP is that they do not consider statistical In the heart, under normal aerobic conditions, the myocardium meets the bulk of its energy requirements Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ properties of measured X-ray projections. What this means is that all CT projections by oxidizing free fatty acids. Most of the exogenous glucose taken up by the myocyte is converted into first IR technology that integrated a correction loop in the raw-data domain (a.k.a. collected in the detectors are weighted the same, regardless of their quality. With glycogen. However, under ischemic conditions, the oxidation of fr ee fatty acids decreases, exogenous “sinogram”) and added a model of the CT system geometry during the data forward the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is glucose becomes the preferred myocardial substrate, glycolysis is stimulated, and glucose taken up by of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image the myocyte is metabolized immediately instead of being converted into glycogen. Under these radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art space is applied iteratively to reduce image noise. SAFIRE has been used extensively conditions, phosphorylated Fludeoxyglucose F 18 accumulates in the myocyte and can be detected with CT scanners have been developed with more advanced technology, known as iterative PET imaging. since its introduction, and a wealth of scientific literature has consistently supported reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in statistical properties of measured CT projection data can be readily incorporated into In the brain, cells normally rely on aerobic metabolism. In e pilepsy, the glucose metabolism varies. applications ranging from routine to specialized body and neuro CT – in both adults the CT image reconstruction process. This would allow, for example, low-quality (noisy) Generally, during a seizure, glucose metabolism increases. Interictally, the seizure focus tends to be and pediatrics.7-10 projections to carry less weight than high-quality projections. hypometabolic. There has been an expanding utilization of IR in clinical practice in recent years, 12.3 Pharmacokinetics primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help Distribution: In four healthy male volunteers, receiving an intravenous administration of 30 seconds in to consistently achieve the right dose, for the right diagnostic task, for every patient. duration, the arterial blood level profile for Fludeoxyglucose F 18 decayed triexponentially. The This was in line with the ALARA principle, that is to use a dose that is “As Low As effective half-life ranges of the three phases were 0.2 to 0.3 minutes, 10 to 13 minutes with a mean and Reasonably Achievable” to deliver diagnostic image quality. standard deviation (STD) of 11.6 (±) 1.1 min, and 80 to 95 minutes with a mean and STD of 88 (±) 4 min. Plasma protein binding of Fludeoxyglucose F 18 has not been studied. Metabolism: Fludeoxyglucose F 18 is transported into cells and phosphorylated to [ F]FDG-6- 18 * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical phosphate at a rate proportional to the rate of glucose utilization within that tissue. [F 18]-FDG-6- location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. phosphate presumably is metabolized to 2-deoxy-2-[F 18]fluoro-6-phospho-D-mannose([F 18]FDM-6- ** phosphate). In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to Fludeoxyglucose F 18 Injection may contain several impurities (e.g., 2-deoxy-2-chloro-D-glucose determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed (ClDG)). Biodistribution and metabolism of ClDG are presumed to be similar to Fludeoxyglucose F 18 with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 45 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite and would be expected to result in intracellular formation of 2deoxy-2-chloro-6-phospho-D-glucose (ClDG-6-phosphate) and 2-deoxy-2-chloro-6phospho-D-mannose (ClDM-6-phosphate). The phosphorylated deoxyglucose compounds are dephosphorylated and the resulting compounds (FDG, ADMIRE: FDM, ClDG, and ClDM) presumably leave cells by passive diffusion. Fludeoxyglucose F 18 and related compounds are cleared from non- cardiac tissues within 3 to 24 hours after administration. Advanced Modeled Iterative Clearance from the cardiac tissue may require more than 96 hours. Fludeoxyglucose F 18 that is not involved in glucose metabolism in any tissue is then excreted in the urine. Reconstruction Elimination: Fludeoxyglucose F 18 is cleared from most tissues within 24 hours and can be eliminated from the body unchanged in the urine. Three elimination phases have been identified in the reviewed literature. Within 33 minutes, a mean of 3.9% of the administrated radioactive dose was measured in the urine. The amount of radiation exposure of the urinary bladder at two hours post-administration sug gests that 20.6% (mean) of the radioactive dose was present in the bladder. by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, Special Populations: and Rainer Raupach, PhD The pharmacokinetics of Fludeoxyglucose F 18 Injection have not been studied in renally-impaired, hepatically impaired or pediatric patients. Fludeoxyglucose F 18 is eliminated through the renal system. Avoid excessive radiation exposure to this organ system and adjacent tissues. Introduction: Evolution of Siemens CT image reconstruction technologies The effects of fasting, varying blood sugar levels, conditions of glucose intolerance, and diabetes Image reconstruction is an essential technology that every computed tomography (CT) mellitus on Fludeoxyglucose F 18 distribution in humans have not been ascertained [see Warnings and Precautions (5.2)]. scanner requires for operation. The function of CT image reconstruction is to translate all of the acquired X-ray data (raw data) into a meaningful three-dimensional representation of the patient. The most well-known method of image reconstruction 13 NONCLINICAL TOXICOLOGY is commonly referred to as filtered back projection (FBP), in which measured X-ray projections are directly translated into images. In most modern scanners, it is likely 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To Animal studies have not been performed to evaluate the Fludeoxyglucose F 18 Injection carcinogenic potential, mutagenic potential or effects on fertility. address this, Siemens Healthineers CT scanners offer an improved three-dimensional FBP, called weighted filtered back projection (WFBP).2 A common characteristic of both FBP and WFBP is that they do not consider statistical 14 CLINICAL STUDIES properties of measured X-ray projections. What this means is that all CT projections collected in the detectors are weighted the same, regardless of their quality. With 14.1 Oncology the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further The efficacy of Fludeoxyglucose F 18 Injection in positron emission tomography cancer imaging was radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art demonstrated in 16 independent studies. These studies prospectively evaluated the use of CT scanners have been developed with more advanced technology, known as iterative Fludeoxyglucose F 18 in patients with suspected or known malignancies, including non-small cell lung reconstruction (IR). Not surprisingly, among the key advantages of IR is that the cancer, colo-rectal, pancreatic, breast, thyroid, melanoma, Hodgkin's and non-Hodgkin's lymphoma, and statistical properties of measured CT projection data can be readily incorporated into various types of metastatic cancers to lung, liver, bone, and axillary nodes. All these studies had at least the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. 50 patients and used pathology as a standard of truth. The Fludeoxyglucose F 18 Injection doses in the studies ranged from 200 MBq to 740 MBq with a median and mean dose of 370 MBq. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens In the studies, the diagnostic performance of Fludeoxyglucose F 18 Injection varied with the type of Healthineers has been placing emphasis on devising technical solutions that can help cancer, size of cancer, and other clinical conditions. False negative and false positive scans were to consistently achieve the right dose, for the right diagnostic task, for every patient. observed. Negative Fludeoxyglucose F 18 Injection PET scans do not exclude the diagnosis of cancer. This was in line with the ALARA principle, that is to use a dose that is “As Low As Positive Fludeoxyglucose F 18 Injection PET scans can not replace pathology to establish a diagnosis Reasonably Achievable” to deliver diagnostic image quality. of cancer. Non-malignant conditions such as fungal infections, inflammatory processes and benign tumors have patterns of increased glucose metabolism that may give rise to false-positive scans. The efficacy of Fludeoxyglucose F 18 Injection PET imaging in cancer screening was not studied. 14.2 Cardiology The efficacy of Fludeoxyglucose F 18 Injection for cardiac use was demonstrated in ten independent, prospective studies of patients with coronary artery disease and chronic left ventricular systolic dysfunction who were scheduled to undergo coronary revascularization. Before revascularization, patients underwent PET imaging with Fludeoxyglucose F 18 Injection (74 to 370 MBq, 2 to 10 mCi) and 46 2 White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction ADMIRE: Advanced Modeled Iterative Reconstruction | White Paper | FlowMotion Multiparametric PET Suite White Paper perfusion imaging with other diagnostic radiopharmaceuticals. Doses of Fludeoxyglucose F 18 Injection ranged from 74 to 370 MBq (2 to 10 mCi). Segmental, left ventricular, wall-motion ADMIRE: assessments of asynergic areas made before revascularization were compared in a blinded manner to assessments made after successful revascularization to identify myocardial segments with functional Advanced Modeled Iterative recovery. Left ventricular myocardial segments were predicted to have reversible loss of systolic function if they Reconstruction showed Fludeoxyglucose F 18 accumulation and reduced perfusion (i.e., flow-metabolism mismatch). Conversely, myocardial segments were predicted to have irreversible loss of systolic function if they showed reductions in both Fludeoxyglucose F 18 accumulation and perfusion (i.e., matched defects). Findings of flow-metabolism mismatch in a myocardial segment may suggest that successful by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, revascularization will restore myocardial function in that segment. However, false-positive tests occur regularly, and the decision to have a patient undergo revascularization should not be based on PET and Rainer Raupach, PhD findings alone. Similarly, findings of a matched defect in a myocardial segment may suggest that myocardial function will not recover in that segment, even if it is successfully revascularized. However, false-negative tests occur regularly, and the decision to recommend against coronary revascularization, or to recommend a cardiac transplant, should not be based on PET findings alone. The Introduction: Evolution of Siemens CT image reconstruction technologies reversibility of segmental dysfunction as predicted with Fludeoxyglucose F 18 PET imaging depends Development of IR methods on successful coronary revascularization. Therefore, in patients with a low likelihood of successful Image reconstruction is an essential technology that every computed tomography (CT) It is well known that the degradation in image quality, most notably an increase revascularization, the diagnostic usefulness of PET imaging with Fludeoxyglucose F 18 Injection is scanner requires for operation. The function of CT image reconstruction is to translate all of the acquired X-ray data (raw data) into a meaningful three-dimensional more limited. in image noise, is the standard tradeoff for achieving a substantial dose reduction. The first IR technology commercially developed by Siemens Healthineers was Iterative representation of the patient. The most well-known method of image reconstruction 14.3 Neurology Reconstruction in Image Space (IRIS*). IRIS directly addressed the problem of increased is commonly referred to as filtered back projection (FBP), in which measured X-ray image noise in reduced dose acquisitions.3 IRIS is a scientifically validated technology projections are directly translated into images. In most modern scanners, it is likely In a prospective, open label trial, Fludeoxyglucose F 18 Injection was evaluated in 86 patients with that is effective in reducing image noise in a variety of clinical applications.4, 5 i.e., not that not all measured data can be used for image reconstruction with FBP,1 epilepsy. Each patient received a dose of Fludeoxyglucose F 18 Injection in the range of 185 to 370 However, it is expected that IR technologies not only aid in noise reduction but also all radiation dose applied to the patient is actually used for image reconstruction. To in reducing spiral artifacts, which can be exacerbated when using CT acquisitions MBq (5 to 10 mCi). The mean age was 16.4 years (range: 4 months to 58 years; of these, 42 patients address this, Siemens Healthineers CT scanners offer an improved three-dimensional with reduced dose or fast acquisition techniques. In response to this, the next IR were less than 12 years and 16 patients were less than 2 years old). Patients had a known diagnosis of FBP, called weighted filtered back projection (WFBP).2 technology developed by Siemens Healthineers was the Sinogram Affirmed Iterative complex partial epilepsy and were under evaluation for surgical treatment of their seizure disorder. A common characteristic of both FBP and WFBP is that they do not consider statistical Reconstruction (SAFIRE**), launched in 2010.6 SAFIRE was Siemens Healthineers’ Seizure foci had been previously identified on ictal EEGs and sphenoidal EEGs. Fludeoxyglucose F 18 properties of measured X-ray projections. What this means is that all CT projections first IR technology that integrated a correction loop in the raw-data domain (a.k.a. Injection PET imaging confirmed previous diagnostic findings in 16% (14/87) of the patients; in 34% collected in the detectors are weighted the same, regardless of their quality. With “sinogram”) and added a model of the CT system geometry during the data forward (30/87) of the patients, Fludeoxyglucose F 18 Injection PET images provided new findings. In 32% the increased focus in dose reduction, the lack of inclusion of statistical properties projection. This correction loop that operates through to the raw-data domain is (27/87), imaging with Fludeoxyglucose F 18 Injection was inconclusive. The impact of these imaging of conventional FBP or WFBP become an important barrier that prevents further particularly helpful for reducing spiral artifacts. A second correction loop in image radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art findings on clinical outcomes is not known. space is applied iteratively to reduce image noise. SAFIRE has been used extensively CT scanners have been developed with more advanced technology, known as iterative since its introduction, and a wealth of scientific literature has consistently supported Several other studies comparing imaging with Fludeoxyglucose F 18 Injection results to subsphenoidal reconstruction (IR). Not surprisingly, among the key advantages of IR is that the the capabilities of SAFIRE to reduce dose while maintaining high image quality in EEG, MRI and/or surgical findings supported the concept that the degree of hypometabolism statistical properties of measured CT projection data can be readily incorporated into applications ranging from routine to specialized body and neuro CT – in both adults corresponds to areas of confirmed epileptogenic foci. The safety and effectiveness of the CT image reconstruction process. This would allow, for example, low-quality (noisy) Fludeoxyglucose F 18 Injection to distinguish idiopathic epileptogenic foci from tumors or other brain and pediatrics.7-10 projections to carry less weight than high-quality projections. lesions that may cause seizures have not been established. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help 15 REFERENCES to consistently achieve the right dose, for the right diagnostic task, for every patient. 1. Gallagher B.M., Ansari A., Atkins H., Casella V., Christman D.R., Fowler J.S., Ido T., MacGregor This was in line with the ALARA principle, that is to use a dose that is “As Low As R.R., Som P., Wan C.N., Wolf A.P., Kuhl D.E., and Reivich M. “Radiopharmaceuticals XXVII. 18F- Reasonably Achievable” to deliver diagnostic image quality. labeled 2-deoxy-2-fluoro-d-glucose as a radiopharmaceutical for measuring regional myocardial glucose metabolism in vivo: tissue distribution and imaging studies in animals,” J Nucl Med, 1977; 18, 990-6. 2. Jones S.C., Alavi, A., Christman D., Montanez, I., Wolf, A.P., and Reivich M. “The radiation * In clinical practice, the use of IRIS may reduce CT patient dose depending on the clinical task, patient size, anatomical dosimetry of 2 [F-18] fluoro-2-deoxy-D-glucose in man,” J Nucl Med, 1982; 23, 613-617. location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. 3. Kocher, D.C. “Radioactive Decay Tables: A handbook of decay data for application to radiation ** In clinical practice, the use of SAFIRE may reduce CT patient dose depending on the clinical task, patient size, anatomical dosimetry and radiological assessments,” 1981, DOE/TIC-I 1026, 89. location, and clinical practice. A consultation with a radiologist and a physicist should be made to determine the appropriate dose to obtain diagnostic image quality for the particular clinical task. The following test method was used to 4. ICRP Publication 53, Volume 18, No. l-4,1987, pages 75-76. determine a 54 to 60% dose reduction when using the SAFIRE reconstruction software. Noise, CT numbers, homogeneity, low-contast resolution, and high contrast resolution were assessed in a Gammex 438 phantom. Low dose data reconstructed with SAFIRE showed the same image quality compared to full dose data based on this test. Data on file. 2 3 47 White Paper | White Paper | ADMIRE: Advanced Modeled Iterative Reconstruction FlowMotion Multiparametric PET Suite 16 HOW SUPPLIED/STORAGE AND DRUG HANDLING Fludeoxyglucose F 18 Injection is supplied in a multi-dose, capped 30 mL and 50 mL glass vial ADMIRE: containing between 0.740 to 7.40GBq/mL (20 to 200 mCi/mL), of no carrier added 2deoxy-2-[F 18] fluoro-D-glucose, at end of synthesis, in approximately 15 to 50 mL. The contents of each vial are Advanced Modeled Iterative sterile, pyrogen-free and preservative-free. NDC 40028-511-30; 40028-511-50 Reconstruction Receipt, transfer, handling, possession, or use of this product is subject to the radioactive material regulations and licensing requirements of the U.S. Nuclear Regulatory Commission, Agreement States or Licensing States as appropriate. Store the Fludeoxyglucose F 18 Injection vial upright in a lead shielded container at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). by Juan C. Ramirez-Giraldo, PhD, Katharine L. Grant, PhD, and Rainer Raupach, PhD Store and dispose of Fludeoxyglucose F 18 Injection in accordance with the regulations and a general license, or its equivalent, of an Agreement State or a Licensing State. The expiration date and time are provided on the container label. Use Fludeoxyglucose F 18 Injection within 12 hours from the EOS time. Introduction: Evolution of Siemens CT image reconstruction technologies 17 Image reconstruction is an essential technology that every computed tomography (CT) PATIENT COUNSELING INFORMATION scanner requires for operation. The function of CT image reconstruction is to translate all of the acquired X-ray data (raw data) into a meaningful three-dimensional Instruct patients in procedures that increase renal clearance of radioactivity. Encourage patients to: representation of the patient. The most well-known method of image reconstruction drink water or other fluids (as tolerated) in the 4 hours before their PET study. is commonly referred to as filtered back projection (FBP), in which measured X-ray void as soon as the imaging study is completed and as often as possible thereafter for at least one hour. projections are directly translated into images. In most modern scanners, it is likely that not all measured data can be used for image reconstruction with FBP,1 i.e., not all radiation dose applied to the patient is actually used for image reconstruction. To Manufactured by: PETNET Solutions Inc. address this, Siemens Healthineers CT scanners offer an improved three-dimensional 810 Innovation Drive FBP, called weighted filtered back projection (WFBP).2 Knoxville, TN 37932 A common characteristic of both FBP and WFBP is that they do not consider statistical Distributed by: PETNET Solutions Inc. properties of measured X-ray projections. What this means is that all CT projections 810 Innovation Drive collected in the detectors are weighted the same, regardless of their quality. With Knoxville, TN 37932 the increased focus in dose reduction, the lack of inclusion of statistical properties of conventional FBP or WFBP become an important barrier that prevents further radiation dose reduction. In an attempt to overcome such limitations, state-of-the-art CT scanners have been developed with more advanced technology, known as iterative reconstruction (IR). Not surprisingly, among the key advantages of IR is that the statistical properties of measured CT projection data can be readily incorporated into the CT image reconstruction process. This would allow, for example, low-quality (noisy) projections to carry less weight than high-quality projections. There has been an expanding utilization of IR in clinical practice in recent years, primarily due to the increased focus on radiation dose optimization. Of note, Siemens Healthineers has been placing emphasis on devising technical solutions that can help to consistently achieve the right dose, for the right diagnostic task, for every patient. This was in line with the ALARA principle, that is to use a dose that is “As Low As Reasonably Achievable” to deliver diagnostic image quality. 2 48 Trademarks and service marks used in this material [a] syngo.via can be used as a standalone device or are property of Siemens Healthcare GmbH. All other together with a variety of syngo.via-based software company, brand, product and service names may options, which are medical devices in their own right. be trademarks or registered trademarks of their syngo.via and the syngo.via based software options are respective holders. not commercially available in all countries. Due to All comparative claims derived from competitive data regulatory reasons its future availability cannot be at the time of printing. Data on file. Siemens reserves the guaranteed. Please contact your local Siemens right to modify the design and specifications contained organization for further details. herein without prior notice. As is generally true for technical specifications, the data contained herein varies within defined tolerances. Some configurations are optional. Product performance depends on the choice of system configuration. Please contact your local Siemens organization for the most current information. Note: Original images always lose a certain amount of detail when reproduced. All photographs © 2018 Siemens Healthcare GmbH. All rights reserved. “Siemens Healthineers” is considered a brand name. Its use is not intended to represent the legal entity to which this product is registered. Please contact your local Siemens organization for further details. FlowMotion Multiparametric PET is not commercially available in all countries. Due to regulatory reasons its future availability cannot be guaranteed. Please contact your local Siemens organization for further details. Siemens Healthineers Headquarters Published by Siemens Healthcare GmbH Siemens Medical Solutions USA, Inc. Henkestr. 127 Molecular Imaging 91052 Erlangen, Germany 2501 North Barrington Road Phone: +49 9131 84-0 Hoffman Estates, IL 60192 siemens-healthineers.com USA Phone: +1 847-304-7700 siemens.com/mi MI-3988.KBK.JV © Siemens Healthcare GmbH, 08.2018