Evidence-Bound Reasoning: Neuro-Semantic Verification of Biomedical AI in Glioblastoma Radiogenomics

Abstract

Background: Biomedical AI can generate plausible explanations without reliably verifying whether each statement is supported by patient-specific evidence. We developed a neuro-semantic verification framework that converts radiomic measurements into addressable evidence records and machine-checkable claims. Methods: UPenn-GBM radiomics were aligned with de novo CaPTk extraction from standardized MRI and expert-validated segmentations in an independent multicenter cohort. The shared space comprised 1,728 features from T1, T1GD, T2, and FLAIR MRI across three tumor regions. Reference-defined semantic states were derived from 611 UPenn cases. We evaluated cross-cohort transportability, model-linked provenance, deterministic verification, controlled predictive degradation, and an LLM claim-extraction pilot; MGMT prediction served only as a transport stress test. Results: Median semantic-state agreement was 0.786 (weighted kappa 0.709), ranging from 0.918 for morphologic to 0.252 for intensity features. The external evidence ledger contained 1,655 model-linked records for 331 patients. The verifier achieved 100% exact-set accuracy in a 6,620-claim corruption benchmark. In a 24-case pilot, GPT-5.6 Sol reproduced 72/72 prespecified atomic claims, and the frozen verifier recovered 24/24 expected conditions. During controlled degradation, ROC AUC declined from 0.899 to 0.500 while verification accuracy remained 1.000. External MGMT discrimination was weak (ROC AUC 0.543). Conclusions: Verifiability can be engineered and evaluated independently of predictive performance. LLMs may structure explanations, while final evidence-consistency checking remains deterministic.