IQ•SPECT: A technical and clinical overview

White paper IQ•SPECT: a technical and clinical overview siemens-healthineers.com/mi SIEMENS Healthineers Table of contents Introduction 3 IQ•SPECT: technical considerations 4 IQ•SPECT: normal patterns 12 Interpreting effects of attenuation with IQ•SPECT: comparison of supine and prone acquisitions 19 IQ•SPECT in 201Tl myocardial perfusion imaging 25 A comparison of relative myocardial tracer distribution in 201Tl myocardial perfusion SPECT on LEHR and IQ•SPECT without CTAC 29 Segmental analysis of myocardial uptake: SPECT/CT vs. IQ•SPECT 29 IQ•SPECT mismatch with SPECT/CT 30 IQ•SPECT prone position: comparison with coronary angiography 30 IQ•SPECT: clinical studies supporting the relative equivalence of IQ•SPECT and LEHR acquisitions 32 IQ•SPECT clinical examples: coronary artery disease 38 Supplement A: normal database generation for IQ•SPECT 56 Supplement B: IQ•SPECT image acquisition 59 Conclusion 63 Acknowledgments 63 References 64 2 White paper · IQ•SPECT: a technical and clinical overview | Effective Date: 16 SEP 2022 | HOOD05162003272903 Introduction One of the key trends in nuclear medicine is the ever-increasing demand for faster myocardial perfusion imaging (MPI). IQ•SPECTTM is a fast cardiac imaging solution that is offered on Symbia™ SPECT and SPECT/CT systems. It uses a combination of converging collimators, modified cardio-centric acquisition, and special reconstruction methods to deliver ultrafast cardiac imaging four times faster than conventional SPECT acquisition, with scan times as low as four minutes per acquisition. This unique approach can be combined with or added to a general-purpose gamma camera or SPECT/CT, so the system is able to perform all routine clinical applications, as well as ultrafast cardiac scans, with just a change in collimators and acquisition mode. This approach improves the flexibility and versatility of the general-purpose gamma camera or SPECT/CT, enabling departments to perform a larger volume and a wider range of procedures without additional dedicated equipment and space requirements. This white paper briefly explains the technical aspects of IQ•SPECT and demonstrates normal patterns and variations, as well as shows a series of clinical examples of ischemia and infarction to familiarize nuclear cardiologists with IQ•SPECT. Normal databases for IQ•SPECT for 99mTc MIBI and 201Tl created to aid reporting are also discussed as well as some aspects of acquisition and positioning for reproducible image quality. White paper · IQ•SPECT: a technical and clinical overview 3 IQ•SPECT: technical considerations In nuclear medicine studies, image quality is limited by the number of detected photons. When imaging a small organ, such as the heart, much of the large-field-of- view detector on a conventional gamma camera is not used. One way to increase the number of detected photons is to utilize more of the detector by using a fan-beam or cone-beam collimator to magnify the projection of the organ on the detector. The cost of this increase in detected photons is a reduction in the transverse or axial field of view (FOV), or both, leading to truncation artifacts in reconstructed images. IQ•SPECT is an advanced MPI solution that avoids the problem of truncated data by employing a variable focus collimator, retaining the magnifying properties of a cone-beam collimator near the center of the FOV, and eliminating truncation at the edges of the FOV, similar to a parallel-hole collimator. IQ•SPECT is an intelligent solution, collecting four times as many counts from the heart during a myocardial perfusion SPECT study on a Symbia imaging system while maintaining the same resolution as a low-energy, high-resolution (LEHR) collimator. The additional count statistics can be used to reduce the acquisition time or reduce the injected dose by up to 75 percent. This flexibility also allows optimized combination of a reduction in injected dose together with a decrease in acquisition time to suit individual department requirements. IQ•SPECT consists of three components: SMARTZOOMTM collimators, a cardio-centric acquisition, and the IQ•SPECT reconstruction. SMARTZOOM collimators are designed so that the center of the FOV magnifies the heart, while the edges sample the entire body to avoid the truncation artifacts common to pinhole and focusing collimators. It is important to note that the SMARTZOOM collimator achieves a gain in count statistics without compromising image resolution, as is the case with conventional, large bore, parallel-hole collimators. IQ•SPECT takes advantage of the flexible gantry motions available on the Symbia platform to perform a cardio-centric acquisition. The cardio-centric orbit allows the detectors to rotate around a virtual center of rotation that is positioned so the heart is always in the most sensitive area of the collimator, also known as the “sweet spot.” The IQ•SPECT reconstruction algorithm models the unique position and shape of each of the 48,000 SMARTZOOM collimator holes and fully characterizes the location and orientation of the detectors as the gantry rotates. IQ•SPECT reconstruction also includes resolution recovery, CT-based attenuation correction (CTAC), and energy window-based scatter correction. 4 White paper · IQ•SPECT: a technical and clinical overview SMARTZOOM collimation Cast collimation manufacturing techniques are used to fabricate the unique geometry of the SMARTZOOM collimators. The focus of each collimator varies continuously, from cone-like in the central region to parallel at the edges. This provides magnification of the cardiac region while avoiding truncation of the surrounding tissue. The unique position and shape of each hole in the collimator, also referred to as a vector map, is measured in our factory and stored with the collimator to be used during reconstruction. SIEMENS Healthineers .. Cardio-centric acquisition For optimal sensitivity gain, the heart should remain in the SMARTZOOM “sweet spot” in all views. IQ•SPECT uses the flexibility of the Symbia gantry to achieve this focus throughout the acquisitions. During patient setup, the location of the heart can be easily identified on the patient positioning monitor. IQ•SPECT then computes and executes an orbit that optimizes the gain and image quality for the specific patient. ealthineers 1 Healthineers 2 SE Unlike a conventional acquisition (or orbit) where the detectors maintain close proximity to the patient, the detectors in the cardio-centric orbit are at a fixed 28 cm from the center of the heart to maintain its position in the collimator “sweet spot.” The larger collimator distance also increases patient comfort and may reduce motion artifacts. White paper · IQ•SPECT: a technical and clinical overview 5 The unique cardio-centric configuration exploits the flexibility of the Symbia gantry to position each detector at the optimal distance from the user-identified heart over the expected variation of patient population. The angular separation of the detectors is slightly less than the traditional 90 degrees, which improves angular sampling over the most information-rich portion of the cardiac orbit. The cardio-centric acquisition has a scan arc of 208 degrees (104 degrees per head) to compensate for the fan angle of the SMARTZOOM collimator and to ensure complete sampling. The angle between the detectors is set to 76 degrees. Acquisition Both gated and non-gated acquisitions of 99mTc or 201Tl are supported. The entire patient setup adds just one additional step to identify the position of the heart on the touch screen patient positioning monitor. The patient is placed on the bed in either a supine or prone position and moved under the nuclear detectors until the heart is approximately centered in the axial direction. The center of the projection of the heart on each detector is marked on the patient positioning monitor, allowing for the calculation of the location of the patient’s heart in three-dimensional space. This will become the center of the cardio-centric orbit. The acquisition can then be started. Reconstruction After data acquisition is complete, the study is transferred to the reconstruction workstation. The projection data should be reviewed for motion and motion correction applied, if necessary. Gated reconstructions with eight time bins are completed within 90 seconds, and non-gated reconstructions are completed in less than 60 seconds. Forward Compare Projection Update Backward Projection 6 White paper · IQ•SPECT: a technical and clinical overview The IQ•SPECT reconstruction method is a proprietary implementation of a conjugate- gradient iterative reconstruction algorithm. It has been developed to achieve the following objectives: • Maintain the same reconstructed resolution as LEHR collimators in a non-circular orbit • Realize the four-fold sensitivity gain of the SMARTZOOM collimator • Correct for the effects of patient attenuation, scatter, and motion • Perform reconstructions in a clinically acceptable time Anthropomorphic chest phantom study The quality of the reconstructed images can be appreciated by reviewing the results of the following phantom study in Figure 1. A Data Spectrum normal male anthropo- morphic torso phantom was loaded with 74, 370, and 407 MBq of 99mTc in the heart, liver, and background, respectively, corresponding to typical clinical concentrations of 99mTc Sestamibi found in humans. Careful examination of the non-attenuation and scatter-corrected data in rows 1 and 3 in Figure 1 show some differences between the LEHR and IQ•SPECT reconstructed data. O Row 1 LEHR - non-AC O O Row 2 LEHR - AC and SC O IQ. SPECT - non-AC Row 3 IQ . SPECT - AC and SC ROW OOO LEHR - non-AC nnnnnn nnnnnn LEHR - AC and sc nnnnnn IQ . SPECT - non-AC nnnnnn IQ. SPECT - AC and sc Figure 1. Torso phantom study (Data Spectrum). White paper · IQ•SPECT: a technical and clinical overview 7 The physical characteristics of the collimator and the data acquisition process that led to these differences can be readily understood by reviewing the images in Figure 2. LEHR images are on the left and IQ•SPECT images are on the right. The bottom two images show a CT scan of the Data Spectrum phantom. Red lines indicating the lines of sight of the collimator holes are overlaid on the CT images. The images on the top are the resulting reconstructed images. LEHR_T2.5 [3D-8148-9mm - Non AC ] ... HLA IOS_T2.5 [Recon - Non AC ], 12/2/2010 HLA % 100 100 12 n B 0 Apex S T: 4.8 P: 304.5 T: 4.8 e AC AC_Cardiac 5.0 B08s. 12/2/2010 P. 306.9 0 Base a AC AC Cardiac 5.0 908s, 1 2/2/2010 HU HU 230.3 In 12: 1574 mm 10:523.1 mm D Figure 2. Data Spectrum T. 4.8 Anterior to 308s phantom showing effects Compressed P. 304.5 Inferior Compressed P: 304.5 of attenuation. A (8.0%. T.100%) D: HU(B .- 85.1.165) B: (8.0%, T:100%) D. HU(B .- 85,7.165) SMARTZOOM NAC SMARTZOOM AC Figure 3. Attenuation geometry for IQ•SPECT in the vertical long-axis view. The inferior wall is more susceptible to attenuation because of a longer path length to the detector. Attenuation correction (AC) will largely improve the inferior wall uniformity. 8 White paper · IQ•SPECT: a technical and clinical overview The myocardial perfusion images by the LEHR collimator and those by IQ•SPECT without attenuation/scatter correction will result in images with visually different impression. Figures 2 and 3 show the physical similarities and differences. LEHR acquisition is performed with the detector close to the phantom without AC. The photons emitted from around the apex of the heart pass through the sternum reaching the detector at the shortest distance resulting in minimal attenuation due to tissue and distance (left arrow). However, the photons emitted from the neighboring tissue are greatly attenu- ated because of the increased thickness of the tissue the photons need to travel, in addition to the increased distance to the detector (right arrow). In the case of IQ•SPECT, these attenuation mechanisms cause even stronger attenuation. In other words, the apex of the heart is affected by exactly the same physical effects as LEHR and is the least attenuated by the tissue and distance, while on the other hand, photons will have traveled through much thicker tissue and greater distance in the neighboring tissue. As shown by the left arrow in the IQ•SPECT image in Figure 2, the region around the inferolateral wall is greatly attenuated, and the apical region indicated by arrow 2 shows high signal. AC considers the effect of physical attenuation during reconstruc- tion, resulting in a uniform distribution. The same is true for the vertical long-axis image, the photons pass through the thicker issue and longer path, resulting in higher attenuation effect at the inferior wall as indicated by the arrow. AC can restore more uniform distribution (Figure 3). Such an attenuation mechanism is influenced by differences in body habitus according to patient’s sex and the presence/absence of defects, exhibiting a characteristic myocardial perfusion distribution. Figures 4-7 show the results of phantom experiments based on sexual dimorphism, the presence/absence of defects, and AC. The normal male phantom example without AC in Figure 4 shows a visible decrease in uptake at the four o’clock position, and this pronounced attenuation effect can be observed in both LEHR and IQ•SPECT. Following AC, the distribution of the inferior wall is improved for both. Furthermore, the AC causes an obvious decrease in the apex in both LEHR and IQ•SPECT. In the case of male phantom with two cold lesions without AC in Figure 5, both LEHR and IQ•SPECT show a deficit at the four o’clock, making it difficult to eval- uate the size of defects. This is improved by AC, and the images become similar between LEHR and IQ•SPECT. In a simulation of female geometry, attenuation bodies that resemble breasts were placed on a phantom during acquisition. This increases the difference in the extent of attenuation between photons emitted from the apical region close to the body surface and those originating from the neighboring tissues (Figure 6). In other words, the photons emitted from the apex through the sternum and intermammary cleft have relatively low attenuation, whereas the photons emitted from the vicinity that pass through much thicker tissues are strongly attenuated. Gamma cameras will not be able to distinguish such an anatomical difference, thus frequently resulting in artifacts such as those shown by the white arrow in Figure 6. This phenomenon can be seen in both LEHR and IQ•SPECT, but it may be more frequently seen as well as more prominent in IQ•SPECT images. By performing AC, the occurrence of such artifacts is suppressed, and the distribution becomes uniform. In the case of a female cardiac phantom that includes defects without AC (Figure 7), the effect of attenuation is pronounced regard- less of which collimator is used, making it difficult to evaluate the inferior wall. The corrected image is similar between LEHR and IQ•SPECT, and the polar map images show similar pattern as in the male model with defects. White paper · IQ•SPECT: a technical and clinical overview 9 LEHR AC NCO LEHR AC NCO O O O IQS AC IQS AC O LEHR NAC NCO LEHR NAC NCO IQS NAC IQS NAC O Figure 4. Anthropomorphic phantom comparison between LEHR and SMARTZOOM with U normal male. LEHR AC NCO LEHR AC NCO C IQS AC IQS AC O C LEHR NAC NCO LEHR NAC NCO IQS NAC IQS NAC O Figure 5. Anthropomorphic phantom comparison between LEHR and SMARTZOOM with male with two cold lesions. 10 White paper · IQ•SPECT: a technical and clinical overview LEHR AC NCO LEHR AC NCO IQS AC QS AC LEHR NAC NCO LEHR NAC NCO IQS NAC IQS NAC Figure 6. Anthropomorphic phantom comparison between LEHR and SMARTZOOM with normal female. LEHR AC NCO LEHR AC NCO IQS AC IQS AC O LEHR NAC NCO LEHR NAC NCO IQS NAC IQS NAC Figure 7. Anthropomorphic phantom comparison between LEHR and SMARTZOOM with female with two cold lesions. Workflow IQ•SPECT is seamlessly integrated with Symbia imaging systems. The SMARTZOOM collimator can be included in the Integrated or Automatic Collimator Changers. Automatic Quality Control will perform all common system calibrations for the SMARTZOOM collimators. Extreme care has been given to ensure simple and intuitive user interaction. White paper · IQ•SPECT: a technical and clinical overview 11 IQ•SPECT: technical considerations: normal patterns Comparisons of standard myocardial perfusion SPECT studies using LEHR collimators with filtered back projection (FBP) and 3D iterative (Flash 3D) reconstruction to IQ•SPECT studies, performed at the same sitting, demonstrate the comparable nature of the two acquisition approaches in terms of tracer distribution patterns, as well as cardiac shape and size. However, there are differences between conventional SPECT and IQ•SPECT reconstructed slices in relation to the shape of the heart, myocardial thick- ness, effect of attenuation, etc., which require familiarization with the normal patterns of IQ•SPECT myocardial perfusion imaging for effective interpretation. The following clinical examples illustrate such normal patterns. LEHR FBP NAC O LEHR Flash3D NAC IQ.SPECT Flash3D NAC LEHR FBP NAC LEHR Flash3D NAC IQ.SPECT Flash3D NAC Figure 8a. A normal male patient underwent myocardial perfusion imaging with 99mTc MIBI using LEHR and IQ•SPECT. The IQ•SPECT acquisition was four times faster than LEHR acquisition based on standard acquisition protocols. FBP and Flash 3D reconstruction from LEHR acquisition (top and middle rows) are compared to IQ•SPECT reconstruction, performed using the dedicated IQ•SPECT reconstruction (bottom row). A comparison of the images shows the sharper ventricular margins, as well as slightly smaller left ventricle (LV) size with IQ•SPECT. Note the increased attenuation effect in the inferior and posterobasal wall (red arrows) with IQ•SPECT, compared to the FBP and Flash 3D reconstructions. Study protocol: Symbia T16; 20 mCi (740 MBq) 99mTc Sestamibi stress injection; IQ•SPECT stress study: 17 frames, 9 seconds per frame (total scan time: 4 minutes). LEHR stress study: 32 frames, 24 seconds per frame (total scan time: 14 minutes). Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. 12 White paper · IQ•SPECT: a technical and clinical overview LEHR NAC O O O LEHR CTAC O O O O IQ-SPECT NAC IQ.SPECT O O CTAC Figure 8b. The same patient data is displayed with stress LEHR and IQ•SPECT short-axis images with and without CTAC. Note the improve- ment in uptake in the inferior wall following CTAC in the LEHR study, which is a typical demonstration of AC. However, the extent of inferior wall attenuation at the same slice level is higher in the IQ•SPECT images with normalization of inferior wall tracer uptake following accurate CTAC (arrows). Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. LEHR NAC LEHR CTAC IQ.SPECT NAC IQ.SPECT CTAC Figure 8c. Horizontal and vertical long axis views of stress MPI of the same patient with the display identical to the short axis shows exag- gerated inferior wall attenuation in the uncorrected IQ•SPECT images, which is corrected following CTAC, with normal inferior wall uptake visualized in the corrected images. Note the slightly different orientation of the mitral valve plane in the IQ•SPECT images compared to the LEHR images. Study protocol: Symbia T16; 20 mCi (740 MBq) 99mTc Sestamibi stress injection; IQ•SPECT stress study: 17 frames, 9 seconds per frame (total scan time: 4 minutes). LEHR stress study: 32 frames, 24 seconds per frame (total scan time: 14 minutes). Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. White paper · IQ•SPECT: a technical and clinical overview 13 LEHR O O O O NAC O LEHR NAC LEHR CTAC LEHR CTAC IQ.SPECT NAC IQ.SPECT CTAC O O O LEHR IQ-SPECT NAC IQ.SPECT CTAC NAC LEHR CTAC IQ.SPECT n NAC Q.SPECT CTAC Figure 9. Above is a comparison of LEHR and IQ•SPECT 99mTc MIBI stress MPI in a normal male without and following CTAC, with the acquisition protocol similar to that of the previous case example. Note the higher inferior wall attenuation levels with IQ•SPECT, which is corrected by CTAC. Also note the posterobasal attenuation (red arrows) in the vertical and horizontal long axis views, which also shows significant improvement in uptake levels following CTAC. Exaggerated posterobasal, as well as inferior wall AC, is common with IQ•SPECT, but is effectively corrected by CTAC. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. As highlighted in the previous clinical images, a characteristic pattern of IQ•SPECT perfusion imaging without AC is high uptake in the apex (hot apex).1 Figure 10 shows non-AC (NAC)-corrected IQ•SPECT stress images in a male patient with normal myocardial perfusion, with a clearly defined hot apex. Although such a hot apex is not visualized in all cases, it is important to be aware of this artifact, especially in supine acquisitions without AC. Multifocal SMARTZOOM collimators used by IQ•SPECT lead to an increase in the counts from the apex, which is close to the body surface and have lower levels of attenuation compared to the counts originating from the inferior wall and septum and base of the heart which encounter higher levels of attenuation. Accurate AC reduces this phenomenon and leads to a normalization of apical uptake leading in some cases to “apical thinning” following AC. Figure 10. Increased uptake in the apex with IQ•SPECT in an NAC 201Tl stress MPI study in a 64-year-old man acquired in supine position. The apex shows increased uptake compared to rest of the normally perfused left ventricle; a phenomenon termed “hot apex.” Data courtesy of Kanazawa University, Kanazawa, Japan. 14 White paper · IQ•SPECT: a technical and clinical overview LEHR NAC 9 LEHR CTAC IQ.SPECT S NAC S IQ.SPECT CTAC Figure 11a. A 99mTc MIBI stress MPI comparison of LEHR and IQ•SPECT in a 37-year-old female with normal perfusion. Note the hot apex in the uncorrected IQ•SPECT images (red arrows), which normalizes following CTAC. A thick apex with increased uptake is a common finding in the uncorrected IQ•SPECT images both in male and female patients due to the non-uniform attenuation levels of apex and the lateral and septal walls. Such a hot apex effect is usually decreased following AC along with renormalization of the uptake throughout the entire LV myocardium. Study protocol: Symbia T16; 20 mCi (740 MBq) 99mTc Sestamibi stress injection; IQ•SPECT stress study: 17 frames, 9 seconds per frame (total scan time: 4 minutes); LEHR stress study: 32 frames, 24 seconds per frame (total scan time: 14 minutes); low-dose CTAC. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. LEHR NAC LEHR CTAC LEHR O O O O O Figure 11b. Short-axis views NAC of the same patient show slight inferior wall attenuation, LEHR O O O O O O O which is corrected in the CTAC CTAC images. Despite this patient IQ.SPECT O IQ.SPECT NAC Q.SPECT CTAC being female, there is very little anterior wall attenuation. NAC IQ.SPECT O O O O Data courtesy of the University CTAC of Michigan, Ann Arbor, Michigan, USA. LEHR O LEHR NAC NAC LEHR O O LEHR CTAC CTAC S IQ-SPECT O Q.SPECT NAC 10.SPECT O O O IQ.SPECT CTAC CTAC SS Figure 12a. A 99mTc MIBI stress MPI in a 59-year-old female patient shows normal perfusion at peak stress. LEHR and IQ•SPECT images show comparable image quality and tracer distribution. Note the predominant anterior wall attenuation (red arrows), which is corrected following CTAC. It is important to note the higher level of anterior wall attenuation with IQ•SPECT without AC (NAC). However, post-CTAC IQ•SPECT images show perfect correction of anterior wall attenuation effects. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. White paper · IQ•SPECT: a technical and clinical overview 15 STRESS LEHR NAC LEHR CTAC IQ-SPECT NAC IQ-SPECT CTAC LEHR NAC LEHR CTAC IQ-SPECT NAC IQ-SPECT CTAC Figure 12b. A 99mTc MIBI stress-rest MPI study was performed on a 48-year-old female patient using LEHR and IQ•SPECT. A comparison of stress LEHR and IQ•SPECT images (NAC and with AC) shows a combination of anterior wall AC along with thick hot apex predominantly in the IQ•SPECT images, but also, to a lesser extent, in the LEHR images. Anterior wall attenuation (red arrows) in uncorrected images is well-corrected following CTAC. Apical thickness and increased apical uptake in NAC images (white arrows) is pronounced in the uncorrected IQ•SPECT images but is normalized following CTAC. Short axis IQ•SPECT slices toward the apex show the combination of increased uptake at the apex and adjacent anterolateral wall (white arrow), along with attenuation effect on the anterior wall, which leads to slight distortion of the shape of the LV in short axis. This is, however, completely corrected following CTAC. The combination of attenuation effects along with apical thickening and increased tracer uptake in the uncorrected IQ•SPECT should be carefully considered during the interpretation of uncorrected data and compared with the CTAC data. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. 16 White paper · IQ•SPECT: a technical and clinical overview REST LEHR NAC LEHR O CTAC IQ.SPECT O O NAC IQ-SPECT CTAC O O O Figure 12c. A comparison of rest images for the same patient also demonstrates the effect of hot apex and subsequent normalization following CTAC (white arrows). However, of note is the tracer uptake in the gut just inferior and adjacent to the inferolateral wall, which is accentuated following AC (red arrows). In this case, the effect is more pronounced in the LEHR images. However, IQ•SPECT images tend to also show increased gut uptake following CTAC. This potential of AC-dependent increased gut uptake and its contribution to inferior and inferolateral wall uptake should be considered during interpretation. A review of the rotating MIP of the acquisition is often helpful to determine the extent of gut uptake and estimate its contribution to the inferior wall uptake. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. Stress LEHR NAC Stress LEHR CTAC O Stress IQ-SPECT NAC Stress IQ-SPECT O O O CTAC O O Stress LEHR NAC Stress LEHR CTAC Stress IQ-SPECT NAC Stress IQ-SPECT CTAC Stress LEHR CP NAC Stress LEHR CTAC Stress IQ-SPECT NAC Stress IQ-SPECT CTAC Figure 13. Comparison of LEHR and IQ•SPECT stress acquisition in a patient with normal myocardial perfusion. Minor inferior wall attenuation seen in NAC LEHR study shows improved uptake following CTAC (arrows). Inferior wall attenuation is more prominent in NAC IQ•SPECT images but shows complete normalization following CTAC. The hot apex in NAC IQ•SPECT study delineated in the vertical and horizontal long axis images (arrows) appears normal following CTAC. The slight variation in left ventricular shape and the mitral valve plane orientation between LEHR and IQ•SPECT is clearly appreciable. Ventricular cavity size is slightly lower with IQ•SPECT as evident in the short axis and horizontal long axis images. The study was performed on Symbia Pro.spectaTM SPECT/CT equipped with IQ•SPECT and CTAC. Data courtesy of Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. White paper · IQ•SPECT: a technical and clinical overview 17 63 65 67 Stress NAC 63 64 65 66 67 Rest NAC 62 63 65 Stress CTAC 63 v 65 66 67 68 Rest CTAC V Figure 14. Above is a low-dose IQ•SPECT study with inferior wall attenuation corrected by CTAC in IQ•SPECT using low-dose protocol with a 10 mCi (370 MBq) sestamibi stress injection and 6-minute acquisition. A 54-year-old female (110 lb/50 kg) was referred for atypical chest pain. The study shows normal perfusion with inferior and posterobasal wall attenuation, which is corrected with CTAC. Similar normal patterns with IQ•SPECT related to attenuation effects and enhanced apical tracer uptake in uncorrected images are also visualized with 201Tl myocar- dial perfusion imaging using IQ•SPECT. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. 18 White paper · IQ•SPECT: a technical and clinical overview Interpreting effects of attenuation with IQ•SPECT: comparison of supine and prone acquisitions Normal myocardial perfusion images and the corresponding polar maps shown in Figures 15a and 15b do not show a hot apex in supine images, but the decrease in inferior wall uptake in NAC images secondary to diaphragmic attenuation is clearly visualized. The extent of inferior wall attenuation is similar to conventional SPECT and appears higher in men than in women. The polar maps showed a prominent sex differ- ence in the inferior wall uptake (myocardial count in the central inferior wall: 65% male, 86% female). AC helps correct the attenuation-induced decrease in the inferior wall counts and also normalizes the hot apex. However, it should be noted that AC causes a phenomenon known as apical thinning, which is characterized by a visible decrease in apical counts as evident in the images as well as in polar maps. This is due to the apex having a thin myocardium and large excursion during systole and diastole with resulting decrease in apical perfusion induced by attenuation correction.2 In Symbia systems without integrated CT or when the CT is not being used for AC, the effect of attenuation can be reduced by performing IQ•SPECT acquisition with the patient in prone position. The prone position causes the heart to move forward, creating a distance between the heart and the liver/diaphragm, which reduces the level of attenuation caused by the diaphragm.3 The same effect is observed in IQ•SPECT. With IQ•SPECT, there are concerns over the unique artifacts in supine imaging without AC. The recommendation is to apply AC with SPECT/CT devices or prone imaging for SPECT-only systems. The next clinical examples illustrate the impact of prone imaging in aiding the interpretation of attenuation related artifacts when using IQ•SPECT. NAC stress and rest images show very high liver and gastric activity in the stress study related to the dobutamine stress, which makes interpretation of inferior wall uptake difficult. The rest study shows slightly reduced inferior wall uptake, which may be related to attenuation effect, but, without a clear inferior wall uptake assessment in the stress study, it is difficult to characterize the uptake. White paper · IQ•SPECT: a technical and clinical overview 19 Male Female Supine-NC O O O O Supine-AC O O O O O Prone-NC O O O O O O Supine-NC Supine-AC Prone-NC Figure 15a. 99mTc MIBI myocardial perfusion imaging using IQ•SPECT in a male and female patient showing normal perfusion in the LV myocardium Supine-NC n at rest. Comparison of supine NAC, supine with CTAC, and S prone NAC in a male and female patient clearly delineates slight inferior wall attenuation in the supine NAC images, which is Supine-AC corrected by supine CTAC as well as normalized in prone NAC images (NC, no correction). Prone-NC Data courtesy of Tokyo Women’s Medical University, Tokyo, Japan. 20 White paper · IQ•SPECT: a technical and clinical overview Male Female 83 02 Supine-NC Supine-AC 85 Prone-NC Figure 15b. Polar maps of the case shown in Figure 15a. 74 Data courtesy of Tokyo Women’s Medical University, Tokyo, Japan. Dobutamine Stress Stress NAC Rest NAC Stress NAC Figure 16a. An 82-year-old male with long-standing diabetes treated by insulin presented with typical angina and dyspnea. There was history of past allergic reaction to aminophylline. A 99mTc MIBI myocardial perfusion IQ•SPECT study was performed using pharmacologic stress test with dobutamine. An 80% maximal predicted heart rate response was achieved after 1 mg atropine. No ST-T changes were observed on the EKG during dobutamine stress. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. White paper · IQ•SPECT: a technical and clinical overview 21 Dobutamine Stress Supine NAC Supine CTAC Prone NAC Supine NAC Supine CTAC Prone NAC Figure 16b. The patient also underwent a stress IQ•SPECT study in a prone position with a separately performed CT immediately after completion of the supine stress study. Supine NAC and CTAC images, along with NAC prone images, are displayed in short axis and the vertical long axis (VLA). Supine images show high hepatic and gastric uptake of tracer, which overlaps the inferior wall, making inferior wall interpretation difficult. Following the CTAC of the supine images, there is further accentuation of the subdiaphragmatic uptake and artificially decreased anterior wall and septal uptake due to renormalization. However, the prone images, even without CTAC, as shown in this image, show homogenous distribution of tracer throughout the LV myocardium with normal appearance of the inferior wall. The study was interpreted as normal. This example clearly demonstrates the value of prone imaging in specific situations, especially related to the interference of inferior wall attenuation and hepatic gastric and bowel uptake with interpretation. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. CT Supine CT Prone Figure 16c. CT slices in both supine and prone positions for the same patient show a significant amount of pleural fluid with shifting of fluid to the dependent part of the thorax between the supine and prone positions. The shift of the ventricles toward the chest wall in the prone position is also well-visualized on the prone CT image, which reflects the absence of hepatic and gastric interference. CT images also show diffuse three vessel calcification. The SPECT/CT study was interpreted as normal. The final diagnosis was global cardiac insufficiency related to atrial fibrillation without significant coronary artery disease (CAD). Clinical follow-up after four months was uneventful. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. 22 White paper · IQ•SPECT: a technical and clinical overview O O O Stress Perfusion (96) Stress Rest O Stress 59 VLA 68 69 Rest Perfu Rest Stress Rest Figure 17a. 201Tl myocardial perfusion study performed on a Symbia S system using IQ•SPECT in an elderly male in supine position without any AC shows normal perfusion throughout the entire left ventricular myocardium both in stress and rest. However, the typical hot apex expected in non-attenuation corrected IQ•SPECT and slightly decreased uptake in the inferobasal wall related to inferior wall attenuation effect is visualized both in stress and rest images. The patient subsequently underwent prone imaging following the supine acquisition using IQ•SPECT for both stress and rest. Data courtesy of Tokyo Women’s Medical University, Tokyo, Japan. Stress O O Stress Perfusion (%) Rest O O Stress 60 VL Rest Perfusion (%) Rest Stress Rest Figure 17b. The stress and rest IQ•SPECT images acquired in prone position without AC shows normalization of inferobasal wall uptake demonstrating the value of prone imaging with IQ•SPECT to reduce attenuation artifacts in situations where CTAC is not available. The hot apex visualized in the supine images is also not so evident in prone images probably due to the normalization of inferior wall uptake and change in the relative attenuation effects of the base of the heart compared to the apex in the prone position. Data courtesy of Tokyo Women’s Medical University, Tokyo, Japan. White paper · IQ•SPECT: a technical and clinical overview 23 4 SAX Stress O O O O Stress Perfusion (%) Rest O 65 68 69 Stress JVLA Rest Perfusion (% ) Rest 69 70 Stress 68 Rest Figure 18a. Tl201 stress-rest MPI in a 70-year-old male performed in the supine position using IQ•SPECT without AC shows normal left ventricular perfusion. However, there is slightly decreased uptake in the inferior wall as well as the lower septum in the stress images. The relative decrease in uptake in the inferior is also evident in the polar maps. This was visually interpreted as an attenuation effect, but a prone acquisition was also performed. Data courtesy of Tokyo Women’s Medical University, Tokyo, Japan. O OOOOOO Stress O Rest Figure 18b. The prone IQ•SPECT acquisition shows normalization of inferior wall Stress uptake as compared to anterior wall both in stress and rest with Rest clear illustration of the impact of prone imaging in reducing attenuation-related artifacts. Stress Data courtesy of Tokyo Rest Women’s Medical University, Tokyo, Japan. As evident from these examples, prone imaging using IQ•SPECT can help reduce attenuation artifacts and decrease interpretational problems due to attenuation-related decrease in uptake both for inferior and anterior wall. 24 White paper · IQ•SPECT: a technical and clinical overview IQ•SPECT in 201Tl myocardial perfusion imaging Attenuation effects are even more prominent with IQ•SPECT when 201Tl is the perfusion tracer. With conventional 201Tl myocardial perfusion SPECT using LEHR collimators, inferior wall attenuation artifacts are often problematic. A decrease in inferior wall uptake in 201Tl MPI is routinely seen for conventional LEHR collimators without AC. This can be exaggerated with IQ•SPECT. Thus, CTAC for 201Tl IQ•SPECT studies is key to proper evaluation of inferior wall uptake and elimination of attenuation-related artifacts. CT acquisition immediately before or after SPECT acquisition also provides information on the soft tissues (including the liver and breasts). Following accurate fusion of SPECT and CT, AC can be performed, thereby reducing any attenuation effect in the inferior wall thereby improving the relative uptake compared to the anterior wall. Conventional IQ.SPECT (w/o AC) IQ.SPECT (with AC) SA VLA Polar map 67 72 80 89 85 83 86 89 63 67 84 89 76 88 89 78 91 88 78 82 89 75 86 62 76 Figure 18. Characteristics of 201Tl myocardial perfusion 75 75 in conventional SPECT images 57 72 57 60 76 58 68 65 70 61 and IQ•SPECT images. 75 56 56 Data courtesy of Kanazawa University, Kanazawa, Japan. White paper · IQ•SPECT: a technical and clinical overview 25 TI 201 Stress-Rest IQ.SPECT Stress NAC Stress CTAC Rest NAC Rest CTAC Figure 19. A 71-year-old female underwent stress-rest 201Tl MPI using IQ•SPECT. A comparison of stress and rest images without and with CTAC shows the typical patterns of anterior wall attenuation (red arrows), which is well-corrected following CTAC. Note the apical thickness and increased apical uptake in both uncorrected stress and rest images, which is well-corrected following CTAC (white arrows). The hot apex in uncorrected images following CTAC and renormalization of tracer uptake throughout the LV myocardium shows slight apical thinning in the CTAC images. Exaggerated apical thinning following CTAC is a regular pattern both in LEHR and IQ•SPECT images. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. TI 201 Stress-Rest IQ.SPECT 24 25 26 27 28 29 30 31 Stress NAC O 23 24 25 26 27 28 29 30 Stress CTAC 24 25 26 28 29 30 3 Rest NAC 23 24 25 26 27 28 29 30 Rest CTAC O O Figure 20. 201Tl stress-rest IQ•SPECT short-axis views of a 56-year-old male patient show inferior wall attenuation (red arrows), which is corrected after CTAC. Note the tracer uptake in the gut in the rest images, particularly the increase in gut uptake following AC (white arrows). Such increase in stomach and intestinal uptake following AC is common in IQ•SPECT and needs to be considered when interpreting inferior wall uptake. Data courtesy of Atrium Medical Center, Heerlen, The Netherlands. 26 White paper · IQ•SPECT: a technical and clinical overview As discussed, prone imaging with IQ•SPECT can improve interpretation of attenuation effects with 201Tl MPI studies. This was evaluated in a series of 201Tl myocardial perfusion studies with both LEHR and IQ•SPECT supine and prone acquisitions performed without CTAC on a Symbia S system at the Tokyo Women’s Medical University. The study showed that the phenomenon of hot apex was more frequently present in supine IQ•SPECT compared to the prone acquisition (35% vs 10%). Table 1: Prevalence of hot apex with IQ•SPECT in supine and prone position acquisitions. IQS supine IQS prone Stress 5/10 (50%) 1/10 (10%) Rest 2/10 (20%) 1/10 (10%) 99mTc TF 3/8 (38%) 0/8 (0%) 201TI 4/12 (30%) 2/12 (17%) The cases with significant attenuation effects with IQ•SPECT in supine position were acquired again in prone position. Prone imaging usually corrected the decreased uptake related to attenuation for confident determination of the absence of significant perfusion abnormality. White paper · IQ•SPECT: a technical and clinical overview 27 supine prone stress rest stress Figure 21. The effect of patient positioning on inferior wall attenuation. Prominent inferolateral wall attenuation seen in supine acquisition is rest largely improved in prone positioning. Data courtesy of Tokyo Tc-99m TF Exercise Women’s Medical University, Tokyo, Japan. As evident from previous images, CTAC improves uptake levels in inferior and anterior walls by reducing attenuation effects, but this leads to a decrease in the uptake in the apex and adjacent antero-apical segment, which is often referred to as apical thinning (Figure 19). IQ•SPECT with CTAC restores inferior wall false-positives even with 201Tl, which is more susceptible to attenuation and scatter. Although the image quality of 201Tl is inferior to that of 99mTc, CT-based corrections can provide perfusion images free of inferior wall attenuation. In addition, the reduced acquisition time with IQ•SPECT is convenient for patients and can reduce artifacts due to patient motion. 28 White paper · IQ•SPECT: a technical and clinical overview A comparison of relative myocardial tracer distribution in 201Tl myocardial perfusion SPECT on LEHR and IQ•SPECT without CTAC Evaluation of average myocardial tracer distribution in a series of 201Tl stress/rest studies show that both IQ•SPECT supine and prone show higher uptake at the apex and adjacent anterior wall compared to LEHR. A quantitative comparison also clearly defines the higher apical uptake seen on the supine IQ•SPECT when compared to LEHR. IQ•SPECT supine shows decreased uptake in the inferobasal wall, posterior septum, and inferolateral wall compared to IQ•SPECT prone. In the IQ•SPECT prone images, uptake in the apex and adjacent anterior wall as well as the posterior wall was higher than in LEHR. Prone IQ•SPECT acquisition shows normalization of inferolateral wall attenuation effects visualized on the supine acquisition. Overall, IQ•SPECT prone showed the most uniform tracer distribution. Segmental analysis of myocardial uptake: SPECT/CT vs. IQ•SPECT A study comparing IQ•SPECT and conventional SPECT/CT in patients undergoing exercise or pharmacological stress myocardial perfusion SPECT for assessment of ischemic heart disease was conducted using a stress-first protocol with 99mTc Tetrofosmin as the perfusion tracer.4 The ratio of injected tracer activity was 1:2 for stress and rest, respectively. The stress dose was roughly 250 MBq, which is about half of the conventional injected dose. In the study, 116 patients underwent both conventional and IQ•SPECT studies, of which 26 patients had significant perfusion defects during stress on conventional SPECT/CT. Following conventional SPECT/CT using LEHR, IQ•SPECT prone and supine positions were acquired successively. SPECT/CT was recon- structed using 3D iterative (OSEM) reconstruction algorithms. A bullseye map was generated based on with and without CTAC for each reconstruction, and the defect size were evaluated in the scale of four. Similarly, in IQ•SPECT, bullseye maps were generated for prone and supine positions. White paper · IQ•SPECT: a technical and clinical overview 29 IQ•SPECT mismatch with SPECT/CT Segmental comparison of LEHR SPECT/CT with IQ•SPECT prone and supine yielded overall concordance and discordance rates. Overall concordance rate was relatively high (Table 2). In IQ•SPECT prone, the percentage discordance in each coronary artery segment was less than 2%. In the IQ•SPECT supine, it was 3% or less. Table 2: Correlation of interpretation between IQ•SPECT supine and prone when compared to LEHR SPECT/CT. Lower false-positive rates (FPR) and false-negative rates (FNR) with prone IQ•SPECT in left anterior descending artery (LAD) and right coronary artery (RCA) territories. Left LAD RCA circumflex artery (LCX) FPR 1/97 (1.0%) 2/114 (1.8%) 1/103 (1.0%) IQ•SPECT prone FNR 1/19 (5.3%) 0/2 (0%) 1/13 (7.7%) Overall FR 2/116 (1.7%) 2/116 (1.7%) 2/116 (1.7%) FPR 1/97% (1.0%) 3/114 (2.6%) 0/103 (0%) IQ•SPECT supine FNR 2/19 (10.5%) 0/2 (0%) 0/13 (0%) Overall FR 3/116 (2.6%) 3/116 (2.6%) 0/116 (0%) IQ•SPECT prone position: comparison with coronary angiography The same group performed a retrospective comparative study of 129 consecutive patients who underwent catheter coronary angiography after IQ•SPECT prone imaging (period of 8 months). The catheterization reports were reviewed, and positive angio- graphic stenosis was defined as having visual stenosis of 75% or more. Exercise Figure 22. A case of suspected lateral wall and septal ischemia. The areas of decreased perfusion are related to attenuation effects since the defect was not corroborated Rest by angiographic results. Data courtesy of Tokyo SAX HLX Women’s Medical University, Tokyo, Japan. 30 White paper · IQ•SPECT: a technical and clinical overview LAD RCA LCX 95% 93% 88% 81% 84% 80% 72% 71% 67% Figure 23. IQ•SPECT prone Sensitivity Specificity Accuracy Sensitivity Specificity Accuracy Sensitivity Specificity Accuracy concordance with coronary angiography. Interpretation of IQ•SPECT was performed by two experienced nuclear cardiologists. Figure 23 shows the results of a comparative study of IQ•SPECT prone imaging and coronary angiography. For each coronary artery, blue indicates sensitivity, orange indicates specificity, and grey indicates accuracy. The number of diseased coronary arteries was almost evenly distributed from all three to none (N=129, 3VD=29, 2VD=31, 1VD=34, 0VD=35), and the branch-based prevalence rate was 47%. The analysis confirmed relatively satisfactory diagnostic results with sensitivity of around 70%, specificity of around 90%, and accuracy of around 80% in all three coronary artery regions. Particularly, in the right coronary artery region, the specificity was comparable to that of the left anterior descending branches. It is possible that improved attenuation of the infero-posterior wall due to the prone position ensured favorable specificity. White paper · IQ•SPECT: a technical and clinical overview 31 IQ•SPECT: clinical studies supporting the relative equivalence of IQ•SPECT and LEHR acquisitions Since the introduction of IQ•SPECT, there have been many independent validation studies to compare the clinical performance between IQ•SPECT and conventional MPI. One of the earliest studies was from the University of Michigan, which compared 4-minute IQ•SPECT MPI with conventional LEHR acquisition performed in 15-20 minutes.5 A total of 110 patients referred for myocardial perfusion imaging underwent a 99mTc MIBI stress-only or stress-rest single-day protocol MPI study, performed initially with parallel-hole collimation using a Symbia T16 SPECT/CT and subsequently with IQ•SPECT, employing SMARTZOOM collimators and cardio-centric orbits on the same system without significant delay between studies. Low-dose CT for AC was acquired initially. A standard LEHR SPECT/CT was performed over 180° orbits at 3° increments for 15-20 seconds per view into 128 x 128 matrices and 4.8 mm pixels. The study time was 15-20 minutes. IQ•SPECT images were acquired over a 208° cardio-centric orbit with 17 views per detector for 9 seconds per view to 128 x 128 matrices and 4.80-mm pixels. The total study time was 4 minutes. Both LEHR and IQ•SPECT images were corrected for attenuation using initially acquired low-dose CT. Normal databases were created from 30 low-likelihood normal males and 22 low-likelihood females. Standard 17 segment scoring and blackout polar map analyses were employed using Corridor4DM™ software. Image quality was similar between LEHR and IQ•SPECT for most patients. Among 13 low-likelihood normal not included in the normal databases, 11 were normal with IQ•SPECT and 12 were normal with LEHR. Fourteen patients were determined to have CAD in both the LEHR and IQ•SPECT studies. The summed stress scores (SSS) were similar to IQ•SPECT and LEHR (13.9 ± 10.2 as 12.4 ± 11.4, respectively). Defect sizes were also similar between the two acquisitions. Angiographic correlation was also similar, with a trend of increased sensitivity with IQ•SPECT (12 vs. 8 true positives by SSS). Overall, a quantitative analysis of IQ•SPECT and LEHR showed comparable image quality, normalcy rates, and sensitivity. The same group presented another abstract comparing LEHR and IQ•SPECT acquisition with CTAC in 54 patients, 37 of which were low-likelihood normals.6 Assessments of normalcy were very similar with values of 91% for LEHR and 97% with IQ•SPECT. Angiographic correlations performed in 7 patients were almost identical. Studies in patients without significant stenoses (< 50%) were normal for both LEHR and IQ•SPECT. Patients with higher stenosis severity on angiography showed consistently higher SSS with IQ•SPECT as compared to LEHR. 32 White paper · IQ•SPECT: a technical and clinical overview A similar study was performed using 201Tl in 40 Japanese patients with normal myocardial perfusion by Matsuo et al who compared IQ•SPECT with and without CTAC with standard NAC LEHR acquisition performed both at rest and following pharmacological stress.7 Visual evaluation showed comparable image quality between IQ•SPECT and LEHR acquisitions. Conventional NAC LEHR 201Tl studies showed a decrease in the mid-inferior segment of the left ventricle probably related to attenuation effects. IQ•SPECT images without AC showed similar inferior wall attenuation effects while IQ•SPECT with AC showed improved uptake in the same mid-inferior segments demonstrating the effects of AC. There was a tendency toward slight decrease in the apical and antero-apical uptake with IQ•SPECT with AC probably related to the phenomenon of apical thinning following CTAC as described earlier. Although myocardial perfusion was comparable between LEHR and IQ•SPECT, left ventricular ejection fraction (LVEF) and end-diastolic volume (EDV) evaluated from gated IQ•SPECT were lower as compared to LEHR in all patients. Another study by Horiguchi et al performed conventional LEHR (15-min acquisition) as well as IQ•SPECT with 17 stops (14 sec per stop; total scan time 4 min) as well as with 36 stops (14 sec per stop; total scan time 8 min) for stress-rest 201Tl myocardial perfusion studies in 21 patients without and with CTAC.8 Visual image quality scores were comparable between 15-minute LEHR and 8-minute IQ•SPECT studies but were rated slightly lower for the 4-minute IQ•SPECT study both without and with CTAC. Defect scores were also comparable between LEHR and 8-minute IQ•SPECT but slightly higher with 4-minute IQ•SPECT. However, there was excellent correlation of defect location and size between LEHR and both IQ•SPECT protocols. Adding CTAC to 4-minute IQ•SPECT resulted in a defect score only slightly lower to 8-minute IQ•SPECT with CTAC. The authors concluded that 8-minute IQ•SPECT was more suitable for imaging with 201Tl, although the difference between 4-minute and 8-minute studies were clinically not significant from a defect evaluation point of view. Comparing LEHR and 4-minute IQ•SPECT in 43 patients undergoing 99mTc Tetrofosmin myocardial perfusion study, Caobelli et al found no significant difference in perfusion scores, visual image quality assessment, and clinical interpretation and concluded that 4-minute IQ•SPECT was clinically equivalent to standard LEHR acquisition, which was 4 times longer.9 The same author subsequently compared an even faster 2.5-minute acquisition protocol using IQ•SPECT with the standard 4-minute IQ•SPECT acquisition in 50 patients and found comparable summed stress and defects scores. Although image quality was scored higher with the 8-minute acquisition, there was clinical equivalence between the 4-minute and 8-minute acquisitions. EDV and end-systolic volume (ESV) were slightly higher with the shorter acquisition, whereas the ejection fraction did not differ. Image quality and LV volumes and LVEF obtained with IQ•SPECT with a one-eighth acquisition time of the standard LEHR acquisition were statistically comparable to the previously validated one-fourth time protocol using IQ•SPECT.10 White paper · IQ•SPECT: a technical and clinical overview 33 Matsutomo et al compared resting gated LEHR and IQ•SPECT MPI studies using either 99mTc Tetrafosmin or 201Tl in 53 patients with suspected CAD.11 Conventional LEHR SPECT MPI (99mTc Tetrofosmin at 9.6 min acquisition and 201Tl at 12.9 min acquisition) was immediately followed by IQ•SPECT (4.3 min for 99mTc Tetrofosmin and 6.2 min for 201Tl) for each patient. Overall, there was good correlation of myocardial uptake patterns between LEHR and IQ•SPECT. The mean differences in uptake percentages between LEHR and IQ•SPECT in 99mTc Tetrofosmin studies were 1.1 ± 6.6% at the apex, 2.8 ± 5.7% in the anterior wall and 4.9 ± 6.7% in the lateral wall. For 201Tl studies, the variation at the apex was 1.6 ± 6.9%, anterior wall 2.0 ± 6.6%, and 3.3 ± 7.2% for lateral wall. Mean LVEF tended to be higher with IQ•SPECT (LEHR SPECT 64.8 ± 11.8% and IQ•SPECT 68.3 ± 12.1% for 99mTc Tetrofosmin; LEHR SPECT 56.0 ± 11.7% and IQ•SPECT 61.5 ± 12.2% for 201Tl). Yoneyama et al compared IQ•SPECT and LEHR using 99mTc MIBI in 98 patients with a large proportion with small hearts with focus on LV function comparison.12 LVEF, EDV and ESV for both studies were also compared with echocardiography. Using Cedars- Sinai QGS for analysis there was a slightly difference in LVEF between conventional SPECT and IQ•SPECT (65.4% ± 13.8% vs. 68.4% ± 15.2%). A subsegment of the group with small hearts shows a similar difference (75.0 ± 9.6 % vs.79.5 ± 8.3%). LEVF on echocardiography was consistently slightly lower (64.8 ± 11.6% for all patients and 70.1 ± 6.8% for patients with small hearts). Further comparison of left ventricular functional parameters between LEHR and IQ•SPECT acquisition performed by Leva et al found mean LVEF of 58%, 57%, and 54% with 8-minute IQ•SPECT, 4-minute IQ•SPECT and 14-minute LEHR studies.13 All studies were performed without AC. EDV and ESV were consistently higher with IQ•SPECT (mean EDV 118 ml, mean ESV 61 ml) compared to LEHR (mean EDV 111 ml mean ESV 59 ml). The slight difference in LVEF estimation between IQ•SPECT and LEHR needs to be considered while interpreting the studies. Comparison of LVEF obtained from 99mTc Sestamibi IQ•SPECT acquisition with planar radionuclide ventriculography performed by Joergensen et al in 28 patients showed mean LVEF OF 68% ± 26% for IQ•SPECT (17 stops, 14 sec per stop; 5-min total acquisition time) calculated using 4DMSPECT compared to 64% ± 24% obtained from radionuclide ventriculography.14 Over a wide range of LVEF values gated IQ•SPECT myocardial perfusion imaging showed slight overestimation compared to planar radio- nuclide ventriculography (RNV), although IQ•SPECT used 8 gates per cardiac cycle while RNV used 16 gates per cardiac cycle. Comparing two reconstruction methods of IQ•SPECT with different iterations and subsets showed significant differences in EDV and ESV but with only minor differences in LVEF, leading the authors to conclude that consistency in reconstruction settings is key to reproducibility of LVEF with IQ•SPECT. 34 White paper · IQ•SPECT: a technical and clinical overview Similar overestimation of LVEF by gated IQ•SPECT myocardial perfusion study by average of 4-6% was shown by Talleruphuus et al based on a comparison of IQ•SPECT and LEHR myocardial perfusion gated SPECT. The ± mean LEHR LVEF values were 60.8% ± 3.0% while that for gated IQ•SPECT was 66.0% ± 4.2%. End-diastolic and end-systolic volumes however were significantly lower with IQ•SPECT which reflects the slight change in left ventricular shape and the position of the myocardial valve plane in IQ•SPECT compared to LEHR.15 Another interesting comparison of LVEF between IQ•SPECT gated bloodpool study, planar RNV, and cardiac MRI by Pelletier-Galarneau et al with 60 patients undergoing planar RNV as well as IQ•SPECT gated myocardial bloodpool SPECT following injection of radiolabeled red blood cells.16 Among this group, 11 also underwent cardiac MRI. LVEF were greater with planar MUGA compared to IQ•SPECT GBPS. Average planar LVEF was 48 ± 11% and ranged from 23% to 70%. Average LVEF measured with IQ•SPECT gated bloodpool SPECT 40 ± 12% (range 16% to 75%) using Cedars-Sinai QBS. Average LVEF on cardiac MRI was 45 ± 10% (range 28% to 58%). Average LVEDV with IQ•SPECT gated blood pool SPECT calculated by QBS was 177 ± 59 mL (range 63 to 342 mL), while average LVEDV with cMRI was 257 ± 78 mL (range 137 to 393 mL). The overall conclusion of the study was that LVEF calculated with GBPS using IQ•SPECT correlates with planar measurements and is independent of LVEDF although the variations with cardiac MRI were wider. The increased count rate capability of IQ•SPECT for MPI studies can be used to reduce acquisition time as well as reduce injected dose. A collaborative study between Brigham & Women’s Hospital Boston and Siemens Healthineers aimed to compare the relative equivalence of full-dose half-time IQ•SPECT to half-dose half-time IQ•SPECT.17 The study evaluated 93 patients who underwent sequential LEHR (13-min) and IQ•SPECT (7-min) following peak stress injection of 25-30 mCi (925-1110 MBq) 99mTc Sestamibi. Full-dose IQ•SPECT data was subsampled to half-, quarter-, and eighth-count levels in order to simulate a low-dose IQ•SPECT stress study. Patient motion was significantly lower in IQ•SPECT studies, with lower need for motion correction. Thirty-one percent of the LEHR acquisitions had significant patient motion, but this was seen in only 13% of the IQ•SPECT acquisitions. Image quality of the stress images were rated as equivalent between full-dose LEHR and full-dose half-time (7-min acquisition) IQ•SPECT as well as simulated half-dose half-time IQ•SPECT. Very low dose IQ•SPECT images (quarter and one-eighth dose equivalent to 6 mCi [222 MBq] and 3 mCi [111 MBq], respectively) were rated as noisy compared to LEHR and higher dose IQ•SPECT images, although these were not clinically significant. The mean SSS was slightly higher for IQ•SPECT, although this was not statistically significant. There was good correlation between defect size and total perfusion defect scores (TPD) between full-dose LEHR and IQ•SPECT at all dose conditions. There was relative equivalence of the mean global TPD score between half-time full-dose IQ•SPECT imaging and full-dose LEHR stress imaging (12.2 ± 16.7% vs. 11.2 ± 16.4%, respec- tively). The mean global stress TPD scores for half-time half-dose IQ•SPECT (11.3 ± 16.5%) and that of LEHR were also equivalent. Mean global TPD was slightly lower for quarter (9.4 ± 15.4%) and one-eighth dose (9.5 ± 15.7%). White paper · IQ•SPECT: a technical and clinical overview 35 Overall clinical interpretation between LEHR and IQ•SPECT was equivalent across all dose levels except minor interpretational discrepancies only at one eight dose level. LVEF and EDV showed small but statistically significant differences between LEHR and IQ•SPECT at all dose levels. The mean LVEF for full-dose LEHR stress was 63 ± 12% while that for full-dose IQ•SPECT was 60 ± 12%. Mean EDV and ESV for LEHR were 114 ± 48 and 47 ± 40 mL, respectively; while for full-dose IQ•SPECT, these values were 107 ± 45 mL and 46 ± 38 mL, respectively. The smaller diastolic LV cavity dimensions seen with IQ•SPECT reflect the change in the ventricular shape due to the nature of the collimation used in IQ•SPECT. Overall, this study established the clinical equivalence of half-dose half-time IQ•SPECT to full-dose LEHR studies. Clinical examples of comparative images of LEHR and IQ•SPECT at various dose simulation levels illustrate the visual and quantitative equivalence (Figures 24 and 25). O O O O nsSS S LEHR IQ.SPECT O S Full Dose IQ.SPECT O Half Dose Figure 24. LEHR and IQ•SPECT images at various dose-level simulations for a 99mTc Sestamibi stress MPI study in a patient with normal perfu- sion. Clinical equivalence in ventricular perfusion and LV cavity dimensions is demonstrated between LEHR and half dose IQ•SPECT images. Data courtesy of Brigham & Women’s Hospital, Boston, Massachusetts, USA. LEHR IQ.SPECT Full Dose O IQ.SPECT Half Dose S Figure 25. LEHR and IQ•SPECT images at various dose-level simulations for a 99mTc Sestamibi stress MPI study in a patient with LAD territory ischemia. Stress-induced perfusion defect in anterior and anteroseptal wall and apex is clearly delineated in LEHR and appears equivalent in extent and uptake level with IQ•SPECT at all dose-level simulations. Clinical equivalence in ventricular perfusion defect extent and dilated LV cavity dimensions is demonstrated between LEHR and all IQ•SPECT images. Data courtesy of Brigham & Women’s Hospital, Boston, Massachusetts, USA. 36 White paper · IQ•SPECT: a technical and clinical overview Comparison of LEHR and IQ•SPECT in large patient populations show clinical equivalence between the two acquisition methods and establishes that IQ•SPECT can provide identical clinical information about myocardial perfusion and defect size and reversibility in a four-times faster imaging protocol. However, the most appropriate correlation is between defect size within individual coronary artery territories with IQ•SPECT myocardial perfusion with respective coronary artery stenosis levels defined on coronary angiography. In a study from Turkey, Dogan et al performed automated quantitative as well as semiquantitative visual analysis of perfusion defects in 165 patients using IQ•SPECT and compared to coronary angiography for correlation of defect in individual arterial territories to coronary stenosis.18 Eighty-four patients had significant CAD on angiography with mean summed stress score of 10.1 and mean stress total perfusion deficit of 16% using automated quantitative evaluation. On the other hand, the 81 patients without significant CAD had a mean summed stress score of 5.5 and stress perfusion deficit of 9.2%. A summed stress score >5.5 was deemed the cut-off point for predicting presence of significant CAD. Close correlation of the isch- emic defect size evaluated by quantitative or semiquantitative methods with IQ•SPECT myocardial perfusion in anginal patients with a significant coronary artery lesion (≥70% stenosis) detected by angiography suggests that both methods may be used to identify the clinically important lesions. Correlation of defect size with IQ•SPECT 201Tl stress-rest myocardial perfusion imaging with coronary angiographic findings including fractional flow reserve (FFR) was performed by Tanaka et al in a single center prospective study.19 Myocardial perfusion using adenosine-stress 201Tl IQ•SPECT/CT MPI was performed with 84 consecutive, prospectively identified patients with stable CAD followed by coronary angiography. Subsequently, 212 angiographically identified stenotic coronary arterial segments were evaluated for correlation with myocardial perfusion with IQ•SPECT. The FFR in 136 of the 212 diseased vessels were compared using visual semiquantitative evaluation of corresponding territories on IQ•SPECT images without and with CTAC. FFR inversely correlated most accurately with regional summed difference scores (rSDS) in images without and with CTAC. The optimal FFR cutoff for detection of significant perfusion abnormality with IQ•SPECT with and without CTAC was revealed to be <0.80. Myocardial segments with rSDS ≥2 without or with CTAC-predicted FFR <0.80, with 73% sensitivity and 84% specificity. These findings showed that the IQ•SPECT system can predict FFR at an optimal cutoff of <0.80. Use of CTAC was associated with a significant increase in identification of number of segments defined as normal with corresponding FFR >0.82, which served as a cut off for normal perfusion. White paper · IQ•SPECT: a technical and clinical overview 37 IQ•SPECT clinical examples: coronary artery disease When diagnosing CAD, it is important to quantify the degree of ischemia and infarction. Patients with higher ischemia have an increased probability of cardiac events, and coronary angioplasty improves the patient’s prognosis, especially in patients with more than 10% ischemia.20 As with conventional SPECT, it is necessary to carefully observe and examine perfusion abnormality areas and their degree when searching for abnor- malities in IQ•SPECT images. Figure 26 shows a case of a 74-year-old woman suspected of ischemic heart disease with shortness of breath during exertion who underwent pharmacological stress followed by myocardial perfusion SPECT with 99mTc Tetrofosmin. Images taken with IQ•SPECT show a moderate perfusion defect in the inferolateral wall, which persists even at rest, but with evidence of partial reversibility. Wall motion analysis via Cedars- Sinai’s Quantitative Gated SPECT (QGS) application showed hypokinetic inferolateral wall. Coronary angiography showed significant stenosis of the LCX. Partial reversibility in the context of severe stress ischemia reflects presence of myocardial infarction with peri-infarct reversibility characterized by smaller defect size at rest compared to that see on stress, indicating a mixture of ischemia and infarction. This is depicted in the polar map in Figure 27, which shows percentage uptake of the inferolateral wall in the rest image is 50% or more, reflecting partial reversibility of the peri-infarct zone. Myocardial hibernation is a phenomenon characterized by severe left ventricular wall dysfunction due to a decrease in coronary perfusion. Hibernating myocardium has been shown to recover following revascularization by coronary artery bypass surgery or angioplasty. C Stress Rest Stress Perfusion(%) Rest Perfusion(%) 74 70 89 91 89 80 79 83 91 85 94 89 89 52 92 77 Figure 26. Stress/rest images 81 87 84 and polar maps for patients 74 62 with suspected ischemic heart disease. Data courtesy of Kanazawa 50 University, Kanazawa, Japan. 38 White paper · IQ•SPECT: a technical and clinical overview The extent of hypoperfusion in stress myocardial perfusion scintigraphy is a key factor in deciding between medical management and revascularization. Studies have shown in patients with normal perfusion or minor level of ischemia that the cardiac event rate is similar between those managed conservatively and those under- going revascularization.21 Revascularization should be considered if the reversible perfusion defect is moderate or large. Figure 27 shows a case example of a 66-year-old man with shortness of breath during exertion with suspected of CAD. 99mTc Tetrofosmin was injected following pharma- cological stress and myocardial perfusion scintigraphy was performed with IQ•SPECT. Stress images show decreased perfusion in apex and adjacent anterior wall as well as the periapical inferolateral wall as well as lateral wall. Rest study shows normalization of uptake in apex and adjacent anterior and inferior and lateral walls suggesting severe but reversible myocardial ischemia in LAD and RCA territories. Coronary angiography showed 99% stenosis of RCA, 90% stenosis of LAD, and 90% stenosis of LCX. Based on these results, coronary artery bypass surgery was performed with grafts to the left anterior descending, left circumflex, and obtuse marginal arteries. Myocardial perfusion SPECT visualizes the relative decrease in perfusion, and therefore in cases where there are lesions in three branches, it is easy to underestimate the degree of ischemia because the left ventricular myocardium would show diffuse ischemia. It is necessary to keep such situations of balanced ischemia in mind when interpreting IQ•SPECT or conventional SPECT MPI. While interpreting SPECT, it is important to observe the presence or absence of defects as well as the dilation of left ventricular cavity during stress. Transient ischemic dilata- tion (TID) is a state in which the LV cavity dilates during stress due to left ventricular dysfunction secondary to stress induced ischemia. The LV cavity is usually normal at rest. In such situations, EDV during stress is significantly increased compared to during rest. Such transient ischemic dilatation, as shown in the patient in Figure 28, is usually associated with multivessel CAD and is often the only SPECT feature associated with balanced ischemia. Decreases in LVEF, left ventricular diastolic function, and left ventricular volume after stress are thus indicators of advanced CAD. Recent phase analysis methods reported worsening left ventricular contraction dyssynchrony is associated with multi-vessel diseases. Combination of SPECT with coronary calcium scoring, possible on current state of the art SPECT/CT systems, can further help in ischemia characterization.22 24 25 26 64 65 O Stress 27 28 29 64 64 Figure 27. Detection of induced ischemia in patients O with suspected CAD. Rest Data courtesy of Kanazawa University, Kanazawa, Japan. White paper · IQ•SPECT: a technical and clinical overview 39 A comparison of LEHR and IQ•SPECT short-axis stress images shows a severe perfusion defect in the anterior wall and septum. The lateral wall also shows moderate perfusion defect better defined on CTAC images. The inferior wall shows improved uptake in the CTAC images, suggestive of attenuation. The LV cavity appears dilated, suggestive of severe CAD. Note the comparable extent and intensity of perfusion defect with IQ•SPECT compared to LEHR both in NAC and CTAC images. A CT calcium score was performed as part of the SPECT/CT procedure, which revealed extensive calcification of the LAD with significant calcification in the RCA and LCX. The patient was subjected to coronary angiography, which revealed 90% ostial stenosis in the LAD with another 70% stenosis at mid-LAD at the bifurcation of D2 (second diagonal). The LCX was the dominant vessel with 30% ostial stenosis and mid-20% stenosis. The right coronary artery was non-dominant with a mid-90% stenosis. LEHR Stress NonAC LEHR Stress CTAC IQ-SPECT Stress NonAC IQ.SPECT Stress CTAC Figure 28a. A 78-year-old man with anginal pain underwent 99mTc MIBI stress-rest MPI using both LEHR and IQ•SPECT with low-dose CTAC. Study protocol: Symbia T16; dose: stress–21.5 mCi (79.5 MBq) 30-minute post-injection delay, rest–42 mCi (1554 MBq); low-dose, free-breathing CT for AC.The acquisition parameters of the LEHR and IQ•SPECT were as follows: LEHR stress: 32 frames, 22 seconds per frame (total acquisition time 13 minutes) LEHR rest: 32 frames, 11 seconds per frame (total acquisition time 7 minutes) IQ•SPECT stress: 17 frames, 9 seconds per frame (total acquisition time 4 minutes) IQ•SPECT rest: 17 frames, 9 seconds per frame (total acquisition time 4 minutes) Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. 40 White paper · IQ•SPECT: a technical and clinical overview LEHR Rest NonAC LEHR Rest CTAC IQ-SPECT Rest NonAC IQ-SPECT Rest CTAC Figure 28b. A rest study comparing LEHR and IQ•SPECT short-axis images in the same patient shows significant increase in anterior and anteroseptal segments, suggesting reversible ischemia. Note the inferior wall attenuation, which is corrected following CTAC and also causes a slight increase in the intensity of the gut uptake in the corrected images. Due to renormalization of the LV myocardial uptake, anterior wall uptake is slightly lower in the corrected IQ•SPECT slices compared to the uncorrected. The variation of uptake intensity following CTAC due to renormalization is of consideration during comparative interpretation of NAC and CTAC images. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. LEHR Stress CTAC LEHR Rest CTAC IQ.SPECT Stress CTAC IQ.SPECT Rest CTAC Figure 28c. Stress and rest short-axis slices displayed for both attenuation-corrected LEHR and IQ•SPECT images show severe but reversible ischemia in anterior wall and septum LAD territory, along with moderate reversible lateral wall ischemia LCX. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. White paper · IQ•SPECT: a technical and clinical overview 41 Stress C O LEHR NAC Figure 29a. A 99mTc MIBI stress-rest MPI was performed Rest using LEHR and IQ•SPECT in LEHR NAC a patient with inferolateral infarction. A fixed inferolateral Stress defect in uncorrected and IQ.SPECT C NAC corrected short-axis images reflects large inferolateral Rest C infarction without evidence IQ-SPECT of peri-infarct ischemia. Note NAC the improvement in inferoseptal uptake in the attenuation- Stress IQ-SPECT corrected images. CTAC Data courtesy of Hôpital de R Rest IQ.SPECT C la Cité-de-la-Santé de Laval, CTAC Quebec, Canada. Stress LEHR NAC Rest LEHR NAC Stress IQ-SPECT NAC Rest IQ-SPECT NAC Stress IQ-SPECT CTAC REST IQ- SPECT CTAC Figure 29b. Vertical and horizontal long axis views in the same patient show a fixed lateral and inferolateral wall defect (white arrows) both in NAC and CTAC images. However, the posterobasal defect in uncorrected IQ•SPECT stress and rest images (red arrows) shows significant improvement following CTAC, which suggests significant posterobasal attenuation effect. This study demonstrates the advantage of CTAC in the presence of perfusion defects to improve specificity, as well as correctly define the extent and intensity of ischemia. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. 42 White paper · IQ•SPECT: a technical and clinical overview Stress NAC Stress CTAC Figure 30. Uncorrected and Rest CT-attenuation-corrected stress NAC and rest IQ•SPECT images of a patient with suspected CAD. Rest Stress study shows large infe- CTAC rior and inferolateral wall defect, which shows slightly increased uptake in the postero- basal wall after AC, suggestive Stress of inferolateral infarction with NAC peri-infarct ischemia especially Stress in the posterobasal wall. Rest CTAC study shows improvement in uptake in inferior, lateral, and Rest posterobasal wall uptake both NAC in uncorrected and attenuation corrected images, suggesting Rest severe but reversible ischemia TAC in the inferior and inferolateral walls corresponding to RCA Stress territory. Note the impact of NAC 22 CTAC in accurate delineation of the severity of ischemia Stress especially in the stress images CTAC in the posterobasal segment. The study was performed on Rest a Symbia Pro.specta SPECT/CT NAC equipped with IQ•SPECT and CTAC. Rest CTAC Data courtesy of Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. White paper · IQ•SPECT: a technical and clinical overview 43 Stress CTAC LEHR Rest CTAC LEHR Stress CTAC IQ•SPECT Rest CTAC IQ•SPECT Stress CTAC LEHR Rest CTAC LEHR Stress CTAC IQ•SPECT Rest CTAC IQ•SPECT Figure 31a. A 65-year-old male patient (225 lb/102 kg) with shortness of breath on exertion, hypercholesterolemia, and a family history of CAD underwent 99mTc Sestamibi MPI. The standard LEHR acquisition and an IQ•SPECT acquisition were performed at rest and following treadmill stress. A CT calcium score was performed prior to the SPECT study on a Symbia T6. CT-attenuation-corrected IQ•SPECT stress images show severe ischemia in the anterior wall, septum, and apex with significant reversibility in the resting images. The attenuation- corrected LEHR acquisitions show a similar extent of ischemia and reversibility. The LV cavity size appears similar in both studies. Note the increased severity of perfusion defect in the stress IQ•SPECT images (vertical long-axis slices) compared to that of LEHR. Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. 44 White paper · IQ•SPECT: a technical and clinical overview Stress IQ.SPECT Rest IQ.SPECT Stress IQ.SPECT Rest IQ.SPECT Stress IQ.SPECT Rest IQ-SPECT Arten Ca Sc LAD 814 CX 320 RCA 327 Total 1554 Figure 31b. The calcium score study in the same patient shows a total calcium score of 1554 with extensive calcification in all three vessels, with maximum involvement of LAD. Study protocol: Symbia T6; 27 mCi (999 MBq) 99mTc Sestamibi stress injection, 50 mCi (1850 MBq) 99mTc Sestamibi rest injection after 2 hours. IQ•SPECT stress study: 36 frames, 10 seconds/frame LEHR stress study: 32 frames, 41 seconds/frame IQ•SPECT rest study: 36 frames, 3 seconds/frame LEHR rest study: 32 frames, 12 seconds/frame Data courtesy of the University of Michigan, Ann Arbor, Michigan, USA. IQ.SPECT IQ.SPECT Stress Stress IQ.SPECT O O OO Rest Q.SPECT IQ.SPECT Rest Stress IQ.SPECT Rest Reversibility IQ.SPECT Stress IQ-SPECT Rest Figure 32a. A 67-year-old woman presented with atypical chest pain. An IQ•SPECT study was performed at rest and, using pharmacological stress, showed severe and extensive ischemia in the anterior wall and septum (LAD territory). Post-stress transient ischemic dilatation suggests advanced multi-vessel disease. The patient was referred for coronary angiography. Study protocol: 25 mCi (925 MBq) 99mTc Sestamibi stress injection; 17 frames, 9 second/frame, 4 minutes total IQ•SPECT acquisition; low-dose, free-breathing CT for AC. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. White paper · IQ•SPECT: a technical and clinical overview 45 Figure 32b. Coronary angiography of the same patient showed chronic occlusion of the mid-LAD (white arrow), as well as a 50% stenosis of the proximal LAD (red arrow). The patient underwent bypass surgery after a failed angioplasty attempt. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. STRESS NAC STRESS CTAC REST NAC REST CTAC STRESS NAC STRESS CTAC REST NAC REST CTAC Figure 33. A 99mTc MIBI stress-rest IQ•SPECT MPI was performed with low-dose CTAC in a patient with suspected CAD. NAC stress images show inferior wall perfusion defect, which persists following CTAC, although the intensity is reduced. There is significant improvement in inferior wall uptake both in NAC and CTAC rest images, suggesting reversible inferior wall ischemia. CTAC, in this example, improves diagnostic confidence to identify a small inferior wall defect as true ischemia and not a pure attenuation effect. Study protocol: Symbia T6; dose: stress–20 mCi (740 MBq), rest–7 mCi (259 MBq) 99mTc MIBI; IQ•SPECT: stress 17 frames/9 seconds per frame (scan time: 4 minutes), rest: 17 frames/25 seconds per frame (scan time 8.5 minutes). Data courtesy of the University of Sherbrooke, Sherbrooke, Quebec, Canada. 46 White paper · IQ•SPECT: a technical and clinical overview Figure 34a. Single-vessel disease: a 65-year-old female with exertion-induced chest pain and hypertension was referred for an MPI study to evaluate for inducible ischemia. STRESS STRESS CTAC REST CTAC IQ•SPECT performed at rest and CTAC with pharmacological stress REST shows reversible ischemia in CTAC the inferolateral wall. The rest STRESS of the LV myocardium showed CTAC normal perfusion. The patient REST Reversibility CTAC subsequently underwent coro- nary angiography. STRESS CTAC Data courtesy of the University REST CTAC of Sherbrooke, Sherbrooke, Quebec, Canada. Stenting: Figure 34b. A coronary Guidewire placement angiography for the same patient shows single 95% stenosis of the mid LCX (black arrow), which correlates well with IQ•SPECT findings. The patient underwent stenting of the lesion. Coronary flow was Coronary Angiography: completely restored after the Pre-stent placement successful placement of two stents (white arrows). Post-stent placement Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. White paper · IQ•SPECT: a technical and clinical overview 47 Pre Revascularization STRESS Post Revascularization STRESS $9mTc MIBI IQ.SPECT 39mTc MIBI IQ.SPECT STRESS STRESS O CTAC CTAC REST CTAC REST REST CTAC REST STRESS STRESS CTAC CTAC REST REST CTAC CTAC Reversibility Reversibility STRESS STRESS CTAC CTAC REST REST 999. CTAC CTAC Figure 34c. A follow-up MPI study was performed for atypical chest pain after revascularization, which shows normalization of the reversible defect of the inferolateral wall (white arrows). Attenuation corrected pre- and post-stenting studies (6-month interval between MPI studies) shows significant improvement in the inferolateral defect with normal perfusion throughout the rest of the LV myocardium. Note the promi- nent apical thinning in the post-stent IQ•SPECT study, which is a common post-attenuation correction finding in IQ•SPECT studies. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. Stress 10 19 20 21 NAC Rest 16 NAC 13 20 Stress 18 CTAC 21 Rest CTAC Stress NAC Rest 62 NAC C9 Stress CTAC Rest nnnnnn CTAC Figure 35. A 99mTc MIBI stress-rest MPI performed using IQ•SPECT shows reversible ischemia in the anterior wall and septum (LAD territory— red arrows). The inferior wall defect seen in both NAC stress and rest images shows improvement in uptake in the CTAC images, suggesting diaphragmatic attenuation (white arrows). CTAC defines the true extent of LV ischemia and helps define the LAD territory as the only ischemic segment. Study protocol: Symbia T6; 20.2 mCi (747.4 MBq) 99mTc Sestamibi stress 6.7 mCi (247.9 MBq) rest. IQ•SPECT stress study: 17 frames, 14 seconds per frame (total scan time: 4.7 minutes) IQ•SPECT rest study: 17 frames, 30 seconds per frame (total scan time: 9 minutes) Data courtesy of BWZK Hospital, Koblenz, Germany. 48 White paper · IQ•SPECT: a technical and clinical overview Stress NAC Rest NAC Stress NAC Rest NAC Figure 36a. This clinical example is of a 71-year-old female with multiple CAD risk factors like smoking, hypertension, and a family history of CAD. She underwent a dipyridamole stress IQ•SPECT myocardial perfusion study for unstable angina. A NAC stress perfusion study shows widespread apical, peri-apical, septal, inferior, and inferoseptal ischemia with transient LV dilation, consistent with multi-vessel CAD. The rest study suggests complete reversibility of all ischemic segments. The patient was referred for urgent coronary angiography. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. Figure 36b. Coronary angiography of the patient described above demonstrated severe stenosis in the proximal LAD, LCX, and mid-RCA. The patient was referred for surgical revascularization. Data courtesy of Hôpital de la Cité-de-la-Santé de Laval, Quebec, Canada. White paper · IQ•SPECT: a technical and clinical overview 49 NonAC Stress CTAC Rest NonAC Rest CTAC Figure 37a. A 77-year old female with anginal symptoms underwent 99mTc MIBI IQ•SPECT with pharmacological stress and at rest. Study shows large reversible defect in the apex, adjacent anterior wall, and septum, suggestive of moderate reversible ischemia in distal LAD territory. Data courtesy of University of Sherbrooke, Sherbrooke, Quebec, Canada. Figure 37b. Polar plot and volume-rendered images of Stress Stress NonAC CTAC Rest Rest the left ventricle of the patient NonAC CTAC described above demonstrate the severity of the ischemia of the patient above in the apex and adjacent anterior wall and septum and the complete reversibility at rest. The patient was referred for coronary angiography. Data courtesy of University Stress Stress Rost NonAC CTAC Rest NonAC CTAC of Sherbrooke, Sherbrooke, Quebec, Canada. Figure 37c. Coronary angiography shows two sequential stenoses (80%) at mid-LAD level. Data courtesy of University of Sherbrooke, Sherbrooke, Quebec, Canada. 50 White paper · IQ•SPECT: a technical and clinical overview Figure 37d. Both mid-LAD lesions were treated with angioplasty and stenosis with complete restoration of flow. Data courtesy of University 1 st Angioplasty 2nd Angioplasty of Sherbrooke, Sherbrooke, Quebec, Canada. Stress 0222 NonAC CTAC Rest Rest CTAC Figure 38a: A 60-year-old obese woman with a history of recurrent anginal pain underwent 99mTc MIBI IQ•SPECT with pharmacological stress and at rest. Study shows moderate perfusion defect in anterior wall, apex, and lateral wall, which appears reversible on the resting images. Small, fixed defect in the anterior wall was interpreted as non-transmural infarction. Data courtesy of University of Sherbrooke, Sherbrooke, Quebec, Canada. 71 86 87 Stress Stress Rest Rest NonAC CTAC NonAC CTAC Figure 38b. Polar plots of the patient described above show the extent of reversible defect in anterior wall and a small area of fixed defect probably related to nontransmural infarction. Inferior wall, lateral wall, as well as septum, show normal perfusion. Percentage of ischemic myocardium was calculated as 25% of the LV by analysis of polar plot. Patient was referred for coronary angiography. Data courtesy of University of Sherbrooke, Sherbrooke, Quebec, Canada. White paper · IQ•SPECT: a technical and clinical overview 51 Figure 38c. Coronary angiography in this patient shows patent normal looking dominant RCA in this patient. LAD was completely occluded at the proximal level. Attempt to cannulate the occluded LAD was unsuccessful. In spite of the total LAD occlusion, the limited extent of LV ischemia was probably related to dominant RCA and good collateral circulation. Data courtesy of University of Sherbrooke, Sherbrooke, Patent RCA LAD Occlusion Quebec, Canada. Stress NonAC Stress CTAC Rest NonAC Rest CTAC U U Figure 39a. A 79-year-old female with history of chest pain underwent 99mTc MIBI IQ•SPECT during treadmill stress and at rest. Study shows severe perfusion defect in anterior wall and apex with partial reversibility. Part of the anterior wall appears significantly thinned out with a fixed defect, which is suggestive of nontransmural infarction. Data courtesy of University of Sherbrooke, Sherbrooke, Quebec, Canada. 52 White paper · IQ•SPECT: a technical and clinical overview Figure 39b. Polar plots and volume-rendered images of the patient described above show large severe perfusion defect in the anterior wall and apex. The area of fixed defect in resting images suggests nontransmural infarction with significant reversible peri-infarct ischemia. Patient was referred for coronary angiography. Stress Stress Rest Rest NonAC CTAC NonAC CTAC Data courtesy of University of Sherbrooke, Sherbrooke, Quebec, Canada. Figure 39c. Coronary angiography in the above patient revealed a sub-total occlusion of the first diagonal (D1) as well as diffuse moderate stenosis of mid-third of LAD (smaller arrows). There was also a mild proximal LCX stenosis. Patient underwent stenting of both D1 and LAD lesions. Data courtesy of University of Sherbrooke, Sherbrooke, Quebec, Canada. White paper · IQ•SPECT: a technical and clinical overview 53 Patterns of ischemia and reversibility are similar with both 99mTc MIBI and 201Tl using IQ•SPECT. The following example of reversible ischemia visualized using 201Tl and IQ•SPECT helps illustrate the point. Stress NonAC Stress CTAC Rest NonAC Rest CTAC Figure 40a. A 58-year-old man with progressive dyspnoea on exertion underwent 201Tl myocardial perfusion scanning at rest and with dipyridamole stress using IQ•SPECT. Short-axis images show severe but reversible anterior and anteroseptal ischemia (LAD territory). Inferior and inferolateral walls also show reversible ischemia. Data courtesy of Chung Shan Medical University Hospital, Taichung City, Taiwan. Stress NonAC Stress CTAC Rest NonAC Rest CTAC Figure 40b. Horizontal and vertical long axis views of the same patient show reversible ischemia in anterior, apical, anteroseptal, and inferior wall, suggestive of LAD and RCA lesion. Note the slight improvement in posterobasal uptake levels following CTAC, which helps define the true level of ischemia. Data courtesy of Chung Shan Medical University Hospital, Taichung City, Taiwan. 54 White paper · IQ•SPECT: a technical and clinical overview Stress CTAC Rest CTAC 81 67 Figure 40c. Bullseye plots and LV volume renderings show severe ischemia in the apex, anterior, and anteroseptal walls, as well as the inferior wall. The lateral wall shows a normal uptake level. Note the post-stress LV dilatation, which reflects advanced disease. The patient was referred for coronary angiography. Data courtesy of Chung Shan Medical University Hospital, Taichung City, Taiwan. Pre- Post- angioplasty angioplasty Figure 40d. Cardiac catheterization demonstrated severe (90%) proximal LAD stenosis, as well as moderate proximal RCA stenosis. A balloon angioplasty was performed at the same sitting, with improved coronary flow and FFR following the procedure. The patient showed significant improvement in exercise tolerance following angioplasty. Data courtesy of Chung Shan Medical University Hospital, Taichung City, Taiwan. White paper · IQ•SPECT: a technical and clinical overview 55 Supplement A: Normal database generation for IQ•SPECT Myocardial perfusion SPECT images are comprehensively evaluated by taking visual interpretation and quantitative scores into account. In order to obtain perfusion defect scores, it is common to make a comparison with a standard normal myocardial perfusion database, and it is necessary to prepare a normal database that matches the image acquisition conditions and imaging agents used. The normal database for IQ•SPECT was generated as a part of the Japanese Society of Nuclear Medicine Working Group activities and is open to public use.1,23 Figure 41 is a normal myocardial perfusion database for 99mTc MIBI/Tetrofosmin and 201Tl. Four facilities contributed IQ•SPECT normal cases, and normal databases were defined for three acquisition types, namely, supine uncorrected, supine attenuation- corrected as well as prone uncorrected, for males and females respectively (Table 3). Although supine imaging was the standard IQ•SPECT acquisition approach, often the facilities participating in the study chose to perform additional prone imaging with IQ•SPECT in order to reduce common attenuation artifacts.1 Thus, normal databases were created for both supine and prone positions. A characteristic of myocardial perfusion distribution in the normal database is that when uncorrected, the supine position has low myocardial counts in the inferior wall. The low value in the inferior wall is not limited to IQ•SPECT, the same tendency is observed in the conventional SPECT. In addition, lower myocardial counts in the inferior wall are more pronounced in men more so than women. Upon closer look at the individual cases that compose the database, high uptake at the apex (or hot apex) may be observed, but this hot apex cannot be observed in the normal database. However, in the prone position, the decrease in counts in the inferior wall appears to have been recovered or normalized reflecting the reduced attenuation effects achieved with prone acquisition as compared to supine. Furthermore, when comparing normal database between male and female, it was shown that men showed lower inferior wall uptake compared to women in NAC supine acquisition. This decrease in uptake was corrected with AC and normal database with corrected supine IQ•SPECT did not show significant difference in inferior wall between men and women. Data for both sexes were combined to generate a normal database that can be shared between both sexes. 56 White paper · IQ•SPECT: a technical and clinical overview Attenuation correction causes a marked decrease in the apical counts, which is a phenomenon called apical thinning.1 Comparing 99mTc and 201Tl, apical thinning is pronounced with 201Tl. Since perfusion images obtained from IQ•SPECT system displays distinct distribution depending on the patient positioning, it is recommended that a normal database with matched conditions be used for quantitative analysis. Typically, the perfusion reduction scores under stress, SSS the perfusion reduction score at rest, and the difference between stress and rest [summed difference score (SDS)] are widely used. Figure 42 shows the results of evaluating the diagnostic ability using the normal database to detect CAD in 36 cases (35 males, 70 ± 10 years old) that underwent 201Tl perfusion imaging.1 The sensitivity, specificity, and accuracy of IQ•SPECT were 89%, 87%, and 87%, respectively, which are higher than those of conventional SPECT (81%, 79%, 79%). However, the area under the receiver operating characteristic (ROC) curve by ROC showed no significant difference between the two; IQ•SPECT was 0.86 (95% confidence interval: 0.68-0.94), and conventional SPECT was 0.77 95% confidence interval: (0.57-0.90). In a similar study, Ogino et al reported the ischemia detectability of 201Tl IQ•SPECT using a semi-quantitative manual scoring in fifty consecutive cases (35 males, 72 ± 11 years old).24 IQ•SPECT sensitivity, specificity, and accuracy by SDS were 85%, 83%, and 84% respectively. Typically, visual evaluation and the scoring method using the normal database have the same diagnostic ability, but the results can be calculated more easily by using the database. Table 3: Number of cases that make up the normal database. 99mTc-MIBI/99mTC Terofosmin 201Tl Female Male Female Male Supine - NC 34 41 39 68 Prone - NC 17 20 28 24 Supine - AC 27 34 39 68 White paper · IQ•SPECT: a technical and clinical overview 57 IQ . SPECT 201Tl Normal Database Prone, No Corrections Supine, No Corrections Supine, ACSC Male Female Male Female Combined 65 65 100 101 102 49 66 68 103 92 97 97 96 94 77 92 95 93 93 95 Stress 6 93 100 60 8 8 62 103 101 102 60 93 101 101 101 96 97 68 102 65 92 87 Rest 93 101 Q . SPECT 99mTc Normal Database Prone, No Corrections Supine, No Corrections Supine, ACSC Male Female Male Female Male Female Combined 92 97 95 98 97 100 80 10 00 93 102 100 91 93 99 101 98 88 102 67 98 102 62 -100 94 101 97 93 101 95 97 81 93 98 18 94 92 92 90 95 95 97 96 96 59 96 95 95 Stress 58 85 102 100 52 47 92 95 98 99 57 97 90 93 105 100 80 90 100 103 97 105 98 104 Figure 41. A normal myocardial 97 96 100 91 101 98 100 97 95 81 95 98 81 Rest perfusion database for 99mTc 90 92 95 98 05 91 9 90 94 97 58 84 95 101 100 MIBI/Tetrofosmin and 201Tl. 40 Sensitivity Specificity Accuracy 100 89 87 87 81 80 79 79 60 40 Figure 42: Diagnostic ability 20 using the normal database to detect CAD: comparison between IQ•SPECT and 0 IQ•SPECT Conventional SPECT conventional SPECT. 58 White paper · IQ•SPECT: a technical and clinical overview Supplement B: IQ•SPECT image acquisition This chapter summarizes MPI acquisition procedures using IQ•SPECT. For general instructions, please refer to the publication “IQ•SPECT Hints and Tips” provided by Siemens Healthineers. This section provides supplementary information to the publication. Patient positioning Supine position imaging For supine position imaging with IQ•SPECT, patients should lie on their backs with arms raised using the IQ•SPECT armrest. At this time, it is necessary to confirm the arms do not extend beyond the edge of the bed. As shown in Figure 43, the arms should be inside the dotted line. If a patient’s arms are outside the bed, the detector may not be able to come to the correct position, thus acquisition may fail. As discussed earlier, IQ•SPECT acquisition takes place in a cardio-centric orbit. When centering the heart in the supine position, the detector must be initially aligned at the furthest radius away from the heart. Therefore, the persistence on the patient positioning monitor (PPM) must be turned up to 99% in order to ensure that the signals are visible. Next, the bed should be moved so that the patient’s heart is visible on PPM. Using the buttons below the images in the Offset Zoom/CT FOV tab of the PPM, move the center of crosshair so that it overlaps with the center of the heart. - - Figure 43. Position of the patient’s upper arms during IQ•SPECT acquisition. As shown by the dotted line, make sure the arms fit inside the bed (left) and that elbows do not extend outside the bed (right). White paper · IQ•SPECT: a technical and clinical overview 59 Table 4: Recommended imaging conditions by patient weight and dose. Patient weight Less than 114 kg (251.3 lb) Dosage 99mTc 10 mCi 99mTc less than 10 mCi (370 MBq) or higher (370 MBq) or 201Tl Time per view 9 sec 14 sec Number of views 17 17 Patient weight More than 114 kg (251.3 lb) Dosage 99mTc 10 mCi 99mTc less than 10 mCi (370 MBq) or higher (370 MBq) or 201Tl Time per view 14 sec 19 sec Number of views 17 17 Prone position imaging For prone position, the patient is laid on the bed face down with the arms crossed above the head. At this time, a thin towel can be placed under the face to the chest area. The patient’s shin to the ankle can be placed on a pillow cushion, so that the lower limbs are bent and tension in the lower back is relieved. This is to alleviate the patient discomfort. As in the supine position, it is important to make certain the patient elbows do not extend beyond the bed. When performing electrocardiogram (ECG)-gated imaging in the prone position, the leads should be mounted on the patient’s back. When centering the patient’s heart, attempting to do so at the acquisition start angle (-121 degrees) would trigger an error message, stating detector 1 is too close to the bed, and the heart cannot be brought to the center of the PPM. Therefore, position detector 1 at -130 to -140 degrees at the beginning to center the heart on the PPM. As in the supine position, set the persistence to 99% on the PPM and move the bed to the position where the subject’s heart can be visualized on the PPM. On the Offset Zoom/CT FOV tab of PPM, set the crosshair to the center of the heart. At the start of imaging, the detector automatically moves to the correct start angle, so that acquisition can be performed under the specified conditions. Recommended acquisition parameters for IQ•SPECT It is a standard practice in nuclear medicine to perform phantom experiments following system installation to determine imaging and reconstruction conditions so that each facility can obtain an image quality preferred by reading physicians. IQ•SPECT incorpo- rates specialized imaging and reconstruction, and it is recommended that the users follow the conditions optimized by the manufacturer. Table 5 shows the recommended imaging conditions by subject weight and dose. 60 White paper · IQ•SPECT: a technical and clinical overview IQ•SPECT quality control During the development of IQ•SPECT, phantom experiments were conducted under various acquisition conditions to determine the image quality reading physicians find most suitable for image interpretation. As a result, the count per pixel of the region of interest (ROI) placed on the lateral wall in the 18th view of the projection data (left anterior oblique [LAO] view of the heart) should contain at least nine counts per pixel. Therefore, as a way to effectively assess image quality after the completion of acquisition, it is recommended the users verify sufficient counts per pixel in the lateral wall ROI. The method for verifying the counts per pixel in the lateral wall ROI is described below: • Immediately after acquisition, load the projection data into the syngo® Viewing tab and select the 18th view • Select a circular or freehand ROI from the Tools drop down menu (Figure 44) • Place the ROI on the lateral wall and confirm that the ROI contains more than nine counts per pixel FRM 18 1 Min/Max: 4 /29 counts 1 Mean/SD: 16.9 /4.6 count: 1 Area: 45.99 sq.cm 1 Pixel: 200 Figure 44: Circular/freehand ROI from the Tools drop down menu. White paper · IQ•SPECT: a technical and clinical overview 61 Example of verifying lateral wall ROI statistical information IQ•SPECT recommended reconstruction parameters As with the acquisition conditions, it is recommended the reconstruction conditions follow the parameters shown in Table 5. However, it is important to determine iteration and subset while considering the injected dose and dwell time for each facility. When setting reconstruction conditions for low-dose imaging, it is desirable to set the itera- tion number as low as possible, since the larger subset will induce higher noise levels. It is also necessary to set appropriate smoothing suitable for image interpretation. Quality control of reconstructed images Table 5: IQ•SPECT‘s recommended reconstruction parameters Nuclide 99mTc Preset SC-Tc99m-NMG ECG gating Gated Non-gated Iterations 12 10 Subsets 1 3 Gaussian filter 10 mm 10 mm Scatter correction Apply Apply Nuclide 201Tl Preset SC-TI201-70-NMG ECG gating Gated Non-gated Iterations 12 10 Subsets 1 3 Gaussian filter 10 mm 10 mm Scatter correction Not apply Not apply As described above, it is important to set imaging conditions so that the heart is located at the center of the FOV. Reconstructed images should be checked again for image distortion caused by centering problems. In the polar map, ensure there is no arc-shaped defect that runs along the circumference or myocardium flattening at the periapical regions in the horizontal long axis (HLA) view indicative of artifacts due to a centering problem. In such cases, it is recommended the acquisition be repeated. 62 White paper · IQ•SPECT: a technical and clinical overview Conclusion IQ•SPECT delivers fast MPI with similar diagnostic confidence to LEHR, but with the advantage of high acquisition speed as well as the possibility of integrated diagnostic CT-based attenuation correction. Calcium scoring in Symbia SPECT/CT systems equipped with that option is an added advantage. As demonstrated in the series of clinical cases, normal as well as ischemic uptake patterns and defect sizes are comparable between LEHR and IQ•SPECT. Familiarity with normal patterns, attenuation effects, typical IQ•SPECT image characteristics, and cardiac shape differences helps improve clinical interpretation accuracy. Acknowledgements 1. Guillaume Bouchard MD, Consultant Physician, Department of Nuclear Medicine, Hôpital de la Cité-de-la-Santé de Laval, Canada 2. Sylvain Prevost MD, Director of Nuclear Medicine, University of Sherbrooke, Quebec, Canada 3. 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A myocardial perfusion imaging system using a multifocal collimator for detecting coronary artery disease: validation with invasive coronary angiography. Ann Nucl Med. 2015;29(4):366-70. doi:10.1007/s12149-015-0955-9. 66 White paper · IQ•SPECT: a technical and clinical overview Trademarks and service marks used in this material are property of Siemens Medical Solutions USA Inc. or Siemens Healthcare GmbH. All other company, brand, product, and service names may be trademarks or registered trademarks of their respective holders. All comparative claims derived from competitive data at the time of printing. Data on file. Siemens Healthineers reserves the right to modify the design and specifications contained herein without prior notice. As is generally true for technical specifications, the data contained herein varies within defined tolerances. Some configura- tions are optional. Product performance depends on the choice of system configuration. 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