Liver stiffness as a cornerstone in heart disease risk assessment.

Metabolic dysfunction-associated steatotic liver disease (MASLD) typically presents with hepatic fibrosis in advanced disease, resulting in increased liver stiffness. A subset of patients further develops liver cirrhosis and hepatocellular carcinoma. Cardiovascular disease is a common comorbidity in patients with MASLD and its prevalence is increasing in parallel. Recent evidence suggests that especially liver stiffness, whether or not existing against a background of MASLD, is associated with heart diseases. We conducted a narrative review on the role of liver stiffness in the prediction of highly prevalent heart diseases including heart failure, cardiac arrhythmias (in particular atrial fibrillation), coronary heart disease, and aortic valve sclerosis. Research papers were retrieved from major scientific databases (PubMed, Web of Science) until September 2023 using 'liver stiffness' and 'liver fibrosis' as keywords along with the latter cardiac conditions. Increased liver stiffness, determined by vibration-controlled transient elastography or hepatic fibrosis as predicted by biomarker panels, are associated with a variety of cardiovascular diseases, including heart failure, atrial fibrillation, and coronary heart disease. Elevated liver stiffness in patients with metabolic liver disease should lead to considerations of cardiac workup including N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide determination, electrocardiography, and coronary computed tomography angiography. In addition, patients with MASLD would benefit from heart disease case-finding strategies in which liver stiffness measurements can play a key role. In conclusion, increased liver stiffness should be a trigger to consider a cardiac workup in metabolically compromised patients.

Enhanced diagnosis of advanced fibrosis and cirrhosis in individuals with NAFLD using FibroScan-based Agile scores.

BACKGROUND & AIMS: Currently available non-invasive tests, including fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM by VCTE), are highly effective at excluding advanced fibrosis (AF) (F ≥3) or cirrhosis in people with non-alcoholic fatty liver disease (NAFLD), but only have moderate ability to rule-in these conditions. Our objective was to develop and validate two new scores (Agile 4 and Agile 3+) to identify cirrhosis or AF, respectively, with optimized positive predictive value and fewer indeterminate results, in individuals with NAFLD attending liver clinics. METHODS: This international study included seven adult cohorts with suspected NAFLD who underwent liver biopsy, LSM and blood sampling during routine clinical practice or screening for trials. The population was randomly divided into a training set and an internal validation set, on which the best-fitting logistic regression model was built, and performance and goodness of fit were assessed, respectively. Furthermore, both scores were externally validated on two large cohorts. Cut-offs for high sensitivity and specificity were derived in the training set to rule-out and rule-in cirrhosis or AF and then tested in the validation set and compared to FIB-4 and LSM. RESULTS: Each score combined LSM, AST/ALT ratio, platelets, sex and diabetes status, as well as age for Agile 3+. Calibration plots for Agile 4 and Agile 3+ indicated satisfactory to excellent goodness of fit. Agile 4 and Agile 3+ outperformed FIB-4 and LSM in terms of AUROC, percentage of patients with indeterminate results and positive predictive value to rule-in cirrhosis or AF. CONCLUSIONS: The two novel non-invasive scores improve identification of cirrhosis or AF among individuals with NAFLD attending liver clinics and reduce the need for liver biopsy in this population. IMPACT AND IMPLICATIONS: Non-invasive tests currently used to identify patients with advanced fibrosis or cirrhosis, such as fibrosis-4 index and liver stiffness measurement by vibration-controlled transient elastography, have high negative predictive values but high false positive rates, while results are indeterminate for a large number of cases. This study provides scores that will help the clinician diagnose advanced fibrosis or cirrhosis. These new easy-to-implement scores will help liver specialists to better identify (1) patients who need more intensive follow-up, (2) patients who should be referred for inclusion in therapeutic trials, and (3) which patients should be treated with pharmacological agents when effective therapies are approved.

Diagnostic Performance of MR Elastography and Vibration-controlled Transient Elastography in the Detection of Hepatic Fibrosis in Patients with Severe to Morbid Obesity.

Purpose To evaluate the diagnostic performance and examination success rate of magnetic resonance (MR) elastography and vibration-controlled transient elastography (VCTE) in the detection of hepatic fibrosis in patients with severe to morbid obesity. Materials and Methods This prospective and HIPAA-compliant study was approved by the institutional review board. A total of 111 patients (71 women, 40 men) participated. Written informed consent was obtained from all patients. Patients underwent MR elastography with two readers and VCTE with three observers to acquire liver stiffness measurements for liver fibrosis assessment. The results were compared with those from liver biopsy. Each pathology specimen was evaluated by two hepatopathologists according to the METAVIR scoring system or Brunt classification when appropriate. All imaging observers were blinded to the biopsy results, and all hepatopathologists were blinded to the imaging results. Examination success rate, interobserver agreement, and diagnostic accuracy for fibrosis detection were assessed. Results In this obese patient population (mean body mass index = 40.3 kg/m2; 95% confidence interval [CI]: 38.7 kg/m2, 41.8 kg/m2]), the examination success rate was 95.8% (92 of 96 patients) for MR elastography and 81.3% (78 of 96 patients) or 88.5% (85 of 96 patients) for VCTE. Interobserver agreement was higher with MR elastography than with biopsy (intraclass correlation coefficient, 0.95 vs 0.89). In patients with successful MR elastography and VCTE examinations (excluding unreliable VCTE examinations), both MR elastography and VCTE had excellent diagnostic accuracy in the detection of clinically significant hepatic fibrosis (stage F2-F4) (mean area under the curve: 0.93 [95% CI: 0.85, 0.97] vs 0.91 [95% CI: 0.83, 0.96]; P = .551). Conclusion In this obese patient population, both MR elastography and VCTE had excellent diagnostic performance for assessing hepatic fibrosis; MR elastography was more technically reliable than VCTE and had a higher interobserver agreement than liver biopsy. © RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on January 25, 2017.

Vibration-controlled transient elastography for noninvasive evaluation of liver steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to a large spectrum of liver disorders and is the most common cause of metabolic liver disease. The current gold standard for diagnosing NAFLD is liver biopsy, which can lead to severe complications. PURPOSE: Among the noninvasive diagnostic options, we chose to use a FibroScan and developed an algorithm applying the Voigt rheological model to assess the viscoelastic properties of the liver and evaluate its performance for the diagnosis of steatosis. METHODS: Twenty-two healthy volunteers and 20 patients with steatosis were included. For each subject, we used a modified FibroScan, whose data had been processed by our algorithm to separate the two viscoelastic components, stiffness µ, and viscosity η. The liver elasticity µFibroscan measured by the FibroScan was also recorded. Mann-Whitney tests and receiver operating characteristics (ROCs) curve analyses were performed to compare the parameters between the two groups, and Pearson's correlation coefficients were used to assess the correlations between the parameters. RESULTS: We found a good correlation between η and µFibroscan (r = 0.75), and poor correlations between µ and both η and µFibroscan (r = 0.33 and r = 0.03, respectively). We also showed that η and µFibroscan were higher in patients with steatosis compared to healthy volunteers, with area under the ROCs (AUROC) curve at 0.814 and 0.891, respectively. Conversely, µ was not different between the two groups (AUROC = 0.557). CONCLUSIONS: Our novel method successfully separated the two viscoelastic properties of the liver, of which the parameter η is a sensitive indicator for steatosis.

Improved Ultrasound Attenuation Measurement Method for the Non-invasive Evaluation of Hepatic Steatosis Using FibroScan.

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.

Vibration-Guided Transient Elastography: A Novel Fibroscan® Examination with Improved Guidance for Liver Stiffness Measurement.

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.

FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study.

BACKGROUND: The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]). METHODS: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009. FINDINGS: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0. INTERPRETATION: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease. FUNDING: Echosens and UK National Institute for Health Research.

Cross-validation of magnetic resonance elastography and ultrasound-based transient elastography: a preliminary phantom study.

PURPOSE: To cross-validate two recent noninvasive elastographic techniques, ultrasound-based transient elastography (UTE) and magnetic resonance elastography (MRE). As potential alternatives to liver biopsy, UTE and MRE are undergoing clinical investigations for liver fibrosis diagnosis and liver disease management around the world. These two techniques use tissue stiffness as a marker for disease state and it is important to do a cross-validation study of both elastographic techniques to determine the consistency with which the two techniques can measure the mechanical properties of materials. MATERIALS AND METHODS: In this study, 19 well-characterized phantoms with a range of stiffness values were measured by two clinical devices (a Fibroscan and an MRE system based respectively on the UTE and MRE techniques) successively with the operators double-blinded. RESULTS: Statistical analysis showed that the correlation coefficient was r(2) = 0.93 between MRE and UTE, and there was no evidence of a systematic difference between them within the range of stiffnesses examined. CONCLUSION: These two noninvasive methods, MRE and UTE, provide clinicians with important new options for improving patient care regarding liver diseases in terms of the diagnosis, prognosis, and monitoring of fibrosis progression, as well for evaluating the efficacy of treatment.

Simulation of shear wave propagation in a soft medium using a pseudospectral time domain method.

Elastography applications require the use of efficient models to simulate the propagation of shear waves in soft media such as human tissues. These models are needed to improve understanding of the measured displacement field, to reconstruct the viscoelasticity of heterogeneous tissues, and to test inversion algorithms. This paper reports a numerical model based on a pseudospectral time domain method developed to simulate shear and compression wave propagation in an axisymmetric heterogeneous viscoelastic medium. This model was adapted to the study of soft tissues where the ratio between the compression and the shear wave velocity was about a thousand and validated in the homogeneous situation by comparison with an analytical model based on elastodynamic Green's functions. Displacements obtained experimentally using transient elastography are presented, compared with simulation results, and discussed.

A Novel FibroScan Examination Dedicated to Spleen Stiffness Measurement.

Esophageal varices (EVs) are among the most severe complications of cirrhosis, with a prevalence of 50% to 60% among cirrhotic patients. International guidelines therefore recommend that cirrhotic patients should be screened for the presence of EVs. The main objective of this study was to introduce a new spleen-dedicated FibroScan (Echosens, Paris, France) examination and to assess its performance in detecting large EVs (grade 2 and 3). This novel examination has been validated in simulation and phantom studies and has been used in a population of patients with chronic liver disease. The study described here suggests that the novel spleen-dedicated FibroScan examination performs better than the standard FibroScan for the detection of large EVs (area under the curve = 0.70 for the standard examination and 0.79 [p <0.01] for the spleen examination), but further clinical studies are needed to investigate the role of spleen stiffness in the management of cirrhotic patients.

Liver stiffness measurement in children using FibroScan: feasibility study and comparison with Fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy.

OBJECTIVE: Transient elastography (FibroScan) is a novel, noninvasive, rapid bedside method to assess liver fibrosis by measuring liver stiffness in adult patients. The usefulness of FibroScan in children with chronic liver diseases is unknown. The aim of this prospective study was to evaluate the feasibility of liver stiffness measurement and to compare FibroScan, Fibrotest, and aspartate transaminase to platelets ratio index (APRI) with liver biopsy for the diagnosis of cirrhosis in children with chronic liver diseases. PATIENTS AND METHODS: Between February 2004 and October 2005, 116 consecutive children with chronic liver diseases were prospectively included. All except 1 child (58 boys, mean age 10.7 years) could have noninvasive tests for fibrosis: FibroScan, Fibrotest, and APRI, and, when necessary, a liver biopsy (n = 33). RESULTS: FibroScan, Fibrotest, and APRI were correlated with clinical or biological parameters of chronic liver diseases, but the FibroScan marker correlated most with all parameters. By histology, the METAVIR fibrosis category score was F1 in 7 cases, F2 in 8 cases, F3 in 6 cases, and F4 in 12 cases. FibroScan, Fibrotest, and APRI were significantly correlated with the METAVIR fibrosis score. For the diagnosis of cirrhosis, the area under the receiver operating characteristic curve was 0.88, 0.73, and 0.73 for FibroScan, Fibrotest, and APRI, respectively. CONCLUSIONS: These results indicate that liver stiffness measurement is feasible in children and is related to liver fibrosis. A specific probe dedicated to children and slender patients has thus been developed and is currently under evaluation. The FibroScan equipped with this specific probe could become a useful tool for the management of chronic liver diseases in children.

Liver Steatosis Assessed by Controlled Attenuation Parameter (CAP) Measured with the XL Probe of the FibroScan: A Pilot Study Assessing Diagnostic Accuracy.

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.

AdipoScan: A Novel Transient Elastography-Based Tool Used to Non-Invasively Assess Subcutaneous Adipose Tissue Shear Wave Speed in Obesity.

We describe a novel device called the AdipoScan that was adapted from the FibroScan to specifically assess shear wave speed (SWS) in human abdominal subcutaneous adipose tissue (scAT). Measurement reproducibility was assessed on tissue-mimicking phantoms with and without repositioning, with resultant coefficients of variation of 1% and 0%, respectively, as well as in vivo (14% and 7%, respectively). The applicability of the AdipoScan was tested on 19 non-obese volunteers, and a scAT thickness >2 cm was found to be mandatory to perform a valid measurement. Abdominal scAT SWS was assessed in 73 severely obese subjects, all candidates for bariatric surgery. Subcutaneous AT SWS was positively associated with scAT fibrosis and obesity-related co-morbidities such as hypertension, glycemic status, dyslipidemia and liver dysfunction. These results suggest that the AdipoScan could be a useful non-invasive tool to evaluate scAT fibrosis and metabolic complications in obesity. Further investigation is required to evaluate the relevance of using the AdipoScan to predict patient weight trajectories and metabolic outcomes after bariatric surgery.

Transient elastography: a new noninvasive method for assessment of hepatic fibrosis.

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.

Shear modulus imaging with 2-D transient elastography.

In previous works, we have shown that time-resolved 2-D transient elastography is a promising technique for characterizing the elasticity of soft tissues. It involves the measurement of the displacements induced by the propagation of low frequency (LF) pulsed shear waves in biological tissues. In this paper, we present a novel apparatus that contains a LF vibrating device surrounding a linear array of 128 ultrasonic transducers that performs ultrafast ultrasonic imaging (up to 10,000 frames/s) and that is able to follow in real time the propagation of a LF shear wave in the human body. The vibrating device is made of two rods, fixed to electromagnetic vibrators, that produce in the ultrasonic image area a large amplitude shear wave. The geometry has been chosen both to enhance the sensitivity and to create a quasi linear shear wave front in the imaging plane. An inversion algorithm is used to recover the shear modulus map from the spatio-temporal data, and the first experimental results obtained from tissue-equivalent materials are presented.

Ultrafast compound imaging for 2-D motion vector estimation: application to transient elastography.

This paper describes a new technique for two-dimensional (2-D) imaging of the motion vector at a very high frame rate with ultrasound. Its potential is experimentally demonstrated for transient elastography. But, beyond this application, it also could be promising for color flow and reflectivity imaging. To date, only axial displacements induced in human tissues by low-frequency vibrators were measured during transient elastography. The proposed technique allows us to follow both axial and lateral displacements during the shear wave propagation and thus should improve Young's modulus image reconstruction. The process is a combination of several ideas well-known in ultrasonic imaging: ultra-fast imaging, multisynthetic aperture beamforming, 1-D speckle tracking, and compound imaging. Classical beamforming in the transmit mode is replaced here by a single plane wave insonification increasing the frame rate by at least a factor of 128. The beamforming is achieved only in the receive mode on two independent subapertures. Comparison of successive frames by a classical 1-D speckle tracking algorithm allows estimation of displacements along two different directions linked to the subapertures beams. The variance of the estimates is finally improved by tilting the emitting plane wave at each insonification, thus allowing reception of successive decorrelated speckle patterns.

Shear elasticity probe for soft tissues with 1-D transient elastography.

Important tissue parameters such as elasticity can be deduced from the study of the propagation of low frequency shear waves. A new method for measuring the shear velocity in soft tissues is presented in this paper. Unlike conventional transient elastography, in which the ultrasonic transducer and the low frequency vibrator are two separated parts, the new method relies on a probe that associates the vibrator and the transducer, which is built on the axis of the vibrator. This setup is easy to use. The low frequency shear wave is driven by the transducer itself that acts as a piston while it is used in pulse echo mode to acquire ultrasonic lines. The results obtained with the new method are in good agreement with those obtained with the conventional one.

Assessment of elastic parameters of human skin using dynamic elastography.

Sonoelastography and transient elastography are two ultrasound-based techniques that facilitate noninvasive characterization of the viscoelastic properties of soft tissues by investigating their response to shear mechanical excitation. Young's modulus is the principle assessment parameter. Because it defines local tissue stiffness, it is of major interest for the medical imaging and cosmetic industries as it could replace subjective palpation by yielding local, quantitative information. In this paper, we describe a new high-resolution device capable of measuring local Young's modulus in very thin layers (1-5 mm) and devoted to the in vivo evaluation of the elastic properties of human skin. It uses an ultrasonic probe (50 MHz) for tracking the displacements induced by a 300 Hz shear wave generated by a ring surrounding the transducer. The displacements are measured using a conventional cross-correlation technique between successive ultrasonic back-scattered echoes. First, this noninvasive technique has been experimentally proven to be accurate for investigating elasticity in different skin-mimicking phantoms. Second, data were acquired in vivo on human forearms. As expected, Young's modulus was found to be higher in the dermis than in the hypodermis and other soft tissues.

Comparison of four different techniques to evaluate the elastic properties of phantom in elastography: is there a gold standard?

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young's modulus over the range of normal and cirrhotic liver stiffnesses. The Young's modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.

Maximum likelihood estimation of shear wave speed in transient elastography.

Ultrasonic transient elastography (TE), enables to assess, under active mechanical constraints, the elasticity of the liver, which correlates with hepatic fibrosis stages. This technique is routinely used in clinical practice to assess noninvasively liver stiffness. The Fibroscan system used in this work generates a shear wave via an impulse stress applied on the surface of the skin and records a temporal series of radio-frequency (RF) lines using a single-element ultrasound probe. A shear wave propagation map (SWPM) is generated as a 2-D map of the displacements along depth and time, derived from the correlations of the sequential 1-D RF lines, assuming that the direction of propagation (DOP) of the shear wave coincides with the ultrasound beam axis (UBA). Under the assumption of pure elastic tissue, elasticity is proportional to the shear wave speed. This paper introduces a novel approach to the processing of the SWPM, deriving the maximum likelihood estimate of the shear wave speed when comparing the observed displacements and the estimates provided by the Green's functions. A simple parametric model is used to interface Green's theoretical values of noisy measures provided by the SWPM, taking into account depth-varying attenuation and time-delay. The proposed method was evaluated on numerical simulations using a finite element method simulator and on physical phantoms. Evaluation on this test database reported very high agreements of shear wave speed measures when DOP and UBA coincide.