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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., (Copyright © 2024 American Association for the Study of Liver Diseases.)

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., Competing Interests: Conflict of interest G.F. has received a speaker honorarium from Canon Medical Systems, Fujifilm Healthcare, Mindray Medical Imaging, Philips Ultrasound, Siemens Healthineers. She has served on advisory boards for Philips Healthcare and Siemens Healthineers and her university has received ultrasound equipment grants and unrestricted research grants from Canon Medical Systems, Esaote SpA, Fujifilm Medical Systems, Philips Ultrasound. She receives royalties from Elsevier Publisher. R.G.B. has received a speaker honorarium from Canon Medical systems, Philips Ultrasound, Siemens Healthineers, Mindray, Samsung Ultrasound, Hologic Ultrasound. He has received research grants from Philips Ultrasound, Canon Ultrasound, Canon MRI, Samsung, Siemens Healthineers, Hologic, Mindray and equipment grants from Canon Medical Systems, Philips Ultrasound, Mindray, Samsung Ultrasound and Siemens Healthineers. He is on the advisory board of Lantheus Medical. He receives royalties from Thieme Publishers and Elsevier Publisher. A.B. is consultant for Boehringer-Ingelheim and has received speaker honoraria from GE Healthcare and Hologic Ultrasound. She has received research ultrasound equipment support from GE Healthcare. I.S. has received speaker fees from Siemens Healthineers, General Electric, Samsung Ultrasound, Canon Medical Systems. V.W.W. served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and Visirna; and a speaker for Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab. He has received a research grant from Gilead Sciences and is a co-founder of Illuminatio Medical Technology. T.R. received grant support from Abbvie, Boehringer Ingelheim, Gilead, Intercept/Advanz Pharma, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, Siemens and W. L. Gore & Associates; speaking honoraria from Abbvie, Gilead, Intercept/Advanz Pharma, Roche, MSD, W. L. Gore & Associates; consulting/advisory board fee from Abbvie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Intercept/Advanz Pharma, MSD, Resolution Therapeutics, Siemens; and travel support from Abbvie, Boehringer Ingelheim, Dr. Falk Pharma, Gilead and Roche. T.K. has received speaker honoraria from Echosens, Falk Foundation and Jazz Pharmaceuticals. He has served on advisory boards for Echosens and his university has received ultrasound equipment and unrestricted research grants from Canon Medical Systems and Echosens. M.T. has received a speaker honorarium from Siemens Healthcare, Echosens, Norgine, Madrigal, Takeda, and Tillotts Pharma. Advisory fee from Boehringer Ingelheim, AstraZeneca, GSK. Co-founder and board member of Evido. Board member for Alcohol & Society (non-governmental organisation). A.C.C. has received speaker honorarium from Novo Nordisk. O.T.A. has served as a consultant or adviser to Novo Nordisk, Resonance Health, Norgine and Sun Pharma. He has received research ultrasound equipment support from Canon Medical Systems. L.C. has served as a consultant for Boston Pharmaceuticals, Echosens, GSK, Madrigal, MSD, Novo Nordisk, Pfizer, Sagimet and Siemens Healthineers; and lecture fees from Echosens, Gilead, Inventiva, Madrigal and Novo Nordisk. C.F.D. has received speaker honorarium from AbbVie, Bracco, Falk Foundation, Fujifilm Healthcare, GE Healthcare, Janssen, Mindray Medical Imaging, Olympus, Pentax, Siemens Healthcare, Sonoscape. H.I. has received research grants from Canon Medical Systems and GE Healthcare. She has received research ultrasound equipment support from Canon Medical Systems. D.H.L. has received research grants and speaker honorarium from Canon Medical Systems. W.K. has received speaker honorarium from Novo Nordisk, Eaisi, Roche. C.P.O. has been a consultant or participant in clinical trials for NovoNordisk, Pfizer, Inventiva, Astra-Zeneca, Boehringer Ingelheim. S.K.S. declares no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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/m 2 ; 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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024 American Institute of Ultrasound in Medicine.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abbattista, Meloni, Ferraioli and Pirri.)

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.

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., (© RSNA, 2022.)

Background & Aims: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis., Methods: A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades., Results: Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively., Conclusions: CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes., Lay Summary: There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Rationale for the Study: This cross-sectional multicenter study was conducted to investigate any difference in liver stiffness measurements (LSM), evaluated by transient elastography, between patients affected by β thalassaemia major, with and without hepatitis C virus (HCV) infection, and healthy blood donors (controls). Secondary aim was to assess any correlation between transient elastography and serum ferritin, liver magnetic resonance imaging (MRI) T2* or superconductive quantum interference device (SQUID) liver susceptometry values., Materials and Methods: The study involved three centers. Transient elastography and MRI T2* examinations were performed in all centers. SQUID liver susceptometry was performed in center1 and center2. T-test for independent data or Mann-Whitney U test was used to analyse differences between two groups. Univariate Pearson's r coefficient was used to test correlations between liver stiffness measurements and all other variables., Results: In a study with 119 patients and 183 controls, patients who had never been infected with HCV showed significantly higher LSMs than controls [5.7 (95% CI, 5.2-6.2) kPa vs. 4.3 (95% CI, 4.1-4.4) kPa, p < 0.0001]. A moderate correlation between LSMs and ferritin values, adjusted for gender and age, was found in patients (r = 0.49, p < 0.0001) but not in controls (r = -0.22, p = 0.6). No correlation between LSMs and MRI T2* or SQUID liver susceptometry values was observed. In conclusion, compared to controls β thalassaemia major patients had a significant increase in LSMs independently from HCV infection.

Objective: The purposes of this study were to assess the feasibility of a sonographic training program at a district hospital in a developing country and to evaluate the effect of the program on public health care services., Subjects and Methods: A sonographic training program is being conducted on Pemba Island, Tanzania. A maximum of 10 trainees participate in the program. Courses in sonography conducted by European physicians are scheduled every 4 months for 2 consecutive weeks each time. The sonographic training program lasts 5 years and is divided into three stages in which basic, advanced, and specialized courses are organized. At the end of every course, the trainees take a multiple-choice test (score, 1-10) and a practical test with patients (score, 1-5). To advance to the next stage, a trainee needs a score of at least 7 on the theory test and at least 3 on the practical., Results: Three courses have been completed. The total mean scores on the multiple-choice test were 7.4 (range, 6.5-9) at the end of the first course, 7.3 (range, 6.5-8.5) at the end of the second course, and 6.2 (range, 4.0-9.5) at the end of the third course. A shortage of electricity hindered the practical test after the first and second courses. At the end of the third course, the total mean score on the practical was 3.5 (range, 1.5-5.0). Seven of 10 trainees were admitted to the second year of the sonographic training program. The mean monthly hospital earnings during the three-course period were 673,200 Tanzanian shillings., Conclusion: Sonography is an affordable technology for developing countries. Training in sonography should be included in the planning of long-term projects in which multiple access and feedback are provided in the same area.

Background: The factors affecting intra-operator variability of two-dimensional shear wave elastography (2D-SWE) have not been clearly established. We evaluated 2D-SWE variability according to the number of measurements, clinical and laboratory features, and liver stiffness measurements (LSM). Methods: At least three LSM were performed in 452 patients who underwent LSM by 2D-SWE (supersonic shear imaging) out of an initial database of 1650 patients. The mean value of the three LSM was our best measurement method. Bland–Altman plots were used to evaluate intra-operator variability when considering only one, or the first two measurements. Variability was assessed by taking the absolute value of the difference between the first LSM and the mean of the three LSM. Logistic regression was used to assess the factors associated with the highest tertile of variability. Results: The limit of agreement was narrower with the mean of the first and second measurements than with each measurement taken separately (− 2.83 to 2.99 kPa vs. − 5.86 to 6.21 kPa and − 5.77 to 5.73 kPa for the first and second measurement, respectively). A BMI ≥ 25 kg/m2 and a first LSM by 2D-SWE ≥ 7.1 kPa increased the odds of higher variability by 3.4 and 3.9, respectively. Adding a second LSM didn't change the variability in patients with BMI < 25 and a first LSM by 2D-SWE < 7.1 kPa. Conclusions: Intra-operator variability of LSM by 2D-SWE increases with both a high BMI and high LSM value. In patients with BMI < 25 kg/m2 and a first LSM < 7.1 kPa we recommend performing only one LSM. [ABSTRACT FROM AUTHOR]

Conventional diagnostic ultrasound images of the anatomy (as opposed to blood flow) reveal differences in the acoustic properties of soft tissues (mainly echogenicity but also, to some extent, attenuation), whereas ultrasound-based elasticity images are able to reveal the differences in the elastic properties of soft tissues (e.g., elasticity and viscosity). The benefit of elasticity imaging lies in the fact that many soft tissues can share similar ultrasonic echogenicities but may have different mechanical properties that can be used to clearly visualize normal anatomy and delineate pathologic lesions. Typically, all elasticity measurement and imaging methods introduce a mechanical excitation and monitor the resulting tissue response. Some of the most widely available commercial elasticity imaging methods are ‘quasi-static’ and use external tissue compression to generate images of the resulting tissue strain (or deformation). In addition, many manufacturers now provide shear wave imaging and measurement methods, which deliver stiffness images based upon the shear wave propagation speed. The goal of this review is to describe the fundamental physics and the associated terminology underlying these technologies. We have included a questions and answers section, an extensive appendix, and a glossary of terms in this manuscript. We have also endeavored to ensure that the terminology and descriptions, although not identical, are broadly compatible across the WFUMB and EFSUMB sets of guidelines on elastography ( Bamber et al. 2013; Cosgrove et al. 2013 ). [ABSTRACT FROM AUTHOR]

Abstract: To assess the comparability of ultrasonographic (US) subcutaneous fat thickness (SFT) measurements in comparison with computed tomography (CT) at reference points (RPs) representative of HIV related adipose redistribution syndrome (HARS) in patients treated with antiretrovirals. US and CT measurements were compared in nine patients with clinical reports of HARS. We obtained the best resolution of facial (at deepest point of Bichat pad), brachial (in the dorsal face of arm) and crural SFT (at mid thigh) by means of minimal transducer pressures avoiding potential biases such as stand off pads pressure on the skin and artefacts due to too abundant quantity of gel. CT scans were obtained in the same RP where US measurements were performed such as identified by means of metallic skin markers. Median US measurement of facial SFT was 8.8 mm (95% CI: 3.1 to 13.4), 3.95 mm (95% CI: 2.62 to 5.84) for brachial SFT and 4 mm (95% CI: 3.4 to 9.4) for crural SFT. Median CT assessments of facial SFT was 8.7 mm (95% CI: 3.5 to 13.5), 4.2 mm (95% CI: 2.6 to 5.88) for brachial SFT and 5 mm (95% CI: 3.9 to 10.3) for crural SFT, with no significant difference at each RP. A linear regression showed good CT/US comparability at each RP, with no significant deviation from linearity (p > 0.10). US shows to be highly comparable with CT, excluding invaliding biases as the transducer pressure on the skin. Given the proven efficacy on the HARS assessments, if well standardized, US could be a reliable method, simpler than CT in the management of body fat changes related to HARS. (E-mail: steinman@imaging.robarts.ca) [Copyright &y& Elsevier]