Best Practices for Detecting Liver Fibrosis with ARFI

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White paper Best Practices for Detecting Liver Fibrosis with ARFI The application of the ultrasound-based technique at The Royal Melbourne Hospital Professor Robert N Gibson Professorial Fellow, University of Melbourne Department of Radiology Royal Melbourne Hospital, Victoria, Australia SIEMENS Healthineers White paper · Best practices for detecting liver fibrosis with ARFI Overview A number of pathological staging systems for liver fibrosis are used but the most common one is the Acoustic Radiation Force Impulse imaging (ARFI) is an METAVIR system, which has the following stages: ultrasound-based quantitative elastography technology that has its major clinical application in the noninvasive F0 = no fibrosis assessment of liver fibrosis. A shear wave elastography F1 = mild fibrosis tool, it relies on the principle that with increasing liver fibrosis there is increasing liver stiffness and decreasing F2 = significant fibrosis liver elasticity. Liver fibrosis is a key marker of the F3 = severe fibrosis severity of liver disease. The detection of liver fibrosis and estimation of severity is fundamental in managing F4 = cirrhosis chronic liver disease with implications for treatment If the causative insult that results in liver fibrosis is not choices, prognosis, and the need for surveillance for removed, there is a tendency for fibrosis to progress from complications of cirrhosis, including hepatocellular lower stages to higher stages. Once F4 is reached, there carcinoma. is the risk of complications that accompany cirrhosis, including liver failure, hepatocellular carcinoma, and portal hypertension. How ARFI Works To assess liver stiffness, ARFI uses brief high-energy ARFI at The Royal Melbourne Hospital ultrasound “push pulses” to excite a narrow region within the liver parenchyma. This excitation results in minute The Department of Radiology at The Royal Melbourne displacements of tissue, resulting in shear waves that has used liver ARFI in routine clinical practice since move laterally away from the line of the push pulse. August 2012, with more than 1,200 patients studied. These shear waves can be tracked by lower energy To obtain liver ARFI measurements, The Royal Melbourne ultrasound beams to allow measurement of their speed. uses these parameters: The shear wave velocity is measured within a small • region of interest and is expressed in meters per second Patient preparation – Patient fasts for at least 4 hours. and/or kilopascals (kPa). • Patient positioning – Supine or, if needed, right side Shear wave velocity increases with liver stiffness and slightly raised. decreasing elasticity. Since the primary determinant (although not the only determinant) of both properties is the degree of fibrosis, an estimate of stage of liver Key Principles for Measurement fibrosis can be made. ARFI measurements are obtained after performing a liver scan, which usually takes the form of targeted liver ultrasound (TUSL)1. As a routine, the measurements are obtained from the right lobe of the liver via an intercostal approach with the probe in the coronal or oblique coronal plane to allow for a good intercostal window. 2 Best practices for detecting liver fibrosis with ARFI · White paper 5C1 Sequoia Abdomen TIB:1.19 TIC:2.97 1 Liver Site 1 TIS: 1.19 E=3.2 kPa MI:1.39 Vs=1.04 m/s 22fps Depth=5.00 cm 98% 2D H Mid 0dB/DR60 PSWE 13cm Cooling 0 Liver Site 1: 5 Valid/5 Total Figure 1: ARFI sample obtained from right lobe of liver where there is a good acoustic window. The ROI is placed 2–4 cm deep to the liver capsule, away from visible portal tracts and veins. The US line of sampling is approximately at right angles to the liver surface in the plane of scanning as well as in the orthogonal plane, which is recognizable by the strong specular reflection (arrow). The measured shear wave speed is displayed on the right. The total number of valid readings is displayed at the bottom of the image. (In this example “5 Valid / 5 Total.”) The key principles in acquiring ARFI measurements • Avoid relative movement between the probe and ROI. are: • The probe must be kept still and measurements • Select a good acoustic window with no shadowing. should only be taken when there is no liver motion. (If motion does occur at the time of pushing the • Place the ROI perpendicular and approximately 2–4 cm deep to the liver capsule. sample button, then this measurement should not be recorded.) • Select an area of liver that is free of major veins and • portal tracks and appears homogenous and free of Obtain one reading per suspended respiration focalpathology. The precise segment (i.e., 5–8) does (attempting to take more than one reading tends not appear to be as important as achieving a good to result in respiratory motion or a part Valsalva). window. • Have the sampling US line cross the liver capsule approximately at right angles in the scanning plane • Use light pressure only when scanning. Firm pressure may artificially elevate the observed shear wave speed (Figure 1). measurement. • The scanning plane should be approximately at right Take measurements during suspended respiration in angles to the liver surface in the orthogonal plane. • a way that provides a good window. Avoid prolonged The latter is achieved by choosing a scanning plane inspiration, expiration, and Valsalva. that generates a specular reflection from the liver capsule (Figure 1). 3 White paper · Best practices for detecting liver fibrosis with ARFI Point Shear Wave Elastography (pSWE) Report of the Liver Liver Shear Velocity (pSWE) Liver Site 1 Vs Depth m/s cm 1.05 4.97 (X 1.04 4.97 ( N 3 1.08 4.99 4 0.97 4.99 5 1.07 4.99 6 1.12 4.99 X 7 1.01 4.99 8 1.06 4.99 9 1.06 4.99 10 1.10 4.99 x Mean 1.06 m/s Std Dev 0.04 m/s Median 1.06 m/s IQR 0.04 m/s IQR/Median 0.04 Overall Statistics Mean 1.06 m/s Std Dev 0.04 m/s Median 1.06 m/s IQR 0.04 m/s IQR/Median 0.04 Figure 2: The 10 valid samples are displayed with depth from skin of each measurement, and summary information derived from the 10 measurements namely mean speed, standard deviation, median speed, interquartile range (IQR), and IQR/Median. Valid Measurements and If there is reason to suspect a macroscopic variation Sampling Volumes in the degree of fibrosis (for example, as can occur in primary sclerosing cholangitis), then it may Routinely 10 valid ARFI measurements are taken from be informative to sample from a wider area of liver. a relatively small area in the right lobe, which meets This, however, is not performed routinely. the key measurement criteria. The measurements can If invalid measurements are obtained, which occur, be separated by a few centimeters provided that these for example, because of poor signal, movement, or criteria are met. (See the 10 valid samples as shown in placement of the ROI over a large vessel, this is signified Figure 2.) by “X.XX m/s” (See Figure 3). These can be saved but The value used for reporting is the median speed. even if not saved, the tally of valid measurements is The interquartile range (IQR) is included in the report shown at the bottom of each attempted measurement as a measure of the dispersion on shear wave velocity (Figures 1 and 3). Additional measurements would measurements around the median, which helps need to be obtained to achieve the necessary 10 valid describe the reliability of the measurement. measurements. 4 Best practices for detecting liver fibrosis with ARFI · White paper 5C1 Sequoia Abdomen TIB:1.22 TIC:3.19 1 Liver Site 1 TIS:1.22 Vs=X.XX m/s MI:1.39 E=XX.X kPa 22fps Depth=5.20 cm 98% 2D H Mid -1dB/DR60 LD 2 UA 2 MapC/T5 P2 PSWE 13cm Liver Site 1: 1 Valid/2 Total Figure 3: ARFI sample obtained that falls outside of measurable range and is recorded as “X.XX m/s” and “XX.X kPa”. The tally of measurements at the bottom of the image reflects this as “1 Valid/2 Total”. Assigning Fibrosis Stage Based on Formatting the Report ARFI Readings Since the study is one part of the liver ultrasound The threshold values used to assign patients into F0, examination, the imaging findings and, where F1, F2, F3, and F4 vary slightly between organizations. appropriate, Doppler findings are first reported. They may also vary slightly depending on the cause The ARFI findings follow including the median of liver disease. The threshold values used in the speed and the IQR. Department of Radiology at The Royal Melbourne It is important to recognize that the thresholds between Hospital are those derived from the large meta-analysis fibrosis grades are not absolute and also that factors of Friedrich-Rust et al2, which used liver biopsy as a other than fibrosis may impact ARFI measurements. reference in a large cohort comprising mainly patients A footnote in the report is useful to draw this to the with hepatitis C-related disease (Figure 4). attention of those reading the report; Figure 4 is also a useful inclusion in the report. Acute inflammatory activity, in particular, tends to elevate the ARFI values and therefore artificially elevate the fibrosis stage. 5 White paper · Best practices for detecting liver fibrosis with ARFI Absent or mild fibrosis Significant fibrosis Severe fibrosis Cirrhosis 1.35 1.55 1.80 after Friedrich-Rust et al J. Viral Hepatitis, 2012, 19, e212-e2192 Figure 4: The threshold values used in our department are those derived from the meta-analysis of Friedrich-Rust et al2. This approach makes no attempt to separate out F0 and F1 as this is of little clinical importance. The graduated arrow is used to emphasize that the threshold values are not 100% accurate. The footnote used by the Department of Radiology • These thresholds are not absolute. at The Royal Melbourne Hospital currently reads: • Results should be interpreted in clinical context. < 1.35 – absent or mild fibrosis (F0 or F1) Factors such as inflammatory activity & venous 1.35–1.55 – significant fibrosis (F2) congestion can elevate the ARFI value. • 1.55–1.80 – severe fibrosis (F3) Values with an IQR of > 0.3 x median velocity should be either discounted or interpreted with caution > 1.80 – cirrhosis (F4) depending on how close they are to this threshold. (Based on meta-analysis of pooled data, which included (i.e., IQR / median velocity should be ideally < 0.3) apredominance of HCV patients – Friedrich-Rust et al J Viralhepatitis 2012, 19 e212-1219.) 6 Best practices for detecting liver fibrosis with ARFI · White paper Identifying Unreliable Measurements3 References If the interquartile range (IQR) is > 0.3 x median speed 1 Gibson RN. Targeted liver ultrasound for chronic (IQR:median > 0.3), then this signifies a wider dispersion liver disease: time to focus? Australasian Journal for of velocities around the median and the median value Ultrasound in Medicine. 2012 Nov;15 (4):121-125. is less reliable. The options are to reject this set of 2 Friedrich-Rust M, Nierhoff J, Lupsor M, Sporea I, measurements (and repeat a further set) or, at the v Fierbinteanu-Braticevici C, Strobel D, Takahashi H, ery least, exercise caution in interpreting the result. Yoneda M, Suda T, Zeumem S, Herrmann E. Performance of Acoustic Radiation Force If the valid measurements (i.e., those that do not Impulse imaging for the staging of liver fibrosis: appear as XXX) are < 60% of total measurements taken, a pooled meta-analysis. J Viral Hepatol. 2012 Feb;19(2):e212-9. doi: 10.1111/j. then this makes the overall validity of measurements 1365-2893.2011.01537.x. Epub 2011 Oct 30 less reliable. The options are to reject this set of 3 measurements (and consider repeating a further set) Bota S, Sporea I, Sirli R, Popescu A, Danila M, Jurchis A, Gradinaru-Tascau O. Factors associated with or, at the very least, exercise caution in interpreting the impossibility to obtain reliable liver stiffness the result. This situation tends to occur because of measurements by means of Acoustic Radiation Force patient factors (poor cooperation, high BMI, and/or Impulse (ARFI) elastography – analysis of a cohort of marked steatohepatosis), and attempts at a second set 1,031 subjects. Eur J Radiol. 2014 Feb;83(2):268-72. doi: 10.1016/j.ejrad.2013.11.019. Epub 2013 Dec. of measurements often fail. 7 Standalone 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 diagnostics and molecular medicine, as well as digital health and enterprise services. 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