TRACE: A Concept Bottleneck Model for Longitudinal 3D Glioblastoma Response Assessment
Authors: Alia Tarek, Hamsa Saberr, Hamza Elghonemy, Youssef Afify, Tamer Basha, Omair Shahzad Bhatti, Abdulrahman M. Selim, Hasan Md Tusfiqur Alam, +1 more
Organizations: Department of Biomedical and Healthcare Data Engineering, Faculty of Engineering, Cairo University, Giza, Egypt · German Research Center for Artificial Intelligence (DFKI), Saarbrücken, Germany · University of Oldenburg, Oldenburg, Germany
Abstract
Longitudinal glioblastoma response assessment requires comparing subtle tumor changes across MRI time points using structured clinical criteria such as RANO. However, most deep learning methods predict response labels directly from imaging features, which limits clinical inspection, verification, and correction. We introduce TRACE, a RANO 2.0-aligned concept bottleneck model for interpretable 4-class glioblastoma response classification on longitudinal 3D MRI. TRACE processes paired baseline and follow-up multimodal MRI scans with a shared 3D vision encoder, predicts clinically meaningful tumor measurements as root concepts, computes downstream RANO-derived concepts through deterministic rules, and incorporates scan interval and new-lesion information as passthrough concepts. This design frames response assessment as structured concept reasoning rather than direct image-to-label prediction. Using 5-fold patient-wise cross-validation on the LUMIERE dataset, TRACE achieves a 4-class macro F1 of 0.4769 and a binary progression-versus-non-progression macro F1 of 0.7085. It improves over a concept bottleneck baseline and remains within the range of published non-interpretable deep learning approaches. Ablation studies show that the expert RANO graph and intervention-consistency training are important for performance, while intervention experiments demonstrate that correcting concepts can improve downstream predictions. These results suggest that structured concept bottlenecks offer a transparent and clinically aligned direction for longitudinal glioblastoma response assessment, while highlighting the need for larger protocol-aligned datasets and external validation.
Medical image segmentation models can achieve strong benchmark performance while remaining sensitive to scanner, protocol, and institutional variation. These context shifts alter image appearance without changing the underlying lesion, allowing models to exploit nuisance cues that Dice and HD95 fail to expose. We present TRACE-Seg3D, a counterfactual context auditing framework for robust 3D medical image segmentation. TRACE-Seg3D preserves lesion-relevant evidence and systematically varies imaging context to quantify prediction stability under controlled context shifts. The framework pairs each segmentation with audit evidence for context sensitivity and anatomical plausibility, enabling case-level reliability assessment beyond overlap-based evaluation. Experiments on BraTS and UTSW glioma segmentation benchmarks demonstrate competitive in-distribution and cross-domain performance. TRACE-Seg3D also exposes context-sensitive failure modes missed by conventional metrics. These results establish counterfactual context auditing as a practical route toward transparent and reliable 3D medical image segmentation under distribution shift. Our code is available at https://github.com/danleneurocom/Counterfactual-Representation-Network.
Nguyen Linh Dan Le, Nguyen Pham Hoang Le, Tran Dang Khoi
Multimodal medical large language models remain structurally weak for neuro-oncology because volumetric evidence is compressed into generic visual tokens and diagnostic conclusions often lack an auditable link to MRI regions. We present NeuroMosaic, a 3D multimodal language model that converts multi-sequence brain MRI into anatomy-indexed regional tokens, aligns them with clinical narrative and molecular concepts, and generates evidence-linked outputs. The architecture combines a multi-resolution volumetric tokenizer, a neuroanatomical graph router, a molecular concept memory, and selective risk control. Across four glioma cohorts, NeuroMosaic achieved an internal subtype macro-F1 of 0.827 and external macro-F1 values of 0.784, 0.761, and 0.742. On UPenn-GBM, it improved over the strongest matched-input baseline by 3.6 percentage points (95% CI: 1.8 to 5.4, adjusted p = 0.0018), with IDH, 1p/19q, and MGMT AUROCs of 0.918, 0.861, and 0.781. Evidence pointing accuracy reached 0.703, and targeted evidence deletion reduced correct-answer probability by 0.187, compared with 0.046 for random deletion. These results establish anatomy-indexed routing as a measurable mechanism for accurate, grounded, and calibrated volumetric medical-language reasoning.
Magnetic Resonance Imaging (MRI) interpretation is fundamental to clinical decision-making, requiring radiologists to integrate multi-view anatomical planes across sequential timepoints while precisely localizing interval changes. However, existing vision-language benchmarks remain confined to single-timepoint, single-view interpretation, failing to capture the temporal-spatial reasoning essential to radiologic practice. We introduce the Time-Aware Multi-View MRI Benchmark, an evaluation framework unifying multi-view anatomical input, temporal reasoning across longitudinal scans, and structured localization guidance. The benchmark comprises 3,920 expert-verified question-answer pairs derived from 890 patients across over 3,200 longitudinal MRI timepoints, drawn from seven clinical cohorts covering glioblastoma, neurodegeneration, vestibular schwannoma, and brain metastases, in open-ended, multiple-choice, and binary formats, requiring models to identify anatomical regions of maximal change, characterize progression across sequences and views, and provide structured guidance specifying boundaries, imaging features, and confounders. Experiments across 16 vision-language models reveal moderate temporal alignment but systematic failure on change direction recognition and volumetric quantification, while multi-view inputs improve spatial localization yet degrade temporal reasoning in compact architectures. Our benchmark provides a systematic framework for evaluating progression tracking, interval change localization, and temporal ordering, which are essential for clinical deployment. Code, evaluation splits, and the dataset are available at: https://github.com/wafaAlghallabi/Time-Aware-MRI.
Wafa Al Ghallabi, Ritesh Thawkar, Sara Ghaboura +6