ACUSON Sequoia 3.5 (VB30) Contrast Enhanced Imaging Knobology Presentation

SIEMENS Healthineers SIEMENS Healthineers ACUSON Sequoia Ultrasound System Introduction to Contrast-enhanced Ultrasound (CEUS) General Imaging Release 3.5 (VB30) 1 Unrestricted © Siemens Healthineers 2024 Speaker Notes: No speaker notes. Notes No. 1 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 2 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 2 SIEMENS Healthineers What is contrast-enhanced ultrasound? SIEMENS ..... Healthineers ... • Contrast-enhanced ultrasound (CEUS) 5C1 combines conventional ultrasound with ITO:0,00 ITC:0,00 ITS:0,00 microbubble contrast agents and specialized IM:0,08 11fps imaging software 0,25% 2D Med 2dB/RD60 • This advanced application provides blood flow Contrasto and tissue perfusion information in real-time -2dB/RD70 • Perfusion characteristics (wash-in or wash- out) provide clinicians with relevant diagnostic information 9cm Hepatocellular Carcinoma - Feeder Vessel mage courtesy of Prof. Mirko D'onofrio, GB University Hospital - Verona, Italy 00:31 3 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Despite advances in 2D ultrasound imaging and image quality, many patients still have sub-optimal imaging exams. Whether these sub-optimal images are related to body habitus, disease processes (i.e., kidney or liver disease) or care setting (i.e., bedridden, intensive care, etc.), the need for good image quality and anatomical definition is still desired. To circumvent these challenges in the imaging world, new techniques and technologies have been developed. In the case of abdominal imaging, contrast-enhanced ultrasound has taken imaging to new levels…but what is contrast- enhanced ultrasound? Contrast-enhanced ultrasound (CEUS), is an advanced application that combines conventional ultrasound with microbubble contrast agents and specialized imaging software. This advanced application provides sensitive blood flow and tissue perfusion information to the clinician in a real- time setting. These perfusion characteristics – that is wash-in and wash-out – are key features used in the diagnosis and determination of focal liver lesions. Notes No. 3 SIEMENS Healthineers Why perform contrast-enhanced ultrasound? SIEMENS ..... Healthineers ... 5C1 'ABD • Temporal resolution advantage 110:0,00 • Provides information in real-time • Vessel morphology and blood flow 0,5% Mittel 0dB/DB60 • Can be added to a routine ultrasound exam LD 1 UA 2 • Cost effective SkalaC/T5 • Can lead to faster patient results Kontrast Niedrig 6ªB/DB70 LD 1 UA Aus • Safe and easily performed technique SkalaF/T1 D2 • No ionizing radiation Nur Kontrast No risk of nephrotoxicity[1] • • Purely intravascular 18cm • Ability to deactivate (“flash”) agents 1 Abst=1,77 cm 2 Abst=1,38 cm 02:22 4 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Why should we be doing contrast-enhanced ultrasound? One of the biggest advantages of ultrasound over other modalities such as CT or MRI, is its ability to image in real- time. This temporal resolution advantage is unique to ultrasound, as it allows for imaging that produces detailed, real- time visualization of vessel morphology and blood flow – this type of perfusion information is not provided by CT and MRI. Contrast can be added to a routine ultrasound exam if a suspicious lesion or area is detected during the scan. This immediate addition can be cost effective, as the patient does not need to be referred to another, perhaps more costly, imaging modality to obtain a diagnosis. Adding CEUS to a routine exam already in progress can potentially lead to better patient outcomes – without the need to wait for additional testing, patients can receive more immediate results, and their pathway of care can be mapped out more quickly. The exam technique to introduce the contrast agent to the body is very simple and requires no specialized equipment, such as the auto-injectors required by other imaging modalities. Contrast agents themselves are safe and do not require ionizing radiation to perform the exam. The agents do not carry a risk of nephrotoxicity[1], thus patients that cannot have contrast agents used in other modalities due to poor renal function, are able to tolerate ultrasound contrast agents. Unlike contrast agents used in other imaging modalities, ultrasound contrast agents, due to their size, are purely intravascular and do not leak out through the lumen of a blood vessel and into the extra-cellular space. This is an important fact and another advantage of CEUS, as this leakage of the contrast medium can lead to an adverse reaction to the contrast agent after injection. Another property unique to ultrasound contrast imaging is the ability to destroy the circulating contrast agent in the region of interest by using a “flash” or “burst” feature. Using this destruction feature will allow the clinician to watch an area of interest re-perfuse with contrast agent, which can be very beneficial in determining the lesion or region of interests’ etiology. Other contrast imaging modalities, such as CT or MRI, do not have this capability. Notes No. 4 SIEMENS Healthineers How are contrast agents imaged? SIEMENS ..... Healthineers ... 501H Addome ITO:0,00 ITC:0,01 ITS:0,00 IM:0,10 9fps 0.5% + = 13cm Liver Lesion - Portal Phase Image courtesy of Prof Mirko D'orohio, GIN University Hospital . Heroina may Sound Tissue/Microbubbles 5 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We now know the “why” and the “what” for contrast imaging, but how are contrast agents imaged? How do we take soundwaves, add them to tissue and microbubbles, and produce a contrast-enhanced ultrasound image? To understand how contrast agents are imaged, we must first investigate what contrast agents are, how they differ from tissue, and how they are affected by soundwaves – all these factors, when combined with specialized software, contribute to the formation of the image that you see on the screen. SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 6 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 6 SIEMENS Healthineers What are contrast agents? SIEMENS Healthineers .. What are contrast agents? • Contrast agents are small, acoustically active microbubbles which enhance the echo brightness (i.e., contrast) of blood or blood-perfused tissue on ultrasound imaging • Agents can also be introduced into a body cavity or space (i.e., bladder) via external catheter • Contrast agents must have specific properties to make them ideally suited for use with ultrasound 7 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We have already established that ultrasound contrast agents are microbubbles, but what is so special about them? Contrast agent microbubbles are small, acoustically active gas-filled microspheres, that, when injected intravenously into the body, enhance the echo brightness (i.e. contrast) of blood or blood-perfused tissue when they are exposed to ultrasound imagery. In short, they allow us to highlight areas with blood flow and see them much better than we do without a contrast agent – but not all bubbles are created equally. In order to be a contrast agent microbubble, they must have special properties that make them ideally suited for use with ultrasound. Notes No. 7 SIEMENS Healthineers Microbubble contrast agents SIEMENS Healthineers .. Properties Microbubble contrast agents are… • Made up of a gas core with a flexible, biocompatible containment shell • A size ratio slightly smaller than a red blood cell • A true blood pool agent making them a purely intraluminal contrast agent • Stable with low toxicity • Easily administered R0 Inert Gas • Acoustically active Flexible Core Biocompatible Shell 8 Unrestricted © Siemens Healthineers 2024 Speaker Notes: The first of these properties is related to composition. Contrast agent bubbles are made up of an inert gas encapsulated in a flexible, biocompatible shell. This shell is typically lipid, however, polymers and proteins have also been used. The gas is of a high molecular weight which equates to low solubility in blood. The low solubility of the gas in blood lowers the possibility of an adverse reaction to the contrast agent. One of the most commonly used contrast agents, from Bracco Diagnostics Inc., is SonoVue® (USA)/Lumason® (Europe, Asia, and Canada). It consists of microbubbles that are made up of the high molecular weight gas, sulfur hexafluoride (SF6 ), encased in a highly elastic lipid-type A shell[2] . Contrast bubbles must also be a specific size in order to accomplish their intended function. Contrast agents are administered intravenously and must be sufficiently small enough to cross the capillary bed during circulation but stable enough to not breakdown in the process. The size of a contrast bubble is slightly smaller than a red blood cell with a range of approximately 1–10 microns, earning them the nickname of “microbubbles”. SonoVue®/Lumason® consists of bubbles that range from 1.5–2.5 microns[3] in size. This size also prevents them from crossing the vascular endothelium as other radiological contrast agents do (CT/MRI) and as a result, ultrasound contrast agents are considered true blood pool agents. Since microbubbles remain intravascular at all times, they act as excellent red blood cell tracers for both cardiology and general imaging applications. Ultrasound contrast agents must have a low toxicity and be stable, as they are non-nephrotoxic. When the microbubbles rupture, the gas is released into the bloodstream. The released gas is then expelled by the lungs rather than metabolized by the liver and kidneys, as other contrast agents found in radiology are (CT/MRI) when they are eliminated from the body. This feature allows ultrasound contrast agents to be considered for usage in patients who cannot tolerate other radiologic contrast agents due to underlying medical conditions such as poor renal function. Lastly, microbubbles must have acoustic properties that can be identified and recorded with ultrasound – without these important acoustic characteristics, using microbubbles as a contrast agent for ultrasound would not be possible. Notes No. 8 SIEMENS Healthineers Microbubbles and soundwaves SIEMENS Healthineers .. Acoustic characteristics • Microbubbles in the ultrasound field react to Bubble Response to Soundwave Pressure Bubble Response to Soundwave Pressure pressure by changing size High Pressure • In situations of high (positive) pressure, the + Crest bubble will contract • In situations of low (negative) pressure, the bubble will expand Pressure Pressure Time • This constant change in size results in bubble oscillation 0 Time Microbubble Low Pressure Trough - 9 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Bubbles, due to their flexible nature, will react to pressure from sound waves when they are in the imaging plane. The compressibility of the contained gas enables microbubbles to be an efficient acoustic reflector. When bubbles are exposed to high pressure conditions, the bubble will contract in size and compress the gas contained inside the bubble to accommodate the change in size. Consequently, if that same bubble finds itself in a low pressure condition, the flexible shell will expand and increase in size. Since ultrasound waves have alternating conditions of high and low pressure aspects, this bubble expansion and contraction will occur repeatedly and rapidly, when the bubble is present in the imaging plane. This rapid movement back and forth, or oscillation, is what is used to track bubbles in the imaging field. The oscillating bubble produces very strong acoustic backscatter or echo that is detected by the ultrasound system and causes the microbubbles to show up brightly in the final reconstructed ultrasound image. We are very fortunate that the natural resonant frequency of contrast bubbles corresponds to the same megahertz (MHz) that is used in medical ultrasound. Notes No. 9 SIEMENS Healthineers Microbubble oscillation SIEMENS Healthineers .. * 10 1 X 10 0.8 0.6 0.4 0.2 0 -0.2 0.4 0.6 -2 2 08 104 06 -0.2 0 02 0.5 ----------- ------- ......... High/low pressure 0 variation in the • Bubble oscillation Pressure -0.5 ........ ...... ultrasound field • Bubbles exhibit a non-linear -1 resonance -3 2 time (s) 104 10 Unrestricted © Siemens Healthineers 2024 Speaker Notes: To help illustrate the concept of a bubble expanding and contracting, here is a dynamic example of a “bubble” oscillating within the imaging plane. The left side of the screen depicts a single bubble traveling through an image – this bubble is magnified for better visualization in the figure on the right. Colors are used to simulate the movement of the bubble through the region of interest (ROI) contained within the image. Below the image is a graph representing a time-varying ultrasound field. This field contains a blue “sound wave” propagating through it, depicting areas of high pressure, known as crests of the wave] and areas of low pressure, known as troughs [of the wave]. As the “bubble structure” in the center of the image is exposed to the ultrasound field, the bubble responds by expanding and contracting in size. When the wave is at its highest pressure point or crest, the bubble contracts; when the wave is at its low pressure point or troughs, the bubble size expands. While the sound wave causes the expansion and contraction process, the bubble itself only has so much latitude to expand and contract. The maximum contraction of the bubble will be limited by the volume of the gas filled interior, as the gas does not escape when the shell contracts. When the shell/bubble contracts, the gas contracts along with it and becomes tightly compressed inside the constricted shell. The expansion limits of the bubble are governed by the flexibility of the shell. When the bubble has very little pressure on it, the shell and the gas expand to fill the “less pressured” space. This expansion can, however, come at a cost of bubble integrity if the expansion during oscillation is too great. If bubble oscillation exceeds the flexibility of the shell to the point where it loses cohesion, the bubble will burst, and the gas will escape. Bursting bubbles will result in a loss of contrast agent in the ROI. From an ultrasound perspective, different frequencies, focal zone locations, and mechanical indices will also effect how bubbles react and resonate. Additionally, while this example shows the bubble expanding and contracting in equal measure, in reality a contrast bubble oscillation is non-linear, meaning that the size change between expansion and contraction is not equal. This non-linear property will be an important factor in how the specialized software separates the bubble signal from the tissue signal to generate the contrast-enhanced ultrasound image. Note to speaker: this is a dynamic slide – in order to appreciate the movement contained within the slide it must be in PowerPoint “Presenter Mode”. Notes No. 10 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 11 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 11 SIEMENS Healthineers Contrast agent signal SIEMENS Healthineers • Contrast agent echoes at a lower mechanical index (MI) are non-linear Contrast Bubble Signal • Non-linear echoes do not scale proportionally with transmit O • Returning echo does not resemble the transmit wave • Using signal processing techniques, this non-linearity can be exploited during contrast imaging to separate Incident Pulse Non-linear Echo out the contrast agent signal from the linear tissue signal 12 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We have already mentioned that the contrast agent signal is non-linear, but what does “non- linear” mean and why is it so important to forming the image? First off, non-linear echoes are not as predictable [in shape] as linear echoes, as they do not scale proportionally with the transmit signal. Not scaling proportionally means that the received echo does not resemble the transmit pulse in amplitude (size or shape) as a linear echo would. Note the difference in the two graphs shown here – the incident pulse does not resemble the echo in any way. This difference relates directly to the concept we discussed earlier in that the bubble does not contract or expand in equal measure with each expansion and contraction cycle. Some cycles will have more or less bubble expansion and/or bubble contraction. This inequality produces a reflected wave that is unpredictable and will differ even between bubbles based on their size and position within the pressure of the transmitted wave. While this idea of “unpredictability” might seem troublesome to the image, it actually allows the ultrasound system to separate the “unpredictable” contrast bubble signal from the “predictable” tissue signal. We will now discuss the tissue signal and how it compares and contrasts to the bubble signal which allows the ultrasound system to produce a contrast-enhanced ultrasound image. Notes No. 12 SIEMENS Healthineers Tissue signal SIEMENS Healthineers .. • Tissue echoes at a lower mechanical index (MI) are Tissue Signal mostly linear • Linear echoes scale proportionally with transmit • Return echoes resemble the incident pulse • Exploit this linear behavior or “predictability” by using specialized software to separate out the linear tissue echoes Incident Pulse Linear Tissue Echo 13 Unrestricted © Siemens Healthineers 2024 Speaker Notes: You just heard how microbubbles exhibit a non-linear resonance when exposed to a low MI ultrasound environment. Tissue, however, has a very different resonance from that of bubbles in these same conditions. Tissue, unlike bubbles when exposed to this low MI ultrasound beam, has a mostly linear resonance. This difference between tissue response and microbubble response is the key factor exploited by the specialized system software to create the contrast image…but what does a linear resonance mean? A linear resonance indicates that the transmit wave sent into the medium returns an echo to the transducer in a “predictable” format. This predictable format is related to scale and appearance. To illustrate this linearity, please refer to the graphs on the right side of this slide. Unlike bubbles, when tissue is exposed to the ultrasound beam it will react in the same manner (to the beam) whether it is in the crest or trough of the ultrasound wave. This reaction makes the tissue signal appearance predictable, as the echo scales proportionally with transmit. This proportionality [with transmit] means the returning signal from the body will resemble the incident pulse [signal] sent into the body from the transducer. The return signal will not be completely identical to the transmit signal, as it has interacted with organs and cellular structures along the way. This interaction causes not all of the original wave to be reflected back. The returning wave will, however, still resemble the incident pulse. We can exploit this linearity or predictability during contrast imaging by using specialized software to separate out the tissue signal from the contrast bubble signal, which has a non-linear echo signal. Notes No. 13 SIEMENS Healthineers Exploiting the signal difference SIEMENS Healthineers • Using a pulse inversion technology, the returning echoes are summed together by the specialized software on the system • Linear echoes will cancel each other out (sum to or near to zero) • Non-linear echoes will sum together and result in a positive (non-zero) echo Tissue Signal Contrast Signal 1 2a 3a 1 2b 3b Incident Pulse Linear Echo Sum Incident Non-linear Pulse Echo Sum 14 Unrestricted © Siemens Healthineers 2024 Speaker Notes: One such separation technique is pulse inversion, also known as phase modulation. Pulse inversion uses two different transmit pulses sent at the same time whose properties only differ in that one is positive, and one is negative (inverted) on the X/Y axis during transmit. The returning echoes will scale proportionately for linear echoes and disproportionately for non-linear. However, each echo type will respect their transmit origin’s positive or negative propagation. Specialized software on the ultrasound system then sums these returning echoes together. This mathematical addition, combined with the phase inversion properties, exploits the differences between the tissue signal and the contrast signal. The linear echoes will cancel each other out whereas the non-linear ones will not and remain to form the image. To better illustrate this idea, we can compare the sums of the tissue and the contrast bubble signal on the graphs provided. The same transmit signals sent by the transducer, indicated by the #1, are used in both the tissue and the bubble signal examples. This transmit signal is identical but opposed. The returning signals, indicated by the #2’s, differ between the tissue and the contrast. The tissue, indicated by 2a, resembles the incident pulse, as previously discussed. The contrast bubble, indicated by 2b, does not. When these signals are received, the specialized software then sums the returning echoes together. The linear tissue signals sum together to produce a result that is at or near to zero, as indicated by 3a. This summation effectively cancels the tissue signal out from the image. The contrast sum, indicated by 3b, does not cancel – the summed signals produce a result that is not zero. In generalized terms, this remaining signal, made up of the contrast bubble, is what the specialized software uses to generate the contrast image and why a contrast image has little or no tissue signal within it. Notes No. 14 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 15 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 15 SIEMENS Healthineers Image generation pathway – a summary of steps SIEMENS ..... Healthineers .. Transducer Echo – mixed tissue and Contrast image consisting of bubble signal incident pulse microbubble signal with tissue signal suppressed (phase inversion) 501 H Addome ITO:0,00 ITC:0,01 ITS:0,00 IM:0,10 9fps 0.5% 20 Med GE ROBO N Non-linear S contrast signal 13cm Liver Lesion - Portal Phase Image courtesy of Prof Mike D'angolo, GIN University Hospital . Hunt may 00:46 Specialized software creates a contrast friendly environment and separates the linear and non-linear echo signals 16 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Contrast image generation is a multi-step process that begins and ends with specialized software on the ultrasound system. First, a low mechanical index, contrast friendly environment is created when the contrast imaging mode is activated. Once activated, the specially sequenced incident pulses (phase inverted) can be sent into the body by the transducer. The waves interact with the tissue and microbubbles (if they are present within the ROI) generating echoes, which reflect back to, and are received by the transducer. So far, with the exception of the low MI environment, this sequence of steps appear to be the same as those involved in generating a non-contrast image – the differences begin to show in the processing of the returned echo. If microbubbles are present, the return echoes are a mix of contrast microbubble and tissue signals and require separation. The signal separation is achieved by using the specialized software to suppresses the linear tissue signals and only display the non-linear contrast signal to the user. If there are no bubbles present in the ROI, then the returning signal is only from that of tissue, which are then suppressed from the image due to the phase inversion. This is why, prior to the microbubbles being introduced into the body that the pre-contrast image is very dark, with little to no tissue signal visible. Once the microbubbles start to populate the ROI, their retuning signal is used to generate an image we can see, as the non-linear signal is not cancelled out. The microbubbles are then easily distinguished by the observer in the image as bright, mobile reflectors contained within the vascularity in the otherwise dark image. Notes No. 16 SIEMENS Healthineers Contrast imaging technologies SIEMENS Healthineers Contrast Pulse Sequencing (CPS) is a three-pulse Contrast Harmonic Imaging (CHI) is a two-pulse sequence in fundamental imaging mode sequence in harmonic imaging mode Advantages: Advantages: • High degree of motion flash suppression • High resolution • Superior penetration • Increased bubble longevity* • Excellent tissue suppression • High frame rates* CPS is excellent for general imaging exams CHI is excellent for cardiac exams and very useful for general imaging in specific conditions 17 * When compared with Contrast Pulse Sequencing (CPS) Unrestricted © Siemens Healthineers 2024 Speaker Notes: Now that we understand the basis of contrast imaging technology, we need to talk about how this technology is utilized and refined on Siemens Healthineers ultrasound products. Ultrasound systems manufactured by Siemens Healthineers currently use two different imaging technologies for contrast imaging – Contrast Pulse Sequencing (CPS), and Contrast Harmonic Imaging (CHI). Both technologies have different advantages and preferred clinical applications related to imaging needs, penetration, frame rates, bubble longevity, and tissue suppression. Knowing which technology to use for an exam requires a greater understanding of what makes up each technology signal, how they are generated, and what their strengths and weaknesses are. We will begin by discussing Contrast Harmonic Imaging (CHI) in greater detail. Notes No. 17 SIEMENS Healthineers Contrast Harmonic Imaging (CHI) SIEMENS Healthineers .. Contrast Harmonic Imaging: Scaling & Transmit Receive from Receive from Overall image • Second harmonic imaging Pulse # Signal Tissue Microbubble make up mode Linear Non-Linear (components) • Two transmit pulses • Pulse [phase] Inversion only 1 Advantages: +1 Scaling Tissue High frame rates* signal sum = • Longer bubble lifespan* 0 • • High resolution + + 2 Bubble -1 Scaling signal sum = = = + (Sum) (Sum) 18 * When compared with Contrast Pulse Sequencing (CPS) Unrestricted © Siemens Healthineers 2024 Speaker Notes: Contrast Harmonic Imaging (CHI), is a low MI contrast imaging technique that uses only pulse inversion in the 2nd harmonic to exploit the non-linear behavior of microbubbles. As discussed in the technology section of this presentation, two pulses of the same amplitude with opposing values (positive and negative) are emitted and sent into the tissue from the transducer. The received linear and non-linear signals are summed (respectively) and thanks to the pulse inversion technique, the linear echoes are cancelled out while the non-linear echoes remain to form the image. It should be noted that any tissue signal remaining within the image is a result of those tissue signals not being cancelled out entirely. This “artifact” is due to the fact that tissue can sometimes generate a very small portion of non-linear echoes which, like a non-linear bubble echo, are not cancelled out during the summation process. A good quality contrast image has little to no tissue signal present in general imaging. CHI has many advantages that make it the “go to” choice for certain imaging exams. One big advantage of CHI is frame rates. Since CHI uses only two pulses, the image takes less time to generate than if there were more than two. Quick image generation means high frame rates. The two-pulse sequence is also thought to maintain bubble integrity longer as there are fewer sound waves to interact with. CHI also has a resolution advantage as it uses the 2nd harmonic rather than a fundamental frequency which tends to have less detail resolution (than harmonic frequency). The ACUSON Sequoia ultrasound system supports CHI imaging technology on many exam presets and transducers to meet many different clinical needs. Notes No. 18 SIEMENS Healthineers Contrast Pulse Sequencing (CPS) SIEMENS Healthineers .. Contrast Pulse Sequencing: Scaling Transmit Receive Receive from Overall image • Fundamental imaging mode & Pulse Signal from Microbubble make up • Three transmit pulses # Tissue Non-Linear (components) • Pulse [phase] inversion and/or Linear phase modulation 1 Tissue signal Advantages: +1 Scaling sum = 0 + • High specificity and sensitivity + • Tissue penetration 2 • Tissue suppression -2 Scaling + + 3 Bubble signal +1 Scaling sum = + 151 = = AR (Sum) (Sum) 19 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Another separation technique, Contrast Pulse Sequencing (CPS), is a low MI contrast imaging technique that uses pulse inversion as well as amplitude modulation to exploit the non-linear behavior of microbubbles in the fundamental imaging mode. CPS uses three pulses during imaging as opposed to the two pulses that CHI employs. Two of the three transmitted pulses are of the same amplitude while one pulse has an altered (scaled) amplitude. The tissue and bubble signal echo summation still occur in the same mathematical manner as CHI, however three signals are involved in the process instead of two. CPS also has many advantages that make it the preferred choice for a clinician or exam type. Since CPS uses three pulses and images at the fundamental frequency, it has a high signal-to-noise ratio that makes small amounts of contrast easily visible (high sensitivity). CPS also has a high microbubble to tissue background ratio, thus contrast is easily distinguished within the imaging field (high specificity). Additional advantages of CPS when compared to CHI is slightly increased penetration, motion flash suppression, and background noise suppression. Notes No. 19 SIEMENS Healthineers Summary comparison of CPS and CHI SIEMENS Healthineers Property Contrast Pulse Sequencing Contrast Harmonic Imaging (CPS) (CHI) Penetration ++++ +++ Resolution +++ ++++ Motion Flash Suppression +++ ++ Specificity +++ ++ Sensitivity +++ ++ Contrast Agent Lifespan +++ ++++ Frame Rate ++ ++++ 20 Unrestricted © Siemens Healthineers 2024 Speaker Notes: When presented with an ultrasound system that is enabled with the both CPS and CHI technologies, some users are presented with a dilemma – what technology should I use? While no decision is truly wrong, as both technologies give rise to excellent image quality, there are always tradeoffs. When choosing a technology for a given exam, the user must take into consideration the type of imaging being performed and how the strengths or perceived “weaknesses” of each technology will contribute to the image quality. For example, if the region of interest is deep in the liver, the user may consider using the CPS technique over the CHI technique, as the CPS has a higher degree of penetration and a higher degree of motion flash suppression when compared to CHI. If the region of interest is small and superficial, the user may consider using CHI over CPS, as CHI is thought to have a higher degree of resolution and lower bubble destruction rates throughout the duration of the exam. For cardiac exams, which require a high frame rate for imaging, CHI is the preferred technology and, on all Siemens Healthineers ultrasound systems, set as the default application. For those exams that have options to change between CPS and CHI, alternating between CPS and CHI occurs by changing the frequency. For more information on the available frequencies and associated technology, refer to the contrast knobology educational PowerPoint that is associated with the system you are using. Notes No. 20 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 21 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 21 SIEMENS Healthineers Contrast imaging conditions and requirements SIEMENS ..... Healthineers .. General imaging Generating a “good” contrast image requires key 5C1 Addome elements and conditions. ITO:0,00 ITC:0,00 ITS:0,00 IM:0,08 11 fps These conditions are: 0, 25% 2D • Optimal sensitivity for contrast agent Med 2dB. RD60 visualization and detail Contrasto Med • Excellent tissue [signal] suppression 2dB/ RD70 P2 • A high-quality 2D image • Low mechanical index (MI) environment Hepatocellular Carcinoma - Feeder Vessel image countery of Pref. taliein D'Orefrin, GB University Horpital - Heraus, Italy 00:31 22 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Generating a contrast image requires a system that provides specific key elements and conditions. These needs differ from that of a conventional ultrasound image. They are: • Optimal sensitivity for contrast agent visualization and detail in real-time including the ability to see individual bubbles. • Excellent tissue signal suppression. As previously discussed, contrast imaging requires removing or “suppressing” the background tissue signal such that only the microbubble information makes up the image. This concept of little to no tissue signal is very different from “conventional” ultrasound, where obtaining an excellent tissue image is our main goal. While optimizing our image is still our focus, our optimization involves the microbubble image, not the tissue. When users are new to contrast imaging, the lack of or “black” tissue appearance can be a difficult parameter for them to embrace. • A high-quality 2D image. In dual mode, the 2D image is separate from the contrast image, whereas in full screen mode, the user can only see the contrast image or the 2D image at one time. Whether or not you are imaging in dual or full screen, the quality of the 2D image should never be ignored. A high quality 2D image plays a key role in locating and referencing the region of interest while in contrast mode, as the tissue signal is suppressed on the contrast side of the image. In cases where the lesion or ROI is very small, the 2D image is especially important - small lesions can be difficult to visually localize or they can move in and out of the visual field with patient breathing. • Lastly, all of these key elements must be accomplished within a low mechanical index (MI) environment. This low MI environment can be particularly challenging when imaging patients of larger body habitus or lesions that are deep, as it affects the system’s ability to penetrate tissue. A low MI environment is not only required for the imaging techniques to be successful but also to keep the microbubble from bursting. Higher mechanical index environments will cause the microbubbles to rupture resulting in little or no contrast agents within the region of interest. Notes No. 22 SIEMENS Healthineers Bubble detection and sensitivity SIEMENS ..... Healthineers ... 10L4 • Bubbles must be seen to be imaged TIB:0.00 TIC:0.00 High sensitivity and high specificity to the TIS:0.00 • MI:0.12 contrast agent are required 6fps 0.4% 2D Low 8dB/DR65 • Sensitivity = level of detection [of agent] by Contrast a given system or technique Low 0dB/DR70 P2 • Specificity = ability to separate agent signal from tissue or clutter • System-dependent 4cm Contrast Enhanced Ultrasound (CEUS) Testicular Torsion Left 00:12 23 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Contrast images, in order to be considered high quality, must demonstrate a high sensitivity and specificity to the contrast agent. These parameters are solely dependent on system architecture, as without the proper tools contained on or with the system (i.e. transducer types) contrast imaging is not possible. Contrast sensitivity is a measure of how small of a contrast signal can be detected and imaged by a given imaging system or technique. Contrast specificity is a measure of how well contrast agent signals are separated from tissue and other clutter by a given system or technique. At Siemens Healthineers, high-quality contrast agent imaging is one of our technology cornerstones and a point of focus on the ultrasound systems that we produce. As a result of this dedication and focus, Siemens Healthineers has been producing powerful ultrasound platforms that meet, or even exceed, these high standards for sensitivity and specificity, for many years. Notes No. 23 SIEMENS Healthineers Gain SIEMENS ..... Healthineers ... • Images will be very dark prior to injection • Gain serves only to amplify the receive signal – it does not influence lesion enhancement but does affect image quality • Gain set too high adds noise, can obscure weaker agent signals or add signal to areas that are non-enhanced (i.e., cysts)   8cm 24 Unrestricted © Siemens Healthineers 2024 Speaker Notes: One of the biggest mistakes a new user can make is to turn up the overall gain in order to visualize the tissue they are used to seeing in conventional ultrasound exams. Remember, the bubble is what is being imaged and tracked during contrast imaging, not the tissue signal. For general contrast imaging, excellent tissue suppression is desired. A good contrast image has little to no tissue signal visible in the image prior to the arrival of the bubble. Strong reflectors, such as the diaphragm, will still be visible within the image at appropriate gain settings. The lack of visualization within the image for structures such as the liver, can be a struggle for some users whose first instinct is to increase the overall gain in an attempt to “optimize” the tissue portion of the contrast image. This instinctive reaction to increase the gain setting should be avoided, as pre-contrast gain should be set very low and not be treated in the same manner as it would be during conventional or non-contrast 2D imaging. Best practice technique involving gain for a contrast image is to remember that it is the bubble that is being imaged and tracked, not the tissue signal. Increasing the gain to “see better”, especially prior to injection, will only result in a decline of your contrast image quality. Within the contrast image, gain serves to only amplify the received signal and will not influence the contrast bubble enhancement of lesion. Increasing or decreasing the gain will affect the quality of the image in a positive or negative way. Gain set too high produces overly bright images with strong contrast signals – high gain levels also enhance image noise, which can become visible within the image. Increasing the noise within a contrast image can also run the risk of obscuring true weaker contrast signals or add “pseudo signals” to areas that would otherwise be non-enhanced, such as cystic lesions. Decreasing the gain to extremely low levels, in an attempt to exclude strong reflectors, such as the diaphragm, from the contrast image is also to be avoided. Too low of a gain setting can prevent weaker echoes from being properly received thereby excluding their clinical information from the image. Gain can also interfere with the accuracy of quantification results. Gain should not be adjusted in real-time during a contrast exam where quantification is to be utilized. Adjusting the gain in either direction during a contrast run will amplify or reduce the received signal intensity in the ROI. When the quantification software analyzes the data, this intensity shift will show up in some frames but not others, resulting in biased or unreliable results, as intensity is compared and quantified for each frame in the data. Overall, good contrast imaging technique dictates that gain settings should be set within the contrast image prior to the injection of a contrast agent to achieve superior results. Notes No. 24 SIEMENS Healthineers Mechanical index and lesion position SIEMENS ..... Healthineers ... • The mechanical index level is automatically 5C1 ABD changed to a low level when software is TIB:0,00 TIC:0,00 activated TIS:0,00 MI:0,09 7B/Sek 0,5% • Affects bubble longevity when increased 2D Mittel 0dB/DB60 LD 1 • Position patient with ROI as close to the UA 2 SkalaC/T5 transducer as possible to avoid increasing D3 Kontrast power level/MI to visualize deeper lesions Niedrig 6dB/DB70 LD 1 UA Aus SkalaF/T1 D2/Peak Hold Nur Kontrast 18cm 1 Abst=1,21 cm Abst=1,58 cm 02:47 25 Unrestricted © Siemens Healthineers 2024 Speaker Notes: A low mechanical index is required for the contrast imaging techniques - CHI and CPS - to perform at optimal levels, but more importantly, it is required to maintain bubble integrity. The mechanical index of conventional, non-contrast imaging, which is much higher than contrast imaging, is too aggressive an environment for a fragile contrast bubble to survive in. High MI’s cause the bubble to oscillate rather violently. This extreme oscillation leads to bubble rupture and loss of circulating contrast agent. Contrast software is specifically designed to avoid this destruction by automatically providing a low MI environment when the software is activated. This low MI does, however, come at a cost to the depth of tissue penetration and can produce an image with poor far field signal. This degraded image often causes a user to try and increase the power output of the system in order to reach deeper levels within the ROI. Increasing the power output will increase the acoustic pressure within the contrast image (higher MI) and can cause the circulating microbubbles to burst. It is important to understand that contrast imaging has certain depth restrictions and increasing the power output during contrast imaging cannot compensate for this limitation. Increasing the power output should only be done with careful consideration as to the effects it will have on the contrast agent. Best practice techniques should involve getting the patient into a position such that the area of interest can be as close to the transducer as possible or utilizing more challenging windows such as those found posteriorly or intercostal. Notes No. 25 SIEMENS Healthineers Focal zone and map selection SIEMENS ..... Healthineers ... Focal zone: 9C3 "ABD • Refer to system manufacturer TIB:0,00 TIC:0,01 recommendations TIS:0,00 MI:0,13 If no recommendations, then it is suggested 9B/Sek • 2% to keep focal zone in the far field 2D Niedrig -3dB/DB60 LD 1 Map: UA 3 SkalaD/T5 • Sepia is most preferred map, however, D3 Kontrast it is an individual choice Niedrig -2dB/DB70 Choose a map that highlights lesion LD 1 • UA Aus conspicuity for the user Skala /T1 D2 Nur Kontrast 11 cm image Courtesy of Prof. Dr. Thomas Fischer, Charite" Berlin - Germany 00:11 26 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Traditionally, focal zones have been placed as far back in the image as possible to minimize bubble destruction, as areas of higher acoustic pressure, such as those found at the level of a traditional focal zone, facilitate higher bubble destruction rates. With the development of more advanced ways to focus an image, these “far field” ideas do not necessarily hold true. With that in mind, it is important to be well informed on the type of focusing technique the system you are imaging with is utilizing. Consideration should also be given to the contrast agent’s manufacturers recommendation, as well. Sometimes the key to good focal zone placement is striking a balance in between the system and the contrast agent design. If no recommendations are made from either the system or the contrast agent manufacturer, then it is suggested to keep the focal zone in the far aspect of the field, as this is thought to minimize bubble rupture. Map choice is an individual choice. Most general imaging is performed with a sepia type tint, which is often the default setting on a general contrast exam preset. Map choice is, however, also an individual choice. Each user should use the appropriate map that that highlights a region of interest or lesion’s conspicuity to their eye – there is no rule that the map should be one color or another. Notes No. 26 SIEMENS Healthineers Contrast agent dose SIEMENS Healthineers .. • Too much contrast agent within the ROI can degrade image quality due to: • Strong attenuation • Blooming effect • Too little a dose can lead to insufficient agent concentration for all the exam phases • Refer to contrast agent manufacturer’s instructions and/or recommendations and reliable published literature • Consideration should be given to the sensitivity level of the system being used Contrast Agent 27 Unrestricted © Siemens Healthineers 2024 Speaker Notes: One of the biggest questions users new to contrast imaging have is “how much contrast should I be using”? While higher doses of contrast agent will produce higher levels of enhancement within the ROI, it should be noted that with contrast agent imaging, more is not necessarily better. Too much contrast agent within the ROI can work against the image quality by degrading it rather than optimizing it. This is due to strong attenuation at depth and a blooming effect[25] . Attenuation occurs with high doses of contrast agent as the ultrasound beam is required to penetrate larger amounts of echogenic (“bubble rich”) tissue resulting in most of the sound waves being reflected or absorbed. In these situations, the signal from the deeper part of the image can no longer be received. Images with “too much” contrast agent will exhibit strong enhancement in the proximal or near portion of the image, and loss of signal in the distal or far portion. Some users, especially those new to contrast agent imaging, may interpret this loss of signal as not enough contrast agent when in fact they have used too much. For extremely sensitive contrast imaging systems, such as the ACUSON Sequoia system, consideration should always be given to the sensitivity level [of the system] before the contrast agent dose is increased after a run that has been deemed unsatisfactory due to “too low of a dose”. Another potential issue with high contrast agent dose levels is known as the blooming effect, where stronger contrast signals can override weaker signals in adjacent structures. In cases of blooming, when two structures have only a small margin of intensity difference between them, the increased enhancement from the high agent level can prevent the system from distinguishing this discreet difference. The inability to distinguish these small differences can affect the user’s visual interpretation of the image as well as affect any quantification results. Dose levels can also be too low to produce high-quality images. A low contrast agent dose means less microbubbles circulating within the body to perfuse and display within the ROI. This poor agent concentration can produce images without a sufficient level of enhancement throughout all the phases of a contrast-enhanced liver study to render it diagnostic. For example, an insufficient contrast agent dose can be particularly troublesome when visualizing and diagnosing small lesions with late phase wash-out. Siemens Healthineers does not manufacture, develop, or distribute contrast agents; thus, our clinical specialists are not qualified to give dose level recommendations for a given patient or exam type. Therefore, all dose related questions should be referred to the contrast agent manufacturer or medical advisor. Siemens Healthineers clinical specialists can however comment on the sensitivity and specificity of our ultrasound products – these comments can be based on clinical validation results and experiences. Notes No. 27 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 28 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 28 SIEMENS Healthineers Global dynamics of liver disease SIEMENS Healthineers Liver Disease: A True Burden on Health Sciences and Economies Hepatocellular Carcinoma (HCC) HCC is the second leading cause of cancer-related deaths worldwide, 3889888 with the incidence on the rise both in the United States and elsewhere. Disease Trends Globally, there are approximately 750,000 new cases of liver cancer Liver diseases are on the rise. per year, with a 5-year survival rate of approximately 26%.[6] Liver disease accounts for 2 million Hepatic Hemangiomas deaths annually and is responsible for They are the most common benign tumor of the liver, with reported 4% of all deaths worldwide.[4] incidence as high as 20% of the entire population in the United Globally, there were 2.05 million new States.[7] Atypical appearances of hemangiomas can be consistent cases and 1.47 million deaths due to with malignancies, making it hard to diagnose. cirrhosis in 2019. [5] Liver, or hepatic, disease is a huge burden on healthcare Liver diseases are extremely costly in terms of human suffering, doctor and hospital visits, and premature loss of productivity. 29 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Liver disease accounts for 2 million deaths annually and is responsible for 4% of all deaths worldwide.[4] The primary risk factor for liver cancer is chronic liver disease. Globally, there were 2.05 million new cases and 1.47 million deaths due to cirrhosis in 2019. [5] Over time, patients with chronic liver disease may develop liver cancer which presents as a liver mass. Globally, there are approximately 750,000 new cases of liver cancer per year, with a 5-year survival rate of approximately 26%.[6] What makes the situation more complex is that hepatic hemangiomas (a benign liver mass) have a reported incidence as high as 20% of the entire population in the United States.[7] Atypical appearances of hemangiomas can be consistent with malignancies, making it hard to diagnose. Therefore, it is critical to be able to characterize these liver lesions in patients with chronic liver disease. Contrast enhanced ultrasound (CEUS) is an excellent tool for investigating and differentiating liver lesions. Notes No. 29 SIEMENS Healthineers The liver contrast exam SIEMENS Healthineers .. Liver perfusion • The liver has a unique dual blood supply • Dual blood supply allows the observer to “track” the contrast agent progression • Portal veins supply ∼ 75% of the liver’s blood supply received from the spleen and gastrointestinal track (nutrient-rich)[8] • The hepatic artery supplies ∼ 25% of blood direct from the aorta (oxygen-rich)[8] 30 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Why the liver? The blood supply to the liver is unique in that it has a dual blood supply. Overall, the blood supply consists of: • Hepatic artery supplies (25%) – arterial/early phase. • Portal vein (75%) and brings in blood and nutrients into the liver from the intestines – portal phase. Hepatic veins bring the oxygenated blood of the liver back to the heart. This dual blood supply allows the observer to “track” contrast progression related to when arteries and veins fill and drain during the cardiac cycle. Notes No. 30 SIEMENS Healthineers Enhancement phases* of the liver SIEMENS Healthineers Signal Arterial Phase intensity 10-35 Portal Phase seconds Late Phase 30-120 seconds +120 seconds OOO Time 31 * Phases determined by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) [9] Unrestricted © Siemens Healthineers 2024 Speaker Notes: This tracking of the dual blood supply from the hepatic artery and the portal vein gives rise to three overlapping vascular phases on a contrast enhanced ultrasound exam. The timing of these phases for the sake of contrast ultrasound, have been determined by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) [22]. They are: •Arterial Phase (AP) → Starts 10 – 20 seconds post injection → Ends approximately at 25 – 35 seconds • Portal Venous Phase (PVP) → Starts 30 – 45 seconds post injection → Ends approximately at 120 seconds • Late Phase (aka Sinusoidal Phase) → Greater than 120 seconds → Ends with bubble disappearance (≈ 240 – 360s) Perfusion kinetics (the wash-in and wash-out of contrast agents) during these phases is the key to characterizing liver lesions on CEUS. Notes No. 31 SIEMENS Healthineers Diagnostic characteristics SIEMENS Healthineers The diagnostic algorithm of liver CEUS is based on the enhancement characteristics of the arterial phase (AP) and the portal venous phase (PVP). Specifically: • Sustained Enhancement (SE) • Wash-out (WO) The PVP will determine the tissue type in the region of interest. Contrast Characteristic Positive Predicted Value (PPV) Sustained Enhancement (SE) 93% PPV of benignancy Wash-out (WO) 92% PPV of malignancy [10] Wilson SR and Burns PN, Algorithm AJR 2006 32 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Why are these phases so important? Different lesions have different characteristics and patterns in the arterial, portal and late phases during a contrast exam. A diagnostic algorithm has been developed and published in the American Journal of Roentgenology by Wilson and Burns in 2006 based on the characteristics of these phases. When performing CEUS on the liver, the diagnostician must observe the arterial and portal venous phase for enhancement characteristics – either sustained enhancement or wash-out [of a lesion]. Wilson and Burns determined that sustained contrast enhancement through the portal venous phase had a 93% positive predictive value (PPV) of being benign, whereas contrast wash-out seen in the same phase had a 92% PPV of being a malignancy [10]. Notes No. 32 SIEMENS Healthineers The importance of the Late Phase SIEMENS Healthineers .. Benign vs Malignant The late phase is also known as the Sinusoidal Phase. ? Observations are related to the cellular structure activity (Kupffer cells). Normal liver tissue typically has normally functioning Kupffer cells • Contrast is taken up and “sticks around” • Sustained or isoenhancement Abnormal (malignant) liver tissue typically lacks Kupffer cells • Contrast does not stay around • Area appears a late phase filling defect when compared to surrounding normal tissue 33 Unrestricted © Siemens Healthineers 2024 Speaker Notes: What about the late phase? The late phase also plays an important role in the benign versus malignant determination that relates to the liver on a cellular level. Normal liver tissue, such as that found in benign lesions, typically has a normally functioning cellular structure in cells known as Kupffer cells. Contrast is taken up by these cells and is held on to within them, resulting in sustained enhancement or isoenhancement in these areas. Abnormal cells, such as those found in suspicious malignant situations, typically have lost or a damaged cellular structure and may lack normal functioning Kupffer cells. It is the lack of these cells to hold on to the contrast agent that leads to wash-out or what is also known as a filling defect. This filling defect may be seen as early as the arterial phase with certain suspicious malignant lesions. Notes No. 33 SIEMENS Healthineers Real-time contrast assessment in the liver SIEMENS Healthineers .. Region of interest Location of contrast Pattern of contrast fill Wash-out enhancement versus enhancement on within the region of characteristics, surrounding tissue initial fill interest presence/absence • Hyperenhanced • Centrally • Nodular/globular • Rapid • Isoenhanced • Peripherally • Stellate/spoke • Slow/weak • Hypoenhanced wheel • Sustained enhancement 34 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Before reviewing the different types of lesions, it is important to have a good understanding of what the diagnostician will be looking for during a contrast exam. When determining enhancement characteristics of a region of interest, it is always compared to the surrounding (normal) liver parenchyma. Enhancement is thought of as hyper-enhanced, iso- enhanced, or hypo-enhanced when compared to the surrounding tissue. The location of the enhancement during the initial fill is very important in determining what type of lesion it is. Does the lesion fill from the center outwards to the periphery or from the periphery in towards the center? The pattern of the fill is a differentiator between specific lesion types. Is the fill nodular or globular or does it have a more stellate or spoke wheel like appearance? Presence or absence of wash-out along with the timing of wash-out, is another key determining factor in lesion type. Now that we understand what the clinician is looking for let’s review the lesion types and their corresponding characteristics. Notes No. 34 SIEMENS Healthineers Benign solid liver lesions SIEMENS Healthineers .. Arterial phase filling patterns Two most common benign solid lesions: • Hemangioma • Focal Nodular Hyperplasia (FNH) Centripetal fill Two directions of fill pattern • Hemangioma; centripetal fill pattern – the contrast agent begins at the edge and progresses toward the center of the ROI • FNH; centrifugal fill pattern – the contrast agent begins centrally and moves out toward the edges Centrifugal fill pattern 35 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Benign focal liver lesions are a common finding during routine ultrasound. The two most common benign solid lesions are hemangiomas and focal nodular hyperplasia. Benign lesions have two distinct directions of fill and characteristic filling patterns that distinguish them from one another. The first direction shows initial contrast fill from the outside edges of the lesion with progression toward the center of the lesion. This is known as centripetal fill, for example as with hemangiomas. The other direction of fill found in benign lesions is the exact opposite of the first, that being initial fill from the center of the lesion that progresses out toward the edges. This is known as centrifugal fill, for example with FNH. The filling patterns associated with these directions will be covered with their respective lesions and how they present in each phase. Notes No. 35 SIEMENS Healthineers Benign solid liver lesions SIEMENS Healthineers .. Hemangiomas Arterial Phase Portal Venous Phase Late Phase • Peripheral nodular hypervascular • Complete or partial fill in • Sustained enhancement enhancement with centripetal progression • Globular fill pattern or Key: Liver tissue Enhancement Iso-enhancement (as Weak/slow Washout (non contrast- compared to normal liver washout enhanced) tissue with contrast) 36 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Hemangiomas are the most common benign lesion seen in ultrasound. Typical presentation on B-mode imaging is a homogenous, hyperechoic, mostly round lesion. During a contrast exam, a hemangioma will typically demonstrate a centripetal filling direction that appears in a nodular or globular pattern as the contrast fills the lesion. This hypervascular peripheral nodular enhancement during the arterial phase typically identifies these lesions as hemangiomas. Contrast will continue to fill the lesion throughout the portal venous phase giving rise to a lesion that is either completely or partially filled in. Since the tissue still has a normal cellular structure, the Kupffer cells will hold on to the contrast through the late phase; we would say the lesion has “sustained enhancement”. Sustained enhancement is a typical characteristic of a benign solid lesion. Notes No. 36 SIEMENS Healthineers Benign solid liver lesions SIEMENS Healthineers Focal Nodular Hyperplasia (FNH) Arterial Phase Portal Venous Phase Late Phase • Hypervascular filling begins • Sustained enhancement • Sustained enhancement centrally, extends outward in a Isoenhanced • spoke wheel or star-like pattern Hyperenhanced • ± Central hypoechoic scar • • Rapid fill-in • ± Central scar (hypoechoic) or or or Key: Liver tissue Enhancement Iso-enhancement (as Weak/slow Washout (non contrast- compared to normal liver washout enhanced) tissue with contrast) 37 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Focal nodular hyperplasia is the second most common benign lesion of the liver and is more frequently found in women aged 30 to 50. Focal nodular hyperplasia or FNH, typically have no specific B-mode characteristics but they do have a unique vascular pattern. An FNH has a fibrous central scar that contains a larger artery for blood supply - it is this vascular pattern that gives the lesion a specific filling pattern during CEUS and potentially differentiates an FNH from other benign lesions. Filling begins centrally (centrifugal) in the arterial phase in a spoke wheel or star like pattern and is very rapid. The portal venous phase of an FNH will show a sustained, more often iso-enhanced lesion, with or without a hypoechoic central scar. This appearance continues into the late phase maintaining the sustained enhancement that is typically a characteristic of a benign lesion. Scanning tip: use a Peak Hold persistence technique to image the vascular fill pattern. Notes No. 37 SIEMENS Healthineers Suspicion of malignancy SIEMENS Healthineers Wash-out timing and appearance Suspicious malignant lesions typically exhibit hypervascular fill followed by wash-out Timing of wash-out is very important to delineate the type of tissue of the presumed malignancy • Non-hepatocyte in origin • Metastasis • Fast appearing, very black wash-out is suggestive of Metastasis • Hepatocyte in origin • Hepatocellular Carcinoma (HCC) • Wash-out appearing late and weak is suggestive of HCC 38 Unrestricted © Siemens Healthineers 2024 Speaker Notes: With benign lesions we learned that fill direction, pattern, and enhancement through all the phases were the key differentiators in confirming a benign lesion, as well as what type of benign lesion we were looking at. Suspicious malignant lesions are not determined by how they fill but rather how and when they wash-out the contrast from the lesion in question. Typically, malignant lesions have a damaged or disrupted cellular structure thus these lesions do not hold on to the contrast in Kupffer cells as is typical with benign lesions. Instead, suspiciously malignant lesions wash-out the contrast and appear hypoenhanced at some point during the three phases. Exactly when this hypoenhancement or filling defect occurs not only tells us the lesion is suspicious for a malignancy but also what tissue type makes up the presumed malignancy, either hepatocyte or non-hepatocyte in origin. Fast appearing wash-out is suggestive of metastasis whereas, later appearing and often weak wash-out is suggestion of a hepatocellular carcinoma (HCC) Notes No. 38 SIEMENS Healthineers Malignant liver lesions SIEMENS Healthineers Suspected metastatic lesions Arterial Phase Portal Venous Phase Late Phase • Rim enhancement • Wash-out (fast) • Hypo enhancement • Two types of wash-in a. Hypervascular b. Hypovascular • Wash-out a. a. b. b. Key: Liver tissue Enhancement Iso-enhancement (as Weak/slow Washout (non contrast- compared to normal liver washout enhanced) tissue with contrast) 39 Unrestricted © Siemens Healthineers 2024 Speaker Notes: For suspected metastatic lesions, the arterial phase will vary depending on the tissue type from where the lesion has arisen. Hyper-enhancement is most commonly associated with tumors of neuroendocrine origin, whereas hypo-enhancement is associated with adenocarcinoma type tumors. Metastatic lesions typically tend to wash-out very quickly, sometimes even before the completion of the short arterial phase. Rim enhancement and irregular tumor vessels are also seen on arterial phase. The portal venous phase demonstrates wash-out that will continue throughout the late phase and appear as a hypoechoic filling defect surrounded by enhanced normal tissues. This late phase filling defect is the key differentiator between a suspected malignant lesion and a typical benign lesion regardless of the suspected malignant tissue type. Notes No. 39 SIEMENS Healthineers Malignant liver lesions SIEMENS Healthineers Suspected HCC lesions Arterial Phase Portal Venous Phase Late Phase • Homogenous hypervascular wash- • Typically shows wash-out • Hypoenhanced (typical) in (typical) • Often slow/weak • Can be weak wash-out and very • Hyperenhanced late (5+ mins) • Hyperenhanced or isoenhanced prior to (weak) wash-out • Late phase key to differentiate variation HCC vs Mets ± or or Key: Liver tissue Enhancement Iso-enhancement (as Weak/slow Washout (non contrast- compared to normal liver washout enhanced) tissue with contrast) 40 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Hepatocellular carcinoma is the most common primary liver malignancy often developing in patients with a history or chronic liver disease or background liver cirrhosis. Ultrasound is one of the most commonly used imaging tools for HCC surveillance around the world and can play an important role in its diagnosis. Adding CEUS to a general ultrasound exam can aid in the diagnostic process. Hepatocellular carcinomas may show a great deal of variation throughout the phases depending on how well differentiated the tumor is. Well differentiated HCCs typically behave isodense in portal venous and late phases, and while poorly differentiated, will wash-out. Typically, HCCs are seen as homogenous hypervascular enhancing lesions in the arterial phase, with rim enhancement being unusual. However, if an HCC is large enough it may show areas of non-enhancement due to tumor necrosis. The portal venous phase is typically where we see some variability. Typically, the portal venous phase shows wash-out, however this wash-out can be slow and weak. HCC can show a variation of iso or hyper enhancement in the portal venous phase as well, which makes the late phase a key determining factor. Typically, HCCs are hypoenhanced in the late phase, however due to the variation in the portal phase, the clinician must remember to observe these lesions for an extended amount of time in the late phase; sometimes as much as five minutes. Wash-out, when it is finally seen, may be weak, but still identifiable as a filling defect when compared to surrounding tissue. Notes No. 40 SIEMENS Healthineers Normal liver tissue SIEMENS ..... Healthineers ... Fatty liver deposition and sparing • Normal cellular structure (typically) 5C1 • Contrast will be homogenous throughout Abdomen TIB:0.00 liver during all phases TIC:0.01 TIS:0.00 MI:0.10 10fps 0.5% Pure cystic structures 2D Mid • No internal cellular structure OdB/DR60 Will not enhance nor wash-out Contrast • Mid dB DR50 P2 41 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We must also consider the exam appearance of areas of “normal” liver tissue, such as fatty depositions and areas of sparing, that give a visual mass effect in B-mode imaging. Since the cellular structure of these areas is typically normal, these areas will enhance in the same manner as surrounding normal tissue. While they may look different on B-mode, the contrast exam will typically show them to be the same. Purely cystic structures are mentioned here because they will neither enhance nor wash-out – true wash-out can only occur if enhancement occurs first; since pure cystic structures lack any cellular structure internally, contrast will not be taken up to cause enhancement. Notes No. 41 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 42 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 42 SIEMENS Healthineers Tips and techniques of the liver contrast exam SIEMENS Healthineers • Optimize your image before injection • Set gain, depth, and focal zone – alterations in these settings during the contrast run can have an adverse effect on calculation/quantification software • Limit depth – get the region of interest as close to the transducer as possible • Use the TEQ ultrasound technology • The image will be very dark until the contrast agent arrives at the region of interest – resist the urge to turn up the gain • When imaging in a dual display mode, train your eye to primarily focus on the contrast side of the image 43 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Optimize your image before injection - get the target area as close to transducer as possible – decubitus position, intercostal windows, etc. Set gain, depth, and focal zone before injection – alterations in these settings during contrast run can have adverse effects on calculation/quantification software. Make use of TEQ technology during contrast exams, however if individual changes of either the contrast or B-mode image is required, the gains for each are found on their individual control panel key. The first few frames will be very dark until the contrast arrives at the region of interest – resist the urge to turn up the gain to try and “see better”. When imaging in dual mode, train your eye to primarily focus on the contrast side of the image - this is where the bubbles will appear, not the B-mode side. Notes No. 43 SIEMENS Healthineers Tips and techniques of the liver contrast exam SIEMENS Healthineers • Do not press too hard when imaging with contrast superficial structures – resulting compression can prevent blood flow into the area • Ensure the default clip length is appropriate and the PACS will handle the clip size • Practice quiet breathing with the patient – sometimes a breath hold is necessary • Small lesions are best visualized in long axis versus transverse • Patient history is very important • Cardiac output issues may delay contrast arrival in the ROI • Right heart failure and/or elevated pulmonary pressure – bubbles may be delayed by > 20 seconds • Mechanical heart valves may destroy bubbles as they pass through them 44 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Do not press too hard when imaging with contrast in superficial structures – resulting compression can prevent blood flow into the area thus preventing good flow of contrast. Ensure the default clip length is appropriate and the PACS will handle the clip size. These files are very large and careful discussion with the PACS administration needs to be had before attempting a contrast exam – sending these large exams can quickly fill up limited storage space or adversely affect image transfer to the PACS for the ultrasound and/or other imaging modalities. Practice quiet breathing with patient before the injection and ensure the area of interest stays within the image viewing area. Sometimes a breath hold is necessary – practice this too with the patient to ensure the patient fully understands where in the breathing cycle you wish them to pause. Small lesions are best scanned in long axis versus transverse, they stay in the imaging field much better. Patient history very important • Cardiac output issues may delay contrast arrival in ROI • Right heart failure and/or elevated pulmonary pressure – bubbles may be delayed by >20 sec • Mechanical heart valves may destroy bubbles as they pass thru them Notes No. 44 SIEMENS Healthineers Tips and techniques of the liver contrast exam SIEMENS Healthineers No contrast or very little contrast contained in the field of view? • Check to see if the contrast has gone interstitial (use a high- resolution linear transducer to scan the injection site) • Too much pressure on the syringe during injection may also cause bubble destruction • Ensure proper needle gauge is used – too small of a gauge can cause the bubbles to burst during injection; refer to manufacturer recommendations • Contrast agent has sat too long after mixing – bubbles have burst • Improperly mixed contrast – not enough bubbles have formed 45 Unrestricted © Siemens Healthineers 2024 Speaker Notes: No contrast or very little contrast contained in the field of view? • Check to see if contrast has gone interstitial (can use a high-resolution linear probe to scan injection site) • Too much pressure [within the syringe] during injection may also cause bubble destruction. It is important to not rush the injection, but rather introduce the agent at a constant rate in keeping with the manufacturer’s specifications • Ensure proper needle gauge is used – too small of a gauge can cause the bubbles to burst during injection. Refer to manufacturer for recommended size • Contrast agent has sat to long after mixing and the bubbles have burst. Always check the liquid appearance within the syringe before it is injected. Should the contrast agent liquid lessen or lose its milky appearance within the syringe, the bubbles have burst and less or no agent will be injected into the patient. If the contrast agent is hand-mixed (as opposed to using a specialized mixing agitator), adding some air to the syringe and re-agitate it by shaking is possible; remember to remove the added air to facilitate this re-agitation prior to injection • Improperly mixed contrast means not enough bubbles have formed. Ensure that anyone mixing contrast has had sufficient training on the mixing application for the contrast agent being used. Not all contrast agents can be hand mixed – some require specialized machines for agitation to facilitate bubble formation Notes No. 45 SIEMENS Healthineers Liver contrast exams - limitations SIEMENS Healthineers Conditions not suitable for CEUS: • Deep lesions • Severe fatty livers (steatosis) – difficult-to-suppress tissue in low mechanical index conditions • Area is not visible on ultrasound Limitations of CEUS: • Lesion size – smallest detectable lesions range between 3–5 mm in diameter (very small lesions can be overlooked) • Subdiaphragmatic lesions may not be accessible • Falciform ligament and surrounding fat may cause enhancement defects and be confused with a focal liver lesion 46 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We have shown the importance of using contrast enhanced ultrasound on the liver for differentiating and diagnosing focal liver lesions. There are, of course, situations where the technology should not be considered as an option or the lesion in question exceeds the limits of the technology. Who should we not be doing contrast exams on? Since contrast software operates at a lower power output than is used during regular ultrasound exams, there is a point where a lesion may be too deep to be visualized with the software settings. The same is true in cases of severe fatty livers. The lower power output can mean lack of penetration to the lesion, as even if the lesion is visualized the fatty tissue is difficult to suppress and there will be more of an interfering tissue signal shown on the image screen. Sometimes lesions are seen in another imaging modality such as CT, but not visualized when scanned with ultrasound. If a lesion is not visualized initially, a contrast enhanced ultrasound cannot be performed on it. Limitations of CEUS include lesions that are too small to be visualized or are perhaps located too high in the liver to be accessible. Lesions that are located too close to the falciform ligament can also be hard to visualize as the ligament and surrounding fat may cause enhancement defects. Notes No. 46 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 47 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 47 SIEMENS Healthineers Contrast enhanced voiding urosonography SIEMENS Healthineers • Contrast enhanced voiding urosonography (ce-VUS) is a potential alternative to cystography performed under fluoroscopy • Urinary reflux is the abnormal flow of urine back up the ureters which may or may not involve the kidneys • Reflux is diagnosed when microbubbles appear in one or both of the ureters and/or kidneys • Reflux is graded on degree of severity and assigned one of five categories 48 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Contrast enhanced voiding urosonography has been widely adopted in Europe and is approved for use in the USA. Ce-VUS is a radiation free alternate to cystography performed under fluoroscopy, primarily on children. Reflux is the abnormal flow of urine back up the ureter with or without kidney involvement when the child urinates. Urinary reflux is also known as vesico-ureteric reflux. Reflux is typically diagnosed when microbubbles appear in one or both of the ureters and/or the kidneys. Reflux is graded on a degree of severity using five categories that are similar to those used to assess voiding cystogram images obtained under fluoroscopy. Notes No. 48 SIEMENS Healthineers Urinary reflux grading SIEMENS Healthineers Reflux Grading[11, 12] Gr I Gr II Gr III Gr IV Gr V Urine refluxes part Urine refluxes up Complete ureter Complete ureter Extensive reflux way up the ureter the entire length of reflux with minor reflux with with twisting and the ureter dilatation of the widening of the widening of ureter renal calyces ureter and renal and renal calyces calyces 49 Unrestricted © Siemens Healthineers 2024 Speaker Notes: There are five different degrees[11, 12] of severity when grading urinary reflux ranging from the mildest form to the most severe form. • Grade one reflux is the mildest, with urine only refluxing up from the bladder part way into the ureter. • Grade two reflux involves the entire length of the ureter, with contrast, filling but not dilating the renal pelvis. • Grade three reflux shows minor widening of the renal pelvis/collecting system (calyces) along with complete filling of the ureter. • Grade four extends the dilatation of the renal pelvis seen in grade three and shows a more marked widening of the collecting system within the kidney. • Grade five is the most severe form of reflux with extensive twisting and widening of the ureter, as well as the collecting system within the kidney. Notes No. 49 SIEMENS Healthineers ce-VUS study procedure SIEMENS Healthineers According to the EFSUMB, the basic steps of voiding urosonography are: • Ultrasound evaluation of kidneys and bladder Guidelines • Intravesical administration of ultrasound contrast agent diluted in sterile saline The EFSUMB Guidelines and Recommendations on the • Repeated scanning of the bladder and kidneys at Clinical Practice of Contrast Enhanced Ultrasound low MI during bladder filling, after bladder filling, (CEUS): Update 2011 on non-hepatic applications and while voiding 50 Unrestricted © Siemens Healthineers 2024 Speaker Notes: According to the EFSUMB Guidelines and Recommendations for non-hepatic applications, the basic steps of a voiding urosonography exam are: • Ultrasound evaluation of kidneys and bladder (B-mode) • Intravesical administration of ultrasound contrast agent diluted in normal sterile saline • Repeated scanning of the bladder and kidneys at low MI during bladder filling, after bladder filling, and while voiding Notes No. 50 SIEMENS Healthineers ce-VUS indications SIEMENS Healthineers According to EFSUMB, the recommended uses and indications for ce-VUS are: • First examination for vesicoureteral reflux in Guidelines females • Follow-up examinations for vesicoureteral reflux in The EFSUMB Guidelines and Recommendations on the males and females after conservative or surgical Clinical Practice of Contrast Enhanced Ultrasound therapy (CEUS): Update 2011 on non-hepatic applications • Screening high-risk patients for reflux (e.g., siblings, transplanted kidney patients) 51 Unrestricted © Siemens Healthineers 2024 Speaker Notes: According to the EFSUMB Guidelines and Recommendations for non-hepatic applications the recommended uses and indications are: • First examination for vesicoureteral reflux in females • Follow-up examinations for vesicoureteral reflux in males and females after conservative or surgical therapy • Screening high-risk patients for reflux (e.g., siblings, transplanted kidney patients) Notes No. 51 SIEMENS Healthineers Objectives SIEMENS Healthineers .. • Outline contrast-enhanced ultrasound (CEUS) and reasons for use • Explain: • What are contrast agents? • Tissue and bubble imaging signals • How contrast agents are imaged • What is a “good” contrast image? • Discuss the liver contrast exam • Identify tips and techniques for liver CEUS • Discuss contrast-enhanced voiding urosonography (ce-VUS) • Identify tips and techniques for ce-VUS 52 Unrestricted © Siemens Healthineers 2024 Speaker Notes: We will begin by outlining the reasons for using contrast-enhanced ultrasound in the clinical environment. Notes No. 52 SIEMENS Healthineers Tips and techniques of the ce-VUS exam SIEMENS Healthineers • Base line scan of bladder and kidneys • Optimize image parameters (gain, depth) before contrast injection – renal fat may be difficult to suppress • Dual imaging important when watching bladder and kidneys fill with contrast • Switching between live dual and full screen imaging may be necessary • Bladder is drained of urine then injected with a small amount of saline prior to contrast administration • Watch for homogenous filling of bladder 53 Unrestricted © Siemens Healthineers 2024 Speaker Notes: Tips and techniques to remember when performing a ce-VUS exam. Base line scan of bladder and kidneys prior to contrast administration and/or catheterization of bladder. Use the baseline scan to optimize the image parameters before contrast is injected – do not adjust these parameters once the contrast infusion begins. Dual mode is important when watching for contrast fill in both bladder and kidneys. As the exam progresses, switching between live dual and full screen imaging may be necessary to see entire structures. Bladder is emptied of urine during catheterization however a small amount of saline will need to be injected into the bladder prior to contrast administration – an empty bladder is too contracted and difficult to locate with ultrasound when empty. While observing the bladder fill, watch for homogenous filling throughout the structure. Notes No. 53 SIEMENS Healthineers Tips and techniques of the ce-VUS exam SIEMENS Healthineers • Prone/decubitus positioning may allow for better visualization of the renal pelvis • Alternate between bladder and kidneys during filling and voiding stages • Transperineal images of the urethra during voiding • If done in conjunction with fluoroscopy voiding cystogram, perform the ce-VUS first • If contrast is too concentrated or too much in the bladder • Flash/burst contrast (bubble destruction) • Add more saline • For infants that cannot hold their bladder, perform constant injections of contrast 54 Unrestricted © Siemens Healthineers 2024 Speaker Notes: During scanning of the kidneys, a prone or decubitus position potentially allows for better visualization of the renal pelvis. As the exam progresses from filling to voiding, alternating between the bladder and the kidneys may be necessary to monitor both structures. Transperineal scanning of the urethra during voiding typically yields images in both males and females as seen on fluoroscopy. Renal fat may be difficult to suppress when in contrast imaging mode – be careful not confuse the renal fat with contrast – dual imaging is helpful. If both fluoroscopic voiding cystogram and ce-VUS are done at the same time, it is important to do the ce-VUS first. Residual X-ray contrast can interfere with the ultrasound contrast exam and could result in false positive or false negative results. This is thought to be due to different densities of contrast agents (x-ray contrast is more dense). If there is too much contrast in the bladder or the contrast is too concentrated, the operator can either destroy the bubbles with a burst or flash, or add more saline to dilute. Infants who cannot hold their bladders will need cyclical (constant) injections of contrast, whereas, older children that can control their bladder will only require a single injection. Notes No. 54 SIEMENS Healthineers References SIEMENS Healthineers .. [1] Wilson SR and Burns PN. An Algorithm for the Diagnosis of Focal Liver Masses Using Microbubble Contrast Enhanced Pulse Inversion Sonography. AJR:186 May 2006; 1401-1412 [2] Porter TR et al. Clinical Applications of Ultrasonic Enhancing Agents in Echocardiography: 2018 American Society of Echocardiography Guidelines Update. J Am Soc Echocardiogr. 2018 Mar:31(3):241-274. doi:10.1016/j.echo.2017.11.013 [3 ] Greis, C. Technical aspects of contrast-enhanced ultrasound (CEUS) examination: Tips and tricks. Clinical Hemorheology and Microcirculation 58 (2014)89-95 DOI 10.3233/CH-141873. IOS Press [4] Journal of Hepatology: Global burden of liver disease: 2023 update. https://www.journal-of- hepatology.eu/article/S0168-8278(23)00194-0/fulltext#:~:text=Keypoints,%E2%80%A2. Accessed December 2024. [5] Changing epidemiology of cirrhosis from 2010 to 2019: results from the Global Burden Disease study 2019. https://pubmed.ncbi.nlm.nih.gov/37647379/ https://pubmed.ncbi.nlm.nih.gov/37647379/. Accessed December 2024. [6] Journal of Liver Cancer. https://www.e-jlc.org/journal/view.php?number=557. Accessed December 2024. [7] Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/liver-hemangioma/symptoms-causes/syc- 20354234. Accessed December 2024. 55 Unrestricted © Siemens Healthineers 2024 Notes No. 55 SIEMENS Healthineers References SIEMENS Healthineers [8] CEUS - Getting Started HOOD05162002552651_152090650 [9] Claudon M et al. Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012 A WFUMB-EFSUMB Initiative in Cooperation with Representatives of AFSUMB, AIUM, FLAUS, and ICUS. Ultrasound in Med & Bio. Pp 1-24, 2012. http://dx.doi.org/10.1016/j.ultrasmedbio.2012.09.002. Accessed December 2024. [10] Wilson SR and Burns PN. An Algorithm for the Diagnosis of Focal Liver Masses Using Microbubble Contrast Enhanced Pulse Inversion Sonography. AJR:186 May 2006; 1401-1412 [11] Tang MX, Mulvana H, Gauthier T, Lim AKP, Cosgrove DO, Eckersley RJ, Stride E. Quantitative contrast- enhanced ultrasound imaging: a review of sources of variability. Interface Focus (2011) 1, 520-539. Published online 18 May 2011. [12] https://www.kidshealth.org.nz/urinary-reflux. Accessed December 2024. 56 Unrestricted © Siemens Healthineers 2024 Notes No. 56 SIEMENS Healthineers Trademarks and disclaimers SIEMENS Healthineers .. ACUSON Sequoia is a trademark of Siemens Medical Solutions USA, Inc. LUMASON is a registered trademark of Bracco Diagnostics Inc. SonoVue is a registered trademark of Bracco Diagnostics Inc. At the time of publication, the United States Food and Drug Administration has cleared ultrasound contrast agents only for use in left ventricular opacification (LVO), liver, and vesicoureteral reflux (VUR). Check the current regulations for the country where you are using this ultrasound system for contrast agent clearance. 57 Unrestricted © Siemens Healthineers 2024 Speaker Notes: No speaker notes. Notes No. 57 SIEMENS Healthineers Thank you for your enthusiasm! SIEMENS Healthineers Questions? 58 Unrestricted © Siemens Healthineers 2024 Speaker Notes: No speaker notes.