Advanced Brain Tissue Imaging with Data-Consistent Diffusion Priors in Laminographic X-Ray Nanoimaging

Accurate longitudinal analysis of brain MRI is often hindered by evolving lesions, which bias automated neuroimaging pipelines. While deep generative models have shown promise in inpainting these lesions, most existing methods operate cross-sectionally or lack 3D anatomical continuity. We present a novel pseudo-3D longitudinal inpainting framework based on Denoising Diffusion Probabilistic Models (DDPM). Our approach utilizes multi-channel conditioning to incorporate longitudinal context from distinct visits (t_1, t_2) and extends Region-Aware Diffusion (RAD) to the medical domain, focusing the generative process on pathological regions without altering surrounding healthy tissue. We evaluated our model against state-of-the-art baselines on longitudinal brain MRI from 93 patients. Our model significantly outperforms the leading baseline (FastSurfer-LIT) in terms of perceptual fidelity, reducing the Learned Perceptual Image Patch Similarity (LPIPS) distance from 0.07 to 0.03 while effectively eliminating inter-slice discontinuities. Furthermore, our model demonstrates high longitudinal stability with a Temporal Fidelity Index of 1.024, closely approaching the ideal value of 1.0 and substantially narrowing the gap compared to LIT's TFI of 1.22. Notably, the RAD mechanism provides a substantial gain in efficiency; our framework achieves an average processing time of 2.53 min per volume, representing approximately 10x speedup over the 24.30 min required by LIT. By leveraging longitudinal priors and region-specific denoising, our framework provides a highly reliable and efficient preprocessing step for the study of progressive neurodegenerative diseases. A derivative dataset consisting of 93 pre-processed scans used for testing will be available upon request after acceptance. Code will be released upon acceptance.

Limited-angle digital breast tomosynthesis (DBT) reconstructs a volume from a few low-dose projections over a narrow arc. At a representative nine-view, $25^{\circ}$ protocol more than 98% of image space is unmeasured, so a learned prior must supply structure in the missing wedge. Conditional diffusion priors achieve strong perceptual quality here but leave three clinical obstacles: inexact data consistency, unlocalized hallucination, and uncalibrated uncertainty. We enforce measurements exactly by replacing the per-step proximal update of a conditional diffusion sampler with exact Euclidean projection onto the data-consistent set, computed via an $m$-dimensional dual system with a one-time Gram matrix $AA^{\top}$ factorization. This projection costs 4.5 ms per step (a $248\times$ speedup) and drives the data residual to the double-precision floor ($2.4\times10^{-13}$). We prove it is the $ρ\to0$ limit of the proximal step, provide a no-harm theorem, and show that exactly consistent sample ensembles have variance supported on null($A$). Thus, the mean's entire error lies in the unmeasured subspace covered by the uncertainty map. On patient-derived breast phantoms, this improves fidelity at no depth-resolution cost. Conversely, a proximal step applied post-update degrades quality, isolating the consistency step's placement as decisive. Isotonic recalibration brings the ensemble spread to a calibrated error scale (expected calibration error $0.029\to0.008$; standardized error $4.7\to0.96$), ranking errors better than the pure prior. We also repair a 20.3% adjoint mismatch in a deployed projector via a materialized operator of record. This is the first data-consistent, uncertainty-calibrated learned reconstruction for limited-angle DBT. The solver naturally relaxes to discrepancy-ball and maximum-a-posteriori modes for noisy measurements.

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.