Comparative diagnostic performance of ultrasound shear wave elastography and magnetic resonance elastography for classifying fibrosis stage in adults with biopsy-proven nonalcoholic fatty liver disease.

OBJECTIVES: To compare the diagnostic accuracy of US shear wave elastography (SWE) and magnetic resonance elastography (MRE) for classifying fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Patients from a prospective single-center cohort with clinical liver biopsy for known or suspected NAFLD underwent contemporaneous SWE and MRE. AUCs for classifying biopsy-determined liver fibrosis stages ≥ 1, ≥ 2, ≥ 3, and = 4, and their respective performance parameters at cutoffs providing ≥ 90% sensitivity or specificity were compared between SWE and MRE. RESULTS: In total, 100 patients (mean age, 51.8 ± 12.9 years; 46% males; mean BMI 31.6 ± 4.7 kg/m2) with fibrosis stage distribution (stage 0/1/2/3/4) of 43, 36, 5, 10, and 6%, respectively, were included. AUCs (and 95% CIs) for SWE and MRE were 0.65 (0.54-0.76) and 0.81 (0.72-0.89), 0.81 (0.71-0.91) and 0.94 (0.89-1.00), 0.85 (0.74-0.96) and 0.95 (0.89-1.00), and 0.91 (0.79-1.00) and 0.92 (0.83-1.00), for detecting fibrosis stage ≥ 1, ≥ 2, ≥ 3, and = 4, respectively. The differences were significant for detecting fibrosis stage ≥ 1 and ≥ 2 (p < 0.01) but not otherwise. At ≥ 90% sensitivity cutoff, MRE yielded higher specificity than SWE at diagnosing fibrosis stage ≥ 1, ≥ 2, and ≥ 3. At ≥ 90% specificity cutoff, MRE yielded higher sensitivity than SWE at diagnosing fibrosis stage ≥ 1 and ≥ 2. CONCLUSIONS: In adults with NAFLD, MRE was more accurate than SWE in diagnosing stage ≥ 1 and ≥ 2 fibrosis, but not stage ≥ 3 or 4 fibrosis. KEY POINTS: • For detecting any fibrosis or mild fibrosis, MR elastography was significantly more accurate than shear wave elastography. • For detecting advanced fibrosis and cirrhosis, MRE and SWE did not differ significantly in accuracy. • For excluding advanced fibrosis and potentially ruling out the need for biopsy, SWE and MRE did not differ significantly in negative predictive value. • Neither SWE nor MRE had sufficiently high positive predictive value to rule in advanced fibrosis.

Repeatability and accuracy of various region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification.

PURPOSE: To evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat fraction (PDFF) and to assess error relative to the 9-ROI PDFF. METHODS: This was a secondary analysis in subjects with known or suspected nonalcoholic fatty liver disease who underwent MRI for magnitude-based hepatic PDFF quantification. Each subject underwent three exams, each including three acquisitions (nine acquisitions total). An ROI was placed in each hepatic segment on the first acquisition of the first exam and propagated to other acquisitions. PDFF was calculated for each of 511 sampling strategies using every combination of 1, 2, …, all 9 ROIs. Intra- and inter-exam intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs) were estimated for each sampling strategy. Mean absolute error (MAE) was estimated relative to the 9-ROI PDFF. Strategies that sampled both lobes evenly ("balanced") were compared with those that did not ("unbalanced") using two-sample t tests. RESULTS: The 29 enrolled subjects (23 male, mean age 24 years) had mean 9-ROI PDFF 11.8% (1.1-36.3%). With more ROIs, ICCs increased, RCs decreased, and MAE decreased. Of the 60 balanced strategies with 4 ROIs, all (100%) achieved inter- and intra-exam ICCs > 0.998, 55 (92%) achieved intra-exam RC < 1%, 50 (83%) achieved inter-exam RC < 1%, and all (100%) achieved MAE < 1%. Balanced sampling strategies had higher ICCs and lower RCs, and lower MAEs than unbalanced strategies in aggregate (p < 0.001 for comparisons between balanced vs. unbalanced strategies). CONCLUSION: Repeatability improves and error diminishes with more ROIs. Balanced 4-ROI strategies provide high repeatability and low error.

Normal range for MR elastography measured liver stiffness in children without liver disease.

BACKGROUND: Magnetic resonance elastography (MRE) can determine the presence and stage of liver fibrosis. Data on normative MRE values, while reported in adults, are limited in children. PURPOSE: To determine the distribution of MRE-measured liver stiffness in children without liver disease. STUDY TYPE: Prospective, observational. POPULATION: Eighty-one healthy children (mean 12.6 ± 2.6 years, range 8-17 years). FIELD STRENGTH/SEQUENCE: 3.0T Signa HDxt, General Electric MR Scanner; 2D GRE MRE sequence. ASSESSMENT: History, examination, laboratory evaluation, and (MR) exams (proton density fat fraction, PDFF, and MRE) were performed. MR elastograms were analyzed manually at two reading centers and compared with each other for agreement and with published values in healthy adults and thresholds for fibrosis in adult and pediatric patients. STATISTICAL TESTS: Descriptive statistics, Bland-Altman analysis, t-test to compare hepatic stiffness values with reference standards. RESULTS: Stiffness values obtained at both reading centers were similar, without significant bias (P = 0.362) and with excellent correlation (intraclass correlation coefficient [ICC] = 0.782). Mean hepatic stiffness value for the study population was 2.45 ± 0.35 kPa (95th percentile 3.19 kPa), which was significantly higher than reported values for healthy adult subjects (2.10 ± 0.23 kPa, P < 0.001). In all, 74-85% of subjects had stiffness measurements suggestive of no fibrosis. DATA CONCLUSION: Mean liver stiffness measured with MRE in this cohort was significantly higher than that reported in healthy adults. Despite rigorous screening, some healthy children had stiffness measurements suggestive of liver fibrosis using current published thresholds. Although MRE has the potential to provide noninvasive assessment in patients with suspected hepatic disease, further refinement of this technology will help advance its use as a diagnostic tool for evidence of fibrosis in pediatric populations. LEVEL OF EVIDENCE: 1 Technical Efficacy: 5 J. Magn. Reson. Imaging 2020;51:919-927.

Reader agreement and accuracy of ultrasound features for hepatic steatosis.

PURPOSE: The purpose of the study is to assess the reader agreement and accuracy of eight ultrasound imaging features for classifying hepatic steatosis in adults with known or suspected hepatic steatosis. METHODS: This was an IRB-approved, HIPAA-compliant prospective study of adult patients with known or suspected hepatic steatosis. All patients signed written informed consent. Ultrasound images (Siemens S3000, 6C1HD, and 4C1 transducers) were acquired by experienced sonographers following a standard protocol. Eight readers independently graded eight features and their overall impression of hepatic steatosis on ordinal scales using an electronic case report form. Duplicated images from the 6C1HD transducer were read twice to assess intra-reader agreement. Intra-reader, inter-transducer, and inter-reader agreement were assessed using intraclass correlation coefficients (ICC). Features with the highest intra-reader agreement were selected as predictors for dichotomized histological steatosis using Classification and Regression Tree (CART) analysis, and the accuracy of the decision rule was compared to the accuracy of the radiologists' overall impression. RESULTS: 45 patients (18 males, 27 females; mean age 56 ± 12 years) scanned from September 2015 to July 2016 were included. Mean intra-reader ICCs ranged from 0.430 to 0.777, inter-transducer ICCs ranged from 0.228 to 0.640, and inter-reader ICCs ranged from 0.014 to 0.561. The CART decision rule selected only large hepatic vein blurring and achieved similar accuracy to the overall impression (74% to 75% and 68% to 72%, respectively). CONCLUSIONS: Large hepatic vein blurring, liver-kidney contrast, and overall impression provided the highest reader agreement. Large hepatic vein blurring may provide the highest classification accuracy for dichotomized grading of hepatic steatosis.

Hepatic steatosis and reduction in steatosis following bariatric weight loss surgery differs between segments and lobes.

OBJECTIVES: The purpose of this study was to (1) evaluate proton density fat fraction (PDFF) distribution across liver segments at baseline and (2) compare longitudinal segmental PDFF changes across time points in adult patients undergoing a very low-calorie diet (VLCD) and subsequent bariatric weight loss surgery (WLS). METHODS: We performed a secondary analysis of data from 118 morbidly obese adult patients enrolled in a VLCD-WLS program. PDFF was estimated using magnitude-based confounder-corrected chemical-shift-encoded (CSE) MRI in each hepatic segment and lobe at baseline (visit 1), after completion of VLCD (visit 2), and at 1, 3, and 6 months (visits 3-5) following WLS. Linear regressions were used to estimate the rate of PDFF change across visits. Lobar and segmental rates of change were compared pairwise. RESULTS: Baseline PDFF was significantly higher in the right lobe compared to the left lobe (p < 0.0001). Lobar and segmental PDFF declined by 3.9-4.5% per month between visits 1 and 2 (preoperative period) and by 4.3-4.8% per month between visits 1 and 3 (perioperative period), but no significant pairwise differences were found in slope between segments and lobes. For visits 3-5 (postoperative period), lobar and segmental PDFF reduction was much less overall (0.4-0.8% PDFF per month) and several pairwise differences were significant; in each case, a right-lobe segment had greater decline than a left-lobe segment. CONCLUSIONS: Baseline and longitudinal changes in fractional fat content in the 5-month postoperative period following WLS vary across segments, with right-lobe segments having higher PDFF at baseline and more rapid reduction in liver fat content. KEY POINTS: • Baseline and longitudinal changes in liver fat following bariatric weight loss surgery vary across liver segments. • Methods that do not provide whole liver fat assessment, such as liver biopsy, may be unreliable in monitoring longitudinal changes in liver fat following weight loss interventions.

Optimization of region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification.

BACKGROUND: Clinical trials utilizing proton density fat fraction (PDFF) as an imaging biomarker for hepatic steatosis have used a laborious region-of-interest (ROI) sampling strategy of placing an ROI in each hepatic segment. PURPOSE: To identify a strategy with the fewest ROIs that consistently achieves close agreement with the nine-ROI strategy. STUDY TYPE: Retrospective secondary analysis of prospectively acquired clinical research data. POPULATION: A total of 391 adults (173 men, 218 women) with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE: Confounder-corrected chemical-shift-encoded 3T MRI using a 2D multiecho gradient-recalled echo technique. ASSESSMENT: An ROI was placed in each hepatic segment. Mean nine-ROI PDFF and segmental PDFF standard deviation were computed. Segmental and lobar PDFF were compared. PDFF was estimated using every combinatorial subset of ROIs and compared to the nine-ROI average. STATISTICAL TESTING: Mean nine-ROI PDFF and segmental PDFF standard deviation were summarized descriptively. Segmental PDFF was compared using a one-way analysis of variance, and lobar PDFF was compared using a paired t-test and a Bland-Altman analysis. The PDFF estimated by every subset of ROIs was informally compared to the nine-ROI average using median intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS: The study population's mean whole-liver PDFF was 10.1 ± 8.9% (range: 1.1-44.1%). Although there was no significant difference in average segmental (P = 0.452) or lobar (P = 0.154) PDFF, left and right lobe PDFF differed by at least 1.5 percentage points in 25.1% (98/391) of patients. Any strategy with ≥4 ROIs had ICC >0.995. 115 of 126 four-ROI strategies (91%) had limits of agreement (LOA) <1.5%, including four-ROI strategies with two ROIs from each lobe, which all had LOA <1.5%. 14/36 (39%) of two-ROI strategies and 74/84 (88%) of three-ROI strategies had ICC >0.995, and 2/36 (6%) of two-ROI strategies and 46/84 (55%) of three-ROI strategies had LOA <1.5%. DATA CONCLUSION: Four-ROI sampling strategies with two ROIs in the left and right lobes achieve close agreement with nine-ROI PDFF. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:988-994.

In vivo triglyceride composition of abdominal adipose tissue measured by 1 H MRS at 3T.

PURPOSE: To investigate the regional variability of adipose tissue triglyceride composition in vivo using 1 H MRS, examining potential confounders and corrections for artifacts, to allow for adipose tissue spectrum estimation. MATERIALS AND METHODS: 1 H magnetic resonance (MR) stimulated echo acquisition mode (STEAM) spectra were acquired in vivo at 3T from 340 adult patients (mean age 48.9 years, range 21-79 years; 172 males, 168 females; mean body mass index [BMI] 34.0, range 22-49 kg/m2 ) with known or suspected nonalcoholic fatty liver disease (NAFLD) in deep (dSCAT), surface (sSCAT) subcutaneous adipose tissue, and visceral adipose tissue (VAT). Triglyceride composition was characterized by the number of double bonds (ndb) and number of methylene-interrupted double bonds (nmidb). A subset of patients (dSCAT n = 80, sSCAT n = 55, VAT n = 194) had the acquisition repeated three times to examine the repeatability of ndb and nmidb estimation. RESULTS: Mean ndb and nmidb showed significant (P < 0.0001) differences between depots except for dSCAT and sSCAT nmidb (dSCAT ndb 2.797, nmidb 0.745; sSCAT ndb 2.826, nmidb 0.737; VAT ndb 2.723, nmidb 0.687). All ndb and nmidb estimates were highly repeatable (VAT ndb ICC = 0.888, nmidb ICC = 0.853; sSCAT: ndb ICC = 0.974, nmidb ICC = 0.964; dSCAT: ndb ICC = 0.959, nmidb ICC = 0.948). CONCLUSION: Adipose tissue composition can be estimated repeatably using 1 H MRS and different fat depots have different triglyceride compositions. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1455-1463.

Accuracy and the effect of possible subject-based confounders of magnitude-based MRI for estimating hepatic proton density fat fraction in adults, using MR spectroscopy as reference.

PURPOSE: To determine the accuracy and the effect of possible subject-based confounders of magnitude-based magnetic resonance imaging (MRI) for estimating hepatic proton density fat fraction (PDFF) for different numbers of echoes in adults with known or suspected nonalcoholic fatty liver disease, using MR spectroscopy (MRS) as a reference. MATERIALS AND METHODS: In this retrospective analysis of 506 adults, hepatic PDFF was estimated by unenhanced 3.0T MRI, using right-lobe MRS as reference. Regions of interest placed on source images and on six-echo parametric PDFF maps were colocalized to MRS voxel location. Accuracy using different numbers of echoes was assessed by regression and Bland-Altman analysis; slope, intercept, average bias, and R2 were calculated. The effect of age, sex, and body mass index (BMI) on hepatic PDFF accuracy was investigated using multivariate linear regression analyses. RESULTS: MRI closely agreed with MRS for all tested methods. For three- to six-echo methods, slope, regression intercept, average bias, and R2 were 1.01-0.99, 0.11-0.62%, 0.24-0.56%, and 0.981-0.982, respectively. Slope was closest to unity for the five-echo method. The two-echo method was least accurate, underestimating PDFF by an average of 2.93%, compared to an average of 0.23-0.69% for the other methods. Statistically significant but clinically nonmeaningful effects on PDFF error were found for subject BMI (P range: 0.0016 to 0.0783), male sex (P range: 0.015 to 0.037), and no statistically significant effect was found for subject age (P range: 0.18-0.24). CONCLUSION: Hepatic magnitude-based MRI PDFF estimates using three, four, five, and six echoes, and six-echo parametric maps are accurate compared to reference MRS values, and that accuracy is not meaningfully confounded by age, sex, or BMI.