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Influence of heterogeneities on liver steatosis evaluation by Fibroscan® (CAP™): relevance of a liver guidance tool
Abstract
Controlled Attenuation Parameter (CAP) is a measure of the liver ultrasound attenuation developed to assess steatosis on the Fibroscan®-vibration-controlled transient elastography based device for the clinical evaluation of liver stiffness. CAP performance was assessed in clinical studies always showing satisfactory results. However, CAP is based on the hypothesis that liver parenchyma is homogeneous whereas it is not everywhere (blood vessel, nodules, etc.). The objective of this work is to determine the influence of heterogeneities on CAP and to show the clinical relevance of a liver guidance tool, based on the statistical properties of ultrasound signals, developed to target the homogeneous parenchyma.
... To do so, the operator relies on A-and TM-mode graphs, which are displayed in real time on the user interface of the FibroScan. An ultrasound liver-targeting tool (US-LTT) indicator (Audiere et al. 2013), based on ultrasound parameters, is also displayed to assist the operator during the localization phase (Fig. 1). The US-LTT was originally developed to ensure an optimal CAP window measurement. ...
... Despite the good results (Audiere et al. 2013), the US-LTT indicator and A-and TM-mode graphs are only indirect means of assisting the operator in locating an optimal measurement window to obtain a valid shear wave speed (SWS) measurement. These graphs and indicator are indeed purely based on ultrasound signals and do not assess the propagation of the shear wave. ...
Vibration-controlled transient elastography-based FibroScan (Echosens, Paris, France) is today considered the reference device for non-invasive assessment of liver stiffness, and has been found to be a good surrogate marker of liver fibrosis. One major issue when using VCTE is the necessity to find an optimal measurement window before triggering measurements. In this article, a new method called vibration-guided transient elastography (VGTE) facilitating the localization of an optimal measurement window is proposed. VGTE relies on a combination of continuous and transient vibrations used to locate the liver and to measure liver stiffness, respectively. Two studies conducted on customized phantoms and on 31 volunteers compared VGTE with standard ultrasound-based tools. VGTE performed significantly better than standard ultrasound-based tools in detection of an optimal measurement window. The operator never failed to find a valid measurement window using VGTE. VGTE can also detect artifacts such as lungs, ribs and blood vessels.
... Similar results were found by Recio et al. (2013) Although CAP has good reproducibility, it appears to be less reproducible than LSM. This phenomenon is because the CAP, and more generally ultrasound attenuation, is very sensitive to heterogeneities such as blood vessels, nodules, etc. (Audiere et al. 2013;Sasso et al. 2013). This is why it is important to perform CAP examinations in a very homogenous part of the parenchyma and why a liver-guidance tool has been developed on the interface of the FibroScan to help the operator accurately conduct a CAP examination (Audiere et al. 2013;Sasso et al. 2013). ...
... This phenomenon is because the CAP, and more generally ultrasound attenuation, is very sensitive to heterogeneities such as blood vessels, nodules, etc. (Audiere et al. 2013;Sasso et al. 2013). This is why it is important to perform CAP examinations in a very homogenous part of the parenchyma and why a liver-guidance tool has been developed on the interface of the FibroScan to help the operator accurately conduct a CAP examination (Audiere et al. 2013;Sasso et al. 2013). ...
To assess liver steatosis, the controlled attenuation parameter (CAP; giving an estimate of ultrasound attenuation ∼3.5 MHz) is available with the M probe of the FibroScan. We report on the adaptation of the CAP for the FibroScan XL probe (center frequency 2.5 MHz) without modifying the range of values (100-400 dB/m). CAP validation was successfully performed on Field II simulations and on tissue-mimicking phantoms. In vivo performance was assessed in a cohort of 59 patients spanning the range of steatosis. In vivo reproducibility was good and similar with both probes. The area under receiver operative characteristic curve was equal to 0.83/0.84 and 0.92/0.91 for the M/XL probes to detect >2% and >16% liver fat, respectively, as assessed by magnetic resonance imaging. Patients can now be assessed simultaneously for steatosis and fibrosis using the FibroScan, regardless of their morphology.
... The main cause of variability is the sensitivity of CAP to the presence of heterogeneities from blood vessels and nodules in the US signal (Audi ere et al. 2013). Furthermore, the distribution of steatosis in the liver may be heterogeneous (Bannas et al. 2015;Qayyum et al. 2012). ...
Controlled attenuation parameter (CAP) is a measurement of ultrasound attenuation used to assess liver steatosis non-invasively. However, the standard method has some limitations. This study assessed the performance of a new CAP method by ex vivo and in vivo assessments. The major difference with the new method is that it uses ultrasound data continuously acquired during the imaging phase of the FibroScan examination. Seven reference tissue-mimicking phantoms were used to test the performance. In vivo performance was assessed in two cohorts (in total 195 patients) of patients using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as a reference. The precision of CAP was improved by more than 50% on tissue-mimicking phantoms and 22%-41% in the in vivo cohort studies. The agreement between both methods was excellent, and the correlation between CAP and MRI-PDFF improved in both studies (0.71 to 0.74; 0.70 to 0.76). Using MRI-PDFF as a reference, the diagnostic performance of the new method was at least equal or superior (area under the receiver operating curve 0.889-0.900, 0.835-0.873). This study suggests that the new continuous CAP method can significantly improve the precision of CAP measurements ex vivo and in vivo.
A method for simulation of pulsed pressure fields from arbitrarily shaped, apodized and excited ultrasound transducers is suggested. It relies on the Tupholme-Stepanishen method for calculating pulsed pressure fields, and can also handle the continuous wave and pulse-echo case. The field is calculated by dividing the surface into small rectangles and then Summing their response. A fast calculation is obtained by using the far-field approximation. Examples of the accuracy of the approach and actual calculation times are given.
: A program for the simulation of ultrasound systems is presented. It is based on the Tupholme-Stepanishen method, and is fast because of the use of a far-field approximation. Any kind of transducer geometry and excitation can be simulated, and both pulse-echo and continuous wave fields can be calculated for both transmit and pulse-echo. Dynamic apodization and focusing are handled through time lines, and different focusing schemes can be simulated. The versatility of the program is ensured by interfacing it to Matlab. All routines are called directly from Matlab, and all Matlab features can be used. This makes it possible to simulate all types of ultrasound imaging systems. INTRODUCTION Modern ultrasound scanners use a number of schemes for attaining high resolution and high contrast images. Multi-element transducers are used to steer the ultrasound beam and to use multiple foci zones. Apodization is used for reducing side-lobe levels and thereby increase the dynamic range of the ima...
Recently, a study showed that Controlled Attenuation Parameter (CAP), evaluated with transient elastography, could efficiently separate steatosis grades. The aim of this study was to prospectively evaluate the performance of CAP for the diagnosis of steatosis in patients with chronic liver disease.
Consecutive patients with chronic liver disease had steatosis diagnosis using CAP, blood sample and liver biopsy. Steatosis was graded as the percentage of hepatocytes with fat: S0 ≤ 10%, S1: 11 ~ 33%, S2: 34 ~ 66%, S3 ≥ 67%.
Characteristics of the 112 patients included were as follows: age 54 years, BMI 26 kg m(-) ², HCV 36%, NAFLD 25%. Steatosis repartition was: S0 52%, S1 19%, S2 14%, S3 15%. CAP was significantly correlated with SteatoTest, Fatty Liver Index (FLI), percentage of steatosis on liver biopsy, steatosis grade and slightly with liver stiffness, but not with fibrosis and activity grade on liver biopsy. Using CAP vs SteatoTest vs FLI score, Area Under the Receiver-Operating Characteristics (ROC) curves (AUROC)s were 0.84 vs 0.72 vs 0.72 for the diagnosis of steatosis ≥ S1, 0.86 vs 0.73 vs 0.71 for the diagnosis of steatosis ≥ S2, and 0.93 vs 0.73 vs 0.75 for the diagnosis of steatosis S3 respectively. For a sensitivity ≥ 90%, cut-offs of CAP were 215 dB m(-1) for S ≥ 1, 252 dB m(-1) for S ≥ 2, and 296 dB m(-1) for S3.
CAP is very efficient to detect even low grade steatosis. CAP being implemented on FibroScan(®) (Echosens, Paris, France), both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of non-invasive techniques for the management of chronic liver diseases.
Accurate tools for the noninvasive detection of hepatic steatosis are needed. The Controlled Attenuation Parameter (CAP) specifically targets liver steatosis using a process based on transient elastography.
Patients with chronic liver disease and body mass index (BMI) ≥28 kg/m(2) underwent biopsy and liver stiffness measurement (LSM) with simultaneous CAP determination using the FibroScan(®) M probe. The performance of the CAP for diagnosing steatosis compared with biopsy was assessed using areas under receiver operating characteristic curves (AUROC).
A total of 153 patients were included: 69% were male, median BMI was 32 kg/m(2); 47% had nonalcoholic fatty liver disease (NAFLD); and 65% had significant (≥10%) steatosis. The CAP was significantly correlated with the percentage of steatosis (ρ = 0.47) and steatosis grade (ρ = 0.51; both P < 0.00005). The median CAP was higher among patients with significant steatosis (317 [IQR 284-339] vs. 250 [227-279] dB/m with <10% steatosis; P < 0.0005) and the AUROC for this outcome was 0.81 (95% CI 0.74-0.88). At a cut-off of 283 dB/m, the CAP was 76% sensitive, 79% specific, and had positive and negative predictive values of 87% and 64%, respectively. CAP performance was not influenced by measurement variability, but was higher in patients with mild (F0-F1) fibrosis (AUROC 0.89 vs. 0.72 with F2-F4; P = 0.03). The AUROCs of the CAP for ≥5%, >33% and >66% steatosis were 0.79, 0.76 and 0.70, respectively.
The CAP is a promising tool for the noninvasive detection of hepatic steatosis. Advantages of CAP include its ease of measurement, operator-independence and simultaneous availability with LSM for fibrosis assessment.
A novel controlled attenuation parameter (CAP) has been developed for Fibroscan(®) to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan(®) and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S(0) : steatosis in <10% of hepatocytes, S(1) : 11-33%, S(2) : 34-66% and S(3) : 67-100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross-validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to differentiate between steatosis grades. In multivariate analysis, CAP was related to steatosis (P < 10(-15) ) independently of fibrosis stage (which was related to LSM). The areas under ROC curves using CAP to detect steatosis were 0.80 (95% CI, 0.75-0.84) for S ≥ S(1) , 0.86 (0.81-0.92) for S ≥ S(2) and 0.88 (0.73-1) S = S(3) . CAP exhibited a good ability to differentiate steatosis grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment confirmed results from previous studies. CAP is a novel tool to assess the degree of steatosis and both fibrosis and steatosis can be evaluated noninvasively during the same procedure using Fibroscan(®) , in patients with CHC.
Spectrum analysis procedures have been developed to improve upon the diagnostic capabilities afforded by conventional ultrasonic images. These procedures analyze the frequency content of broadband, coherent echo signals returned from the body. They include calibration procedures to remove system artifacts and thereby provide quantitative measurements of tissue backscatter. Several independent spectral parameters have been used to establish databases for various organs; several investigations have shown that these parameters can be used with statistical classifiers to identify tissue type. Locally computed spectra have been used to generate sets of images displaying independent spectral parameters. Stained images have been derived by analyzing these parameter images with statistical classifiers and using color to denote tissue type (e.g., cancer). This report describes spectrum analysis procedures, discusses how measured parameters are related to physical tissue properties, and summarizes results describing estimator precision. It also presents illustrative clinical results showing how such procedures are being adapted to address specific clinical problems for a number of organs. This report indicates where further developments are needed and suggests how these techniques may improve image segmentation for three-dimensional displays and volumetric assays.
There is a need for noninvasive methods to detect liver steatosis, which can be a factor of liver fibrosis progression. This work aims to evaluate a novel ultrasonic controlled attenuation parameter (CAP) devised to target, specifically, liver steatosis using a sophisticated process based on vibration control transient elastography (VCTE™). CAP was first validated as an estimate of ultrasonic attenuation at 3.5 MHz using Field II simulations and tissue-mimicking phantoms. Performance of the CAP was then appraised on 115 patients, taking the histological grade of steatosis as reference. CAP was significantly correlated to steatosis (Spearman ρ = 0.81, p < 10(-16)). Area under receiver operative characteristic (ROC) curve (AUC) was equal to 0.91 and 0.95 for the detection of more than 10% and 33% of steatosis, respectively. Furthermore, results show that CAP can efficiently separate several steatosis grades. These promising results suggest that CAP is a noninvasive, immediate, objective and efficient method to detect and quantify steatosis.
A study was performed to find and test quantitative methods of analysing echographic signals for the differentiation of diffuse liver diseases. An on-line data acquisition system was used to acquire radiofrequency (RF) echo signals from volunteers and patients. Several methods to estimate the frequency-dependent attenuation coefficient were evaluated, in which a correction for the frequency and depth-dependent diffraction and focusing effects caused by the sound beam was applied. Using the estimated value of the attenuation coefficient the RF signals themselves were corrected to remove the depth dependencies caused by the sound beam and by the frequency-dependent attenuation. After this preprocessing the envelope of the corrected RF signals was calculated and B-mode images were reconstructed. The texture was analysed in the axial direction by first- and second-order statistical methods. The accuracy and precision of the attenuation methods were assessed by using computer simulated RF signals and RF data obtained from a tissue-mimicking phantom. The phantom measurements were also used to test the performance of the methods to correct for the depth dependencies. The echograms of 163 persons, both volunteers and patients suffering from a diffuse liver disease (cirrhosis, hepatitis, haemochromatosis), were recorded. The mutual correlations between the estimated parameters were used to preselect parameters contributing independent information, and which can subsequently be used in a discriminant analysis to differentiate between the various diseased conditions.
Liver fibrosis has evolved in the past 20 years from a pure laboratory discipline to an area of great bedside relevance to practicing hepatologists. This evolution reflects growing awareness not only of the molecular underpinnings of fibrosis, but also of its natural history and methods of detection in chronic liver disease. These advances have culminated in clear evidence that cirrhosis can be reversible, and in realistic expectations that effective antifibrotic therapy will signifi- cantly alter the management and prognosis of patients with liver disease. In view of this remarkable progress, clinicians must now view liver fibrosis in a new light as a clinical problem in its own right amenable to specific diagnostic tests and therapies that are independent of the etiology. In that spirit, this review will integrate current knowledge about the nature and prognosis of fibrosis in different forms of chronic liver disease with recent advances in elucidating its patho- physiology. These advances form the basis for rational treat- ment of hepatic fibrosis, which are also summarized. This article emphasizes the most recent developments, since many current reviews have focused on broader advances in pathophysiology ( (1) and articles therein, (2,3)).
Chronic hepatitis is accompanied by progressive deposit of hepatic fibrosis, which may lead to cirrhosis. Evaluation of liver fibrosis is, thus, of great clinical interest and, up to now, has been assessed with liver biopsy. This work aims to evaluate a new noninvasive device to quantify liver fibrosis: the shear elasticity probe or fibroscan. This device is based on one-dimensional (1-D) transient elastography, a technique that uses both ultrasound (US) (5 MHz) and low-frequency (50 Hz) elastic waves, whose propagation velocity is directly related to elasticity. The intra- and interoperator reproducibility of the technique, as well as its ability to quantify liver fibrosis, were evaluated in 106 patients with chronic hepatitis C. Liver elasticity measurements were reproducible (standardized coefficient of variation: 3%), operator-independent and well correlated (partial correlation coefficient = 0.71, p < < 0.0001) to fibrosis grade (METAVIR). The areas under the receiver operating characteristic (ROC) curves were 0.88 and 0.99 for the diagnosis of patients with significant fibrosis (>/= F2) and with cirrhosis ( = F4), respectively. The Fibroscan is a noninvasive, painless, rapid and objective method to quantify liver fibrosis.