Multi‐Scale Spatial Heterogeneity of Liver Fibrosis Evaluated by MR Elastography in Rat Models

ABSTRACT Background While liver stiffness heterogeneity by MR elastography (MRE) is clinically important, whether MRE reflects multi‐scale liver fibrosis heterogeneity and explains histopathological‐MRE staging discordance remains unclear. Purpose To assess spatial heterogeneity of liver fibrosis at multiple scales using MRE, correlating with histopathology. Study Type Prospective. Animal Model Male Sprague–Dawley rats ( N = 72) with liver fibrosis via carbon tetrachloride intoxication or bile duct ligation ( N = 27 in each) and sham controls ( N = 18). Field Strength/Sequence 3.0 T spin‐echo echo‐planar imaging multi‐frequency (60–200 Hz) three‐dimensional vector MRE sequence. Assessment Three‐dimensional vector MRE at 200 Hz quantified liver stiffness across four lobes. Liver fibrosis heterogeneity was evaluated at three scales via histopathology and MRE: whole‐liver (≥ 2 stage difference; liver stiffness variability as percentage difference between highest and lowest mean lobar stiffness), inter‐lobe (1–3 stage difference; stiffness comparisons between paired lobes), and intra‐lobe (≥ 2 stage difference between predominant and secondary fibrosis patterns; coefficient of variation of stiffness). Statistical Tests Spearman correlation, Kruskal–Wallis test with Dunn correction, area under the receiver operating characteristic curves (AUC), and DeLong's test. p < 0.05 was considered significant. Results Fibrotic livers (2.84 ± 0.59 kPa) showed significantly higher stiffness than non‐fibrotic livers (1.90 ± 0.23 kPa). AUCs for fibrosis staging were lower at the rat level (0.78–0.94) than at the lobe level (0.94–0.98), significant for ≥ F2 and ≥ F3 stages. Based on optimal cutoffs, liver stiffness variability classified 80.6% (58/72) of whole‐liver heterogeneity, and CV of liver stiffness identified 85.5% (53/62) of intra‐lobe heterogeneity. Additionally, liver stiffness detected 75% (120/160) of inter‐lobe heterogeneity. MRE‐defined heterogeneity explained 70.6% (whole‐liver scale) and 78.6% (intra‐lobe scale) of cases with ≥ 2 stage MRE‐histopathology discordance. Data Conclusion MRE depicts multi‐scale hepatic fibrosis heterogeneity that correlates with histopathology and may provide a mechanism to explain histopathological‐MRE staging discordance, potentially improving diagnostic accuracy with sampling limitations. Evidence Level 1. Technical Efficacy Stage 2.