TRACED: In vivo imaging of extracellular intrinsic diffusivity, tortuosity, cell size distribution and cell density in human glioma patients

Understanding the human brain requires access to its microscopic tissue architecture. Diffusion magnetic resonance imaging (MRI) provides the only noninvasive window into whole-brain microstructure in vivo, yet reliable quantitative mapping remains confined to specialized research settings requiring dense sampling and optimized acquisition protocols. To address this gap, we present a physics-informed generative microstructure network (PIGMENT) that learns a universal generative prior of human brain microstructure and adapts it zero-shot to each participant's measured data to recover subject-specific maps. Trained on 11375 scans spanning multiple sites, vendors, and field strengths, PIGMENT enabled reliable quantitative mapping for tensor, kurtosis, and NODDI models across external datasets from five independent centers. It remains effective where conventional fitting becomes unreliable, recovering meaningful maps from extremely sparse acquisitions while supporting downstream tractography and structural connectivity mapping. PIGMENT estimates demonstrated strong biological validity, preserving submillimeter cortical microarchitectural patterns and early-childhood white matter developmental trajectories from 10-fold accelerated scans. Furthermore, PIGMENT enables reliable quantitative tensor mapping on cost-efficient low-field systems and the extraction of tumor-related biomarkers using ultra-fast clinical protocols. Together, these results establish PIGMENT as a physics-informed foundation model that extends quantitative diffusion MRI into regimes traditionally too sparse, heterogeneous, or clinically constrained for reliable analysis.

Tracking neurite morphology over time helps characterize structural changes during neuronal development and deterioration, but long-term time-lapse imaging is resource-intensive and difficult to scale. Forecasting future morphology could reduce this burden. Existing neurite digital-twin models such as gated spatiotemporal attention (gSTA) produce a single deterministic forecast without representing variability among plausible futures. We introduce Morphology-Gated Residual Diffusion (MGRD), a compact stochastic surrogate that jointly forecasts twenty future neurite-morphology frames from ten observed frames while conditioning on morphology features derived from the latest observation. On controlled phase-field trajectories, MGRD reduces trajectory-wise mean MAE by 9.7% relative to a matched control while updating 4.46 times fewer parameters. On human iPSC-derived neuron microscopy, MGRD improves all four reported metrics over gSTA, including a 39.6% reduction in trajectory-wise mean MAE and a 45.3% increase in skeleton F1. Without mouse-domain retraining or fine-tuning, MGRD also improves MAE and skeleton F1 on mouse cortical-neurosphere microscopy across 10-40-min sampling intervals and forecast horizons beyond 13 hours. Repeated sampling provides a case-level variance score for ranking forecast difficulty. Retaining approximately 60% of the lowest-variance cases reduces mean MAE by 17.6% on iPSC microscopy and 16.8% on simulation data. MGRD uses 1.01% of gSTA's parameters, requires less than one tenth of its training-update time, and generates a 50-step DDIM trajectory 7.9% faster when morphology features are cached. These results establish MGRD as a compact stochastic surrogate for neurite-morphology forecasting and case prioritization across simulation and microscopy datasets.

Accurate brain tumor segmentation from multiparametric magnetic resonance imaging (MRI) is critical for treatment planning, response assessment, and neuro-oncology research. However, automated segmentation remains a difficult task in computer vision because of variation in tumor appearance and MRI protocols across patient scans. Moreover, clinically important regions such as enhancing tumor and tumor core are often small relative to the full brain volume, further increasing the difficulty of achieving high voxel-level precision. These challenges are amplified in multi-site datasets, where differences in scanner hardware and acquisition parameters can introduce non-biological variation. To address this, networks must learn tumor-specific features while remaining robust to site-dependent noise. In this paper, we show that an ensemble of multi-fold predictions from a modern 3D convolutional segmentation network with corrective diffusion (CorrDiff) post-processing improves brain tumor segmentation across datasets. We propose CoMNet, an ensembled MedNeXt-CorrDiff framework for accurate multi-site brain tumor segmentation. In this framework, we use MedNeXt as the primary segmentation model for feature learning, while a corrective diffusion block learns to refine the residual errors in the individual prediction maps before probabilistic thresholding. This process reduces the variance across fold predictions by correcting fold-specific residual errors and aggregating them into a consensus mask that is less sensitive to site-dependent imaging variability. Our proposed framework achieved the highest Dice score compared to two baseline models on the UTSW-Glioma and BraTS-SSA datasets. Experimental results support the use of corrective diffusion and fold-level probability ensembling as meaningful additions to existing state-of-the-art models for accurate glioma segmentation on multi-site datasets.