Cross-Modality Structural Guidance in 3D Latent Diffusion for Robust FLAIR Super-Resolution
Authors: Haoyu Lan, Jiazhen Zhang, John Onofrey, Bino Varghese, Nasim Sheikh-Bahaei, Arthur W. Toga, Jeiran Choupan
Organizations: University of Southern California · Yale University
Abstract
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.
Magnetic Resonance Imaging (MRI) is often acquired with anisotropic resolution to reduce scan time, producing stair-step artifacts along the through-plane direction. In through-plane MRI super-resolution, an efficiency-fidelity trade-off arises: feed-forward regressors are fast but oversmooth at large slice-thicknesses, while sampling-based methods improve fidelity at high inference cost. We propose DRIFT, a two-stage thickness-conditioned rectified flow framework for through-plane MRI super-resolution with continuous input slice-thickness. Stage 1 employs an Anatomical Projection Network (APN) to map low-resolution patches to a coarse high-resolution manifold, providing a deterministic anatomical initialization that shortens the residual transport of Stage 2 and stabilizes slice-wise refinement. Stage 2 refines details via rectified flow and introduces a Physics-Aware Difficulty (PAD) metric derived from slice-thickness induced through-plane bandwidth deficit to guide an Adaptive Integration Scheduler (AIS), allocating ODE steps by thickness. A Consistent Endpoint Trajectory Alignment (CETA) loss enforces thickness-consistent reconstructions. Experiments show that DRIFT outperforms super-resolution baselines while reducing inference cost. Code, models, and interactive demos are available at https://yoonseokchoi-ai.github.io/drift-eccv2026/.
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.
White matter hyperintensities (WMH), bright regions on Fluid-attenuated Inversion Recovery (FLAIR) scans are associated with cerebrovascular pathology and neurodegeneration. FLAIR is usually acquired with thick slices in clinical settings, giving it poor through-plane resolution. Super-resolution (SR) is a widely used method for recovering an isotropic volume from an anisotropic scan. Yet whether applying it prior to WMH segmentation preserves lesion content remains unknown: a model may erase small real lesions or hallucinate absent ones. We used 1-mm isotropic high-resolution (HR) FLAIR scans from 29 individuals in the ADNI cohort, each manually segmented for WMH by an expert. Then, we degraded each to simulated 3 and 5 mm through-plane acquisitions. Multi-contrast implicit neural representation (INR), a single-contrast self-supervised model (ECLARE), and cubic interpolation were used to upsample them onto the HR grid. WMH segmentation from a simulated thick slice and the original HR FLAIR set the floor and ceiling, respectively, for the per-lesion analysis. Of four WMH segmentation methods (WMH-SynthSeg, segcsvd, MARS-WMH, TrUE-Net), we ran the analysis under the most sensitive one to small lesions on HR (MARS-WMH) with the evaluation metrics of detection sensitivity, erasure rate (HR-detected lesions lost after reconstruction), and hallucination rate (predicted components absent from both the manual and HR segmentation). The dominant effect of SR was erasure of small real lesions, not hallucination, and it increased with slice thickness, though every reconstruction still improved lesion detection over the raw thick slice. ECLARE recovered small lesion signal best at both thicknesses, while the INR was no better than cubic interpolation.