HP-DIL: Deep heterogeneity profiling with graph-informed disentangled interaction learning for MRI-based liver fibrosis staging

Liver fibrosis staging (LFS) informs treatment decisions and prognostic assessment in liver disease. Multiparametric MRI enables non-invasive, quantitative characterization of fibrosis-related tissue changes across the whole liver. Although deep-learning-based MRI analysis has advanced automated LFS, two bottlenecks remain: (i) etiology- and tissue-level heterogeneities reduce feature consistency across patients and liver regions; (ii) the lack of explicit modeling of inter-regional and inter-biomarker interactions biases models toward isolated imaging cues, leading to spurious correlations and limited generalizability. Here, we introduce a deep heterogeneity profiling framework with graph-informed disentangled interaction learning (HP-DIL) to enable accurate and interpretable LFS. HP-DIL first performs a biologically inspired, unsupervised subregion discovery stage, which fuses multiparametric MRI signals, spatial-texture coherence, and anatomical priors to construct subject-level graphs for heterogeneity profiling while preserving hepatic morphology. Within each subject, identified subregions are encoded as graph nodes carrying spatial coordinates, geometry, and multiparametric MRI attributes, forming a spatial-semantic interaction graph. A global-local graph transformer subsequently captures higher-order interactions among node-level representations within the constructed graph. Based on causal inference principles, we introduce a disentangled interaction mechanism (DIM) that decouples representative node-level features from whole-graph embeddings. An information-theoretic optimization is adopted to preserve disease-relevant signals while mitigating spurious correlations. Experiments on two external test cohorts from three external multi-vendor centers demonstrate that HP-DIL achieves competitive accuracy and cross-center generalizability. Moreover, we clarify the imaging relevance of the subregions identified by HP-DIL, with qualitative analysis showing close agreement between DIM-highlighted regions and radiological assessment. These findings support HP-DIL's potential for reliable clinical deployment in non-invasive LFS.