Multiparameter Uncertainty Mapping in Quantitative Molecular MRI using a Physics-Structured Variational Autoencoder (PS-VAE)

Quantitative imaging methods, such as magnetic resonance fingerprinting (MRF), aim to extract interpretable pathology biomarkers by estimating biophysical tissue parameters from signal evolutions. However, the pattern-matching algorithms or neural networks used in such inverse problems often lack principled uncertainty quantification, which limits the trustworthiness and transparency, required for clinical acceptance. Here, we describe a physics-structured variational autoencoder (PS-VAE) designed for rapid extraction of voxelwise multi-parameter posterior distributions. Our approach integrates a differentiable spin physics simulator with self-supervised learning, and provides a full covariance that captures the inter-parameter correlations of the latent biophysical space. The method was validated in a multi-proton pool chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) molecular MRF study, across in-vitro phantoms, tumor-bearing mice, healthy human volunteers, and a subject with glioblastoma. The resulting multi-parametric posteriors are in good agreement with those calculated using a brute-force Bayesian analysis, while providing an orders-of-magnitude acceleration in whole brain quantification. In addition, we demonstrate how monitoring the multi-parameter posterior dynamics across progressively acquired signals provides practical insights for protocol optimization and may facilitate real-time adaptive acquisition.

From Pre- to Intra-operative MRI: Predicting Brain Shift in Temporal Lobe Resection for Epilepsy Surgery

Introduction: In neurosurgery, image-guided Neurosurgery Systems (IGNS) highly rely on preoperative brain magnetic resonance images (MRI) to assist surgeons in locating surgical targets and determining surgical paths. However, brain shift invalidates the preoperative MRI after dural opening. Updated intraoperative brain MRI with brain shift compensation is crucial for enhancing the precision of neuronavigation systems and ensuring the optimal outcome of surgical interventions. Methodology: We propose NeuralShift, a U-Net-based model that predicts brain shift entirely from pre-operative MRI for patients undergoing temporal lobe resection. We evaluated our results using Target Registration Errors (TREs) computed on anatomical landmarks located on the resection side and along the midline, and DICE scores comparing predicted intraoperative masks with masks derived from intraoperative MRI. Results: Our experimental results show that our model can predict the global deformation of the brain (DICE of 0.97) with accurate local displacements (achieve landmark TRE as low as 1.12 mm), compensating for large brain shifts during temporal lobe removal neurosurgery. Conclusion: Our proposed model is capable of predicting the global deformation of the brain during temporal lobe resection using only preoperative images, providing potential opportunities to the surgical team to increase safety and efficiency of neurosurgery and better outcomes to patients. Our contributions will be publicly available after acceptance in https://github.com/SurgicalDataScienceKCL/NeuralShift.

SLIM-Diff: Shared Latent Image-Mask Diffusion with Lp loss for Data-Scarce Epilepsy FLAIR MRI

Focal cortical dysplasia (FCD) lesions in epilepsy FLAIR MRI are subtle and scarce, making joint image--mask generative modeling prone to instability and memorization. We propose SLIM-Diff, a compact joint diffusion model whose main contributions are (i) a single shared-bottleneck U-Net that enforces tight coupling between anatomy and lesion geometry from a 2-channel image+mask representation, and (ii) loss-geometry tuning via a tunable $L_p$ objective. As an internal baseline, we include the canonical DDPM-style objective ($ε$-prediction with $L_2$ loss) and isolate the effect of prediction parameterization and $L_p$ geometry under a matched setup. Experiments show that $x_0$-prediction is consistently the strongest choice for joint synthesis, and that fractional sub-quadratic penalties ($L_{1.5}$) improve image fidelity while $L_2$ better preserves lesion mask morphology. Our code and model weights are available in https://github.com/MarioPasc/slim-diff

A Reproducible Framework for Bias-Resistant Machine Learning on Small-Sample Neuroimaging Data

We introduce a reproducible, bias-resistant machine learning framework that integrates domain-informed feature engineering, nested cross-validation, and calibrated decision-threshold optimization for small-sample neuroimaging data. Conventional cross-validation frameworks that reuse the same folds for both model selection and performance estimation yield optimistically biased results, limiting reproducibility and generalization. Demonstrated on a high-dimensional structural MRI dataset of deep brain stimulation cognitive outcomes, the framework achieved a nested-CV balanced accuracy of 0.660\,$\pm$\,0.068 using a compact, interpretable subset selected via importance-guided ranking. By combining interpretability and unbiased evaluation, this work provides a generalizable computational blueprint for reliable machine learning in data-limited biomedical domains.

Hybrid Topological and Deep Feature Fusion for Accurate MRI-Based Alzheimer's Disease Severity Classification

Early and accurate diagnosis of Alzheimer's disease (AD) remains a critical challenge in neuroimaging-based clinical decision support systems. In this work, we propose a novel hybrid deep learning framework that integrates Topological Data Analysis (TDA) with a DenseNet121 backbone for four-class Alzheimer's disease classification using structural MRI data from the OASIS dataset. TDA is employed to capture complementary topological characteristics of brain structures that are often overlooked by conventional neural networks, while DenseNet121 efficiently learns hierarchical spatial features from MRI slices. The extracted deep and topological features are fused to enhance class separability across the four AD stages. Extensive experiments conducted on the OASIS-1 Kaggle MRI dataset demonstrate that the proposed TDA+DenseNet121 model significantly outperforms existing state-of-the-art approaches. The model achieves an accuracy of 99.93% and an AUC of 100%, surpassing recently published CNN-based, transfer learning, ensemble, and multi-scale architectures. These results confirm the effectiveness of incorporating topological insights into deep learning pipelines and highlight the potential of the proposed framework as a robust and highly accurate tool for automated Alzheimer's disease diagnosis.

Improving Neuropathological Reconstruction Fidelity via AI Slice Imputation

Neuropathological analyses benefit from spatially precise volumetric reconstructions that enhance anatomical delineation and improve morphometric accuracy. Our prior work has shown the feasibility of reconstructing 3D brain volumes from 2D dissection photographs. However these outputs sometimes exhibit coarse, overly smooth reconstructions of structures, especially under high anisotropy (i.e., reconstructions from thick slabs). Here, we introduce a computationally efficient super-resolution step that imputes slices to generate anatomically consistent isotropic volumes from anisotropic 3D reconstructions of dissection photographs. By training on domain-randomized synthetic data, we ensure that our method generalizes across dissection protocols and remains robust to large slab thicknesses. The imputed volumes yield improved automated segmentations, achieving higher Dice scores, particularly in cortical and white matter regions. Validation on surface reconstruction and atlas registration tasks demonstrates more accurate cortical surfaces and MRI registration. By enhancing the resolution and anatomical fidelity of photograph-based reconstructions, our approach strengthens the bridge between neuropathology and neuroimaging. Our method is publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/mri_3d_photo_recon

A Hybrid Mamba-SAM Architecture for Efficient 3D Medical Image Segmentation

Accurate segmentation of 3D medical images such as MRI and CT is essential for clinical diagnosis and treatment planning. Foundation models like the Segment Anything Model (SAM) provide powerful general-purpose representations but struggle in medical imaging due to domain shift, their inherently 2D design, and the high computational cost of fine-tuning. To address these challenges, we propose Mamba-SAM, a novel and efficient hybrid architecture that combines a frozen SAM encoder with the linear-time efficiency and long-range modeling capabilities of Mamba-based State Space Models (SSMs). We investigate two parameter-efficient adaptation strategies. The first is a dual-branch architecture that explicitly fuses general features from a frozen SAM encoder with domain-specific representations learned by a trainable VMamba encoder using cross-attention. The second is an adapter-based approach that injects lightweight, 3D-aware Tri-Plane Mamba (TPMamba) modules into the frozen SAM ViT encoder to implicitly model volumetric context. Within this framework, we introduce Multi-Frequency Gated Convolution (MFGC), which enhances feature representation by jointly analyzing spatial and frequency-domain information via 3D discrete cosine transforms and adaptive gating. Extensive experiments on the ACDC cardiac MRI dataset demonstrate the effectiveness of the proposed methods. The dual-branch Mamba-SAM-Base model achieves a mean Dice score of 0.906, comparable to UNet++ (0.907), while outperforming all baselines on Myocardium (0.910) and Left Ventricle (0.971) segmentation. The adapter-based TP MFGC variant offers superior inference speed (4.77 FPS) with strong accuracy (0.880 Dice). These results show that hybridizing foundation models with efficient SSM-based architectures provides a practical and effective solution for 3D medical image segmentation.

Training Beyond Convergence: Grokking nnU-Net for Glioma Segmentation in Sub-Saharan MRI

Gliomas are placing an increasingly clinical burden on Sub-Saharan Africa (SSA). In the region, the median survival for patients remains under two years, and access to diagnostic imaging is extremely limited. These constraints highlight an urgent need for automated tools that can extract the maximum possible information from each available scan, tools that are specifically trained on local data, rather than adapted from high-income settings where conditions are vastly different. We utilize the Brain Tumor Segmentation (BraTS) Africa 2025 Challenge dataset, an expert annotated collection of glioma MRIs. Our objectives are: (i) establish a strong baseline with nnUNet on this dataset, and (ii) explore whether the celebrated "grokking" phenomenon an abrupt, late training jump from memorization to superior generalization can be triggered to push performance without extra labels. We evaluate two training regimes. The first is a fast, budget-conscious approach that limits optimization to just a few epochs, reflecting the constrained GPU resources typically available in African institutions. Despite this limitation, nnUNet achieves strong Dice scores: 92.3% for whole tumor (WH), 86.6% for tumor core (TC), and 86.3% for enhancing tumor (ET). The second regime extends training well beyond the point of convergence, aiming to trigger a grokking-driven performance leap. With this approach, we were able to achieve grokking and enhanced our results to higher Dice scores: 92.2% for whole tumor (WH), 90.1% for tumor core (TC), and 90.2% for enhancing tumor (ET).

A Geometric Multimodal Foundation Model Integrating Bp-MRI and Clinical Reports in Prostate Cancer Classification

Prostate cancer (PCa) is one of the most common cancers in men worldwide. Bi-parametric MRI (bp-MRI) and clinical variables are crucial for PCa identification and improving treatment decisions. However, this process is subjective to expert interpretations. Furthermore, most existing computer-aided diagnosis methods focus on imaging-based models, overlooking the clinical context and suffering from data scarcity, limiting their ability to learn robust representations. We propose a geometric multimodal Foundation Model (FM), named MFM-Geom, that learns representations from bp-MRI and clinical reports, encoding visual findings and information from the context of clinical variables. In the representations classification head, the approach leverages symmetric positive definite (SPD) matrices and Riemannian deep learning to integrate imaging-text representations from a biomedical multimodal FM. Using 10% of the training data, MFM-Geom outperformed baseline class token embedding-based classification (+8.3%, AUC-PR of 90.67). Generalization on external dataset confirmed the robustness of fine-tuning biomedical FM, achieving an AUC-PR of 90.6.

Scale-Cascaded Diffusion Models for Super-Resolution in Medical Imaging

Diffusion models have been increasingly used as strong generative priors for solving inverse problems such as super-resolution in medical imaging. However, these approaches typically utilize a diffusion prior trained at a single scale, ignoring the hierarchical scale structure of image data. In this work, we propose to decompose images into Laplacian pyramid scales and train separate diffusion priors for each frequency band. We then develop an algorithm to perform super-resolution that utilizes these priors to progressively refine reconstructions across different scales. Evaluated on brain, knee, and prostate MRI data, our approach both improves perceptual quality over baselines and reduces inference time through smaller coarse-scale networks. Our framework unifies multiscale reconstruction and diffusion priors for medical image super-resolution.