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.
Existing BraTS-GLI datasets provide a widely used benchmark for adult glioma MRI segmentation, but their task definition focuses on tumor subregions and does not systematically represent coexisting white matter hyperintensities (WMH). In joint segmentation settings, such unlabeled abnormalities introduce task-specific label noise by treating pathological regions as normal tissue. To address this limitation, we introduce BraTS-GLI Anatomy-Lesion, a controlled-access, labels-only derived resource built from the BraTS 2023-GLI training cohort. The resource provides 1,251 unified eight-class anatomy-lesion label sets aligned with the original four-modal MRI cases, including image-repair labels for 116 cases requiring repaired imaging inputs. The cohort is organized into a 394-case purified subset and an 857-case extended subset, with case-level metadata covering label source, image-repair requirements, quality-control status, access conditions, checksums, and release boundaries. Compared with the original BraTS-GLI annotations, the resource substantially expands foreground supervision by incorporating healthy brain tissues and previously unlabeled coexisting abnormalities within a unified label space. A validation study using MedNeXt and T1/FLAIR inputs suggests that WMH-aware supervision preserves healthy-tissue segmentation performance across both in-domain GLI and external WMH datasets, while improving sensitivity to coexisting lesions relative to noisy-control training. The resource is intended for scientific research and supports joint anatomy-lesion supervision, label-noise analysis, and reproducible evaluation. Data are available at https://www.synapse.org/Synapse:syn75210889/wiki/, and code is available at https://github.com/xyx200/brats-gli-anatomy-lesion-code. The data resource DOI is https://doi.org/10.7303/SYN75210889.
Nguyen Linh Dan Le, Nguyen Pham Hoang Le, Tran Dang Khoics.CV
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.
High-grade gliomas integrate into neural circuits through functional synapses with neurons, raising the question of which noncoding elements shape synaptogenic gene expression in tumor cells. The regulatory program written across the dark genome, what we call the $\textit{dark regulome}$, is the natural substrate to probe, and sequence foundation models offer a zero-shot route through in-silico mutagenesis (ISM); yet likelihood-based scoring is tautologically coupled to local sequence predictability, leaving the regulatory interpretation underdetermined. Across three architecturally distinct foundation models (Caduceus-Ph, HyenaDNA, Enformer) and 30,448 dark genome elements at 92 glioma-relevant loci, we introduce a residualization-and-permutation diagnostic that separates predictability-driven from regulation-driven RIS variance. A sharp 10kb proximal-regulatory horizon survives every control we apply, but the LM-derived element-class hierarchy does not: a six-feature linear baseline matches Caduceus top-decile membership at AUC $= 0.985$. Cross-architecture decomposition cleanly separates a sequence-predictability layer (the two language models co-rank long well-predicted transposable elements) from a regulatory-output layer (Enformer alone retains residual cCRE-discriminative signal), with literally zero overlap between the two top-100 lists. Conservation, brain cis-eQTL, and STRING-PPI cross-checks then anchor what biology survives: top-100 elements across all three models are $3.3\times$ enriched per model for matching brain eQTLs ($p_\mathrm{emp} < 5\times 10^{-3}$), while a tempting transposable-element regulatory layer and a striking NRXN1+NLGN1 protein-pair convergence both fail proper permutation tests once those tests are constructed. We deliver the diagnostic as a general methodological tool for any ISM-based regulatory study.
Joshua K. Marchant, Hong-Hsi Lee, Elizabeth R. Gerstner +2physics.med-ph cs.LG eess.IV
The lack of analytical models describing diffusion time dependence at intermediate time scales in complex tissue microstructure limits the accurate quantification of extracellular diffusivity and tissue microstructure. We introduce TRACED, a biophysical model that incorporates diffusion time dependence in cell distributions to quantify pathologically-relevant properties in solid tumors. Neural networks were trained on Monte Carlo diffusion simulations using sphere distribution-based geometries to enable the rapid computation of time-dependent diffusion MRI signals in cell populations of variable cell size. Model sensitivity and fit performance were assessed via simulation. Diffusion data from eight mixed-grade glioma patients was fitted using the TRACED model. Data fitting was performed using a novel physics-informed transfer learning pipeline, Sim2PINN. In two patients, cell size measurements were compared directly with image-localized histology. Simulation results indicate improved parameter estimation compared to the simple two-compartment model. TRACED enabled the simultaneous in vivo quantification of intracellular volume fraction, cell size distribution, extracellular intrinsic diffusivity, and tortuosity in glioma patients. Neural network implementations of diffusion time-dependence and tortuosity showed behavior consistent with coarse-graining and effective medium theory, respectively. Future work will explore the clinical utility of TRACED parameters in additional patients.