Development and Evaluation of Ultrasound Image Learning Pipelines for MASLD Risk Stratification

Differentiating non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver disease (NAFLD) using ultrasound remains challenging due to subtle tissue alterations and the limited information available in conventional B-mode imaging. In this work, we investigate whether complementary ultrasound representations derived from the same acquisition can improve NASH versus NAFLD classification. Specifically, we combine conventional B-mode ultrasound with physics-guided and local phase-based image representations and evaluate their effectiveness using self-supervised masked autoencoders (MAEs) and graph convolutional networks (GCNs). Experiments were conducted on a multi-site Mayo Clinic cohort consisting of 2,547 liver ultrasound scans from 125 patients. Compared with conventional B-mode ultrasound alone, complementary ultrasound representations consistently improved classification performance, yielding gains of up to 32.4% in accuracy and 91.2% in F1-score. Furthermore, performance improvements were consistently observed across age groups, sex, race, ethnicity,and acquisition sites.

Accurate assessment of Schistosoma japonicum-associated liver fibrosis is essential for disease management and long-term follow-up in endemic regions. Ultrasound provides non-invasive imaging, but complex local echogenic patterns and anatomical structures make fine-grained grading challenging. Existing deep learning methods can predict fibrosis scores, yet directly incorporating acquisition views and regional cues into grading while retaining spatial information for inspection remains an open problem. Here we present VCRE-Fib, a view-conditioned regional evidence framework that integrates anatomical context, local information, and global image assessment for fine-grained ultrasound grading. The framework forms view-conditioned local grading evidence before spatial pooling, uses weak localization to guide its aggregation, and combines it with global predictions. Image-only inference jointly returns a fibrosis score, acquisition view, and candidate abnormal-region map. We developed and evaluated the method on a re-curated cohort of 108,709 ultrasound images from 6,373 patients across 35 centers. On a patient-disjoint test set of 4,107 images from 240 patients across four centers, VCRE-Fib reduced the prespecified composite grading risk by 7.115% relative to SFibAI trained and evaluated on the same data split. Image-level mean absolute error decreased from 0.391 to 0.378, alongside lower patient-max, patient-median, and center-balanced risks. The full model also achieved lower composite grading risk than variants that separately removed view conditioning or weak localization. These results support incorporating anatomical context and regional evidence into ultrasound grading while exposing spatial predictions for inspection alongside severity estimates.

Advanced fibrosis is a major determinant of liver-related morbidity in metabolic dysfunction-associated steatotic liver disease (MASLD). FIB-4 is widely used as a first-line non-invasive test, but its fixed formula may underuse diagnostic information contained in age, aspartate aminotransferase, alanine aminotransferase, and platelet count. We evaluated whether machine-learning-enhanced non-invasive testing (MLE-NIT) can improve advanced fibrosis detection while preserving this FIB-4 variable space. We used three biopsy-confirmed MASLD cohorts from China, Malaysia, and India (n=784). The Chinese cohort was split into 486 training and 54 internal validation/tuning patients; final performance was reported only on the Malaysian and Indian external cohorts. Models used five variables: age, FIB-4, aspartate aminotransferase, platelet count, and alanine aminotransferase. We compared FIB-4 with a shallow-deep neural network (s-DNN), TabPFN, and gpt-4o-2024-08-06. FIB-4 achieved external ROC-AUCs of 0.75 and 0.60 in Malaysia and India, respectively. TabPFN achieved 0.69 and 0.66, fine-tuned GPT-4o achieved 0.75 and 0.63, and the s-DNN achieved 0.77 and 0.67, respectively. The s-DNN contained only 354 trainable parameters, compared with 7,244,554 for TabPFN, yet provided a more balanced external operating profile. Calibration showed s-DNN Brier scores of 0.18 and 0.22, and permutation importance identified AST and FIB-4 as dominant variables. Compact non-linear MLE-NITs may enhance FIB-4-based fibrosis assessment without increasing clinical data requirements.