Layer Selection in Feature-Based Losses Affects Image Quality and Microstructural Consistency in Deep Learning Super-Resolution of Brain Diffusion MRI

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.

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.

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 $4\times$ 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 $6\times$ 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/ .