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ACUSON Sequoia™ Ultrasound System Contrast-enhanced Ultrasound Imaging

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White paper Contrast-enhanced Ultrasound Imaging ACUSON Sequoia ultrasound system David P. Duncan, Ph.D. Michele Baillie, B.Sc., RDMS, RDCS Siemens Medical Solutions USA, Inc., Ultrasound Business Area Issaquah, Washington siemens-healthineers.com/sequoia SIEMENS Healthineers White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Introduction The ACUSON Sequoia ultrasound system with BioAcoustic imaging technology provides an integrated user experience with detailed and information-rich images that dramatically improves the way ultrasound is performed today. The general imaging system was developed in response to one of the most prevalent challenges in ultrasound imaging – the ability to image different sized patients with consistency and clarity. Benefits • A fast, fully-focused B-mode image from near field to far field • Unique and patented technologies that allow the ACUSON Sequoia system to virtually eliminate color flash artifacts • The DAX transducer can penetrate as deep as 40 cm to deliver unprecedented images at depth without compromising diagnostic quality • Improved contrast-enhanced ultrasound (CEUS) penetration and bubble longevity 2 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper siemens-healthineers.com/sequoia 3 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging CEUS and Microbubbles Contrast-enhanced ultrasound (CEUS) imagery has to travel throughout the body’s entire cardiovascular become a mainstay in the modern clinic. Ultrasound system but still keeps them intravascular. To help the contrast agents are low-cost, non-toxic, and can provide microbubbles persist long enough in the body for clinical a safer alternative to the contrast agents of other medical utility, they are filled with a high molecular-weight gas imaging modalities. When used effectively, they can and typically come with an elastic shell to slow their be a valuable tool in helping clinicians make a diagnosis breakdown. and strengthen diagnostic confidence. When microbubbles are present in the body and are The BioAcoustic imaging technology of the ACUSON imaged with ultrasound, they help a clinician visualize Sequoia system improves CEUS bubble longevity. CEUS the blood and blood-perfused areas of the body by uses microbubble-based contrast agents to improve differentiating them from non-blood-filled areas with the visualization and assessment of lesions. With the enhanced image contrast. The higher frame rates typical ACUSON Sequoia system, the view time of contrast in ultrasound allow clinicians not only to see blood-filled agents is significantly longer, allowing clinicians more areas of the body with great detail, but also to better time to scan for additional incidental lesions during observe the hemodynamics of wash-in and wash-out their examinations and with up to twice the sensitivity.1 perfusion patterns with greater fidelity. Ultrasound contrast agents consist of very small bubbles When a microbubble is isonified by an ultrasonic pressure with diameters of 1–10 microns known as “microbubbles.” wave, the bubble resonates, and its size rapidly oscillates. Microbubble contrast agents are introduced into the The frequency at which a bubble resonates is tied closely bloodstream with a bolus injection or as a continuous to its nominal resting size. When a bubble is resonating, intravenous (IV) infusion. Their small size allows them it generates very strong acoustic backscatter (or echoes) 1.4 10 1.2 9 8 1.0 7 0.8 6 5 0.6 4 Number (%) 0.4 3 2 Bubble diameter (µm) 0.2 1 0.0 0 0 1 10 100 1 2 3 4 5 6 7 8 9 10 Bubble diameter (µm) Resonance frequency (MHz) Figure 1: Bubble size distribution of a typical vial of SonoVue contrast agent and a bubble resonance frequency chart. It is important for clinicians to consider the resonance of the agent when deciding on the transducer and imaging frequency range for a given clinical application so as to set imaging expectations appropriately.2 4 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper that make the microbubble show up brightly in the Eventually, microbubbles will break down, but they final reconstructed ultrasound image. As such, most also can be prematurely destroyed. Intentional commercially available contrast agents consist of a wide microbubble destruction is caused most often by distribution of bubble sizes to allow them to cover a setting high transmit power levels. Higher transmit large number of potential clinical applications and pressures cause microbubble shell disruption and imaging frequencies. A typical distribution of SonoVue® bubble destabilization, speeding up the bubble’s bubble sizes and associated resonance frequency chart destruction process. While high transmit power is the is shown in Figure 1. most common reason for bubble destruction, it also could be caused by other biological processes. Microbubbles not only resonate near their natural frequency when exposed to ultrasound, but also Injecting small gas bubbles into a circulatory system generate multiple, higher harmonics when resonating. may seem potentially hazardous, but extensive clinical (Figure 2) experience has shown that the tiny given volume of air or gas (under 200 μl) is not dangerous, and the safety This generation of higher harmonics occurs even at of microbubbles compares well to that of conventional relatively low ultrasound pressures, i.e. low transmit agents used in other modes of imaging.3 Although power levels. The fact that microbubbles generate microbubbles originally were designed to enhance harmonics at low transmit power levels is a key factor conventional ultrasound scanning, their use and that drives a majority of current ultrasound agent evolution has opened up powerful applications and imaging techniques. This will be discussed in more improved patient results. detail in the next section. -90 -100 -110 Transmit Echo dB -120 ~ -130 Pressure -140 V Time Time V 0 5 10 15 MHz Figure 2: Microbubbles generating multiple, higher harmonics when resonating. siemens-healthineers.com/sequoia 5 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging CEUS Technology As microbubbles generate strong harmonics at lower Conversely, any echo that does scale with the power levels and tissue generally does not, most contrast transmitted ultrasound level is termed “linear.” agent imaging techniques exploit this property to image only the echoes from the contrast agent while The most common and effective known technique to simultaneously suppressing those from tissue. isolate and separate non-linear echoes from linear ones is contrast pulse sequencing. A contrast pulse sequence Another term that is frequently used when describing is a series of scaled (or weighted) transmissions and the echoes from the contrast agent is “non-linear.” receptions that work to isolate, enhance, and detect A non-linear echo is any echo that was generated the non-linear responses from bubbles and attempt to from a contrast bubble or tissue that does not scale reject any linear echo contributions from tissue – which proportionally with the transmitted ultrasound level. as mentioned previously, does not generate many harmonics at low power levels. +1 Scaling Linear part; Linear part; Non-linear part; Total spectrum tissue (+1) bubble (+1) bubble (+1) Echo 1 Transmit 1 1 Amplitude + + + Frequency -1 Scaling Linear part; Linear part; Non-linear part; Total spectrum tissue (-1) bubble (-1) bubble (-1) Echo 2 on Transmit 2 -1 Amplitude Frequency Linear part; Linear part; Non-linear part; Sum spectrum tissue sum bubble sum bubble sum Amplitude Frequency Figure 3: Contrast Harmonic Imaging (CHI) sequence 6 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper In ultrasound, the contrast pulse sequencing technique [1, 1]. This sequence is designed to suppress signals in is most often used in two difference sequence the fundamental frequency band while amplifying the arrangements – a 2-pulse sequence and a 3-pulse second harmonic content in each echo. The negative sequence. transmission weight can be viewed as changing a pulse’s phase by 180 degrees, thus this type of contrast pulse Contrast Harmonic Imaging (CHI) sequencing is commonly known as “phase inversion”. On Siemens Healthineers products that support contrast The 2-pulse sequence exploits the second harmonic agent imaging using this type of pattern sequence, the during imaging. The pulse arrangement has signals with technology is known as Contrast Harmonic Imaging, or a transmission weight of [1, -1] and reception weights of CHI. (Figure 3) +0.5 Scaling Linear part; Linear part; Non-linear part; Total spectrum tissue (+1) bubble (+1) bubble (+1) Echo 1 An Transmit 1 0.5 Amplitude + + Frequency + -1 Scaling Linear part; Linear part; Non-linear part; Total spectrum tissue (-2) bubble (-2) bubble (-2) Echo 2 Transmit 2 -1 Amplitude + + Frequency + +0.5 Scaling Linear part; Linear part; Non-linear part; Total spectrum tissue (+1) bubble (+1) bubble (+1) Echo 3 Transmit 3 0.5 Amplitude Frequency = Linear part; Linear part; Non-linear part; Sum spectrum tissue sum bubble sum bubble sum Amplitude Frequency Figure 4: Contrast Pulse Sequencing (CPS) arrangement siemens-healthineers.com/sequoia 7 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Contrast Pulse Sequencing (CPS) To form a typical contrast agent image, the transducer array forms focused-beam transmissions and builds up The 3-pulse sequence technique, which is used most the image in a line-by-line format, scanning the focused commonly on Siemens Healthineers platforms, uses beam transmissions across the surface of the array. the fundamental imaging mode and a combination of For any given line of the contrast image, a single power and phase modulation. The pulse sequence in this contrast pulse sequence is fired (one transmission after instance has transmission weights of [0.5, -1, 0.5] and the other) until all the echoes from the sequence have receive weights of [1, 1, 1]. In this sequence, using the been captured. Once the echoes are collected, they composite method of power and phase modulation, is are processed and then displayed on the output image. designed to reject tissue signals within the echo while (Figure 5) enhancing any non-linear components found within the fundamental frequency band from the contrast agent. As each contrast pulse sequence has a different number In Siemens Healthineers products which support this of firings per image line, each sequencing method type of patterned sequence, the feature takes its name will differ also in its overall performance and in any from the actual technique and is known as Contrast trade-offs. The next section discusses important metrics Pulse Sequencing or CPS. (Figure 4) of what makes a superior contrast agent image. X hmmm/ww + = Figure 5: Image formation process in conventional CEUS imaging. The transducer scans in a line-by-line format (left image). At each line position, multiple firings are transmitted – in this example, a 3-pulse sequence is used in the middle CPS image. The 3 echoes from each firing at a given line position are summed (center image) and then laid onto the output image (right image). 8 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper Performance Metrics – Contrast-Agent Sensitivity and Specificity The quality of any ultrasound contrast agent imagery difficult to be confident in microbubble detection and from a given system and it’s imaging technique is localization. When a system suppresses tissue and other typically measured by two metrics: contrast agent clutter well, the contrast agent is better visualized and sensitivity and specificity. clinical decisions are made with more confidence. Within the context of contrast agent imaging, sensitivity The contrast agent imaging techniques (CPS and CHI) is a measure of how small of a contrast signal can be differ slightly in sensitivity, specificity, detail resolution, detected and imaged by a given imaging system or and frame rates (Figure 6). Since CPS uses more pulses technique. A system or technique is said to have high and images at the fundamental frequency band (typically sensitivity when it can detect and image very tiny wider), it tends to enjoy higher sensitivity than CHI. concentrations of a contrast agent. A system with Also, since there is generally few non-linear echoes higher sensitivity also can mean that a given agent generated by tissue, CPS also tends to have very good can be imaged for longer periods of time. specificity. These advantages, however, come with a trade-off as a CPS image will take longer to collect Contrast specificity is a measure of how well contrast because the sequence is three pulses instead of two and agent signals are separated from tissue and other hence will have lower frame rates. Also, CPS images at clutter when imaged by a given system or technique. the fundamental frequency band tend to have lower As any tissue-generated echoes that are not effectively detail resolution, although optimization and hardware suppressed are intermixed and visualized along with setups may allow the results to vary. the echoes from the contrast agent, this makes it more CPS (Contrast Pulse Sequencing) CHI (Contrast Harmonic Imaging) • 3-pulse, low-MI sequence • 2-pulse, low-MI sequence (fundamental imaging mode) (2nd harmonic imaging mode) • Higher specificity • Lower specificity 1+ • Higher sensitivity • Lower sensitivity I+ - • Slight increase in penetration • Slight decrease in penetration + + + Lower frame rates - • • Higher frame rates + • Lower resolution - • Higher resolution + Figure 6: CPS versus CHI Characteristics. Contrast agent imaging techniques (CPS and CHI) differ slightly in sensitivity, specificity, detail resolution, and frame rates. siemens-healthineers.com/sequoia 9 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Clinical Performance DAX ABD *ABD TIB:0,00 TIB:0,00 TIC:0,01 TIC:0,01 TIS:0,00 TIS:0,00 MI:0,09 MI:0,09 7B/Sek 6B/Sek 0,5% 0,25% 2D 2D Mittel Niedrig 0dB/DB60 0dB/DB60 LD 1 LD 1 UA 2 UA 2 SkalaC/T5 SkalaD/T5 Kontrast + D2 Kontrast Mittel Mittel AdB/DB70 B70 LD 1 LD 1 UA Aus UA Aus SkalaF/T1 SkalaF/T1 D2 D2/Peak Hold Nur Kontrast Nur Kontrast 17cm 18cm 1 Abst=2,03 cm 1 Abst=1,15 cm 2 Abst=2,06 cm 2 Abst=1,49 cm 01:01 3 Abst=1,81 cm 4 Abst=1,22 cm 04:15 Figure 7: The DAX transducer provides a 30% improvement in penetration for imaging larger patients, thereby giving clinicians visual access to deeper areas within the liver that have not been previously seen. As shown in this example, a larger body habitus patient has been imaged with the 5C1 (left image) and the DAX (right image). While lesion detection was excellent on the 5C1, the DAX provided visualization of an additional lesion at a much deeper level – a level that conventional contrast imaging struggles to image. The increasing prevalence of obesity in many countries4, 5 introduced with the ACUSON Sequoia system is the can present a problem when evaluating technically deep abdominal transducer (DAX). difficult patients with ultrasound as a first-line imaging modality. Concerns about long-term effects of radiation With the ability to penetrate as deep as 40 cm, DAX exposure from X-ray and computed tomography (CT) expands the population of patients who can be scans have made the ability to image large patients diagnosed successfully with ultrasound. The benefits more important than ever. One of the breakthroughs extend to all imaging modes, including contrast and 1D Transducer Multi-D Transducer Depth Figure 8: The advanced Multi-D beam formation of the Deep Abdominal Transducer (DAX) enables thinner slice thickness enabling imaging throughout a range of up to 40 cm. 10 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper shear wave elastography, making DAX a powerful InTune Coherent Pulse Formation technology is also an transducer for larger and technically difficult patients. important factor in contrast imaging, with increased tissue cancellation and maximum bubble response The ACUSON Sequoia system also offers several other for higher specificity. Extremely low distortion of the new transducers that take ultrasound sensitivity to transmit pulse and precise phase control achieve a new level by using new materials and construction 10 times the acoustic fidelity of previous systems.1 techniques. When coupled with high signal-to-noise ratio (SNR) signal processing, the system yields Support for a wide frequency range improves high- penetration improvements in harmonic imaging frequency imaging and allows third harmonics imaging of up to 65% over prior systems with comparable on some transducers for improved near-field contrast transducer types.1 Next-generation micro-pinless resolution. transducer connectors maintain low noise and signal fidelity and are easy to use. Another design improvement is the ability to maintain a constant and sustainable energy delivery over deep InTune Coherent Pulse Formation depths and with long pulses, such as those used in shear wave elastography employing acoustic radiation force Key acoustic performance elements in contrast and impulse (ARFI) techniques. A capable transmit power harmonic imaging are the agile, dual-linear transmitters supply helps overcome many limitations of conventional of the ACUSON Sequoia system. With 16-point pro- systems to provide uniform, consistent, acoustic energy grammability of the InTune pulse former, ultrasound over the field of view. This results in better contrast pulses can be precisely tuned for superior harmonic studies and more accurate, repeatable, and reproducible performance and penetration on all transducers. For stiffness measurements. example, in 4.0 MHz harmonic mode, sensitivity is increased three times over previous systems through precision transmit wave shaping and higher receive InTune Coherent Pulse sensitivity.1 This allows harmonic imaging to be used as Formation technology is a default mode for most ultrasound exams, improving spatial and contrast resolution. a key factor in improved harmonic and contrast imaging. 3x Sensitivity Sensitivity ƒ Frequency 2ƒ Figure 9: InTune Coherent Pulse Formation siemens-healthineers.com/sequoia 11 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Clinical Application Contrast imaging Clinical case studies Overcoming technical barriers CEUS has gained widespread global acceptance as the The enormous architectural power of the ACUSON method of choice for sensitive visualization of blood Sequoia system can provide visualization of contrast flow. With a focus on value-based healthcare, as well as deeper and with greater clarity than ever before. Tissue the cumulative impact of ionizing radiation for patients, cancellation has been improved over the ACUSON CEUS offers a low-cost and well-tolerated alternative Sequoia legacy 512 ultrasound system1 transmit power to help clinicians observe tissue perfusion, which is supplies with high-voltage scale agility, contributing often a key indicator for disease states such as lesion to a high linear-response rejection ratio. characterization in the liver. Contrast sensitivity up to two times higher than the The following clinical case studies highlight the practical original ACUSON Sequoia legacy system allows the use of CEUS for the characterization of focal liver visualization of small vessel perfusion and in many cases lesions. They provide technical information about the the ability to visualize a diagnostic level of contrast ACUSON Sequoia ultrasound system and the benefits agent for a much longer, late-phase contrast perfusion of BioAcoustic imaging technology, which allow assessment.1 This may increase diagnostic confidence significantly longer bubble visualization, increased by offering a differentiation of focal liver lesions using penetration in contrast imaging, and up to twice the the CEUS LI-RADS algorithm.6 (Figure 10) sensitivity in contrast mode in abdominal imaging.1 CEUS uniquely balances the sophisticated interaction between the contrast agent and the ultrasound wave. Average Contrast Sensitivity as a Function of Time This technology harmonizes the vascularization and 1:50000 Dose of SonoVue / Lumason timing of liver perfusion, and leverages the expertise of the clinician and sophistication of the technology. 25 20 15 10 5 Contrast Sensitivity (dB) 0 5 10 15 20 25 30 35 K Time Figure 10: The ACUSON Sequoia (blue line) has approximately 6 dB (2 times) more sensitivity at depth in contrast imaging than its predecessor, the ACUSON Sequoia legacy system (orange line), in the first 10 minutes post-injection, with 10 times better tissue cancellation, potentially leading to higher diagnostic confidence. 12 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper Liver CEUS real-time characteristics CEUS is a dynamic study that allows the user to Depending on the lesion type, the wash-in and wash-out characterize a lesion in real time by examining the will vary. The timing of these events is critical in allowing wash-in and wash-out enhancement of the CEUS agent. the clinician to determine the lesion type. Real-time assessment CEUS characteristics Region of interest Location of contrast Pattern of contrast fill within Wash-out characteristics, enhancement versus enhancement on initial fill the region of interest presence / absence surrounding tissue • Centrally • Nodular/ globular • Rapid • Hyper-enhanced • Peripherally • Stellate / spoke wheel • Slow/weak • Iso-enhanced • Sustained enhancement • Hypo-enhanced Enhancement phases of the liver Dual blood supply of the liver from the hepatic artery can be characterized according to the wash-in and and the portal vein gives rise to three overlapping wash-out enhancement phases. A diagnostic algorithm vascular phases on a CEUS exam. The timing of these was developed to map these characteristics with phases is demonstrated in the signal intensity /time a positive predictive value (PPV) of malignancy vs. chart (Figure 11), and it has been found that liver lesions benignancy of more than 90%.7, 8 Signal intensity Arterial phase: 10–30 seconds Portal phase: 30–120 seconds Late phase: +120 seconds Time Figure 11: Demonstrates the timing of the three overlapping vascular phases on a contrast-enhanced ultrasound exam.8 siemens-healthineers.com/sequoia 13 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Benign Lesion – Hemangiomas Characteristics Hemangiomas are the most common type of benign liver lesion. They are composed of an abnormal collection of entangled vessels that usually present themselves as a well-defined hyperechoic lesion in the parenchyma. GA ) Approximately 20–30% of hemangiomas present as atypical in appearance.1 CEUS is an excellent complimentary exam as it can distinguish quickly the presence of hemangiomas, including the atypical type. Flow phases Liver tissue (non or contrast-enhanced) Enhancement Arterial phase Portal venous phase Late phase • Peripheral nodular hypervascular • Complete or partial fill-in • Sustained enhancement enhancement with centripetal progression • Globular fill pattern Signal Arterial phase intensity Portal phase Late phase Time Figure 12: Demonstrates the typical ultrasound characteristics for helping to characterize hemangiomas on CEUS. 14 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper Case study The 2D ultrasound image shows the typical appearance of a subtle hemangioma – a well-defined hyperechoic lesion with some color flow noted within it. In the early arterial phase (12 seconds), note the centripetal fill pattern with the periphery of the mass filling first. 5C1 *ABD TIB:0,00 TIC:0,01 TIS:0,00 MI:0, 10 19B/Sek 0,5% 2D Mittel -2dB/DB60 LD 1 UA 3 SkalaD/15 D2 Kontrast ....... Niedrig -3dB/DB70 LD 1 UA Aus SkalaF/T1 02 Nur Kontrast 11.7cm HD Z 00-12 Arterial phase: 10–35 seconds siemens-healthineers.com/sequoia 15 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Benign Lesion – Focal Nodular Hyperplasia Characteristics Focal nodular hyperplasia (FNH) is the second most common type of a benign liver lesion, and is usually asymptomatic and vascular in nature. FNH is usually found incidentally and associated with young women but can be found in men as well. FNH is believed to occur as a result of a localized hepatocyte response to an underlying congenital arteriovenous malformation.9 There have been no reports of FNH becoming malignant, however due to the fact that FNH and a fibrolamellar variant of hepatocellular carcinoma have a similar imaging feature,8 CEUS is an excellent way to help distinguish between the two. Early arterial centrifugal flow (spoke-like from the center out to the periphery), sustained contrast enhancement, and the possible presence of a central scar in the late phase are classic flow characteristics of FNH. Flow phases Liver tissue (non or or contrast-enhanced) x Enhancement Arterial phase Portal venous phase Late phase O Iso-enhancement (as compared to • Hypervascular fill beginning • Sustained enhancement • Sustained enhancement normal liver tissue centrally Hyper-enhanced • ± Central scar - with contrast) • Spoke-wheel or star-like pattern ± hypoechoic central scar Rapid fill-in Iso-enhanced Hypo-enhanced • - ± hypoechoic central scar Signal Arterial phase intensity Portal phase Late phase Time Figure 13: Demonstrates the typical ultrasound characteristics for helping to characterize FNH on CEUS. 16 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper Case study This case demonstrates the classic appearance of FNH on CEUS. The arterial contrast phase (11–13 secs) displays the typical centrifugal (spoke-like) filling pattern of the lesion. SC1 8 TIS:0,00 MI:0,09 8B/Sek 0,5% 2D Mittel -2dB/DB60 LD 1 UA 3 SkalaD/T5 3 Kontrast Niedrig -4dB/DB70 LD 1 UA Aus SkalaF/T1 D2 Nur Kontrast Arterial phase: 10–35 seconds Case study Showing how CEUS can be further enhanced by The arterial phase images show classic hyper- fusion imaging, these images demonstrate a lesion enhancement of the lesion with what appears to be during the arterial phase of a CEUS exam, fused a central scar and show typical CEUS characteristics with the corresponding CT data in real time. of FNH. Schallkopf 3 5C1 *ABD Nadel Ausgesteckt TIB:0,00 TIC:0,0 TIS:0,00 MI:0, 11 10B/Sek 0,5% Arterial phase: 10–35 seconds siemens-healthineers.com/sequoia 17 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Malignant Lesions Characteristics Suspicious malignant lesions typically exhibit hypervascular fill followed by wash-out. The timing of wash-out is very important in helping to determine malignancy.8 Non-hepatocyte in origin: Metastasis • Fast appearing and rapid wash-out is suggestive of metastasis Hepatocyte in origin: Hepatocellular carcinoma (HCC) • Wash-out appearing late and weak is suggestive of HCC Flow phases Suspected metastatic lesions Liver tissue (non a a contrast-enhanced) Enhancement O b b Iso-enhancement (as compared to Arterial phase Portal venous phase Late phase normal liver tissue with contrast) • Rim enhancement • Wash-out (fast) • Wash-out Two types of wash-in Weak/slow wash-out • a. Hypervascular with fast wash-out Wash-out b. Hypovascular with wash-out • Fast wash-out can sometimes occur before the end of the arterial phase Suspected HCC lesions ± or or Arterial phase Portal venous phase Late phase • Homogenous hypervascular • Hyper-enhanced or iso-enhanced • Wash-out (hypo-enhanced) wash-in (typical) prior to wash-out variation is typical presentation • Hyper-enhanced • Typically shows wash-out which • Can have weak wash-out is often slow/weak and very late (5+ minutes) • Late-phase timing is key to differentiate HCC vs. Mets Figure 14: Illustration of phases for suspected metastatic and HCC lesions. 18 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper Case study The lesions displayed are all consistent with the classic CEUS appearance for malignant metastasis. In the largest lesion, rapid and complete wash-out is seen. -2dB/DE UA SkalaD/T D Kontras Mitte -2dB/DB7 UA Au SkalaF /T Nur Kontras Late phase: +120 seconds siemens-healthineers.com/sequoia 19 White paper · ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging Conclusion Microbubble ultrasound contrast agents are an important Providing an intuitive workflow coupled with high-end element of imaging as they provide an inexpensive, safe technology, the ACUSON Sequoia platform offers world- alternative to contrast agents of other modalities and class contrast-agent imaging with unmatched contrast can be a valuable tool in assisting clinicians to make a sensitivity and specificity. The system supports current diagnosis and strengthen diagnostic confidence. and future advanced diagnostic capabilities with an The ACUSON Sequoia ultrasound platform was built unmatched image quality, user experience, contrast from the ground up and designed to be the best clinical imaging, and elastography capabilities. The longevity of tool for imaging ultrasound contrast agents. The the imaging engine hardware and flexible upgrade path platform provides enhanced sensitivity and specificity design of the computing engine ensures the integration in contrast-agent imaging with high fidelity. This is of future diagnostic ultrasound technologies to enhance achieved as linear InTune transmitters, cleaner power system performance and investment protection. supplies, low-noise amplifiers, and innovative signal processing all work together to make the contrast-agent imaging performance the best in the market. 20 siemens-healthineers.com/sequoia ACUSON Sequoia ultrasound system – Contrast-enhanced Ultrasound Imaging · White paper References 1. Data on file with Siemens Healthineers. 6. Wilson SR, Lyshchik A, Piscaglia F, Cosgrove D, Jang 2. Greis, Christian. (2004). Technology overview: H, Sirlin C, Dietrich C, Kim TK, Willmann JK, Kono Y. SonoVue (Bracco, Milan). European radiology. CEUS LI-RADS: algorithm, implementation, and key 14 Suppl 8. P11-5. 10.1007/s10406-004-0076-3. differences from CT / MRI. Abdominal Radiology. 2017. DOI: 10.1007/s00261-017-1250-0. 3. Blomley, Martin J K, Jennifer C. Cooke, Evan C. Unger, Mark J. Monaghan, David O. Cosgrove. 7. Wilson SR and Burns PN. An Algorithm for the “Microbubble contrast agents: a new era in diagnosis of Focal Liver Masses Using Microbubble ultrasound.” May 19, 2001. https://www.ncbi.nim. Contrast-Enhanced Pulse Inversion Sonography. nih.gov/pmc/articles/PMC1120332/. AJR:186 May 2006; 1401-1412 2. 4. Ezzati M et al. Worldwide trends in body-mass index, 8. Ham et al. 1994 Focal Liver Lesions: Characterization underweight, overweight, and obesity from 1975 to with Non-enhanced and Dynamic Contrast Material- 2016: a pooled analysis of 2416 population-based enhanced MR. Imaging Radiology 1994; 190:417- measurement studies in 128.9 million children, 423. adolescents, and adults. Lancet. 2017; 390:2627-42. 9. https://emedicine.medscape.com/article/368377- 5. Seidell JC. Obesity, insulin resistance and diabetes – overview a worldwide epidemic. British Journal of Nutrition n. 2000, 83(Suppl 1):S5-S8. siemens-healthineers.com/sequoia 21 Stand-alone clinical images may have been cropped At Siemens Healthineers, our purpose is to enable to better visualize pathology. The products/features healthcare providers to increase value by empowering mentioned in this document may not be commercially them on their journey towards expanding precision available in all countries. Due to regulatory reasons, medicine, transforming care delivery, and improving their future availability cannot be guaranteed. patient experience, all enabled by digitalizing healthcare. Please contact your local Siemens Healthineers An estimated 5 million patients globally everyday benefit organization for further details. from our innovative technologies and services in the areas of diagnostic and therapeutic imaging, laboratory ACUSON Sequoia, BioAcoustic, and InTune are diagnostics and molecular medicine, as well as digital trademarks of Siemens Medical Solutions USA, Inc. health and enterprise services. SonoVue and LUMASON are registered trademarks of We are a leading medical technology company with the Bracco Group. over 170 years of experience and 18,000 patents globally. With more than 48,000 dedicated colleagues in 75 countries, we will continue to innovate and shape the future of healthcare. Siemens Healthineers Headquarters Legal Manufacturer Siemens Healthcare GmbH Siemens Medical Solutions USA, Inc. Henkestr. 127 Ultrasound 91052 Erlangen, Germany 22010 S.E. 51st Street Phone: +49 9131 84-0 Issaquah, WA 98029, USA siemens-healthineers.com Phone: 1-888-826-9702 siemens-healthineers.com/ultrasound Published by Siemens Medical Solutions USA, Inc. · HOOD05162003114745 · 9282 0820 online © Siemens Medical Solutions USA, Inc., 2020