Diffusion MRI
MRI: Magnetic Resonance Imaging
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3 papers in the last four weeks, level with the four weeks before. 0.0% of all new papers.
Latest papers 29
Machine learning (ML) has emerged as a promising approach for improving diffusion MRI (dMRI) tractography, a task that remains limited by the intrinsic tension between local diffusion information and global anatomical plausibility. In this work, we systematically evaluate recurrent neural networks (RNNs) and Transformer models for iterative tractography, with particular attention to training strategies, input representations (including convolutional neural network (CNN)-based embeddings and end-of-sequence (EOS) tokens), and hyperparameter selection. We introduce a generation-validation phase enabling supervision at the streamline level during training, allowing supervision despite the mismatch between local loss functions and global streamline quality. Using the ISMRM2015 tractography challenge dataset, our models achieve the highest reported performance to date. Through controlled experiments, we quantify the impact of missing bundles, noisy or imperfect training streamlines, and invalid fibers in the training set. Finally, we demonstrate the applicability of our best-performing models for in vivo data from the Tractoinferno database. Overall, our results highlight both the potential and the limits of sequence-based deep learning models such as Transformers and RNNs for tractography, and emphasize the need for improved phantoms and evaluation methods for in vivo validation. We provide takeaways and recommendations for future researchers training and validating sequence-based supervised methods for tractography.
Fiber-Resolved Microstructure Quantification from Multi-Shell Diffusion MRI using Detection Transformers
Fiber orientation and compartmental microstructure are central to the characterization of white matter tissue in diffusion MRI, yet existing methods either resolve fiber orientations without quantifying microstructure, or quantify microstructure while assuming a fixed number of compartments and a single fiber direction. Nonparametric approaches that recover both require tensor-valued diffusion encoding and computationally expensive Monte-Carlo inversion of an ill-posed inverse Laplace transform. We propose to reframe this problem as an object detection-like task, adopting the Detection Transformer (DETR) architecture to jointly predict mean diffusivity (MD), fractional anisotropy (FA), main fiber direction, and signal fraction for a variable number of compartments per voxel from standard multi-shell diffusion MRI with linear encoding. Hungarian matching during training resolves permutation invariance across compartments. We introduce mean Average Precision as a reproducible benchmark metric. Evaluated on synthetic test data with up to five compartments per voxel, our model achieves for MD, for FA, and a median angular error of 4.2°, with performance scaling naturally with compartmental signal fraction.
GraphSVR: q-Space--Aware Graph-Based Slice-to-Volume Registration for Diffusion MRI
Diffusion-weighted imaging (DWI) remains highly vulnerable to subject motion, particularly in time-efficient protocols and in motion-prone populations. While slice-to-volume registration (SVR) can mitigate inter-slice and inter-stack misalignment, diffusion MRI introduces additional complexity due to diffusion-direction-dependent contrast and the requirement to align dozens of measurements within a common reference frame, effectively yielding a 4D registration problem. Existing approaches rely primarily on sequential modeling or pairwise similarity and often degrade under sparse gradient sampling or severe motion. We introduce GraphSVR, a q-space-aware graph-based framework for 4D SVR registration in DWI. GraphSVR represents slice groups as nodes in an acquisition-structured graph, with edges encoding temporal proximity, spatial slice geometry and diffusion encoding relationships. A graph neural network predicts globally consistent stack-wise rigid motion, optimized in a self-supervised, zero-shot manner using only an anatomical reference image, without requiring paired ground-truth motion. We evaluate GraphSVR using both fully synthetic diffusion simulations and realistic recombination-based simulations from real acquisitions with controllable motion severity and gradient sparsity. Performance is quantified using grid error (mm) and rotation error relative to known ground-truth transforms. Under severe motion, GraphSVR reduces grid error and rotation error by 73% compared to FSL eddy, the standard DWI motion-correction method, with the largest gains observed in sparse-direction regimes. These results demonstrate that explicitly modeling acquisition structure through graph-based reasoning improves robustness and global consistency in 4D DWI motion estimation. Code is available at https://github.com/nogakertes/GraphSVR.git.
Diffusion-Encoding Gaussian Field for Joint k-q dMRI Reconstruction
Diffusion MRI requires repeated k-space acquisitions over multiple diffusion-encoding directions, making acquisition time dependent on both spatial and angular sampling. Existing joint k-q methods either associate directional parameters with fixed voxels or separate spatial reconstruction from angular completion. However, diffusion-weighted images acquired under different directions share the same anatomical organization, while their local signal intensities vary with diffusion encoding. Existing formulations do not fully exploit the complementarity between shared anatomy and direction-dependent signal variation. Consequently, residual spatial errors may be misinterpreted as genuine angular variation and propagated to unobserved directions. We propose a subject-specific spatial-angular Gaussian field for self-supervised joint k-q dMRI reconstruction. Shared 3D Gaussian primitives provide local spatial support, with each primitive carrying a continuous q-conditioned tensor-residual response. The signal at each location is synthesized from multiple overlapping primitive responses, coupling neighboring spatial regions and diffusion directions. The field is progressively optimized from undersampled k-space measurements of observed directions, without fully sampled targets or held-out-direction supervision. Experiments on three HCP diffusion shells under multiple acceleration settings demonstrated consistent improvements in missing-direction DWI reconstruction, tensor-derived metrics, and principal diffusion orientation estimation.
Prior-Guided Implicit Neural Representations for Single-Subject Diffusion MRI Super-Resolution
Resolving complex fiber geometries in brain white matter requires high-resolution diffusion MRI at the cost of long acquisition times. This leads many clinical protocols to opt for low-resolution scans, making downstream microstructure estimation and tractography challenging. Implicit neural representations (INRs) can model the diffusion signal continuously, enabling native single-subject super-resolution by querying the network at arbitrary spatial coordinates, yet existing methods often suffer from long training times and lack a mechanism to incorporate anatomical priors to regularize super-resolution by constraining the space of plausible reconstructions. To address these limitations, we propose a novel transfer-learning framework that pre-trains an INR on a high-resolution template and then adapts it to subject-specific scans via registration and fine-tuning. For through-plane super-resolution from 5 mm to 1.25 mm on Human Connectome Project (HCP) data, our method reduces NRMSE by 36-49% and increases FSIM by 24-43% over a recent baseline with faster training, outperforming competing INR-based methods across both image quality and domain-specific metrics. Code is available on the project page at https://abdulkaderghandoura.github.io/research/msc-thesis/ .
A Deep RL based Framework for Targeted White Matter Tractography
Fiber tractography's ability to reconstruct the brain's structural pathways, has made it a crucial component of modern neuroimaging, enabling detailed, non-invasive mapping of structural connectivity and supporting a wide range of neurological research and clinical applications. However, despite its importance, tractography remains a challenging task due to the inherent complexity of white matter structure and its susceptibility to false positives, which can lead to the misrepresentation of critical pathways. To overcome these limitations, in this thesis, we propose a hybrid framework that integrates reinforcement learning with supervised learning for refining RL policies, specifically tailored for tract-specific tractography. Notably, our framework does not rely on ground-truth fibers for training. Moreover, the tract-specific formulation bypasses the need for an explicit segmentation process, simplifying the overall pipeline. Our work includes two main contributions, each building upon the previous. First, we introduce a hybrid approach that combines reinforcement learning with supervised learning (specifically, GPT-based policy learning) to refine policies in a tract-specific context. Second, we propose a scalable framework for data-driven multi-policy fusion, which leverages the complementary strengths of multiple RL policies to improve tractography performance and robustness. We demonstrate the effectiveness of our framework through extensive validation on benchmark public datasets including TractoInferno, HCP, and ISMRM-2015, highlighting its ability to generalize across data sources and accurately reconstruct brain white matter tracts. We believe that these contributions represent significant advancements in the field of tractography, improving robustness, reliability, and accuracy while reducing dependence on ground-truth annotations.
MRI super-resolution in ten sampling steps using a diffusion bridge model
Objective. MRI provides excellent soft-tissue contrast, but long acquisition times can cause patient discomfort and lead to motion artifacts, forcing a trade-off between spatial resolution and scan time. Diffusion-based super-resolution (SR) reconstructs high-resolution (HR) images from low-resolution (LR) inputs, but typically needs many sampling steps and initializes from a Gaussian prior ill-suited to image restoration. We developed an efficient diffusion framework that reconstructs HR MRI directly from LR data. Approach. We propose super-resolution diffusion bridge model (SR-DBM), a super-resolution diffusion bridge model that casts SR as a stochastic transport between the LR and HR image distributions. Through a Doob's h-transform of a mean-reverting stochastic differential equation, SR-DBM pins the process to the paired HR and LR images at its endpoints, initializing reconstruction from the measured anatomy rather than from Gaussian noise. The HR image is recovered by a deterministic reverse trajectory in which a network predicts the clean image at each of only ten sampling steps. We evaluated SR-DBM on ultra-high-field 7T brain T1 MP2RAGE maps and pelvic T2-weighted prostate images against nine comparison methods using PSNR, SSIM, GMSD, and LPIPS. Main results. SR-DBM attained the highest PSNR and SSIM and the lowest GMSD on both datasets (brain: 27.66+-1.52 dB, 0.96+-0.02, 7.96+-1.86$; prostate: 27.87+-2.29 dB, 0.80+-0.05, 8.38+- 1.44), with statistically significant gains over every comparison method (two-sided Wilcoxon signed-rank test with Holm correction, p<0.05). The strongest baseline, SR-EMamba, ranked second. Qualitatively, SR-DBM produced the smallest residual errors and best preserved fine structures and lesions.
Protocol generalisation for brain tissue microstructure estimation via hypernetwork-controlled geometric deep learning
Brain tissue microstructure estimation with machine learning provides higher computational efficiency than conventional fitting. However, machine learning still presents important limitations that hamper its clinical utility. Specifically, current models typically lack generalisation across diffusion MRI acquisition protocols and require retraining whenever b-vectors or b-values change. Moreover, the recent machine learning methods that were developed to address protocol generalisation lack rotational equivariance. Particularly suitable for dMRI parameter estimation is a geometric deep learning model known as spherical convolutional neural network (SCNN), which guarantees rotational equivariance and b-vector generalisation. However, this architecture currently does not account for b-values. Therefore, obtaining a model that combines protocol generalisation and rotational equivariance remains an open challenge. In this paper, we directly address this issue by incorporating explicit b-value dependence into an SCNN architecture via a hypernetwork. This new approach is illustrated using NODDI as an example forward model for estimating brain tissue microstructure. To evaluate b-value generalisation, the original and newly proposed SCNN architectures are trained on synthetic data and tested on both synthetic and real data across different b-value pairs. Results demonstrate that the proposed method achieves reduced RMSE and bias on synthetic data, as well as higher agreement with conventional NODDI fitting on real data, indicating improved robustness to unseen b-values and a reduced need for retraining. By combining generalisation across b-values with generalisation across b-vectors and rotational equivariance, the proposed framework enhances the applicability of deep learning to clinical diffusion MRI parameter estimation. Code available at https://github.com/aerdnairo/arXiv\_generalisedSCNN.
Eddeep: a deep-learning framework for fast eddy-current distortion correction in diffusion MRI
Diffusion MRI (dMRI) relies on diffusion-weighted echo-planar imaging, which is highly susceptible to eddy-current-induced geometric distortions. These distortions vary across diffusion volumes according to gradient strength and direction, causing between-volume misalignment that can bias downstream microstructural analyses. Current state-of-the-art correction methods, such as FSL Eddy, achieve high-quality correction through iterative prediction-correction schemes but are computationally expensive. We propose Eddeep, a deep-learning framework for fast eddy-current distortion correction in dMRI. Eddeep decomposes the problem into two stages. First, a supervised image translation network standardises the appearance of diffusion-weighted and b=0 images, removing contrast differences that hinder reliable registration. Second, an unsupervised registration network estimates both eddy-current distortion and between-volume head motion parameters under a physics-constrained quadratic distortion model, enabling correction in a single forward pass. The method was trained on UK Biobank data and evaluated on both in-domain (UK Biobank) and out-of-domain (Memodyn) datasets. Across a range of complementary metrics, including between-volume jitter, diffusion kurtosis imaging residuals, signal irregularity, and mutual information, Eddeep achieved correction quality comparable to that of FSL Eddy while substantially reducing inference time. These results demonstrate that deep learning can provide accurate and efficient eddy-current distortion correction without relying on iterative optimisation, supporting the development of faster diffusion MRI processing pipelines for large-scale studies and clinical deployment. The code is available at: https://github.com/CIG-UCL/eddeep.
SIINR: Structurally Informed Implicit Neural Representations for super-resolution with uncertainty quantification of clinical quality diffusion MRI datasets
Diffusion Magnetic Resonance Imaging (dMRI) is a powerful tool for probing brain microstructure, but clinical acquisitions are often limited by low out-of-plane resolution, resulting in degraded structural information and reduced utility for advanced analysis. We introduce SIINR (Structurally Informed Implicit Neural Representations), a general framework for super-resoltion of clinical dMRI datasets while quantifying uncertainty in the reconstructed outputs. SIINR utilizes a supervised 3D U-net as a prior and combines it with a self-supervised implicit neural representation (INR) that fuses the high-resolution prior and the original low-resolution data. The INR enables joint modeling across spatial and angular domains, enforces data consistency, and provides analytic approximate posterior distributions for downstream uncertainty quantification. We validate the framework on a diverse set of open-access dMRI datasets, demonstrating that SIINR outperforms standard interpolation methods in both quantitative error metrics and qualitative anatomical fidelity. Experiments on clinical cases, including subjects with multiple sclerosis and brain lesions, illustrate the framework its ability to propagate intensity changes and flag uncertain regions in challenging scenarios. SIINR is flexible, modular, and can be adapted to different upsampling ratios and downstream tasks, providing a principled approach for enhancing clinical dMRI and supporting robust interpretation of derived neuroimaging metrics.
EPRA U-Net: An Efficient Pyramid Residual Attention Framework for Accurate Infarct Segmentation in Diffusion-Weighted MRI
Objective: Accurate identification of acute ischemic infarcts on diffusion-weighted magnetic resonance imaging (DWI) is a critical prerequisite for reliable lesion quantification and effective clinical decision support in the management of cerebrovascular events. Methods: This study presents EPRA U-Net (Efficient Pyramid Residual Attention U-Net), a task-specific integrated architecture for efficient and accurate infarct segmentation of DWI images. In the proposed architecture, an EfficientNet-based encoder was used as a hierarchical feature extractor with a minimized parameterization. In addition, a Residual-Recurrent (R2) block (recurrent unrolling step t = 2, following the original formulation) and Atrous Spatial Pyramid Pooling (ASPP) were integrated to enhance the performance of spatial dependency modeling. Additionally, a dual attention mechanism was incorporated to highlight lesion-related activations while concurrently enabling the suppression of extraneous background responses. To prioritize lesion detection consistent with clinical imperative, a Tversky loss function was adopted, emphasizing the sensitivity of detection over its specificity during the optimization process. Results: Experimental evaluations were conducted utilizing an in-house dataset comprising 167 patients with 4,895 DWI slices; subsequently, the performance of the proposed EPRA U-Net was assessed in comparison with state-of-the-art models, specifically UNet++, DeepLabV3+, and TransUNet. The experimental results suggest that EPRA U-Net attained superior performance, evidenced by a pixel-aggregated Dice of 0.8984, a per-sample Dice of 0.9469, an IoU of 0.8155, a Recall of 0.8887, a Lesion F1 of 0.9378, and an HD95 of 11.62 px. Furthermore, a clear reduction in the rate of missed lesions, specifically by 16%, 25%, and 29%, was observed when compared with UNet++, DeepLabV3+, and TransUNet, respectively.
High-dimensional Embedding Prior for Noisy K-space Domain MRIReconstruction
Magnetic resonance imaging (MRI) reconstruction under realistic acquisition conditions can be fundamentally viewed as estimating the underlying k-space distribution from incomplete and noise-corrupted measurements. While diffusion models have recently shown strong potential as generative prior for inverse problems,existingapproachesstruggletohandlenoisyreconstruction settings, especially when operating directly in k-space domain. In this work, we propose a unified high-dimensional k-space reconstruction framework tailored for noisy inverse problems, whichenhancesdiffusion-based solversthroughrepresentation lifting.Ratherthanmodifyingthe underlying optimization procedures, the proposed framework augments the data representation space, enabling existing diffusion-based solvers to operate on enriched k-space embeddings with improved expressiveness. Extensive experiments on both in-house and public datasets across varying noise levels and undersampled factors demonstrate that the proposed frame work consistently improves reconstruction quality for multiple diffusion-based inverse solvers. Notably, the largest gains are observed in high-noise regimes, which is consistent with our theoretical analysis of error propagation under high-dimensional representation. These results suggest that high-dimensional representation provides a general and model-agnostic mechanism for improving diffusion-based MRI reconstruction in noisy settings, offering a new perspective on robust k-space generative modeling for practical inverse problems. The code will be available at https://github.com/yqx7150/HEP-MRIRec.
BrainFIBRE: A Foundation Model via Information Decomposition for Brain Microstructure
Diffusion MRI probes brain microstructure with particular sensitivity to early cerebrovascular and neurodegenerative changes. Neurite Orientation Dispersion and Density Imaging (NODDI) decomposes the diffusion signal into three biophysically interpretable maps: neurite density index (NDI), orientation dispersion index (ODI), and free water fraction (FWF), capturing neurite packing, fiber coherence, and extracellular fluid. These 3D maps offer a rich substrate for transferable microstructural representations, yet integrating them is challenging: standard representation learning struggles to disentangle the unique information in each map from their shared and synergistic interactions. We present BrainFIBRE, the first foundation model for brain microstructure, pretrained on NODDI-derived maps from 55,592 UK Biobank participants. We propose Self-supervised Partial Information Decomposition (SPID), which extends PID-guided multimodal learning to the self-supervised regime for the first time. A novel Counterfactual Candidate Construction (CCC) paradigm perturbs inter-modality alignment through modality dropping and swapping, providing the contrastive signal for a Mixture-of-Experts architecture to disentangle unique, synergistic, and redundant information without any downstream label. On both Caucasian and Asian cohorts, BrainFIBRE achieves state-of-the-art performance across diverse tasks predicting age, sex, cerebrovascular and neurodegenerative markers, and cognition, while yielding neurobiologically interpretable representations that reveal task- and cohort-specific interaction patterns. BrainFIBRE establishes a versatile foundation for neuroimaging analysis at the microstructural level.
Distortion-Corrected Diffusion MRI Using Rotated-View EPI and Joint Field-Map/Image Estimation with Gaussian Primitives
Echo Planar Imaging (EPI) is the standard acquisition technique for diffusion and functional neuroimaging, enabling rapid imaging but suffering from geometric distortions caused by B0 field inhomogeneities. Existing correction methods first reconstruct distorted images using parallel imaging, then estimate the B0 field and correct the distortion in the image domain. In this sequential process, reconstruction artifacts at high acceleration factors and low SNR at high diffusion b-values degrade B0 estimation and limit the overall correction quality. We propose a physics-informed framework that jointly estimates the B0 field and distortion-free image directly from k-space data, without depending on an intermediate parallel-imaging reconstruction for the correction. The image and the B0 field are each represented as a superposition of Gaussian primitives embedded within an MRI physics forward model. The explicit, continuous parameterization captures both smooth regions and tissue boundaries and supports rotated-view EPI acquisitions without interpolation. The diffusion-weighted image is modeled as real and non-negative, with the image phase absorbed into a per-shot phase factor. Rotated views distribute distortions across multiple phase-encoding orientations, improving point spread function isotropy and providing stronger constraints for B0 estimation. On in vivo brain diffusion EPI, the proposed method attains the closest brain-boundary agreement with a distortion-free structural reference, with the largest improvement over sequential methods at high b-value and high acceleration. Extensive visual comparisons further show improved detail fidelity and noise suppression.
Measured-Subspace Consistency: A Plug-and-Play Operator for Diffusion Posterior Sampling in Accelerated MRI Reconstruction
Diffusion posterior samplers for accelerated MRI can reconstruct accurately yet still disagree on the acquired k-space across samples, placing posterior variability on coefficients the scanner has already measured. We identify this measured-subspace leakage as a physical-admissibility failure. Under a hard-constraint model it violates the measurement constraint and inflates the reported uncertainty with disagreement about coefficients the scanner has already determined. To quantify this leakage, we introduce complementary measured- and unmeasured-subspace k-space dispersion metrics (MSD/USD). We then present Measured-Subspace Consistency (MSC), a training-free terminal correction that wraps any compatible image-space posterior sampler with a standard multi-coil consistency lock. The ideal lock follows classical range/null-space data consistency. Our contribution is to repurpose it as a black-box posterior audit and correction rather than a new reconstructor or learned sampler. Theoretically, we prove that the ideal transform confines pairwise sample differences to the MRI null space and bound the residual cross-subspace coupling left by practical sensitivity-weighted implementations. Across six base samplers and two MRI anatomies, including out-of-distribution transfer where a knee prior reconstructs brain, MSC substantially reduces measured-subspace dispersion for Soft samplers (a median 16.5x reduction for DPS across five brain contrasts, up to ~29x), while preserving unmeasured-subspace diversity and acting as a near-identity map for Consistent ones. Furthermore, MSC maintains or modestly improves PSNR/SSIM, with no retraining, retuning, or significant computational overhead.
TensorLDM: A Component-Wise Latent Diffusion Model for Volumetric DTI Reconstruction from Sparse DWIs
Reconstructing diffusion tensors from sparse DWIs is critical for accelerating Diffusion Tensor Imaging (DTI) in clinical settings, yet current deep learning approaches frequently yield anatomically inconsistent or physically implausible tensors. We introduce TensorLDM, a component-wise latent diffusion model that processes the six tensor components through two group-specific encoders (for diagonal and off-diagonal elements) while maintaining anatomical consistency via shared DWI conditioning. TensorLDM uses an Anatomy-Conditioned Autoencoder that encourages the latent to focus on tensor properties rather than re-encoding structural information. A shared Cross-Component Attention (CCA) mechanism, applied in both autoencoder refinement and diffusion fine-tuning, models inter-component dependencies, while a Mixture-of-Experts (MoE) DWI conditioner provides component-adaptive conditioning. On the Human Connectome Project (HCP) dataset under a single-shell, four-volume sparse acquisition, TensorLDM produces the most accurate downstream tractography and tensors with near-ground-truth physical validity (SPD-violation rate 1.54% vs. 1.40%), with the best or comparable voxel-wise reconstruction accuracy. Geodesic tensor error measured by the Log-Euclidean Metric (LEM) corroborates these gains.
Cross-Modality Structural Guidance in 3D Latent Diffusion for Robust FLAIR Super-Resolution
High-resolution (HR) MRI acquisition is often hampered by scan time constraints, resulting in anisotropic or low-resolution scans (e.g., thick-slice FLAIR) that limit diagnostic accuracy. While deep learning-based super-resolution (SR) methods show promise, they often hallucinate anatomical details, which can compromise brain structural integrity. To mitigate this limitation, we introduce MR-DiffuSR, a Multi-Resolution Diffusion-based Super-Resolution framework that incorporates HR T1w structural image priors to guide the restoration of thick-slice FLAIR scans and operates in the 3D latent space. Our architecture introduces cross-modality structural swin-attention, which derives structural attention maps from the HR T1w and applies them to the low-resolution FLAIR latent features. This design disentangles anatomical structure from modality-specific contrast, effectively preventing hallucinations. Furthermore, we employ a mixed-scale degradation strategy, training the model on a continuum of downsampling factors to ensure robustness to varying slice thicknesses, while optimizing with a DINOv3-based perceptual loss to preserve high-frequency semantic details. Evaluated on the ADNI-4 dataset, MR-DiffuSR surpasses both CNN and 2D diffusion approaches, achieving an average PSNR of 32.46dB, SSIM of 0.97, and LPIPS of 0.07 across all downsampling factors. In downstream white matter hyperintensity segmentation, our model demonstrates exceptional robustness. While baseline performance collapses at 10x down-sampling (Dice: 0.51), MR-DiffuSR maintains a Dice score of 0.63, preserving utility even at 7mm equivalent slice thickness.
BrainG3N: A Dual-Purpose Tokenizer for Controllable 3D Brain MRI Generation
Three-dimensional (3D) brain MRI is central to clinical neurology and neuro-oncology, where generative models could augment under-represented cohorts, simulate disease trajectories, and support privacy-preserving data sharing. Latent diffusion has been the go-to solution for modeling imaging data, but it places two competing demands on the tokenizer: encoder embeddings must retain the clinical information that downstream tasks act on, and the decoder must reconstruct anatomically faithful volumes. Existing reconstruction-driven tokenizers achieve the second at the expense of the first. To address this, we introduce a fully volumetric masked-autoencoder (MAE) based tokenizer for 3D brain MRI latent diffusion, decoupling encoder and decoder: a frozen 3D MAE encoder produces clinically informative embeddings, while a dedicated CNN decoder reconstructs voxels from a linear projection of those embeddings. We pretrain the encoder on 35,309 volumes from 18 public cohorts spanning four modalities, ten disease categories, and 200+ acquisition sites, and demonstrate its dual utility in two settings. First, on a 23-task linear-probing benchmark, the encoder outperforms or matches SOTA models (i.e., BrainIAC, BrainSegFounder, and MedicalNet) on 21 of 23 tasks. Second, a conditional diffusion transformer (DiT) trained on these clinically informative embeddings supports both conditional generation across six variables and patient-specific longitudinal forecasting. Together these results establish a single 3D brain-MRI embedding space capable of both downstream clinical tasks and controllable generation.
Lesion-DDPM: Lesion-Enhanced 3D Diffusion for MS MRI Synthesis
3D FLAIR MRI is widely recommended as one of the standard MRI sequences for brain imaging in multiple sclerosis (MS), but publicly available MS datasets remain relatively small and vary across scanners, acquisition protocols, and lesion patterns. This scarcity and variability hinder the development of robust neuroimaging machine learning models and are particularly challenging for generative models that aim to synthesize images while preserving small, sparse lesions. We propose Lesion-DDPM, a 3D conditional diffusion framework for lesion-aware FLAIR synthesis that incorporates multi-level anatomical mask injection together with a lesion-weighted reconstruction loss to emphasize lesion voxels while maintaining global brain structure. Using a curated subset of the MSLesSeg dataset, we compare Lesion-DDPM with representative state-of-the-art GAN- and diffusion-based models, assessing both image-generation metrics and downstream 3D U-Net segmentation. In our experiments, Lesion-DDPM achieved the lowest lesion-region reconstruction error among all methods. In a downstream 3D U-Net lesion segmentation task, a model trained only on Lesion-DDPM-generated scans and evaluated on real MRIs reached a Dice score of 0.616 compared with 0.569 for the best competing synthetic dataset. When Lesion-DDPM images were added to the real training set, the Dice score further increased to 0.685.
Tractogram foundation model
Diffusion MRI (dMRI) tractography is the only noninvasive approach for mapping white-matter pathways in the living human brain. It represents each brain as a tractogram: a large, unordered set of three-dimensional streamlines that includes information about both local streamline geometry and whole-brain anatomical organization. This structure makes tractograms a natural but challenging target for representation learning. Existing methods treat streamline classification and subject-level prediction as separate problems: streamline classifiers focus on geometric patterns, whereas subject-level prediction often depends on hand-crafted features. As a result, current methods do not learn reusable representations that connect streamline anatomy with whole-brain inter-subject variation. Here we introduce TractFM, a tractogram foundation model that learns reusable representations directly from whole-brain streamline sets. TractFM combines a local streamline encoder with a permutation-equivariant tractogram encoder, allowing all streamlines from a subject to be contextualized jointly in a single forward pass. Pretraining on dense anatomical tract parcellation, i.e., assigning anatomical labels to individual streamlines, yields two complementary representations: contextualized streamline-level embeddings for tract parcellation and compact subject-level descriptors for downstream prediction of subject phenotypes. Across three tractography algorithms and five dMRI datasets, TractFM transfers to both streamline-level and subject-level tasks. Its frozen representations achieve accurate tract parcellation and predict age and sex across independent datasets. These results show that whole-brain geometric context, learned once, can generalize across tractography pipelines, datasets, and prediction tasks.
An Attention-Based Denoising Model for Diffusion Weighted Imaging
Diffusion-weighted imaging (DWI) is used for whole-body cancer screening, but it typically requires a long acquisition time. When the scan time is reduced, the image quality often suffers, leading to increased noise in the scans. Magnitude reconstruction in DWI introduces signal-dependent Rician noise, which makes denoising more challenging for conventional convolution-based methods. To address this limitation, we propose a noise-aware attention-driven denoising framework that integrates hierarchical Swin Transformer window attention with transformer-based multi-dimensional gated refinement for DWI restoration. The model incorporates explicit noise-level conditioning and residual reconstruction to enable adaptive suppression of heteroscedastic noise across a wide range of corruption levels. Experimental evaluation on corrupted DWI scans demonstrates strong restoration performance. Our model achieves a mean PSNR of 33.69~dB and SSIM of 0.8539 across noise levels from 1% to 15%, while maintaining stable behavior under severe noise conditions. These results indicate that attention-guided contextual modeling combined with channel-adaptive refinement provides a robust and generalizable solution for DWI denoising.
Realistic noise synthesis reduces bias and improves tissue microstructure estimation with supervised machine learning
Diffusion MRI enables non-invasive probing of tissue microstructure, but accurate parameter estimation is challenged by noise-related effects. In supervised machine learning frameworks trained on simulated data, discrepancies between the noise characteristics of simulated and acquired signals introduce a form of covariate shift, whereby the input signal distribution differs between training and inference. We investigated the impact of this mismatch on microstructure parameter estimation and propose a realistic noise synthesis (RNS) framework to mitigate it. RNS incorporates both the Rician expectation and the effective post-processing noise variance into simulated training signals. The Rician expectation was modelled using a noise standard deviation estimated with MPPCA, while the effective standard deviation was derived from spherical harmonic residuals of preprocessed data. The method was evaluated using the cylinder-zeppelin and the SANDI models on simulated datasets across multiple SNR levels and on in vivo diffusion data with repeated acquisitions. Sensitivity to noise misestimation was also assessed. Ignoring magnitude-induced noise effects during training produced systematic, SNR-dependent parameter bias, particularly at low SNR. Incorporating the Rician expectation substantially reduced bias to the level of noise-aware nonlinear least-squares fitting. Modelling the effective standard deviation further improved precision. Performance was largely independent of regression architecture but sensitive to accurate noise estimation. These findings demonstrate that realistic noise modelling in simulated training data mitigates signal-domain covariate shift and is essential for unbiased supervised microstructure estimation, particularly in low-SNR regimes associated with high b-values or high spatial resolution.
Wavelet-Fusion Diffusion Model for Multimodal Brain MRI Synthesis with Modality and Metadata Conditioning
Multimodal MRI provides complementary information for neuroimaging analysis, where different imaging modalities capture distinct anatomical, tissue, and pathological features that support the development and evaluation of downstream AI applications. Although large-scale structural MRI resources are increasingly available, their modality coverage is often uneven across public and pooled neuroimaging datasets. This uneven modality coverage is further complicated by heterogeneity across sites, scanners, and acquisition protocols, as well as demographic and clinical variables that are often sparse, inconsistently recorded, or unavailable across studies. Synthetic MRI generation can help address this imbalance by synthesizing target-modality volumes for dataset augmentation and controlled synthetic cohort creation. However, many existing MRI synthesis approaches are trained on narrow modality sets or relatively homogeneous cohorts, limiting their applicability to large pooled neuroimaging resources where modality availability, acquisition protocols, and metadata coverage vary substantially across datasets. Diffusion models have become an attractive approach for MRI synthesis because of their strong sample fidelity and diversity, but sampling directly in 3D voxel space is computationally expensive and slow at inference. Latent diffusion improves practicality by synthesizing MRI in a learned, 3D latent space, although generation quality depends on the autoencoder's reconstruction fidelity and the resulting latent distribution. Our approach combines a Wavelet-Fusion variational autoencoder (WF-VAE) latent compressor with a conditional 3D U-Net diffusion model trained in the learned latent space using explicit modality and metadata conditioning. Our proposed Wavelet-Fusion Diffusion Model (WFDM) achieved the strongest distributional alignment among the evaluated synthetic MRI generators.
AutoIQ: An Ensemble Framework for Automatic Assessment of Geometric Distortion in Prostate Diffusion-Weighted Imaging
Geometric distortion in prostate diffusion-weighted imaging (DWI) can impair lesion localization and reduce the reliability of MRI-based clinical assessment. We propose AutoIQ, an ensemble machine learning framework for automatic quantification and classification of DWI geometric distortion severity. A total of 140 retrospective prostate biparametric MRI examinations were analyzed, including 33 scans with severe distortion requiring repeat acquisition and 107 scans with acceptable distortion based on expert radiologist assessment. AutoIQ combines two complementary distortion quantification strategies: a segmentation-based method measuring prostate boundary mismatch between T2-weighted imaging (T2WI) and DWI, and a registration-based method estimating deformation magnitude after DWI-to-T2WI alignment. The resulting distortion scores were used to train individual classifiers and a logistic-regression ensemble model. Both computational methods significantly differentiated severe from acceptable distortion cases (p < 0.001). On an independent test set, the ensemble model achieved an accuracy of 0.95, F1-score of 0.93, and AUC of 0.98, outperforming individual models. These results suggest that AutoIQ can provide automated, quantitative quality assessment for prostate DWI and may help identify scans that require repeat acquisition.
A physics-informed foundation model for quantitative diffusion MRI
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.
Layer Selection in Feature-Based Losses Affects Image Quality and Microstructural Consistency in Deep Learning Super-Resolution of Brain Diffusion MRI
Clinical application of high-resolution diffusion MRI is hindered by hardware limitations and prohibitive scan times, motivating computational super-resolution. This study investigates the efficacy of a feature-based loss function in preserving diffusion signal consistency in deep learning super-resolution. Using 7T data from the human connectome project to generate pairs of low- and high-resolution diffusion weighted images (DWI), we trained UNets for 2D super-resolution. Ablation and isolation studies evaluated different VGG16-layers for feature-based losses against an image-based L1 baseline. Deeper layers and combinations thereof resulted in grid-like artifacts in super-resolution DWIs, which persisted in diffusion parameters like quantitative and fractional anisotropy. No such artifacts were present when using the shallowest layer. Downstream analysis for this layer showed great consistency with the ground truth, even for 9-fold super-resolution. Image SNR and used VGG16-layer depths modulated artifact appearance and severity, mandating careful selection of contributing layers for application in and beyond diffusion MRI.
Product-of-Gaussian-Mixture Diffusion Models for Joint Nonlinear MRI Reconstruction
Recently, diffusion models have attracted considerable attention for magnetic resonance image reconstruction due to their high sample quality. However, most existing methods rely on large networks with opaque time-conditioning mechanisms, and require offline coil sensitivity estimation. This results in limited interpretability of the reconstruction process and reduced flexibility in the acquisition setup. To address these limitations, we jointly reconstruct the image and the coil sensitivities by combining the parameter-efficient product-of-Gaussian-mixture diffusion model as an image prior with a classical smoothness prior on the coil sensitivities. The proposed method is fast and robust to both contrast and anatomical distribution shifts as well as changing k-space trajectories. Finally, we propose a more expressive parameterization of the image prior which improves results in denoising and magnetic resonance image reconstruction.
Self-Supervised Spatial And Zero-Shot Angular Super-Resolution by Spatial-Angular Implicit Representation For Rotating-View SNR-Efficient Diffusion MRI
Rotating-view thick-slice acquisition is highly SNR-efficient for mesoscale diffusion MRI (dMRI) but requires numerous rotating views to satisfy Nyquist sampling, resulting in long scan time. We propose a self-supervised Spatial-Angular Implicit Neural Representation (SA-INR) that reconstructs high-resolution dMRI from a single view per diffusion direction, representing a massive acceleration. Our model, an MLP conditioned on a b=0 structural prior and the b-direction via FiLM, is trained end-to-end on the anisotropic input. The framework not only accurately reconstructs the trained b-directions (spatial SR) but also learns a continuous q-space representation, enabling high-fidelity "zero-shot" synthesis of unseen b-directions (angular SR). On simulated data, our method achieved high fidelity for both trained (34.82 dB) and unseen (33.08 dB) directions. Most importantly, the synthesized angular data also improved the quantitative accuracy of downstream DTI model fitting. Our SA-INR framework breaks the classical sampling limits, paving the way for fast, quantitative high-resolution dMRI.
BrainNormalizer: Anatomy-Informed Pseudo-Healthy Brain Reconstruction from Tumor MRI via Edge-Guided ControlNet
Brain tumors induce complex structural deformations that obscure the patient' s original neuroanatomy, making it difficult to distinguish tumor-induced changes from inherent anatomical variability. Reconstructing a subject-specific pseudo-healthy brain can provide a critical reference for such analysis, but this task is inherently counterfactual, as paired pre-tumor scans and explicit healthy guidance are unavailable. We propose BrainNormalizer, a diffusion-based framework for subject-specific pseudo-healthy brain MRI reconstruction that enables anatomy-informed reconstruction without requiring paired data or explicit healthy references. The framework learns anatomical priors and edge-based structural conditioning through a two-stage training strategy consisting of inpainting-based diffusion fine-tuning and ControlNet-based edge conditioning. At inference, counterfactual pseudo-healthy reconstruction is achieved through a deliberate misalignment strategy, where tumorous inputs are paired with non-tumorous prompts and mirrored contralateral edge maps. This allows subject-specific anatomical guidance to be constructed from the patient's own anatomy, enabling anatomically consistent pseudo-healthy reconstruction that preserves individual structural characteristics. Experiments on the BraTS2020 dataset demonstrate that BrainNormalizer achieves improved distributional realism, symmetry-based structural consistency, and reduced false positive detection compared to existing methods. These results indicate that the proposed framework provides a principled approach for subject-specific counterfactual reconstruction and supports downstream analysis of tumor-induced deformation.