NeuroMosaic: Anatomically Grounded Multimodal Large Language Modeling for Molecularly Aware Glioma Reasoning from 3D MRI and Clinical Narratives

Glioma grading and survival prediction require the integration of heterogeneous information collected at different spatial and biological scales. Histopathology describes tissue morphology, mRNA expression captures molecular activity, and magnetic resonance imaging provides a non-invasive view of tumor extent and radiological heterogeneity. Existing glioma prognosis models often combine only two of these sources, while their alignment objectives remain mostly pairwise. This paper introduces GLORIA, a novel trimodal framework for GLioma Omics - Radiology - hIstopathology Alignment. GLORIA processes whole-slide image regions, gene-expression profiles, and 3D MRI volumes through modality-specific encoders, projects them into a shared latent space, and aligns them with a Gramian contrastive loss that measures the volume spanned by the three modality embeddings. The aligned representations are fused through a cross-modal gating module and optimized jointly for three-class glioma grading and overall survival prediction. We evaluate GLORIA on a matched TCGA-GBM/LGG and BraTS21 cohort, comprising 132 patients with all three modalities. On the shared trimodal test set, GLORIA improves over the bimodal WSI-mRNA baseline in all the metrics considered.

Background: Accurate glioma subregion delineation is important for radiotherapy planning and longitudinal monitoring, but manual contour correction is time-consuming. Models such as nnU-Net may generalize imperfectly and lack clinician-directed text correction. Purpose: We investigated adapting a three-dimensional (3D) vision-language foundation model for text-guided brain tumor segmentation refinement. Methods: We developed a lightweight VoxTell-based framework. Pretrained VoxTell generated initial masks. Oracle prompts derived from segmentation errors encoded target, action, location, imaging evidence, edit size, and preservation constraints. Frozen Qwen/VoxTell prompt embeddings were injected through trainable projections into its multiscale decoder conditioning; other weights remained frozen. Training, validation, and testing used 901, 100, and 250 BraTS-GLI cases. Cross-dataset transfer was evaluated on 100 meningioma, metastasis, pediatric tumor, and UPENN-GBM cases. Results: On the internal test set using post-contrast T1-weighted input, correct instructions improved subregion Dice similarity coefficient (DSC; enhancing tumor, edema, and necrotic/non-enhancing core) from $0.774\pm0.158$ to $0.796\pm0.137$. They outperformed blank prompts ($0.762\pm0.155$; Holm-adjusted $p<0.001$, $d_z=0.71$) and contradictory prompts ($0.770\pm0.163$; $p<0.001$, $d_z=0.48$). In cross-dataset testing, correct instructions improved DSC from $0.527\pm0.287$ to $0.550\pm0.278$ and outperformed contradictory instructions ($0.504\pm0.275$; $p<0.001$, $d_z=0.43$). Conclusion: A 3D vision-language foundation model can perform instruction-guided refinement of glioma subregion segmentations. Sensitivity to correct, blank, and contradictory prompts suggests text-dependent contour editing rather than nonspecific post-processing, supporting further evaluation as a clinician-in-the-loop tool.

Multi-parametric magnetic resonance imaging (mpMRI) is a cornerstone for brain tumor diagnosis and treatment, yet current AI models face critical limitations: their lack of natural language interaction and interpretability impedes spatial information integration and cross-modal reasoning required clinically. Key challenges arise from significant physical meaning differences across modalities, spatial misalignment due to scan intervals, and the need for complex multi-feature interpretation in tasks like glioma grading. While visual-language models (VLMs) show promise in cross-modal understanding, existing methods focus mainly on 2D image modeling, neglecting direct perception of 3D volumetric space. Although 3D VLMs have been proposed for report generation and feature alignment in 3D CT imaging, mpMRI applications demand collaborative inference across multiple imaging modalities-a requirement unmet by current solutions. To address this, we introduce Mr3D-VL, a dedicated visual-language foundation model for multi-parametric 3D MRI. With 4 billion parameters, it employs an unsupervised pre-trained shared 3D encoder and 4D rotational positional embedding for dual modality-spatial integration. Its cross-modal projection layer uses a multi-resolution feature implantation strategy to enhance feature perception across resolutions. Experimental results show significant improvements over existing 4B/7B/30B domain-specific and general-purpose models in text generation tasks, achieving a BERTScore of 0.856 for report generation, with question-answering accuracy at 0.713 and multiple-choice accuracy at 0.912.