PURPOSE: It has been reported that the estimate of ultrasound attenuation coefficient (AC) is affected by depth of measurement, with linear decrease of values with depth. It is unknown whether backscatter coefficient (BSC) has similar behavior. METHODS: This retrospective study was performed with Sequoia US system equipped with ultrasound derived fat fraction (UDFF) algorithm (Siemens Healthineers, Issaquah, WA, USA) that combines BSC with AC. UDFF was obtained positioning upper edge of the region of interest at 1.5,2,3,4,5 cm below liver capsule. BSC data were extracted from UDFF offline. A fractional polynomial regression, which selects the best model considering the polynomial development of the variables of interest, was used. Covariates included were age, sex, skin-to-liver-capsule distance, stiffness. Distance was included as linear factor or with a power ranging from - 2 to 3, and the best fitting model was chosen according to partial F test. Body mass index (BMI) was not included because of collinearity with skin-to-liver capsule distance. RESULTS: 104 individuals (56 females; age: 57.9 ± 13.0 years; BMI: 29.0 ± 6.5 kg/m2; skin-to-liver-capsule distance: 2.3 ± 0.7 cm; liver stiffness: 7.5 ± 5.5 kiloPascal) were studied. Best fitting model for BSC included a combination of depth as linear factor and square root. BSC showed a decrease of - 13.98 dB/cm-steradian for each logarithmic increase of 1 cm depth (coefficient: - 13.98; 95% CI: - 21.016; - 5.379; p = .001). Skin-to-liver-capsule distance and stiffness also were independent predictors of BSC. CONCLUSIONS: The estimation of the BSC in the liver exhibits a depth dependence that significantly affects results. A standardized acquisition protocol is needed to compare results and reliably assess changes over time.
The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.
OBJECTIVES: To assess whether meal or water intake may affect the measurement of the ultrasound (US) attenuation coefficient (AC) imaging, a parameter that is directly related to liver fat content. METHODS: The study was performed in two centers (Italy and USA). AC was obtained using the ATI algorithm implemented in the Aplio i-series US systems (Canon Medical Systems, Japan) by one operator at each center. Measurements were performed at baseline and 5, 15, 30, 45 minutes after drinking 500 mL of water (group 1), or 30, 45, 60, 90, 120 minutes after eating a meal of about 600 kcal (group 2). Multilevel generalized estimating equations for repeated measures were used for the statistical analysis to consider the clustered nature of the data. RESULTS: Twenty-six individuals were enrolled: 11 (10 females; age, 43.7 ± 12.5 years) in Italy and 15 (10 females; age, 60.7 ± 6.3 years) in USA. At B-mode US, 10 (38.5%) had liver steatosis. The baseline AC values, in decibel/centimeter/megahertz, were 0.64 (0.12) in group 1 and 0.66 (0.13) in group 2. There was not any significant difference in AC values at every time-point after water or meal intake either in group 1 or group 2. This result did not change including sex, age, and skin-to-liver capsule into the models. CONCLUSIONS: The measurement of the AC, which is a biomarker of liver steatosis, does not require a fasting state and drinking water does not affect the result.
The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.
BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.
Due to the steatosis epidemic, noninvasive quantification of liver fat content is of great interest. Magnetic resonance (MR) techniques, including proton MR spectroscopy (MRS) and MR chemical shift imaging can quantify liver fat by measuring, directly or indirectly (the latter), the proton density fat fraction (PDFF). They have shown excellent diagnostic accuracy and are currently the reference standard for the noninvasive assessment of liver steatosis and are used in clinical trials for evaluating the change in liver fat over time. Using ultrasound (US), three different quantitative parameters can be obtained to estimate liver fat: attenuation coefficient, backscatter coefficient, and speed of sound. Controlled attenuation parameter (CAP), which estimates the attenuation of the US beam, was the first algorithm available and is performed with a non-imaging system. Currently, several other algorithms are available on B-mode imaging ultrasound systems, and they have shown an accuracy similar to or higher than the CAP. This article reports the current knowledge about their application in patients with metabolic dysfunction-associated steatotic liver disease.
Fatty Liver , Ultrasonography , Humans , Fatty Liver/diagnostic imaging , Fatty Liver/diagnosis , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Liver/diagnostic imaging , Liver/pathology
Quantitative MRI and ultrasound biomarkers of liver fibrosis have become important tools in the diagnosis and clinical management of children with chronic liver disease (CLD). In particular, MR elastography (MRE) is now routinely performed in clinical practice to evaluate the liver for fibrosis. Ultrasound shear-wave elastography has also become widely performed for this purpose, especially in young children. These noninvasive methods are increasingly used to replace liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. Although ultrasound has advantages of portability and lower equipment cost, available evidence indicates that MRI may have greater reliability and accuracy in liver fibrosis evaluation. In this AJR Expert Panel Narrative Review, we describe how, why, and when to use MRI- and ultrasound-based elastography methods for liver fibrosis assessment in children. Practical approaches are discussed for adapting and optimizing these methods in children, with consideration of clinical indications, patient preparation, equipment requirements, acquisition technique, as well as pitfalls and confounding factors. Guidance is provided for interpretation and reporting, and representative case examples are presented.
PURPOSE: This study evaluated ElastQ, a two-dimensional shear wave elastography (2D-SWE) technique, for the non-invasive assessment of liver fibrosis risk using liver stiffness measurement (LSM). The aim was to determine its diagnostic accuracy and establish LSM cutoffs for clinical risk stratification. METHODS: A prospective multicenter study was conducted, employing vibration-controlled transient elastography (VCTE) as a reference standard. The statistical analysis utilized Pearson correlations and Lin concordance correlation coefficients, diagnostic areas under the curve (AUCs), and 90%-specific rule-in and 90%-sensitive rule-out ElastQ cutoffs. RESULTS: The study included 875 patients at risk for liver disease, of whom 816 (376 women, 46.1%; median age, 57.0 years [interquartile range, 19.0]) had successful and reliable VCTE- and ElastQ-LSMs. The median LSM was 13.0 kPa (range, 2.0 to 75.0 kPa) for VCTE and 6.6 kPa (range, 2.9 to 26.5 kPa) for ElastQ. The correlation between VCTE-LSM and ElastQ-LSM was adequate for VCTE-LSM <15 kPa (Pearson r=0.63) but lower for VCTE-LSM ≥15.0 kPa (Pearson r=0.27). VCTE-LSM indicated no fibrosis risk (<5.0 kPa) in 178 cases (21.8%), gray zone (5.0-9.9 kPa) in 347 cases (42.5%), and advanced chronic liver disease (ACLD; ≥10.0 kPa) in 291 cases (35.7%). The diagnostic AUC for ElastQ-LSM was 0.82 for fibrosis risk and 0.90 for ACLD. The clinically relevant ElastQ cutoffs for ruling out fibrosis risk and ruling in compensated ACLD (cACLD) were <5.0 kPa and ≥9.0 kPa, respectively. CONCLUSION: ElastQ 2D-SWE enables accurate, non-invasive assessments of liver fibrosis and cACLD risk. In clinical practice, ElastQ-LSM <5.0 kPa rules out fibrosis, while ElastQ-LSM ≥9.0 kPa rules in cACLD.
PURPOSE: This study's primary aim was to assess factors affecting ultrasound attenuation coefficient (AC) measurement repeatability using the Canon ultrasound (US) system. The secondary aim was to evaluate whether similar results were obtained with other vendors' AC algorithms. METHODS: This prospective study was performed at two centers from February to November 2022. AC was obtained using two US systems (Aplio i800 of Canon Medical Systems and Arietta 850 of Fujifilm). An algorithm combining AC and the backscatter coefficient was also used (Sequoia US System, Siemens Healthineers). To evaluate inter-observer concordance, AC was obtained by two expert operators using different transducer positions with regions of interest (ROIs) varying in terms of depth and size. Intra-observer concordance was evaluated on measurements performed intercostally, subcostally, and in the left liver lobe. Lin's concordance correlation coefficient was used. RESULTS: Thirty-four participants (mean age, 49.4±15.1 years; 18 females) were studied. AC values progressively decreased with depth. The measurements in intercostal spaces on bestquality US images using a 3-cm ROI with its upper edge 2 cm below the liver capsule during breath-hold showed the highest intra-observer and inter-observer concordance (0.92 [95% confidence interval, 0.88 to 0.95] and 0.89 [0.82 to 0.96], respectively). Measurements in the left lobe showed the lowest intra-observer and inter-observer concordance (0.67 [0.43 to 0.90] and 0.58 [0.12 to 1.00], respectively). Intercostal space measurements also had the highest repeatability for the other two ultrasound systems. CONCLUSION: AC values obtained in intercostal spaces on best-quality images using a 3-cm ROI placed with its top 2 cm below the liver capsule were highly repeatable.
Quantitative imaging biomarkers of liver disease measured by using MRI and US are emerging as important clinical tools in the management of patients with chronic liver disease (CLD). Because of their high accuracy and noninvasive nature, in many cases, these techniques have replaced liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. The most commonly evaluated imaging biomarkers are surrogates for liver fibrosis, fat, and iron. MR elastography is now routinely performed to evaluate for liver fibrosis and typically combined with MRI-based liver fat and iron quantification to exclude or grade hepatic steatosis and iron overload, respectively. US elastography is also widely performed to evaluate for liver fibrosis and has the advantage of lower equipment cost and greater availability compared with those of MRI. Emerging US fat quantification methods can be performed along with US elastography. The author group, consisting of members of the Society of Abdominal Radiology (SAR) Liver Fibrosis Disease-Focused Panel (DFP), the SAR Hepatic Iron Overload DFP, and the European Society of Radiology, review the basics of liver fibrosis, fat, and iron quantification with MRI and liver fibrosis and fat quantification with US. The authors cover technical requirements, typical case display, quality control and proper measurement technique and case interpretation guidelines, pitfalls, and confounding factors. The authors aim to provide a practical guide for radiologists interpreting these examinations. © RSNA, 2023 See the invited commentary by Ronot in this issue. Quiz questions for this article are available in the supplemental material.
Elasticity Imaging Techniques , Iron Overload , Liver Diseases , Humans , Iron , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Liver/diagnostic imaging , Liver/pathology , Magnetic Resonance Imaging/methods , Liver Diseases/pathology , Iron Overload/diagnostic imaging , Elasticity Imaging Techniques/methods , Radiologists , Biomarkers
OBJECTIVES: The primary aim was to estimate the influence of various depths on ultrasound attenuation coefficient (AC) of multiple vendors in the liver. The secondary aim was to evaluate the impact of region of interest (ROI) size on AC measurements in a subset of participants. METHODS: This Institutional Review Board (IRB)-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study was carried out in two centers using AC-Canon and AC-Philips algorithms and extracting AC-Siemens values from ultrasound-derived fat fraction algorithm. Measurements were performed positioning ROI upper edge (3 cm size) at 2, 3, 4, 5 cm from the liver capsule with AC-Canon and AC-Philips and at 1.5, 2, 3 cm with Siemens algorithm. In a subset of participants, measurements were obtained with 1 and 3 cm ROI size. Univariate and multivariate linear regression models and Lin's concordance correlation coefficient (CCC) were used for statistical analysis as appropriate. RESULTS: Three different cohorts were studied. Sixty-three participants (34 females; mean age: 51 ± 14 years) were studied with AC-Canon, 60 (46 females; mean age: 57 ± 11 years) with AC-Philips, and 50 (25 females; 61 ± 13 years) with AC-Siemens. There was a decrease in AC values per 1 cm increase in depth in all. In multivariable analysis, the coefficient was -0.049 (-0.060; -0.038 P < .001) with AC-Canon, -0.058 (-0.066; -0.049 P < .001) with AC-Philips and -0.081 (-0.112; -0.050 P < .001) with AC-Siemens. AC values with 1 cm ROI were significantly higher than those obtained with 3 cm ROI at all depths (P < .001) but the agreement between AC values obtained with different ROI size was excellent (CCC 0.82 [0.77-0.88]). CONCLUSIONS: There is depth dependence in AC measurement that affects results. A standardized protocol with fixed ROI's depth and size is needed.
Algorithms , Liver , Female , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Reproducibility of Results , Liver/diagnostic imaging , Ultrasonography/methods
BACKGROUND: Since nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in the Western world, clinicians need reliable noninvasive tools for the identification of NAFLD-associated fibrosis. Limited evidence on the performance of the novel shear wave elastography technique Elast-PQ (EPQ) in NAFLD is available. METHOD: In this prospective, European multinational study we assessed the diagnostic accuracy of EPQ using vibration-controlled transient elastography (VCTE) as a reference standard. RESULTS: Among 353 NAFLD patients, 332 (94.1%) fulfilled reliability criteria of VCTE and EPQ (defined by IQR/median ≤0.3; 41.3% female, mean age: 59 [IQR: 16.5], mean BMI: 29.0 (7.1)). 4/353 (1.1%) and 17/353 (4.8%) had unreliable VCTE and EPQ measurements, respectively. VCTE-based NAFLD fibrosis stages were F0/F1: 222(66.9%), F2: 41 (12.3%), F3: 30 (9.1%), F4: 39 (11.7%). We found a strong correlation (Pearson R=0.87; p<0.0001) and concordance (Lin's concordance correlation coefficient =0.792) of EPQ with VCTE. EPQ was able to identify NAFLD-fibrosis risk with the following EPQ cutoffs: ≥6.5 kPa for significant fibrosis (≥F2) (≥1.47 m/s; sensitivity: 78%; specificity: 95%; AUROC: 0.94), ≥6.9 kPa for advanced fibrosis (≥F3) (≥1.52 m/s; sens.: 88%, spec.: 89%; AUROC: 0.949), and ≥10.4 kPa for cirrhosis (F4) (≥1.86 m/s; sens.: 87%; spec.: 94%; AUROC: 0.949). CONCLUSION: The point shear wave elastography technique EPQ shows excellent correlation to and concordance with VCTE. EPQ can reliably exclude NAFLD fibrosis <6.0 kPa (<1.41 m/s) and indicate a high risk of advanced fibrosis ≥10.4 kPa (≥1.86 m/s).
Elasticity Imaging Techniques , Non-alcoholic Fatty Liver Disease , Humans , Female , Middle Aged , Male , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Prospective Studies , Elasticity Imaging Techniques/methods , Vibration , Reproducibility of Results , Liver Cirrhosis/diagnostic imaging , Fibrosis , Liver/diagnostic imaging
The diagnosis of liver fibrosis and the assessment of its severity are important to provide appropriate management, to determine the prognosis or the need for surveillance. Currently, for fibrosis staging, liver stiffness measurement (LSM) with the shear wave elastography (SWE) techniques is considered a reliable substitute for liver biopsy in several clinical scenarios. Nonetheless, it should be emphasized that stiffness value is a biomarker of diffuse liver disease that must be interpreted taking into consideration anamnesis, clinical and laboratory data. In patients with diffuse liver disease, it is more clinically relevant to determine the likelihood of advanced disease rather than to obtain an exact stage of liver fibrosis using a histologic classification. In this regard, a 'rule of five' for LSMs with vibration-controlled transient elastography (VCTE) and a 'rule of four' for LSMs with the acoustic radiation force impulse (ARFI)-based techniques have been proposed. In patients with advanced chronic liver disease (CLD), the risk of liver decompensation increases with increasing liver stiffness value. SWE has been proposed as a tool to predict the risk of death or complications in patients with CLD. LSM by VCTE combined with platelets count is a validated non-invasive method for varices screening, with very good results in terms of invasive procedures being spared. ARFI-based techniques also show some promising results in this setting. LSM, alone or combined in scores or algorithms with other parameters, is used to evaluate the risk of hepatocellular carcinoma occurrence. Due to the high prevalence of CLD, screening the population at risk is of interest but further studies are needed.
Background: The primary aim of our study was to assess the correlation between an improved version of the attenuation coefficient available on the Arietta 850 ultrasound system (iATT, Fujifilm Healthcare, Tokyo, Japan) and controlled attenuation parameter (CAP). The secondary aim was to assess whether focusing only on iATT acquisition without following the strict protocol for liver stiffness measurements would affect iATT measurement. Methods: Consecutive individuals were enrolled. Pearson's r was used to test the correlation between ATT and CAP values. The concordance between iATT and CAP was tested using Lin's concordance correlation coefficient (CCC). Results: 354 individuals (203 males, 151 females) were studied. The overall Pearson correlation between CAP and iATT values obtained following or not following the liver stiffness measurement protocol, respectively, were r = 0.73 and r = 0.71. The correlation was affected by the interquartile range/median (IQR/M) of the 10 measurements: it was r = 0.75 for IQR/M ≤ 15% and r = 0.60 for IQR/M > 15%. CCC showed that there was a moderate to good concordance between iATT and CAP values. Conclusion: iATT shows a strong correlation with CAP that does not decrease when the protocol for liver stiffness acquisition is not followed. The correlation between iATT and CAP values is higher when the IQR/M ≤ 15%.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an estimated prevalence of up to 30% in the general population and higher in people with type 2 diabetes. The assessment of liver fat content is essential to help identify patients with or who are at risk for NAFLD and to follow their disease over time. The American Institute of Ultrasound in Medicine-RSNA Quantitative Imaging Biomarkers Alliance Pulse-Echo Quantitative Ultrasound Initiative was formed to help develop and standardize acquisition protocols and to better understand confounding factors of US-based fat quantification. The three quantitative US parameters explored by the initiative are attenuation, backscatter coefficient, and speed of sound. The purpose of this review is to present the current state of attenuation imaging for fat quantification and to provide expert opinion on examination performance and interpretation. US attenuation methods that need further study are outlined.
Non-alcoholic Fatty Liver Disease/diagnostic imaging , Ultrasonography/methods , Humans , Reference Standards
