Atlases Are Already Inside: Recovering Population Templates from Pretrained Diffusion Models

This work introduces MedForj, a suite of 3D foundational generative priors based on diffusion models. The MedForj models were trained on $72{,}659$ 1~mm isotropic 3D $T_1$-weighted MRI human brain image volumes from $38{,}174$ subjects, drawn from a curated corpus of $80{,}675$ volumes from $42{,}506$ subjects spanning $38$ publicly available datasets. These training images were manually inspected to exclude those with poor quality and excessive pathology, and otherwise were minimally processed. The models include six different diffusion training strategies: rectified flow, latent diffusion rectified flow, flow matching, velocity prediction, clean prediction, and noise prediction. Image samples produced by each of these models were compared to each other and against real, ground truth data under downstream segmentation distributions, FID, five inverse problems, and blind human inspection in an observer study. Flow matching was the strongest strategy overall, achieving the best inverse problem solving results at $28.80$~dB PSNR and $0.874$ SSIM averaged over the five forward problems, the highest rate of reconstructions judged real by blind human raters at $72.6\%$, and the closest per-structure match to real segmented anatomy in a permutation test. It was not best everywhere: rectified flow produced the most convincing unconditional samples in the observer study and the best FID, and the latent rectified-flow model achieved the smallest joint distributional distance to real anatomy. No other strategy, however, performed consistently well across all four evaluations. We therefore recommend flow matching as the default MedForj prior, while releasing every strategy so that the choice can be revisited per application. All model weights and corresponding code are publicly available at https://github.com/piksl-research/medforj.

Spatio-temporal fetal brain atlases are important for characterizing normative neurodevelopment and identifying congenital anomalies. However, existing atlas construction pipelines necessitate days for slice-to-volume reconstruction (SVR) to generate high-resolution 3D brain volumes and several additional days for iterative volume registration, thereby rendering atlas construction from large-scale cohorts prohibitively impractical. We address these limitations with INFANiTE, an Implicit Neural Representation (INR) framework for high-resolution Fetal brain spatio-temporal Atlas learNing from clinical Thick-slicE MRI scans, bypassing both the costly SVR and the iterative non-rigid registration steps entirely, thereby substantially accelerating atlas construction. Extensive experiments demonstrate that INFANiTE outperforms existing baselines in subject consistency, reference fidelity, intrinsic quality and biological plausibility, even under challenging sparse-data settings. Additionally, INFANiTE reduces the end-to-end processing time (i.e., from raw scans to the final atlas) from days to hours compared to the traditional 3D volume-based pipeline (e.g., SyGN), facilitating large-scale population-level fetal brain analysis. Code: https://github.com/hu2274898/INFANiTE

The prevailing inference framework for diffusion models formulates generation fundamentally as a problem of numerical integration. This perspective casts the model as an exact estimator, neglecting the inherent statistical uncertainty of the denoising process. In this work, we propose Forward-Process Aligned Diffusion prediction (DiFA), a training-free framework that reframes inference-time data prediction refinement as a sequential state estimation problem. Rather than reusing past outputs solely for numerical integration, DiFA treats iterative data predictions along the reverse trajectory as correlated observations to build a forward-aligned temporal consensus. Inspired by Kalman filtering, this consensus aggregates historical predictions according to structural consistency and noise-level compatibility. To counteract the over-smoothing tendency of temporal consensus, we introduce a deviation guidance mechanism to adaptively preserve residual details. Empirically, DiFA yields significant improvements on CIFAR-10 and ImageNet across the evaluated metrics, including FID, IS, and FD-DINOv2, demonstrating that aligning inference with the forward statistical structure substantially improves generative fidelity.