Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement. METHODS: Adult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI. RESULTS: Treatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively). CONCLUSIONS: In adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF. CLINICAL TRIAL NUMBER: NCT01265498. IMPACT AND IMPLICATIONS: Although central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.

A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

Point-of-care magnetic resonance technology to measure liver fat: Phantom and first-in-human pilot study.

PURPOSE: To assess feasibility and accuracy of point-of-care (POC) NMR-proton density fat fraction (PDFF) in phantoms and in a human pilot study in a POC setting. METHODS: POC NMR (LiverScope, Livivos, San Diego CA) PDFF measurements were obtained of certified phantoms with known PDFF values (0%-40%). In an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective human study, a convenience sample of participants from an obesity clinic was enrolled (November 2020 to June 2021). The inclusion criteria required body mass index (BMI) = 27-40 kg/m2 and willingness to undergo POC NMR and MRI-PDFF measurements. Liver PDFF was measured by POC NMR and, within 35 days after, by a confounder corrected CSE MRI PDFF acquisition and reconstruction method. The adverse events were documented and linear regression analyses were performed. RESULTS: POC NMR-PDFF measurements agreed with known phantom PDFF values (R2  = 0.99). Fourteen participants were enrolled in the pilot human study. MRI-PDFF could not be obtained in 4 participants (claustrophobia reaction, n = 3, exceeded size of MR scanner bore, n = 1). POC NMR was unevaluable in 2 participants (insufficient signal penetration depth, n = 1, failure to comply with instructions, n = 1). Technical success was 11 of 13 (85%) for POC NMR PDFF. In 7 participants (4 female; 31-74 years old; median BMI 35 kg/m2 ), MRI-PDFF (range, 2.8%-18.1%), and POC NMR-PDFF (range, 3%-25.2%), agreed with R2  = 0.94. POC NMR had no adverse events. CONCLUSION: POC NMR measures PDFF accurately in phantoms and, in a first-in-human pilot study, is feasible and accurate in adults with obesity. Further testing to determine precision and accuracy across larger and more diverse cohorts is needed.

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.

MR elastography in nonalcoholic fatty liver disease: inter-center and inter-analysis-method measurement reproducibility and accuracy at 3T.

OBJECTIVES: To assess reproducibility and fibrosis classification accuracy of magnetic resonance elastography (MRE)-determined liver stiffness measured manually at two different centers, and by automated analysis software in adults with nonalcoholic fatty liver disease (NAFLD), using histopathology as a reference standard. METHODS: This retrospective, cross-sectional study included 91 adults with NAFLD who underwent liver MRE and biopsy. MRE-determined liver stiffness was measured independently for this analysis by an image analyst at each of two centers using standardized manual analysis methodology, and separately by an automated analysis. Reproducibility was assessed pairwise by intraclass correlation coefficient (ICC) and Bland-Altman analysis. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analyses. RESULTS: ICC of liver stiffness measurements was 0.95 (95% CI: 0.93, 0.97) between center 1 and center 2 analysts, 0.96 (95% CI: 0.94, 0.97) between the center 1 analyst and automated analysis, and 0.94 (95% CI: 0.91, 0.96) between the center 2 analyst and automated analysis. Mean bias and 95% limits of agreement were 0.06 ± 0.38 kPa between center 1 and center 2 analysts, 0.05 ± 0.32 kPa between the center 1 analyst and automated analysis, and 0.11 ± 0.41 kPa between the center 2 analyst and automated analysis. The area under the ROC curves for the center 1 analyst, center 2 analyst, and automated analysis were 0.834, 0.833, and 0.847 for distinguishing fibrosis stage 0 vs. ≥ 1, and 0.939, 0.947, and 0.940 for distinguishing fibrosis stage ≤ 2 vs. ≥ 3. CONCLUSION: MRE-determined liver stiffness can be measured with high reproducibility and fibrosis classification accuracy at different centers and by an automated analysis. KEY POINTS: • Reproducibility of MRE liver stiffness measurements in adults with nonalcoholic fatty liver disease is high between two experienced centers and between manual and automated analysis methods. • Analysts at two centers had similar high diagnostic accuracy for distinguishing dichotomized fibrosis stages. • Automated analysis provides similar diagnostic accuracy as manual analysis for advanced fibrosis.

Magnetic resonance elastography biomarkers for detection of histologic alterations in nonalcoholic fatty liver disease in the absence of fibrosis.

OBJECTIVES: To investigate associations between histology and hepatic mechanical properties measured using multiparametric magnetic resonance elastography (MRE) in adults with known or suspected nonalcoholic fatty liver disease (NAFLD) without histologic fibrosis. METHODS: This was a retrospective analysis of 88 adults who underwent 3T MR exams including hepatic MRE and MR imaging to estimate proton density fat fraction (MRI-PDFF) within 180 days of liver biopsy. Associations between MRE mechanical properties (mean shear stiffness (|G*|) by 2D and 3D MRE, and storage modulus (G'), loss modulus (G″), wave attenuation (α), and damping ratio (ζ) by 3D MRE) and histologic, demographic and anthropometric data were assessed. RESULTS: In univariate analyses, patients with lobular inflammation grade ≥ 2 had higher 2D |G*| and 3D G″ than those with grade ≤ 1 (p = 0.04). |G*| (both 2D and 3D), G', and G″ increased with age (rho = 0.25 to 0.31; p ≤ 0.03). In multivariable regression analyses, the association between inflammation grade ≥ 2 remained significant for 2D |G*| (p = 0.01) but not for 3D G″ (p = 0.06); age, sex, or BMI did not affect the MRE-inflammation relationship (p > 0.20). CONCLUSIONS: 2D |G*| and 3D G″ were weakly associated with moderate or severe lobular inflammation in patients with known or suspected NAFLD without fibrosis. With further validation and refinement, these properties might become useful biomarkers of inflammation. Age adjustment may help MRE interpretation, at least in patients with early-stage disease. KEY POINTS: • Moderate to severe lobular inflammation was associated with hepatic elevated shear stiffness and elevated loss modulus (p =0.04) in patients with known or suspected NAFLD without liver fibrosis; this suggests that with further technical refinement these MRE-assessed mechanical properties may permit detection of inflammation before the onset of fibrosis in NAFLD. • Increasing age is associated with higher hepatic shear stiffness, and storage and loss moduli (rho = 0.25 to 0.31; p ≤ 0.03); this suggests that age adjustment may help interpret MRE results, at least in patients with early-stage NAFLD.

The relationship between liver triglyceride composition and proton density fat fraction as assessed by 1 H MRS.

The aim of this study was to estimate parameters determining liver triglyceride composition (TC) using 1 H MRS and to assess how TC estimability is affected by proton density fat fraction (PDFF) in adults with nonalcoholic fatty liver disease (NAFLD). In this prospective single-site study, 199 adults with known or suspected NAFLD in whom other causes of liver disease were excluded underwent two 1 H MRS STimulated Echo Acquisition Method (STEAM) sequences at 3 T. A respiratory-gated water-suppressed free breathing sequence (TE 10 ms, 16 signal averages) was used to assess TC in terms of the number of double bonds (ndb) and methylene-interrupted double bonds (nmidb), and a single breath-hold-long TR, multi-TE sequence (TR 3500 ms), which acquired five single average spectra over TE 10-30 ms, was used to estimate liver PDFF. Ndb and nmidb estimability was qualitatively assessed for each case and summarized descriptively. The consistency of ndb and nmidb estimation was examined using ROC analysis. The relationship between ndb and nmidb values and PDFF was presented graphically. Quality-of-fit of ndb and nmidb versus PDFF was evaluated by Pearson-r correlation. A significance level of 0.05 was used. In 263 1 H MRS examinations performed on 199 adult participants, ndb and nmidb were successfully estimated in 7/53 (13.2%) examinations with PDFF < 4%, 13/30 (43.3%) examinations with PDFF between 4% and 7%, 33/41 (80.5%) examinations with PDFF between 7% and 10%, and 124/139 (89.2%) examinations with PDFF > 10% (maximum PDFF 38.1%). Liver TC could be estimated consistently for PDFF > 6.7%. Both ndb and nmidb decreased with increasing PDFF (ndb = 2.83-0.0160·PDFF, r = -0.449, P < 0.0001); nmidb = 0.75-0.0088·PDFF, r = -0.350, P < 0.0001). In a cohort of adults with known or suspected NAFLD, liver TC becomes more saturated as PDFF increases.

Prospective comparison of longitudinal change in hepatic proton density fat fraction (PDFF) estimated by magnitude-based MRI (MRI-M) and complex-based MRI (MRI-C).

PURPOSE: To compare longitudinal hepatic proton density fat fraction (PDFF) changes estimated by magnitude- vs. complex-based chemical-shift-encoded MRI during a weight loss surgery (WLS) program in severely obese adults with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: This was a secondary analysis of a prospective dual-center longitudinal study of 54 adults (44 women; mean age 52 years; range 27-70 years) with obesity, biopsy-proven NAFLD, and baseline PDFF ≥ 5%, enrolled in a WLS program. PDFF was estimated by confounder-corrected chemical-shift-encoded MRI using magnitude (MRI-M)- and complex (MRI-C)-based techniques at baseline (visit 1), after a 2- to 4-week very low-calorie diet (visit 2), and at 1, 3, and 6 months (visits 3 to 5) after surgery. At each visit, PDFF values estimated by MRI-M and MRI-C were compared by a paired t test. Rates of PDFF change estimated by MRI-M and MRI-C for visits 1 to 3, and for visits 3 to 5 were assessed by Bland-Altman analysis and intraclass correlation coefficients (ICCs). RESULTS: MRI-M PDFF estimates were lower by 0.5-0.7% compared with those of MRI-C at all visits (p < 0.001). There was high agreement and no difference between PDFF change rates estimated by MRI-M vs. MRI-C for visits 1 to 3 (ICC 0.983, 95% CI 0.971, 0.99; bias = - 0.13%, p = 0.22), or visits 3 to 5 (ICC 0.956, 95% CI 0.919-0.977%; bias = 0.03%, p = 0.36). CONCLUSION: Although MRI-M underestimates PDFF compared with MRI-C cross-sectionally, this bias is consistent and MRI-M and MRI-C agree in estimating the rate of hepatic PDFF change longitudinally. KEY POINTS: • MRI-M demonstrates a significant but small and consistent bias (0.5-0.7%; p < 0.001) towards underestimation of PDFF compared with MRI-C at 3 T. • Rates of PDFF change estimated by MRI-M and MRI-C agree closely (ICC 0.96-0.98) in adults with severe obesity and biopsy- proven NAFLD enrolled in a weight loss surgery program. • Our findings support the use of either MRI technique (MRI-M or MRI-C) for clinical care or by individual sites or for multi-center trials that include PDFF change as an endpoint. However, since there is a bias in their measurements, the same technique should be used in any given patient for longitudinal follow-up.

Monitoring Fatty Liver Disease with MRI Following Bariatric Surgery: A Prospective, Dual-Center Study.

Purpose To longitudinally monitor liver fat before and after bariatric surgery by using quantitative chemical shift-encoded (CSE) MRI and to compare with changes in body mass index (BMI), weight, and waist circumference (WC). Materials and Methods For this prospective study, which was approved by the internal review board, a total of 126 participants with obesity who were undergoing evaluation for bariatric surgery with preoperative very low calorie diet (VLCD) were recruited from June 27, 2010, through May 5, 2015. Written informed consent was obtained from all participants. Participants underwent CSE MRI measuring liver proton density fat fraction (PDFF) before VLCD (2-3 weeks before surgery), after VLCD (1-3 days before surgery), and 1, 3, and 6-10 months following surgery. Linear regression was used to estimate rates of change of PDFF (ΔPDFF) and body anthropometrics. Initial PDFF (PDFF0), initial anthropometrics, and anthropometric rates of change were evaluated as predictors of ΔPDFF. Mixed-effects regression was used to estimate time to normalization of PDFF. Results Fifty participants (mean age, 51.0 years; age range, 27-70 years), including 43 women (mean age, 50.8 years; age range, 27-70 years) and seven men (mean age, 51.7 years; age range, 36-62 years), with mean PDFF0 ± standard deviation of 18.1% ± 8.6 and mean BMI0 of 44.9 kg/m2 ± 6.5 completed the study. By 6-10 months following surgery, mean PDFF decreased to 4.9% ± 3.4 and mean BMI decreased to 34.5 kg/m2 ± 5.4. Mean estimated time to PDFF normalization was 22.5 weeks ± 11.5. PDFF0 was the only strong predictor for both ΔPDFF and time to PDFF normalization. No body anthropometric correlated with either outcome. Conclusion Average liver proton density fat fraction (PDFF) decreased to normal (< 5%) by 6-10 months following surgery, with mean time to normalization of approximately 5 months. Initial PDFF was a strong predictor of both rate of change of PDFF and time to normalization. Body anthropometrics did not predict either outcome. Online supplemental material is available for this article. © RSNA, 2018.

Pilot study on longitudinal change in pancreatic proton density fat fraction during a weight-loss surgery program in adults with obesity.

BACKGROUND: Quantitative-chemical-shift-encoded (CSE)-MRI methods have been applied to the liver. The feasibility and potential utility CSE-MRI in monitoring changes in pancreatic proton density fat fraction (PDFF) have not yet been demonstrated. PURPOSE: To use quantitative CSE-MRI to estimate pancreatic fat changes during a weight-loss program in adults with severe obesity and nonalcoholic fatty liver disease (NAFLD). To explore the relationship of reduction in pancreatic PDFF with reductions in anthropometric indices. STUDY TYPE: Prospective/longitudinal. POPULATION: Nine adults with severe obesity and NAFLD enrolled in a weight-loss program. FIELD STRENGTH/SEQUENCE: CSE-MRI fat quantification techniques and multistation-volumetric fat/water separation techniques were performed at 3 T. ASSESSMENT: PDFF values were recorded from parametric maps colocalized across timepoints. STATISTICAL TESTS: Rates of change of log-transformed variables across time were determined (linear-regression), and their significance assessed compared with no change (Wilcoxon test). Rates of change were correlated pairwise (Spearman's correlation). RESULTS: Mean pancreatic PDFF decreased by 5.7% (range 0.7-17.7%) from 14.3 to 8.6%, hepatic PDFF by 11.4% (2.6-22.0%) from 14.8 to 3.4%, weight by 30.9 kg (17.3-64.2 kg) from 119.0 to 88.1 kg, body mass index by 11.0 kg/m2 (6.3-19.1 kg/m2 ) from 44.1 to 32.9 kg/m2 , waist circumference (WC) by 25.2 cm (4.0-41.0 cm) from 133.1 to 107.9 cm, HC by 23.5 cm (4.5-47.0 cm) from 135.8 to 112.3 cm, visceral adipose tissue (VAT) by 2.9 L (1.7-5.7 L) from 7.1 to 4.2 L, subcutaneous adipose tissue (SCAT) by 4.0 L (2.9-7.4 L) from 15.0 to 11.0 L. Log-transformed rate of change for pancreatic PDFF was moderately correlated with log-transformed rates for hepatic PDFF, VAT, SCAT, and WC (ρ = 0.5, 0.47, 0.45, and 0.48, respectively), although not statistically significant. DATA CONCLUSION: Changes in pancreatic PDFF can be estimated by quantitative CSE-MRI in adults undergoing a weight-loss surgery program. Pancreatic and hepatic PDFF and anthropometric indices decreased significantly. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1092-1102.

Assessment of a high-SNR chemical-shift-encoded MRI with complex reconstruction for proton density fat fraction (PDFF) estimation overall and in the low-fat range.

BACKGROUND: Improving the signal-to-noise ratio (SNR) of chemical-shift-encoded MRI acquisition with complex reconstruction (MRI-C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients with hepatic steatosis. PURPOSE: To assess the accuracy of high SNR (Hi-SNR) MRI-C versus standard MRI-C acquisition to estimate hepatic PDFF in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using an MR spectroscopy (MRS) sequence as the reference standard. STUDY TYPE: Prospective. POPULATION/SUBJECTS: In all, 231 adult and pediatric patients with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE: PDFF estimated at 3T by three MR techniques: standard MRI-C; a Hi-SNR MRI-C variant with increased slice thickness, decreased matrix size, and no parallel imaging; and MRS (reference standard). ASSESSMENT: MRI-PDFF was measured by image analysts using a region of interest coregistered with the MRS-PDFF voxel. STATISTICAL TESTS: Linear regression analyses were used to assess accuracy and precision of MRI-estimated PDFF for MRS-PDFF as a function of MRI-PDFF using the standard and Hi-SNR MRI-C for all patients and for patients with MRS-PDFF <10%. RESULTS: In all, 271 exams from 231 patients were included (mean MRS-PDFF: 12.6% [SD: 10.4]; range: 0.9-41.9). High agreement between MRI-PDFF and MRS-PDFF was demonstrated across the overall range of PDFF, with a regression slope of 1.035 for the standard MRI-C and 1.008 for Hi-SNR MRI-C. Hi-SNR MRI-C, compared to standard MRI-C, provided small but statistically significant improvements in the slope (respectively, 1.008 vs. 1.035, P = 0.004) and mean bias (0.412 vs. 0.673, P < 0.0001) overall. In the low-fat patients only, Hi-SNR MRI-C provided improvements in the slope (1.058 vs. 1.190, P = 0.002), mean bias (0.168 vs. 0.368, P = 0.007), intercept (-0.153 vs. -0.796, P < 0.0001), and borderline improvement in the R2 (0.888 vs. 0.813, P = 0.01). DATA CONCLUSION: Compared to standard MRI-C, Hi-SNR MRI-C provides slightly higher MRI-PDFF estimation accuracy across the overall range of PDFF and improves both accuracy and precision in the low PDFF range. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:229-238.

Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease.

BACKGROUND: The liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates. PURPOSE: To identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD). STUDY TYPE: Retrospective analysis of prospectively acquired data. POPULATION: Baseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials. FIELD STRENGTH: 1.5T and 3T; chemical-shift encoded multiecho gradient echo. ASSESSMENT: Correlation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*. STATISTICAL TESTS: Pearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method. RESULTS: Hepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P < 0.0001) and at 3T (r = 0.586, P < 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength. DATA CONCLUSION: Hepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1456-1466.

Longitudinal evolution of CT and MRI LI-RADS v2014 category 1, 2, 3, and 4 observations.

OBJECTIVES: This study assesses the risk of progression of Liver Imaging Reporting and Data System (LI-RADS) categories, and the effects of inter-exam changes in modality or radiologist on LI-RADS categorization. METHODS: Clinical LI-RADS v2014 CT and MRI exams at our institution between January 2014 and September 2017 were retrospectively identified. Untreated LR-1, LR-2, LR-3, and LR-4 observations with at least one follow-up exam were included. Three hundred and seventy-two observations in 214 patients (149 male, 65 female, mean age 61 ± 10 years) were included during the study period (715 exams total). Cumulative incidence curves for progression to malignant LI-RADS categories (LR-5 or LR-M) and to LR-4 or higher were generated for each index category and compared using log-rank tests with a resampling extension. Relationships between inter-exam changes in LI-RADS category and modality or radiologist, adjusted for inter-exam time intervals, were modeled using mixed effect logistic regressions. RESULTS: Median inter-exam follow-up interval and total follow-up duration were 123 and 227 days, respectively. Index LR-1, LR-2, LR-3, and LR-4 differed significantly in their cumulative incidences of progression to malignant categories (p < 0.0001), which were 0%, 2%, 7%, and 32% at 6 months, respectively. Index LR-1, LR-2, and LR-3 differed significantly in cumulative incidences of progression to LR-4 or higher (p = 0.003). MRI-MRI exam pairs had more stable LI-RADS categorization compared to CT-CT (OR = 0.460, p = 0.0018). CONCLUSIONS: LI-RADS observations demonstrate increasing risk of progression to malignancy with increasing category ranging from 0% for LR-1 to 32% for LR-4 at 6 months. Inter-exam modality changes are associated with LI-RADS category changes. KEY POINTS: • While the majority of LR-2 observations remain stable over long-term follow-up, LR-3 and especially LR-4 observations have a higher risk for category progression. • Category transitions between sequential exams using different modalities (CT vs. MRI) may reflect modality differences rather than biological change. MRI, especially with the same type of contrast agent, may provide the most reproducible categorization, although this needs additional validation. • In a clinical practice setting, in which radiologists refer to prior imaging and reports, there was no significant association between changes in radiologist and changes in LI-RADS categorization.

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.

Interreader Reliability of LI-RADS Version 2014 Algorithm and Imaging Features for Diagnosis of Hepatocellular Carcinoma: A Large International Multireader Study.

Purpose To determine in a large multicenter multireader setting the interreader reliability of Liver Imaging Reporting and Data System (LI-RADS) version 2014 categories, the major imaging features seen with computed tomography (CT) and magnetic resonance (MR) imaging, and the potential effect of reader demographics on agreement with a preselected nonconsecutive image set. Materials and Methods Institutional review board approval was obtained, and patient consent was waived for this retrospective study. Ten image sets, comprising 38-40 unique studies (equal number of CT and MR imaging studies, uniformly distributed LI-RADS categories), were randomly allocated to readers. Images were acquired in unenhanced and standard contrast material-enhanced phases, with observation diameter and growth data provided. Readers completed a demographic survey, assigned LI-RADS version 2014 categories, and assessed major features. Intraclass correlation coefficient (ICC) assessed with mixed-model regression analyses was the metric for interreader reliability of assigning categories and major features. Results A total of 113 readers evaluated 380 image sets. ICC of final LI-RADS category assignment was 0.67 (95% confidence interval [CI]: 0.61, 0.71) for CT and 0.73 (95% CI: 0.68, 0.77) for MR imaging. ICC was 0.87 (95% CI: 0.84, 0.90) for arterial phase hyperenhancement, 0.85 (95% CI: 0.81, 0.88) for washout appearance, and 0.84 (95% CI: 0.80, 0.87) for capsule appearance. ICC was not significantly affected by liver expertise, LI-RADS familiarity, or years of postresidency practice (ICC range, 0.69-0.70; ICC difference, 0.003-0.01 [95% CI: -0.003 to -0.01, 0.004-0.02]. ICC was borderline higher for private practice readers than for academic readers (ICC difference, 0.009; 95% CI: 0.000, 0.021). Conclusion ICC is good for final LI-RADS categorization and high for major feature characterization, with minimal reader demographic effect. Of note, our results using selected image sets from nonconsecutive examinations are not necessarily comparable with those of prior studies that used consecutive examination series. © RSNA, 2017.

Fibrinogen and the prediction of residual obstruction manifested after pulmonary embolism treatment.

Residual pulmonary vascular obstruction (RPVO) and chronic thromboembolic pulmonary hypertension (CTEPH) are both long-term complications of acute pulmonary embolism, but it is unknown whether RPVO can be predicted by variants of fibrinogen associated with CTEPH.We used the Akaike information criterion to select the best predictive models for RPVO in two prospectively followed cohorts of acute pulmonary embolism patients, using as candidate variables the extent of the initial obstruction, clinical characteristics and fibrinogen-related data. We measured the selected models' goodness of fit by analysis of deviance and compared models using the Chi-squared test.RPVO occurred in 29 (28.4%) out of 102 subjects in the first cohort and 46 (25.3%) out of 182 subjects in the second. The best-fit predictive model derived in the first cohort (p=0.0002) and validated in the second cohort (p=0.0005) implicated fibrinogen Bß-chain monosialylation in the development of RPVO. When the derivation procedure excluded clinical characteristics, fibrinogen Bß-chain monosialylation remained a predictor of RPVO in the best-fit predictive model (p=0.00003). Excluding fibrinogen characteristics worsened the predictive model (p=0.03).Fibrinogen Bß-chain monosialylation, a common structural attribute of fibrin, helped predict RPVO after acute pulmonary embolism. Fibrin structure may contribute to the risk of developing RPVO.

Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease.

Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two-dimensional (2D) MRE in children with NAFLD. MR elastograms were analyzed manually at two reading centers, and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross-validated. In 90 children with a mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r = 0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ = 0.53; center 2, ρ = 0.55; and automated analysis, ρ = 0.52; P < 0.001). Overall cross-validated accuracy for detecting any fibrosis was 72.2% for all methods (95% confidence interval [CI], 61.8%-81.1%). Overall cross-validated accuracy for assessing advanced fibrosis was 88.9% (95% CI, 80.5%-94.5%) for center 1, 90.0% (95% CI, 81.9%-95.3%) for center 2, and 86.7% (95% CI, 77.9%-92.9%) for automated analysis. CONCLUSION: 2D MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and validation of automated analysis techniques will be an important step in standardizing MRE. How to best integrate MRE into clinical protocols for the assessment of NAFLD in children will require prospective evaluation. (Hepatology 2017;66:1474-1485).

MRI proton density fat fraction is robust across the biologically plausible range of triglyceride spectra in adults with nonalcoholic steatohepatitis.

BACKGROUND: Proton density fat fraction (PDFF) estimation requires spectral modeling of the hepatic triglyceride (TG) signal. Deviations in the TG spectrum may occur, leading to bias in PDFF quantification. PURPOSE: To investigate the effects of varying six-peak TG spectral models on PDFF estimation bias. STUDY TYPE: Retrospective secondary analysis of prospectively acquired clinical research data. POPULATION: Forty-four adults with biopsy-confirmed nonalcoholic steatohepatitis. FIELD STRENGTH/SEQUENCE: Confounder-corrected chemical-shift-encoded 3T MRI (using a 2D multiecho gradient-recalled echo technique with magnitude reconstruction) and MR spectroscopy. ASSESSMENT: In each patient, 61 pairs of colocalized MRI-PDFF and MRS-PDFF values were estimated: one pair used the standard six-peak spectral model, the other 60 were six-peak variants calculated by adjusting spectral model parameters over their biologically plausible ranges. MRI-PDFF values calculated using each variant model and the standard model were compared, and the agreement between MRI-PDFF and MRS-PDFF was assessed. STATISTICAL TESTS: MRS-PDFF and MRI-PDFF were summarized descriptively. Bland-Altman (BA) analyses were performed between PDFF values calculated using each variant model and the standard model. Linear regressions were performed between BA biases and mean PDFF values for each variant model, and between MRI-PDFF and MRS-PDFF. RESULTS: Using the standard model, mean MRS-PDFF of the study population was 17.9 ± 8.0% (range: 4.1-34.3%). The difference between the highest and lowest mean variant MRI-PDFF values was 1.5%. Relative to the standard model, the model with the greatest absolute BA bias overestimated PDFF by 1.2%. Bias increased with increasing PDFF (P < 0.0001 for 59 of the 60 variant models). MRI-PDFF and MRS-PDFF agreed closely for all variant models (R2 = 0.980, P < 0.0001). DATA CONCLUSION: Over a wide range of hepatic fat content, PDFF estimation is robust across the biologically plausible range of TG spectra. Although absolute estimation bias increased with higher PDFF, its magnitude was small and unlikely to be clinically meaningful. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:995-1002.