Diagnostic Review of Liver Fibrosis-USA

This tutorial includes a discussion of liver stiffness due to fibrosis and the resulting sonographic appearance

List the 2D-mode and Doppler characteristics of the normal liver, Describe Virtual Touch™ quantification (VTq), and Explain ultrasound detection of liver stiffness. Upon completion of this tutorial, the learner will be able to: Congratulations! You have completed the Diagnostic Review of Liver Fibrosis course. Listed below are the key presented points. Take time to review the material before you try the final quiz.   Click here to view, download, and print a copy of the Course Review.   In this tutorial, you have learned to: List the 2D-mode and Doppler characteristics of the normal liver Describe VTq Explain ultrasound detection of liver stiffness Siemens Healthineers would like to express our appreciation to Dr. Richard G. Barr M.D., PhD. for sharing his knowledge and providing a critical review of the tutorial content. The reproduction, transmission or distribution of this training or its contents is not permitted without express written authority. Offenders will be liable for damages.   All names and data of patients, parameters and configuration dependent designations are fictional and examples only.   All rights, including rights created by patent grant or registration of a utility model or design, are reserved.   Please note that the learning material is for training purposes only!   For the proper use of the software or hardware, please always use the Operator Manual or Instructions for Use (hereinafter collectively “Operator Manual”) issued by Siemens Healthineers. This material is to be used as training material only and shall by no means substitute the Operator Manual. Any material used in this training will not be updated on a regular basis and does not necessarily reflect the latest version of the software and hardware available at the time of the training.   The Operator Manual shall be used as your main reference, for relevant safety information like warnings and cautions. Note: Some functions shown in this material are optional and might not be part of your system. The information in this material contains general technical descriptions of specifications and options as well as standard and optional features that do not always have to be present in individual cases.   Certain products, product related claims or functionalities described in the material (hereinafter collectively “Functionality”) may not (yet) be commercially available in your country. Due to regulatory requirements, the future availability of said Functionalities in any specific country is not guaranteed. Please contact your local Siemens Healthineers sales representative for the most current information.   Copyright © Siemens Healthcare GmbH, 2019 The development of fibrosis is the liver’s reaction to disease1 which may develop into hepatocellular carcinoma (HCC), portal hypertension, and hepatic insufficiency.1, 2 The World Health Organization (WHO) reported in 2012 that 700,000 new cases of HCC arose making it the second most common cause of cancer globally.3 HCC has a grim survival rate with few patients making it beyond two years.4 Men have double the occurrence rate to women, possibly linked to the higher incidence of hepatitis and alcohol use.4 Up to a third of adults with chronic hepatitis infections develop either cirrhosis or HCC.5 Another known cause of liver cancer is the exposure to fungi or aflatoxins found in food crops such as corn, legumes, and nuts.4 To help you understand the changes occurring in the liver due to the fibrosis, this tutorial has images from multiple patients and imaging modalities.    Each patient presents with their own unique set of signs and symptoms. In this case, the clinical problem results in liver fibrosis. In-depth comparisons are beyond the scope of this tutorial: however, you will find the following information pertinent to imaging the chronically diseased liver. Each imaging modality gives clues to the puzzles that our patients present. One method, computed tomography (CT), uses multiple focused X-ray beams that rotate around the patient to create a data set. Another, magnetic resonance imaging (MRI or MR), uses a large magnet to align the magnetic poles of our cells, detecting the changes as they return to normal.  Learn More about CT and MRI Systems Learn more about CT and MRI systems.   The MRI (left photo) and CT (right photo) systems appear quite similar. Learn More about the CT Image Learn more about the CT image. This axial or transverse CT image of the abdomen demonstrates the normal liver (yellow), gallbladder (green), and the two kidneys lateral to the spine (asterisk). The inferior vena cava (IVC) (blue) and aorta (red) lie anterior to the spine and posterior to the pancreas (light gray). Learn More about the MRI Image Learn more about the MRI image. This coronal abdominal image shows the normal appearance of multiple organs on an MRI image. Double arrows – liver; Open arrow – IVC; Dots – colon; Asterisk – small bowel; Arrow heads – portal vein; Open square – stomach; Solid arrow – spleen; Heart – heart. Ultrasound imaging of the liver and adjacent abdominal organs is a common occurrence. Located in the right upper quadrant (RUQ) of the abdomen, the liver is the second largest organ of the body.6 This homogenous organ has veins, arteries, ducts, and fibrofatty tissue within the dense Glisson’s capsule.7, 8 The liver provides an acoustic window to image abdominal organs such as the gallbladder, right kidney, and pancreas.7 However, the liver itself easily images with ultrasound modalities such as 2D-mode, color and spectral Doppler.   The ultrasound exam requires the acquisition of a series of images on both the transverse and sagittal planes.  Vascular landmarks, such as the IVC, portal veins, or hepatic veins, give the location for specific images. The 2D-mode technique needs the proper setting of the time gain compensation (TGC) and the overall gain. The desired result is an image with a uniform brightness regardless of depth. The 2D-mode image must be optimized before obtaining images with other modes.   There are many optimization tools available for the 2D-mode. Click on the icons below to learn more about liver anatomy and two image processing methods that help the sonographer obtain the best 2D-mode image. Learn More about Liver Anatomy Learn more about liver anatomy. This image shows the homogeneous pattern of the normal right lobe of the liver. The anechoic vessels (asterisks) image as both long and round structures dependent on the imaging plane. The right kidney (open arrow) has a hypoechoic appearance when compared to the normal liver. The muscular diaphragm (double arrows) is a strong reflector appearing as an echogenic curved structure.   When complete, select the X in the upper-right corner to close the window and continue.  Learn More about Compound Imaging Learn more about compound imaging. Tab TitleTextCompound ImagingWe all know that the closer the angle of incidence is to 90 degrees the better our image. To keep this angle while imaging, we move the transducer and roll the patient. At times, no matter what we try, we cannot keep the organ of interest at this angle. Compound imaging solves this problem by steering the beam angle of the sound produced by the transducer.9 The returning information then undergoes averaging between the image frames.9   Frame                Frame                Frame 1                             2                               3 This is an example of three angle directions used to obtain a spatially compounded image. The first angle is to the right (frame 1), the second angle is at 90 degrees (frame 2), while the third angle is to the left (frame 3). The system then averages the frames without a loss of frame rate.9 These angle changes maintain the desired perpendicular angle of insonation to ensure optimal detail.The Image   This image has all the processing technology removed (i.e., Advanced SieClear™ spatial compounding, Dynamic TCE™ contrast enhancement technology, Tissue Harmonic Imaging).   This image shows the changes seen when activating Advanced SieClear compounding. This 2D optimization technique uses multiple frames to create the image.10 This allows detection of tissue differences10 resulting in a decrease in speckle and clutter (acoustic noise). The multiple angles result in an increase in boundary detail while structures or borders found within posterior shadowing become visible.9, 11 This all becomes possible due to the angle of incidence coming closer to the desired 90 degrees.11 Learn More about Tissue Harmonic Imaging Learn more about tissue harmonic imaging. Tab TitleTextTHITissue properties distort the transmitted sound resulting in the creation of harmonics. These tissue-generated waves are twice the transmitted frequency.  For example, the 2 MHz transmitted signal returns as not only the 2 MHz but also as a 4 MHz.9, 11 There are more harmonics but for this example we use only the first harmonic.  When the signal returns, the ultrasound system uses only the harmonics to create the image.     The original wave transmitted (left) into the body changes with tissue interaction.  The top of the waveform distorts moving forward (arrow) with the lower part traveling slower.9The Image This image of the liver has all the processing features deactivated.     This image shows the same liver anatomy with THI active. The send frequency is between 5 and 2  MHz (upper box) with a receive frequency of 4.4 MHz (lower box). This image has fewer artifacts due to the narrow beam width (i.e., grating lobe, reverberation).11 As a result, structures visualize better with harmonics increasing confidence in the reading clinician’s diagnosis.12 Doppler ultrasound applications allow for both qualitative and quantitative evaluation of the liver. Detailed descriptions of the mathematics and signal processing abound but in its most basic form, Doppler detects the speed of flow within vessels. When using Color Doppler Velocity (CDV) color hues overlay the 2D-mode image to stand for the speed and direction of flow. Color Doppler Energy (CDE) uses the amplitude of the signal within a vessel in either a directional or nondirectional format to create the overlay. Spectral Doppler provides a waveform of flow characteristics within a sample volume allowing for examination of flow changes within the vessel. The tracing usually displays with a static or real-time 2D reference image.9, 11 An extension of 2D-mode imaging, CDV is one method that allows us to show blood flow in and out of the liver. Using the Doppler shift, the ultrasound system converts blood movement to a color hue.9, 11 The 2D-mode image and the color display in real-time allowing adjustment of technical factors for each mode. Each color hue shows the mean velocity of flow within the region of interest (ROI).9 Learn More about CDV Learn more about CDV. This image shows the normal portal vein entering the liver and the transverse, round IVC. This vein measures 13 -16 millimeters increasing in size during deep inspiration and portal hypertension.13, 14 Flow away from the transducer has the color coding of blue while flow towards the transducer has the color coding red. The color bar, found to the right of the image, shows the upper and lower range of color velocities (31.3 cm/s). The horizontal black line between the color hues is the baseline showing the area without flow movement.9, 11 CDE overcomes some drawbacks of CDV imaging such as angle dependence, aliasing, and lack of flow detection due to slow flow in organs such as the breast or thyroid. CDE imaging is an overlay, just as with color velocity, however, the strength of the signal helps create the image rather than the velocity or direction of flow. The color hue assignment with CDE indicates the amount of energy rather than the velocity.11 The number of red blood cells (RBC), and attenuation from the tissue determines the intensity of the signal.9      Learn More about CDE Learn more about CDE. Tab TitleTextCDE Three hepatic veins join the IVC high in the liver.8, 13 This dual image shows a normal right hepatic vein with a nondirectional CDE image (left) next to a 2D-mode image (right).  The color overlay shows the amount or strength of flow within the ROI which occurs at the pixel level.15 This image does not show blood flow velocity, flow reversal, or pulsatility.9     When complete, select the X in the upper-right corner to close the window and continue. Directional CDE Hepatic veins enlarge and empty into the IVC helping the sonographer separate these veins from the portal vein.13 This CDE images uses a directional color Doppler map that looks quite like the CDV image. The system not only displays the amplitude of the signal but also the direction.9, 15 The color bar found on the right of the image lacks a velocity limit showing this is a CDE image.     When complete, select the X in the upper-right corner to close the window and continue. CDE with Clarify This dual image of the portal system entering the liver shows Clarify™ vascular enhancement (VE) technology on the left side with the addition of CDE on the right side. Clarify VE technology uses the raw data from the Doppler flow and the 2D-mode allowing enhancement of both image types.16 This technology decreases slice thickness artifacts, and reduces noise within vascular structures.16, 17 Thus, tissue characterization increases as well as contrast resolution and boundary detection.16, 17   When complete, select the X in the upper-right corner to close the window and continue. Drawbacks & BenefitsDrawbacks to CDE include:9, 11, 15 Artifacts due to motion No display of velocities Some maps do not have directional information Temporal resolution low Qualitative flow mapping Lacks flow characterization Benefits of CDE include:9, 11, 15 Small vessel flow visualization due to low pulse repetition frequency (PRF) Display independent of flow direction and velocity Decreased angle dependency Increased vessel lumen definition Frame averaging improves the signal-to-nose ratio Gives global perfusion information Eliminates aliasing When complete, select the X in the upper-right corner to close the window and continue.  The portal vein, hepatic veins, and hepatic artery are the main vessels interrogated with spectral Doppler to determine the presence or absence of disease in the liver.15 Each has a characteristic spectral Doppler appearance in the normal patient; however, liver and cardiac disease changes the velocity and pulsatility patterns.15 Learn More about Liver Doppler Learn More about liver Doppler. Tab TitleTextHepatic Veins This is an example of a normal hepatic vein spectral wave tracing with the characteristic ‘W’ pattern.13 The triphasic waveform is the result of normal cardiac activity and flow reversal into the liver.13, 15 The reference image uses directional CDE to help ensure correct placement of the sample volume.  The color hues show that flow away from the transducer have a blue hue while the flow towards the transducer have a red hue. The normal flow direction is from the hepatic vein into the inferior vena cava away from the liver (hepatofugal).18Portal Veins Transporting blood flow from the bowel and spleen, the portal vein enters the porta hepatis (red color flow) of the liver bringing flow into (hepatopetal) the liver.13 This image shows normal unidirectional flow above the baseline (towards the transducer)7, 13 with respiratory variations. The reference image (top half) shows both 2D-mode and CDV imaging.      This diagram shows two normal portal venous flow patterns. The direction and waveform shows the phasicity or the amount of change in the waveform. The top drawing illustrates flow direction in the normal portal veins is antegrade (up red arrow), or hepatopetal, which corresponds to a waveform above the baseline on a spectral Doppler tracing. Retrograde flow out of the liver via the portal venous system displays below the baseline (blue arrow; hepatofugal).  Normal phasicity may range from low (bottom left) to high (bottom right). Abnormally low phasicity results in a nonphasic waveform, while abnormally high phasicity results in a pulsatile waveform.  The pulsatility index or PI helps to quantify pulsatility. Normal phasicity results in a PI greater than 0.5. To calculate the PI, use the formula:   PI = Peak systolic – End diastolic / Mean velocity9, 11   Peak systolic – yellow arrow End Diastolic – down red arrow   Graphic used with permission from: Dean Alexander McNaughton; Monzer M. Abu-Yousef; Doppler US of the liver made simple. RadioGraphics 2011, 31, 161-188. DOI: 10.1148/rg.311105093 © RSNA, 2011.Hepatic Artery   The proper hepatic artery follows the portal vein into the liver at the porta hepatis.13 The hepatic artery has a low resistance pattern with continuous diastolic flow traveling into the liver (hepatopetal).7, 13, 19 The reference image (top half) shows both the 2D-mode and CDE imaging using a blue flow map.   High resistance artery (normal)                 Low resistance artery (normal)   Schematics illustrate that a high-resistance artery (left) allows less blood flow during end diastole (the trough is lower) than does a low-resistance artery (right). Calculating the RI gives a quantitative measure of resistance in a vessel. High-resistance arteries normally have RIs over 0.7, while low-resistance arteries have RIs ranging from 0.55 to 0.7. The hepatic artery is a low-resistance artery. Yellow line – peak systolic; Red line – end diastolic; White line – Peak systolic – End diastolic   Resitive Index (RI) = Peak systolic – End diastolic                                             Peak systolic   Published in: Dean Alexander McNaughton; Monzer M. Abu-Yousef; Doppler US of the liver made simple. RadioGraphics 2011, 31, 161-188. DOI: 10.1148/rg.311105093 © RSNA, 2011.   The severity of liver fibrosis has little correlation to changes in the hepatic artery flow.19, 20 A high-resistance flow pattern occurs with compression of the microvascular system in the liver; however, age, nonfasting, and hepatic vein obstruction influence the resistive index in the hepatic artery.20, 21  When liver fibrosis develops into HCC, clinicians often use percutaneous ablation to treat focal masses. This requires mentally locating the treatment areas from static imaging modalities such as CT or MRI. A challenging prospect when using yet another modality, real-time ultrasound, to image the liver in surgery! Add the changes in liver position, patient respiration, and sonographic window limitations, it is easy to see the difficulty in finding the desired location.    Fusion imaging, the simultaneous use of two imaging modalities, addresses this problem. Using an electromagnetic field created by a magnetic field generator, position sensors, and a position sensor unit, results in tracking of the transducer. The system then uses this data to calculate the transducer position in relation to the imported CT or MRI image.22, 23   Learn More about eSieFusion imaging Learn more about eSieFusion imaging. Tab TitleTextVideoClick below view a video explaining eSieFusion imaging ACUSON S3000™ Ultrasound System, HELX™ Evolution with Touch Control.  Quick CardClick below to open and download a copy of the eSieFusion Imaging Quick Card for the ACUSON S3000™ Ultrasound System, HELX™ Evolution with Touch Control.   Image This example of eSieFusion imaging shows a side-by-side display with the CT on the left and a CDV of the same area (right). VTq gives a numerical value of shear wave speed related to tissue stiffness at a precise anatomic location. Acoustic radiation force impulse imaging (ARFI) creates an acoustic push pulse between 1 and 10 milliseconds, occurring within the fixed-size ROI.24, 25 These sequential push pulses begin the tissue generation of shear waves lateral to the push pulse.24, 26 When the detection pulses interact with a shear wave, they reveal the wave’s location at a specific time, allowing for calculation of the shear wave speed.25 Tissue with higher elasticity displaces more than one with lower elasticity resulting in a higher shear wave velocity.24   Important! Shear Wave Speed (Vs) and Elasticity (E) values may vary among manufacturers! Learn More about VTq Learn more about VTq. Tab TitleTextInvalid Velocity The adjacent image displays a failed measurement resulting from an invalid shear wave velocity.24    Reasons for an invalid measurement include: Removal of the transducer during acquisition sequence. Individual velocity estimates between tracking varies resulting in an unreliable measurement. Close proximity to the liver capsule. Rib shadowing. Sampling non-perpendicular to the liver capsule. Inclusion of vessels in the sample area. Presence of ascites. Excessive tissue motion, such as cardiac pulsations in the tissue, disrupt the shear wave velocity. High attenuation of the signal in large patients makes it difficult for the system to show the shear wave peak consistently during propagation. Very high stiffness of the tissue that causes the shear wave velocity estimate to become difficult (velocity out of range), lowering the confidence interval. Site Sampling This is a section of the system report showing measurements taken at four different sites. The current report displays velocity (Vs) in the first column; however, you can set the report for kilopascals (kPa). The second column shows the depth of the ROI within the liver. The best depth for sampling is with the ROI placed 2 to 3-centimeters deep to the liver capsule which shows as a 3 to 6-centimeter depth on the report.2, 10, 27 Take the samples within liver segments 5 or 8 whenever possible.   Important!  Obtain 10 measurements in the same location for each site.10 Note: The Elasticity measurements (E; kPa) are only available with Virtual Touch IQ active.   Note:  To set the displayed shear wave measurement check your User Manual for availability and setup procedures.The Numbers The report page displays quantitative values to help find the reliability of your samples. This is an example of data from ten velocity samples at one site. The report displays the same data for all your velocity measurements. The median is the middle of all your measurements while the mean is the average.   The standard deviation is how different are your measurements from each other. The smaller the number value shows similarities in your sample velocities.   IQR (interquartile range) gives an assessment of the data quality1 or the variability between elastography measurements.2 The smaller the number shows less variability between your samples.   An IQR/Median shear wave ratio less than 0.3 shows a reliable liver assessment with VTq.1 2, 28  A higher ratio shows significant variability in the shear wave velocity measurements, decreasing the reliability of measurement results.10The Sequence The full sequence, focused push pulse transmission, shear wave production, and tracking occurs within the green ROI. On this image, orange waves represent the longitudinal push pulse, blue waves represent the transverse shear waves, and the yellow waves the detection pulses.26 The numerical values, found in the upper left of the image, relate to the stiffness of the liver tissue found within the ROI. The stiffer the tissue, the greater the shear wave speed. Thus, the speeds, expressed in velocity per second (Vs) or elasticity (E) directly relate to the tissue composition allowing for reproducible values.   Important! During the push pulse, shear wave, detection cycle the image freezes. Keep the transducer stationary until the system displays shear wave velocities Sonographers and clinicians often describe the liver in terms of right and left lobes using the main portal fissure as the dividing point.8 This designation includes the quadrate and caudate lobes which lie between the anatomic left and right lobe. The right lower thorax and diaphragm protect the right lobe while the left lobe of the liver often extends across the midline. A mobile organ, the liver moves superior and inferior with respiration and medial with the body in the left lateral decubitus (LLD) position.8 To review the liver location in reference to the surrounding organs, please refer to the MRI images in the Complementary Imaging section. In addition to the anatomic designation of the right and left liver, surgeons use a method based on the vascularity within the liver. A French physician, C. Couinaud, developed a method to identify liver segments in the late 1960’s. Now referred to as Couinaud’s anatomy, the liver divisions start in the posterior caudate lobe with segments numbered in a clockwise fashion.8, 18 Each segment has a portal vein branch, hepatic artery, and bile duct.18, 21 The hepatic veins designate the vertical boundaries while the right and left portal vein provide the horizontal division.7, 18, 21 These segments become important during surgery and when showing pathology locations with sonography. Keep in mind when imaging the liver that patient segmental anatomy varies.8 Learn More about Liver Segments Learn more about liver segments. Tab TitleTextUpper Segments This transverse image of two of the three hepatic veins shows segments IVA, VII, and VIII. The right hepatic vein (asterisk) courses between the right intersegmental fissure dividing the anterior and posterior portions of the right lobe. The main hepatic vein (dot) courses through the main lobar fissure dividing the right and left portions of the liver. The left hepatic vein (not shown) travels through the left intersegmental fissure dividing the medial and lateral segments of the left lobe at the cephalic aspect.21Lower Segments This transverse image of the liver, taken at the level of the liver hilum shows segments III, IVB, V, and VI. The proper portal vein (dot) divides into the right and left portal vein. The anterior branch of the right portal vein, lies in the intrasegmental, anterior part of the right lobe coursing in the central anterior segment. The posterior branch of the right portal vein lies in the intrasegmental, posterior part of the right lobe coursing in the central posterior segment. The horizontal segment of the left portal vein lies anterior to the caudate lobe separating this lobe from the medial part of the left lobe.21 IVC – asterisk.Segment III   This midsagittal image of the left lobe of a normal liver shows VTq sampling of the inferior, lateral segment (III).   Note:  The velocity measurement display has been moved and enlarged for easier viewing.  Segment IV   This transverse image of a normal liver demonstrates VTq sampling of the medial part of the posterior right lobe (segment VI). Right kidney – arrow; IVC – dot; Gallbladder - asterisk.   Note:  The velocity measurement display has been moved and enlarged for easier viewing. Segment IVA This oblique image of the liver showing VTq sampling of a normal IVA segment. IVC – dot; Gallbladder – asterisk; Arrow – left hepatic vein.   Note:  The velocity measurement display has been moved and enlarged for easier viewing.  Liver Segments   Segment I – Caudate lobe Segment II – Superior lateral left lobe Segment III – Inferior lateral left lobe Segment IVA – Superior medial left lobe Segment IVB – Inferior medial left lobe Segment V – Inferior anterior right lobe Segment VI – Inferior posterior right lobe Segment VII - Superior posterior right lobe Segment VIII – Superior anterior right lobe Direct or indirect injury to the liver results in the formation of fibrous tissue8 due to the cycle of cell death, fibrosis creation, and regeneration.7 The WHO data shows that the most common cause of death, liver cirrhosis (the late stage of scarring or fibrosis), is due to low childhood weight followed by viral hepatitis and alcohol consumption.29   The process begins with liver cell death, continuing with parenchymal degeneration, and finally regeneration.14, 30 Cirrhosis, the end stage of liver disease, results in bridging fibrosis or scarring between lobules.8 Nodules occur when the liver attempts to regenerate resulting in disruption of the liver tissue. This permanent liver damage results in a characteristic imaging appearance.               Normal Liver  Liver with Cirrhosis This diagram shows nodules that form with the development of liver cirrhosis. The liver progresses through stages of fibrosis regardless of cause (i.e., hepatitis, alcoholism) resulting in nodular cirrhosis or HCC.2 2D-mode imaging may or may not show liver changes in the first stages of liver scarring. In the acute phase, the liver may enlarge21 with echogenic vessel walls due to bridging fibrosis;30 however, the chronically diseased liver decreases in size.21 Learn More about the Liver Capsule Learn more about the liver capsule. Tab TitleTextNormal Capsule This image shows the smooth capsule (double arrows) seen with a normal liver. The use of a higher frequency transducer aids in imaging the liver capsule and thus the presence of surface nodularity.  Nodular Capsule This sagittal image shows abdominal ascites (asterisk) which helps visualize the nodular liver surface (double arrows). Caution must be taken when using the 2D-mode appearance of the liver as a gauge for fibrosis as incorrect system settings may result in a course echo texture.21 Both the liver size and echo texture are subjective gauges of liver damage which can vary between examiners.7, 21 However, identification of a nodular liver surface corresponds to regeneration nodules and the formation of fibrosis.21 In the patient with ascites, these surface nodules image easily.  Other specific findings with late stage cirrhosis include not only a small liver and surface nodularity but also loss of internal liver vascular, splenomegaly, portal hypertension, and increased liver stiffness.7    The Doppler exam, whether CDV or a spectral tracing, is an essential part of the liver examination in patients with fibrosis. Three vessels directly related to liver are the portal vein, hepatic vein, and the hepatic artery. The venous spectral waveform helps in qualifying the increases in microvascular compression as cirrhosis develops. Phasicity reflects the physiologic pressure changes created by the heart20 and, as fibrosis develops, the extent of liver malfunction. Learn More about Liver Flow Learn more about liver flow. Tab TitleTextNormal Flow The laminar flow pattern seen in the normal vessel is the result of friction at the wall / blood interface. The flow closer to the vessel wall moves slower than that seen in the central part creating a parabolic flow pattern.9 The body maintains a constant blood volume thus, in the absence of disease, vessels into and out of the liver have the same flow volume.31Vessel Narrowing Fibrosis in the liver results in the squeezing of a vessel30 and a dampening of the normal flow patterns.31 Think of a stream that flows faster as it narrows. The change in the stream width does not change the volume of water, thus, the flow speed increases. The same process describes vessel narrowing in the liver due to fibrosis. In the presence of severe liver fibrosis, the vessels become increasingly narrower effectively damming flow into and out of the liver.13, 31 The vessels spectral Doppler signal begins to lack variation, eventually stopping.13Hepatic Veins It is important to understand how to determine flow direction. As liver fibrosis progresses venous flow changes in both waveform patterns and direction.  The liver vasculature becomes so narrowed, the portal flow into the liver (hepatopetal) reverses (hepatofugal).7, 21 Determining the flow direction is as simple as comparing the spectral tracing to the color velocity bar, found in the upper right of this image.  Flow towards the transducer and above the baseline (orange arrow) has a color hue from red to yellow.9, 11 Flow away has a blue to green hue (turquoise arrow) displaying below the spectral baseline.9, 11 To interpret this image, we see the hepatic vein coded blue flows away from the transducer towards the IVC and heart. Hepatic veins have a complex flow pattern influenced by right atrial function20, 21 and IVC status (i.e., the presence of thrombus, coarctation).20 A normal hepatic vein spectral tracing ranges from biphasic to tetraphasic.20 Hepatic vein waveforms may show a velocity increase with a decrease in portal vein flow in the presence of fibrosis.14   These diagrams illustrate varying degrees of severity of decreased phasicity in the hepatic vein. Farrant and Meire32 first described this qualitative scale for describing abnormally decreased phasicity in the hepatic veins, a finding that is seen with cirrhosis. The key to understanding this scale lies in seeing the position of the a wave relative to the baseline and peak negative S wave excursion. As the distance between the a wave and peak negative excursion decreases, phasicity becomes severely decreased. a – atrial contraction; S – systole; D – diastole; v – tricuspid valve opening; White line – baseline; Lower dotted line – peak negative excursion; Upper dotted line – half-way; Spectral window – yellow arrows.  Published in: Dean Alexander McNaughton; Monzer M. Abu-Yousef; Doppler US of the liver made simple. RadioGraphics 2011, 31, 161-188. DOI: 10.1148/rg.311105093 © RSNA, 2011.Portal VeinLiver fibrosis directly changes the portal vein flow in the first stages. However, as fibrotic tissue increases, flow begins to change direction from into the liver (normal, hepatopetal) to back and forth, with reversed (abnormal, hepatofugal) flow.7, 20 The presence of reversed portal vein flow prompts a search for collaterals such as a recanalized peraumbilical vein,7, 14 and the coronary vein.14 Eventually, flow may even cease.20     This spectral Doppler image shows a pulsatile waveform with flow reversal in the right portal vein. Flow patterns describing flow include predominantly antegrade, pulsatile, biphasic-bidirectional, and di-inflectional.    This spectral Doppler image shows retrograde (hepatofugal) flow in the main portal vein, a finding that appears blue on the color Doppler reference image displaying below the baseline on the spectral waveform. Hepatofugal flow is due to severe portal hypertension from any cause.   Published in: Dean Alexander McNaughton; Monzer M. Abu-Yousef; Doppler US of the liver made simple. RadioGraphics 2011, 31, 161-188. DOI: 10.1148/rg.311105093 © RSNA, 2011.Phasicity Types of Waveforms Pulsatile / High fluctuation Phasic / Low fluctuation Nonphasic / No fluctuation Aphasic / No flow The terms describing the degree of spectral Doppler phasicity include the velocity and acceleration features of the waveform. Note that pulsatile, phasic, and nonphasic flow waveforms all have phasicity (fluctuation). Exaggerated pulsatile flow, a normal finding in arteries, also occurs in diseased veins. Nonphasic flow does in fact have a phase; however, the phase has no velocity variation (nonphasic could be thought of as meaning “nonvariation”). The term aphasic means “without phase,” which is the absence of flow.   Published in: Dean Alexander McNaughton; Monzer M. Abu-Yousef; Doppler US of the liver made simple. RadioGraphics 2011, 31, 161-188. DOI: 10.1148/rg.311105093 © RSNA, 2011. Hepatic fibrosis occurs secondary to chronic liver damage resulting in an increase in liver stiffness. VTq elastography helps measure liver stiffness using mechanical stress. We learned earlier that shear waves occur when using a longitudinal push pulse allowing measurement of the transverse, tissue-created shear waves. The speed of the shear waves increases with the increase in fibrosis and displays as Vs or kPa.     Learn More about Liver Stiffness Learn more about liver stiffness. Tab TitleTextMeasuring Stiffness   Many research studies report tissue fibrosis levels in kPa making a direct comparison difficult when the system displays velocity measurements. To convert to kPa, simply place the Vs value into the following formula:33   kPa = 3Vs2        = 3(2.38)2        = 3(5.66)        = 16.9   Important! This formula assumes a tissue density of 1.   This image of a cirrhotic liver shows surface nodular changes and ascites. The Vs of 3.03 converts to 27.5 kPa indicating a stiff, fibrotic liver.   Note:  The velocity measurement displays have been enlarged for easier viewing. Alcoholic LiverAge: 65-year-old female   Ultrasound imaging findings:      The placement of the VTq ROI is approximately 2.5 centimeters deep to the liver capsule. The depth samples range from 3.0 to 4.5 for an average depth of 3.7 for the six samples. The low standard deviation (Std Dev), IQR, and IQR/Median values show the series of VTq samples has low variability and thus high reliability.1, 2, 28 The high velocity and elasticity values indicate a stiff liver.2   Note:  The velocity measurement displays have been enlarged for easier viewing. Explore the links below for the Glossary, References, and Further Reading opportunities. Glossary Glossary 2D-mode imaging (i.e., brightness mode, grayscale, B-mode) – Ultrasound display of the amplitude of echoes returning from the body.  The higher the amplitude, the brighter the display.   Acoustic radiation force impulse imaging (ARFI) – This Siemens technology uses a track, push pulse, and detect sequence to create a qualitative elastogram.   Color Doppler Energy (CDE) – Color overlay displaying amplitude of the Doppler signal.   Color Doppler Velocity (CDV) – Color overlay displaying velocity of the Doppler signal.   Elasticity – Ability of a structure to return to its original shape after compression.   Elastogram – The image demonstrating the conversion of tissue strain.   Elastography – An imaging method to map the elastic properties of tissue (i.e., stiff vs. soft) to provide information on changes due to disease.   Hepatofugal – Flow away from the liver.   Hepatopetal – Flow towards the liver.   Interquartile range (IQR) – The distance between the 75th percentile and the 25th percentile for all measurements with an assigned label.   IQR/Median Ratio – Unitless method to find the variability between measurements. Longitudinal wave (i.e., compression wave) – A sound wave from the transducer into the tissue and vice versa.   Mean – The mid-point of a group of measurements.  Median – The average of a group of measurements.   Point shear wave elastography (pSWE) – ARFI generation of shear wave within a fixed ROI that gives an average velocity measurement in m/s or kPa.   Quality Factor (QF) – Measure of movement on an elastogram between image frames.   Region of interest (ROI) – Defined area showing the sample area for obtaining shear wave data.  The user selects ROI depth and location but cannot change the size.   Shear wave – Wave produced perpendicular to the transmit pulse.   Spectral Doppler – Graphic display of Doppler velocities within a sample volume.   Standard Deviation (Std Dev) – Calculation for all measurements associated with the assigned label.   Stiffness – Tissue deformation in response to force (i.e., compression, acoustic radiation force).   Tissue Harmonic Imaging (THI) – Waveforms produced by the tissue that are half the transmitted frequency.   Virtual Touch™ Quantification (VTq) – Pinpoint measurement (m/s and kPa) of shear wave velocity to obtain a qualitative measurement of tissue stiffness using a fixed size ROI.  There is no elasticity image associated with this type of tissue stiffness measurement. References / Further Reading References / Further Reading 1. Barr, R.G., Ferraioli, G., Palmeri, M.L., Goodman, Z.D., Garcia-Tsao, G., Rubin, J., . . . Levine, D. (2015). Elastography assessment of liver fibrosis: Society of Radiologists in ultrasound consensus conference statement. Radiology. 276(3): 845-861.   2. Ferraioli, G., Filice, C., Castera, L., Choi, B.I., Sporea, L., Wilson, S.R., . . . Kudo, M. (2015). WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3: Liver. Ultrasound in Medicine & Biology. 41(5): 1161-1179.   3. WHO. (2012). Liver cancer: Estimated incidence, mortality and prevalence worldwide in 2012. GLOBCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012; Available from:   4. Theise, N.D. (2014). Liver cancer. In Stewart, B.W. and Wild, C.P., (Eds.), World Cancer Report 2014 (pp. 403-412). Geneva: World Health Organization International Agency for Research on Cancer.   5. WHO. (2016). Hepatitis B. Available from:   6. Claudon, M., Tranquart, F., Evans, D.H., Lefèvre, F., and Correas, M. (2002). Advances in ultrasound. European Radiology. 12(1): 7-18.   7. Grube, J.A. (2012). The liver. In Kawamura, D.M. and Lunsford, B.M., (Eds.), Diagnostic medical sonography: Abdomen and superficial structures (pp. 101-164). Philadelphia: Wolters Kluwer Health | Lippincott Williams & Wilkins.   8. Moore, K.L., Dalley, A.F., and Agur, A.M.R. (2010). Abdomen. In Moore, K.L., Dalley, A.F., and Agur, A.M.R., (Eds.), Clinically Oriented Anatomy (pp. 181-325). 6th  ed, Philadelphia: Wolters Kluwer Health | Lippincott Williams & Wilkins.   9. Hedrick, W. (2013). Technology for diagnostic sonography. St. Louis, MO: Elsevier.   10. Siemens. (2016). ACUSON S1000TM S2000TM S3000TM diagnostic ultrasound system instructions for use, Siemens Medical Solutions USA, Inc: Mountain View, CA.   11. Kremkau, F.W. (2016). Sonography: Principles and Instruments. 9th ed., St. Louis: Elsevier.   12. Choudhry, S., Gorman, B., Charboneau, J.W., Tradup, D.J., Beck, R.J., Kofler, J.M., and Groth, D.S. (2000). Comparison of Tissue Harmonic Imaging with conventional US in abdominal disease. RadioGraphics. 20(4): 1127-1135.   13. Pellerito, J.S. (2012). Anatomy and normal Doppler signatures of abdominal vessles. In Pellerito, J.S. and Polak, J.F., (Eds.), Introduction to vascular ultrasonongraphy (pp. 439-449). 6th ed, Philadelphia: Elsevier Saunders.   14. Middleton, W.D. and Robinson, K.A. (2012). Ultrasound assessment of the hepatic vasculature. In Pellerito, J.S. and Polak, J.F., (Eds.), Introduction to Vascular Ultrasonography (pp. 495-516). 6th ed, Philadelphia: Elsevier Sanders.   15. Pozniak, M.A. (2006). Doppler ultrasound of the liver. In Allen, P.L., Dubbins, P.A., Pozniak, M.A., et al., (Eds.), Clinical Doppler Ultrasound (pp. 141-184). 3rd ed, Philadelphia: Churchill Livingstone Elsevier.   16. Liu, X., Duan, Y., Wang, J., Sun, S.G., Li, J., Hou, W., and Cao, T. (2009). In vitro model test and preliminary clinical application of a new method of ultrasonographic imaging: Vascular Enhancement Technology. Ultrasound in Medicine & Biology. 35(9): 1502-1509.   17. Wang, Y., Chen, J., Liu, X., Wang, J., Li, L.H., Deng, J., and Duan, Y. (2013). Evaluation of the combined application of ultrasound imaging techniques for middle cerebral artery stent surveillance and follow-up study. PLoS ONE. 8(11): e79410.   18. Chami, L., Chebil, M., Clevert, D., Lassau, N., E, L., Low, G., . . . Xu, H. (2013). Liver. In Weskott, H., (Eds.), Contrast-enhanced ultrasound (pp. 49-120). 2nd ed, Bremen: Uni-Med.   19. Iranpour, P., Lall, C., Houshyar, R., Helmy, M., Yang, A., Choi, J., . . . Goodwin, S.C. (2016). Altered Doppler flow patterns in cirrhosis patients: an overview. Ultrasonography. 35(1): 3-12.   20. McNaughton, D.A. and Abu-Yousef, M.M. (2011). Doppler US of the liver made simple. RadioGraphics. 31(1): 161-188.   21. Wilson, S.R. and Withers, C.E. (2011). The liver. In Rumack, C.M., Wilson, S.R., Charboneau, J.W., et al., (Eds.), Diagnostic Ultrasound (pp. 78-145). 4th ed, Philadelphia: Elsevier Mosby.   22. Lee, M. (2014). Fusion imaging of real-time ultrasonography with CT or MRI for hepatic intervention. Ultrasonography. 33(4): 227-239.   23. Kang, T. and Rhim, H. (2015). Recent advances in tumor ablation for hepatocellular carcinoma. Liver Cancer. 4(3): 176-187.   24. Jaffer, O.S., Lung, P.F.C., Bosanac, D., Patel, V.M., Ryan, S.M., Heneghan, M.A., . . . Sidhu, P.S. (2012). Acoustic radiation force impulse quantification: repeatability of measurements in selected liver segments and influence of age, body mass index and liver capsule-to-box distance. The British Journal of Radiology. 85(1018): e858-e863.   25. Shiina, T., Nightingale, K.R., Palmeri, M.L., Hall, T.J., Bamber, J.C., Barr, R.G., . . . Kudo, M. (2015). WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 1: Basic principles and terminology. Ultrasound in Medicine and Biology. 41(5): 1126-1147.   26. Benson, J. and Fan, L. (2014). Understanding ARFI and new elastography quantification technologies, in Siemens Medical Solutions, USA, Inc: Mountain View, California.   27. Cosgrove, D., Piscaglia, F., Bamber, J., Bojunga, J., Correas, J.M., Gilja, O.H., . . . Dietrich, C.F. (2013). EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 2: Clinical applications. Ultraschall in Med. 34(03): 238-253.   28. Yoo, H., Lee, J., Yoon, J.H., Lee, D.H., Chang, W., and Han, J.K. (2016). Prospective comparison of liver stiffness measurements between two point shear wave elastography methods: Virtual Touch Quantification and Elastography Point Quantification. Korean Journal of Radiology. 17(5): 750-757.   29. WHO. (2017). Age-standardized death rates of liver cirrhosis. Available from:   30. Crawford, J.M., The liver and biliary tract. In Kumar, V., Cotran, R.S., and Robbins, S.L., (Eds.), Basic Pathology (pp. 516-555). 6th ed, W.B. Saunders Company: Philadelphia.   31. Hoskins, W., McDicken, N., and Allen, P.L. (2006). Haemodynamics and blood flow. In Allan, P., Dubbins, P.A., Pozniak, M.A., et al., (Eds.), Clinical Doppler Ultrasound  (pp. 27-40). 3rd ed, Philadelphia: Churchill Livingstone Elsevier.   32. Desser, T.S., Sze, D.Y., and Jeffrey, R.B. (2003). Imaging and Intervention in the Hepatic Veins. American Journal of Roentgenology. 180(6): 1583-1591.   33. Barr, R.G. (2015). Breast elastography. New York: Thieme.

  • Diagnostic Review of liver Fibrosis