Understanding confounding factors allows for accurate interpretation of liver stiffness measurements by ElastQ, a novel 2D shear wave elastography technique.

PURPOSE: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) or two-dimensional shear wave elastography (2D-SWE) is recommended to assess the risk of liver fibrosis and advanced chronic liver disease. Even though both techniques measure liver stiffness, their numerical results often diverge. Confounders and reliability criteria for 2D-SWE have not been systematically investigated. MATERIALS AND METHODS: We prospectively recruited participants with paired LSM by VCTE and the novel 2D-SWE technique ElastQ (Philips) in three European tertiary centers. The following parameters were recorded: sex, age, body mass index (BMI), etiology, laboratory markers of liver damage and function, as well as cholestasis, LSM by VCTE and controlled attenuation parameter (CAP), interquartile range (IQR)/median for VCTE-LSM and ElastQ-LSM, and the skin-to-liver capsule distance. RESULTS: We included 840 participants: 447 (53.2%) males; median age 57.0 [IQR:19.0] years; median BMI 25.4 [6.0] kg/m2; median VCTE-LSM 7.25 [9.2] kPa; median ElastQ-LSM 6.7 [5.4] kPa. On uni- and multivariable modeling (adjusted for LSM), we found that the discrepancy increased with liver stiffness and markers of disease severity. Skin-to-liver capsule distance and BMI affected VCTE-LSM more compared to ElastQ-LSM and significantly increased the discordance between the two measurements. CONCLUSION: The discrepancy of ElastQ-LSM to VCTE-LSM increases with liver stiffness and disease severity. BMI and skin-to-liver capsule distance increase the discrepancy between VCTE- and ElastQ-LSM but affect ElastQ-LSM less. The quality criterion IQR/median ≤ 30% indicates reliable ElastQ-LSM.

US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study.

Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.

The urgent need to extend the appropriate use of ultrasound in Africa and worldwide. Overview, experiences and perspectives.

It is known that in African countries the health condition is problematic, both from a diagnostic and therapeutic point of view. Patients have to travel long distances to access medical care. Many cannot afford the cost of transportation to a medical facility. Ultrasound its into the scenario of healthcare imaging with limited resources, as an effective, economical, repeatable diagnostic tool, requiring low maintenance. Ultrasound tools in fact are relatively cheap and machines are easy to move, making them adapt to be taken to a rural setting where they are most needed. However ultrasound exams are not easy to perform and they need an adequate training. The spread of POCUS (point-of-care "focused" ultrasound) worldwide could be useful in Africa to identify high-risk patients. These cases selected in rural setting by POCUS can be referred to hospitals for further treatment. To deal with these situations it is necessary to form doctors and/or paramedical staff capable of guaranteeing a qualitatively adequate service. Therefore the need for basic training is greater in developing countries. Sharing successful educational strategies should advance the integration of ultrasound into the university medical school curricula. This will ensure that recently qualified doctors can practice their basic skills accurately and independently.

Ultrasound backscatter coefficient for fat quantification is affected by the measurement depth.

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.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

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.

Does Meal or Water Intake Affect Ultrasound Attenuation Coefficient Estimate?

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.

WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification.

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.

Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation.

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.

Recent advances in noninvasive assessment of liver steatosis.

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.

MR and Ultrasound Elastography for Fibrosis Assessment in Children: Practical Implementation and Supporting Evidence-AJR Expert Panel Narrative Review.

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.

Two-dimensional shear wave elastography (ElastQ) accurately rules out liver fibrosis and rules in advanced chronic liver disease across liver disease etiologies: a prospective multicenter study.

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.

Toward acquisition protocol standardization for estimating liver fat content using ultrasound attenuation coefficient imaging.

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.

Liver Fat Quantification With Ultrasound: Depth Dependence of Attenuation Coefficient.

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.

Liver Fibrosis, Fat, and Iron Evaluation with MRI and Fibrosis and Fat Evaluation with US: A Practical Guide for Radiologists.

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.