Brentuximab vedotin with dacarbazine or nivolumab as frontline cHL therapy for older patients ineligible for chemotherapy.

ABSTRACT: Older patients with advanced-stage classical Hodgkin lymphoma (cHL) have inferior outcomes compared with younger patients, potentially due to comorbidities and frailty. This noncomparative phase 2 study enrolled patients aged ≥60 years with cHL unfit for conventional chemotherapy to receive frontline brentuximab vedotin (BV; 1.8 mg/kg) with dacarbazine (DTIC; 375 mg/m2) (part B) or nivolumab (part D; 3 mg/kg). In parts B and D, 50% and 38% of patients, respectively, had ≥3 general comorbidities or ≥1 significant comorbidity. Of the 22 patients treated with BV-DTIC, 95% achieved objective response, and 64% achieved complete response (CR). With a median follow-up of 63.6 months, median duration of response (mDOR) was 46.0 months. Median progression-free survival (mPFS) was 47.2 months; median overall survival (mOS) was not reached. Of 21 patients treated with BV-nivolumab, 86% achieved objective response, and 67% achieved CR. With 51.6 months of median follow-up, mDOR, mPFS, and mOS were not reached. Ten patients (45%) with BV-DTIC and 16 patients (76%) with BV-nivolumab experienced grade ≥3 treatment-emergent adverse events; sensory peripheral neuropathy (PN; 27%) and neutropenia (9%) were most common with BV-DTIC, and increased lipase (24%), motor PN (19%), and sensory PN (19%) were most common with BV-nivolumab. Despite high median age, inclusion of patients aged ≤88 years, and frailty, these results demonstrate safety and promising durable efficacy of BV-DTIC and BV-nivolumab combinations as frontline treatment, suggesting potential alternatives for older patients with cHL unfit for initial conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806.

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.

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.

LI-RADS ancillary feature prediction of longitudinal category changes in LR-3 observations: an exploratory study.

PURPOSE: To determine whether LI-RADS ancillary features predict longitudinal LR-3 observation category changes. MATERIALS AND METHODS: This exploratory, retrospective, single-center study with an independent reading center included patients who underwent two or more multiphase CT or MRI examinations for hepatocellular carcinoma assessment between 2011 and 2015. Three readers independently evaluated each observation using CT/MRI LI-RADS v2017, and observations categorized LR-3 using major features only were included in the analysis. Prevalence of major and ancillary features was calculated. After excluding low-frequency (< 5%) features, inter-reader agreement was assessed using intraclass correlation coefficient (ICC). Major and ancillary feature prediction of observation upgrade (to LR-4 or higher) or downgrade (to LR-1 or LR-2) on follow-up imaging was assessed using logistic regression. RESULTS: 141 LR-3 observations in 79 patients were included. Arterial phase hyperenhancement, washout, restricted diffusion, mild-moderate T2 hyperintensity, and hepatobiliary phase hypointensity were frequent enough for further analysis (consensus prevalence 5.0-66.0%). ICCs for inter-reader agreement ranged from 0.18 for restricted diffusion to 0.48 for hepatobiliary phase hypointensity. On follow-up, 40% (57/141) of baseline LR-3 observations remained LR-3. 8% (11/141) were downgraded to LR-2, and 42% (59/141) were downgraded to LR-1. A small number were ultimately upgraded to LR-4 (2%, 3/141) or LR-5 (8%, 11/141). None of the assessed major or ancillary features was significantly associated with observation category change. Longer follow-up time was significantly associated with both observation upgrade and downgrade. CONCLUSION: While numerous ancillary features are described in LI-RADS, most are rarely present and are not useful predictors of LR-3 observation category changes.

MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial).

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n = 25) or placebo (n = 25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (± standard deviation) of age and body mass index were 48.2 ± 10.3 years and 30.7 ± 4.6 kg/m2 , respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P = 0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P = 0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P = 0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

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.

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.

Inter-reader agreement of magnetic resonance imaging proton density fat fraction and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis.

PURPOSE: To determine the inter-reader agreement of magnetic resonance imaging proton density fat fraction (PDFF) and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis (NASH). STUDY TYPE: We performed a secondary analysis of a placebo-controlled randomized clinical trial of a bile acid sequestrant in 45 adults with NASH. A six-echo spoiled gradient-recalled-echo magnitude-based fat quantification technique was performed at 3 T. Three independent readers measured MRI-PDFF by placing one primary and two additional regions of interest (ROIs) in each segment at both time points. Cross-sectional agreement between the three readers was evaluated using intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Additionally, we used Bland-Altman analyses to examine pairwise agreement between the three readers at baseline, end of treatment (EOT), and for longitudinal change. RESULTS: Using all ROIs by all readers, mean PDFF at baseline, at EOT, and mean change in PDFF was 16.1%, 16.0%, and 0.07%, respectively. The 27-ROI PDFF measurements had 0.998 ICC and 1.8% CV at baseline, 0.998 ICC and 1.8% CV at EOT, and 0.997 ICC for longitudinal change. The 9-ROI PDFF measurements had corresponding values of 0.997 and 2.6%, 0.996 and 2.4%, and 0.994. Using 27 ROIs, the magnitude of the bias between readers for whole-liver PDFF measurement ranged from 0.03% to 0.06% points at baseline, 0.01% to 0.07% points at EOT, and 0.01% to 0.02% points for longitudinal change. CONCLUSION: Inter-reader agreement for measuring whole-liver PDFF and its longitudinal change is high. 9-ROI measurements have only slightly lower agreement than 27-ROI measurements.

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.

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.

Automated CT and MRI Liver Segmentation and Biometry Using a Generalized Convolutional Neural Network.

PURPOSE: To assess feasibility of training a convolutional neural network (CNN) to automate liver segmentation across different imaging modalities and techniques used in clinical practice and apply this to enable automation of liver biometry. METHODS: We trained a 2D U-Net CNN for liver segmentation in two stages using 330 abdominal MRI and CT exams acquired at our institution. First, we trained the neural network with non-contrast multi-echo spoiled-gradient-echo (SGPR)images with 300 MRI exams to provide multiple signal-weightings. Then, we used transfer learning to generalize the CNN with additional images from 30 contrast-enhanced MRI and CT exams.We assessed the performance of the CNN using a distinct multi-institutional data set curated from multiple sources (n = 498 subjects). Segmentation accuracy was evaluated by computing Dice scores. Utilizing these segmentations, we computed liver volume from CT and T1-weighted (T1w) MRI exams, and estimated hepatic proton- density-fat-fraction (PDFF) from multi-echo T2*w MRI exams. We compared quantitative volumetry and PDFF estimates between automated and manual segmentation using Pearson correlation and Bland-Altman statistics. RESULTS: Dice scores were 0.94 ± 0.06 for CT (n = 230), 0.95 ± 0.03 (n = 100) for T1w MR, and 0.92 ± 0.05 for T2*w MR (n = 169). Liver volume measured by manual and automated segmentation agreed closely for CT (95% limit-of-agreement (LoA) = [-298 mL, 180 mL]) and T1w MR (LoA = [-358 mL, 180 mL]). Hepatic PDFF measured by the two segmentations also agreed closely (LoA = [-0.62%, 0.80%]). CONCLUSIONS: Utilizing a transfer-learning strategy, we have demonstrated the feasibility of a CNN to be generalized to perform liver segmentations across different imaging techniques and modalities. With further refinement and validation, CNNs may have broad applicability for multimodal liver volumetry and hepatic tissue characterization.

Gadoxetate-enhanced Abbreviated MRI for Hepatocellular Carcinoma Surveillance: Preliminary Experience.

Purpose: To describe a single-center preliminary experience with gadoxetate disodium-enhanced abbreviated MRI for hepatocellular carcinoma (HCC) screening and surveillance in patients with cirrhosis or chronic hepatitis B virus (cHBV). Materials and Methods: This was a retrospective study of consecutive patients aged 18 years and older with cirrhosis or cHBV who underwent at least one gadoxetate-enhanced abbreviated MRI examination for HCC surveillance from 2014 through 2016. Examinations were interpreted prospectively by one of six abdominal radiologists for clinical care. Clinical, imaging, and other data were extracted from electronic medical records. Diagnostic adequacy was assessed in all patients. Diagnostic accuracy was assessed in the subset of patients who could be classified as having HCC or not having HCC on the basis of a composite reference standard. Results: In this study, 330 patients (93% with cirrhosis; 45% women; mean age, 59 years) underwent gadoxetate-enhanced abbreviated MRI. In the 330 patients, 311 (94.2%) baseline gadoxetate-enhanced abbreviated MRI examinations were diagnostically adequate. Of 141 (43%) of the 330 patients, 91.4% (129 of 141) could be classified as not having HCC and 8.6% (12 of 141) could be classified as having HCC. Baseline gadoxetate-enhanced abbreviated MRI had 0.92 sensitivity (95% confidence interval [CI]: 0.62, 1.00) and 0.91 specificity (95% CI: 0.84, 0.95) for detection of HCC. Of the 330 patients who underwent baseline gadoxetate-enhanced abbreviated MRI, 187 (57%) were lost to follow-up. Conclusion: Gadoxetate-enhanced abbreviated MRI is feasible clinically, has a high diagnostic adequacy rate, and, on the basis of our preliminary experience, accurately depicts HCC in high-risk patients. Strategies to enhance follow-up compliance are needed.© RSNA, 2019Keywords: Abdomen/GI, Cirrhosis, Liver, MR-Imaging, Oncology, ScreeningSupplemental material is available for this article.

Cross-sectional correlation between hepatic R2* and proton density fat fraction (PDFF) in children with hepatic steatosis.

PURPOSE: To determine the relationship between hepatic proton density fat fraction (PDFF) and R2* in vivo. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board (IRB)-approved, cross-sectional study, we conducted a secondary analysis of 3T magnetic resonance imaging (MRI) exams performed as part of prospective research studies in children in whom conditions associated with iron overload were excluded clinically. Each exam included low-flip-angle, multiecho magnitude (-M) and complex (-C) based chemical-shift-encoded MRI techniques with spectral modeling of fat to generate hepatic PDFF and R2* parametric maps. For each technique and each patient, regions of interest were placed on the maps in each of the nine Couinaud segments, and composite whole-liver PDFF and R2* values were calculated. Pearson's correlation coefficients between PDFF and R2* were computed for each MRI technique. Correlations were compared using Steiger's test. RESULTS: In all, 184 children (123 boys, 61 girls) were included in this analysis. PDFF estimated by MRI-M and MRI-C ranged from 1.1-35.4% (9.44 ± 8.76) and 2.1-38.1% (10.1 ± 8.7), respectively. R2* estimated by MRI-M and MRI-C ranged from 32.6-78.7 s-1 (48.4 ± 9.8) and 27.2-71.5 s-1 (42.2 ± 8.6), respectively. There were strong and significant correlations between hepatic PDFF and R2* values estimated by MRI-M (r = 0.874; P < 0.0001) and MRI-C (r = 0.853; P < 0.0001). The correlation coefficients (0.874 vs. 0.853) were not significantly different (P = 0.15). CONCLUSION: Hepatic PDFF and R2* are strongly correlated with each other in vivo. This relationship was observed using two different MRI techniques. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:418-424.

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.

Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review.

The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.

Technical report: gadoxetate-disodium-enhanced 2D R2* mapping: a novel approach for assessing bile ducts in living donors.

PURPOSE: Gadoxetate-disodium (Gd-EOB-DTPA)-enhanced 3D T1- weighted (T1w) MR cholangiography (MRC) is an efficient method to evaluate biliary anatomy due to T1 shortening of excreted contrast in the bile. A method that exploits both T1 shortening and T2* effects may produce even greater bile duct conspicuity. The aim of our study is to determine feasibility and compare the diagnostic performance of two-dimensional (2D) T1w multi-echo (ME) spoiled gradient-recalled-echo (SPGR) derived R2* maps against T1w MRC for bile duct visualization in living liver donor candidates. MATERIALS AND METHODS: Ten potential living liver donor candidates underwent pretransplant 3T MRI and were included in our study. Following injection of Gd-EOBDTPA and a 20-min delay, 3D T1w MRC and 2D T1w ME SPGR images were acquired. 2D R2* maps were generated inline by the scanner assuming exponential decay. The 3D T1w MRC and 2D R2* maps were retrospectively and independently reviewed in two separate sessions by three radiologists. Visualization of eight bile duct segments was scored using a 4-point ordinal scale. The scores were compared using mixed effects regression model. RESULTS: Imaging was tolerated by all donors and R2* maps were successfully generated in all cases. Visualization scores of 2D R2* maps were significantly higher than 3D T1w MRC for right anterior (p = 0.003) and posterior (p = 0.0001), segment 2 (p < 0.0001), segment 3 (p = 0.0001), and segment 4 (p < 0.0001) ducts. CONCLUSIONS: Gd-EOB-DTPA-enhanced 2D R2* mapping is a feasible method for evaluating the bile ducts in living donors and may be a valuable addition to the living liver donor MR protocol for delineating intrahepatic biliary anatomy.

Imaging Outcomes of Liver Imaging Reporting and Data System Version 2014 Category 2, 3, and 4 Observations Detected at CT and MR Imaging.

Purpose To determine the proportion of untreated Liver Imaging Reporting and Data System (LI-RADS) version 2014 category 2, 3, and 4 observations that progress, remain stable, or decrease in category and to compare the cumulative incidence of progression in category. Materials and Methods In this retrospective, longitudinal, single-center, HIPAA-compliant, institutional review board-approved study, 157 patients (86 men and 71 women; mean age ± standard deviation, 59.0 years ± 9.7) underwent two or more multiphasic computed tomographic (CT) or magnetic resonance (MR) imaging examinations for hepatocellular carcinoma surveillance, with the first examination in 2011 or 2012. One radiologist reviewed baseline and follow-up CT and MR images (mean follow-up, 614 days). LI-RADS categories issued in the clinical reports by using version 1.0 or version 2013 were converted to version 2014 retrospectively; category modifications were verified with another radiologist. For index category LR-2, LR-3, and LR-4 observations, the proportions that progressed, remained stable, or decreased in category were calculated. Cumulative incidence curves for progression were compared according to baseline LI-RADS category (by using log-rank tests). Results All 63 index LR-2 observations remained stable or decreased in category. Among 166 index LR-3 observations, seven (4%) progressed to LR-5, and eight (5%) progressed to LR-4. Among 52 index LR-4 observations, 20 (38%) progressed to a malignant category. The cumulative incidence of progression to a malignant category was higher for index LR-4 observations than for index LR-3 or LR-2 observations (each P < .001) but was not different between LR-3 and LR-2 observations (P = .155). The cumulative incidence of progression to at least category LR-4 was trend-level higher for index LR-3 observations than for LR-2 observations (P = .0502). Conclusion Observations classified according to LI-RADS version 2014 categories are associated with different imaging outcomes. (©) RSNA, 2016 Online supplemental material is available for this article.

Spontaneous complete remission of type 1 diabetes mellitus in an adult - review and case report.

Type 1 diabetes mellitus (T1DM) is an autoimmune condition that results in low plasma insulin levels by destruction of beta cells of the pancreas. As part of the natural progression of this disease, some patients regain beta cell activity transiently. This period is often referred to as the 'honeymoon period' or remission of T1DM. During this period, patients manifest improved glycemic control with reduced or no use of insulin or anti-diabetic medications. The incidence rates of remission and duration of remission is extremely variable. Various factors seem to influence the remission rates and duration. These include but are not limited to C-peptide level, serum bicarbonate level at the time of diagnosis, duration of T1DM symptoms, haemoglobin A1C (HbA1C) levels at the time of diagnosis, sex, and age of the patient. Mechanism of remission is not clearly understood. Extensive research is ongoing in regard to the possible prevention and reversal of T1DM. However, most of the studies that showed positive results were small and uncontrolled. We present a 32-year-old newly diagnosed T1DM patient who presented with diabetic ketoacidosis (DKA) and HbA1C of 12.7%. She was on basal bolus insulin regimen for the first 4 months after diagnosis. Later, she stopped taking insulin and other anti-diabetic medications due to compliance and logistical issues. Eleven months after diagnosis, her HbA1C spontaneously improved to 5.6%. Currently (14 months after T1DM diagnosis), she is still in complete remission, not requiring insulin therapy.