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.

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).

Liver histology and diffusion-weighted MRI in children with nonalcoholic fatty liver disease: A MAGNET study.

PURPOSE: To determine potential associations between histologic features of pediatric nonalcoholic fatty liver disease (NAFLD) and estimated quantitative magnetic resonance diffusion-weighted imaging (DWI) parameters. MATERIALS AND METHODS: This prospective, cross-sectional study was performed as part of the Magnetic Resonance Assessment Guiding NAFLD Evaluation and Treatment (MAGNET) ancillary study to the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Sixty-four children underwent a 3T DWI scan (b-values: 0, 100, and 500 s/mm2 ) within 180 days of a clinical liver biopsy of the right hepatic lobe. Three parameters were estimated in the right hepatic lobe: apparent diffusion coefficient (ADC), diffusivity (D), and perfusion fraction (F); the first assuming exponential decay and the latter two assuming biexponential intravoxel incoherent motion. Grading and staging of liver histology were done using the NASH CRN scoring system. Associations between histologic scores and DWI-estimated parameters were tested using multivariate linear regression. RESULTS: Estimated means ± standard deviations were: ADC: 1.3 (0.94-1.8) × 10-3 mm2 /s; D: 0.82 (0.56-1.0) × 10-3 mm2 /s; and F: 17 (6.0-28)%. Multivariate analyses showed ADC and D decreased with steatosis and F decreased with fibrosis (P < 0.05). Associations between DWI-estimated parameters and other histologic features were not significant: ADC: fibrosis (P = 0.12), lobular inflammation (P = 0.20), portal inflammation (P = 0.27), hepatocellular inflammation (P = 0.29), NASH (P = 0.30); D: fibrosis (P = 0.34), lobular inflammation (P = 0.84), portal inflammation (P = 0.76), hepatocellular inflammation (P = 0.38), NASH (P = 0.81); F: steatosis (P = 0.57), lobular inflammation (P = 0.22), portal inflammation (P = 0.42), hepatocellular inflammation (P = 0.59), NASH (P = 0.07). CONCLUSION: In children with NAFLD, steatosis and fibrosis have independent effects on DWI-estimated parameters ADC, D, and F. Further research is needed to determine the underlying mechanisms and clinical implications of these effects. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1149-1158.

Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2-4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. CONCLUSIONS: Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child.