Precise molecular subtyping of gliomas, including isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion, directly guides surgical and therapeutic decisions, yet currently relies on invasive tissue sampling. Deep learning on structural MRI has emerged as a non-invasive alternative, but anatomy-only approaches cannot capture the hemodynamic signatures that distinguish molecular subtypes. Radiogenomics based on dynamic susceptibility contrast (DSC) MRI holds immense potential for non-invasively characterizing glioma molecular subtypes, yet clinical deployment has been hindered by inter-site variability and the limitations of voxel-wise analysis. We introduce HiPerfGNN, a framework that first learns discrete hemodynamic representations from raw time-intensity curves using a vector-quantized variational autoencoder (VQ-VAE). These quantized perfusion codes define coarse-level graph nodes representing functional tumor habitats, each of which is hierarchically subdivided into fine-level subregions guided by structural MRI. A hierarchical graph neural network then propagates information across scales for molecular prediction. On an internal cohort (n=475), the model achieved AUCs of 0.96 (IDH), 0.89 (1p/19q), and 0.84 (WHO grade), and maintained robust IDH performance (AUC 0.89) on an independent external cohort (n=397) without recalibration. Gradient-based saliency analysis confirms biologically grounded attention patterns aligned with known glioma pathophysiology. Our results demonstrate the added value of integrating perfusion dynamics into radiogenomic pipelines for glioma molecular subtyping. Code is available at https://github.com/janghana/HiPerfGNN.
Background: Radiogenomics allows identification of radiological biomarkers for genomic phenotypes. In glioblastoma, these biomarkers could potentially complement patient stratification strategies. We aim to develop and analytically validate radiological biomarkers that capture immune cell signatures within IDH-wildtype glioblastoma microenvironment using radiogenomic analysis. Methods: This was a retrospective multicenter study using curated open-access anonymized imaging and genomic data from TCGA-GBM, CPTAC, IvyGAP, REMBRANDT and CGGA datasets. Imaging data consisted of MRI-based radiomic features extracted from necrotic core, enhancing and edema regions of deep learning-based auto-segmented tumors. Radiomic feature selections were performed using nested cross-validated LASSO. Support vector machine and ensemble models were trained using seventeen immune and cell-specific score labels extracted from deconvoluted transcriptomic data using pan-cancer and glioblastoma immune signature matrices as reference standards. Seventeen classifier models trained in three cross-cohort strategies were validated on three held-out datasets assessing stability and generalizability. Results: One-hundred-and-seventy-six patients were included in the study. The immune-related radiomic signatures obtained after feature selection were shape, first order and higher order radiomic features. Models predicting macrophage subtype immune signature showed stable mean performance on balanced accuracy (0.67) and precision (0.89) metrics for three independent holdout datasets with ensemble model outperforming support vector machine model. Conclusion: Radiogenomic models non-invasively predicted the macrophage subtype M0 immune signature in IDH-wildtype glioblastoma. These biomarkers have the potential to stratify patients for immunotherapy within prospective glioblastoma clinical trials.
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.
Tracking residual tumor after surgery is essential for catching recurrence early, but automating post-operative glioma segmentation remains a difficult task. Although transformer-based architectures, such as SwinUNETR, achieved impressive results, few studies test how well they generalize across clinical protocols. In this paper, we conduct an ablation study on the MU-GLIOMA-POST and UCSF-ALPTDG datasets and show that the standard Generalized Dice Loss (GDL) is unstable under domain shift: the Whole Lesion (WL) Dice drops from 0.88 on the internal validation set to 0.73 on the external UCSF test set. To address this, we pair brain-masked percentile normalization with voxel-level contrastive learning. We also propose a Subspace-Aware Class Attention (SACA) module that re-calibrates the bottleneck features and raises Enhancing Tumor (ET) sensitivity by 8% (9.1% relative improvement) on internal validation. Ensembling these refinements with nnU-Net brings every stable configuration to a WL Dice of 0.94, and the SACA variant ensemble achieves the best boundary error (HD95) of 2.92 mm on MU-GLIOMA-POST.