Large-Scale Deployment and Analytical Implications of Structured Quality Control in Diffusion Magnetic Resonance Imaging

Purpose: Diffusion MRI (dMRI) provides a diverse set of quantitative measures and derived datatypes to assess white matter microstructure and macrostructure. Coupled with the increasing size of imaging studies using dMRI, the number of downstream outputs requiring quality control (QC) will continue to grow. Previous work has shown that failure modes which are often not evident from aggregate metrics or summary statistics can be identified through structured visual inspection. This work aims to better understand common failure modes and the expected characteristics of valid dMRI processing outputs to ensure the validity and interpretability of quantitative findings. Approach: We deployed a structured QC framework to assess 18,328 dMRI scans across nine datasets, visually evaluating the outputs of seven processing pipelines representative of conventional dMRI analyses. Results: Downstream outputs that pass visual QC may still rely on failed upstream dependencies; such failures may only be visually detectable through systematic inspection of the full pipeline hierarchy. Additionally, appropriate QC granularity is algorithm-specific, as the spatial structure of each algorithm's outputs determines whether failures warrant selective or global exclusion. Conclusion: This work demonstrates the feasibility and analytical value of large-scale, structured QC for dMRI processing pipelines. Our results highlight the need for systematic QC spanning the full processing hierarchy to ensure the validity and interpretability of quantitative findings.

Unsupervised learning of acquisition variability in structural connectomes via hybrid latent space modeling

Acquisition differences across sites, scanners, and protocols in dMRI introduce variability that complicates structural connectome analysis. This motivates deep learning models that can represent high-dimensional connectomes in a low-dimensional space while explicitly separating acquisition-related effects from biological variation. Conventional dimensionality reduction methods model all variance as continuous, so acquisition effects often get absorbed into a continuous latent space. Recent hybrid latent-space models combine discrete and continuous components to address this, but typically require manual capacity tuning to ensure the discrete component captures the intended variability. We introduce an unsupervised framework that removes this manual tuning by architecturally annealing encoder outputs before decoding, allowing the model to adaptively balance discrete and continuous latent variables during training. To evaluate it, we curated a dataset of N=7,416 structural connectomes derived from dMRI, spanning ages 2 to 102 and 13 studies with 25 unique acquisition-parameter combinations. Of these, 5,900 are cognitively unimpaired, 877 have mild cognitive impairment (MCI), and 639 have Alzheimer's disease (AD). We compare against a standard VAE, PCA with k-means clustering, and hybrid models that anneal only through the loss function. Our architectural annealing produces stronger site learning (ARI=0.53, p<0.05) than these baselines. Results show that a hybrid continuous-discrete latent space, with architectural rather than loss-based annealing, provides a useful unsupervised mechanism for capturing acquisition variability in dMRI: by jointly modeling smooth and categorical structure, the Joint-VAE recovers clusters aligned with scanner and protocol differences.

Field-of-View Extension for Diffusion MRI via Deep Generative Models

Purpose: In diffusion MRI (dMRI), the volumetric and bundle analyses of whole-brain tissue microstructure and connectivity can be severely impeded by an incomplete field-of-view (FOV). This work aims to develop a method for imputing the missing slices directly from existing dMRI scans with an incomplete FOV. We hypothesize that the imputed image with complete FOV can improve the whole-brain tractography for corrupted data with incomplete FOV. Therefore, our approach provides a desirable alternative to discarding the valuable dMRI data, enabling subsequent tractography analyses that would otherwise be challenging or unattainable with corrupted data. Approach: We propose a framework based on a deep generative model that estimates the absent brain regions in dMRI scans with incomplete FOV. The model is capable of learning both the diffusion characteristics in diffusion-weighted images (DWI) and the anatomical features evident in the corresponding structural images for efficiently imputing missing slices of DWI outside of incomplete FOV. Results: For evaluating the imputed slices, on the WRAP dataset the proposed framework achieved PSNRb0=22.397, SSIMb0=0.905, PSNRb1300=22.479, SSIMb1300=0.893; on the NACC dataset it achieved PSNRb0=21.304, SSIMb0=0.892, PSNRb1300=21.599, SSIMb1300= 0.877. The proposed framework improved the tractography accuracy, as demonstrated by an increased average Dice score for 72 tracts (p < 0.001) on both the WRAP and NACC datasets. Conclusions: Results suggest that the proposed framework achieved sufficient imputation performance in dMRI data with incomplete FOV for improving whole-brain tractography, thereby repairing the corrupted data. Our approach achieved more accurate whole-brain tractography results with extended and complete FOV and reduced the uncertainty when analyzing bundles associated with Alzheimer's Disease.

Evaluation of Mean Shift, ComBat, and CycleGAN for Harmonizing Brain Connectivity Matrices Across Sites

Connectivity matrices derived from diffusion MRI (dMRI) provide an interpretable and generalizable way of understanding the human brain connectome. However, dMRI suffers from inter-site and between-scanner variation, which impedes analysis across datasets to improve robustness and reproducibility of results. To evaluate different harmonization approaches on connectivity matrices, we compared graph measures derived from these matrices before and after applying three harmonization techniques: mean shift, ComBat, and CycleGAN. The sample comprises 168 age-matched, sex-matched normal subjects from two studies: the Vanderbilt Memory and Aging Project (VMAP) and the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD). First, we plotted the graph measures and used coefficient of variation (CoV) and the Mann-Whitney U test to evaluate different methods' effectiveness in removing site effects on the matrices and the derived graph measures. ComBat effectively eliminated site effects for global efficiency and modularity and outperformed the other two methods. However, all methods exhibited poor performance when harmonizing average betweenness centrality. Second, we tested whether our harmonization methods preserved correlations between age and graph measures. All methods except for CycleGAN in one direction improved correlations between age and global efficiency and between age and modularity from insignificant to significant with p-values less than 0.05.

A Statistical Recurrent Model on the Manifold of Symmetric Positive Definite Matrices

In a number of disciplines, the data (e.g., graphs, manifolds) to be analyzed are non-Euclidean in nature. Geometric deep learning corresponds to techniques that generalize deep neural network models to such non-Euclidean spaces. Several recent papers have shown how convolutional neural networks (CNNs) can be extended to learn with graph-based data. In this work, we study the setting where the data (or measurements) are ordered, longitudinal or temporal in nature and live on a Riemannian manifold -- this setting is common in a variety of problems in statistical machine learning, vision and medical imaging. We show how recurrent statistical recurrent network models can be defined in such spaces. We give an efficient algorithm and conduct a rigorous analysis of its statistical properties. We perform extensive numerical experiments demonstrating competitive performance with state of the art methods but with significantly less number of parameters. We also show applications to a statistical analysis task in brain imaging, a regime where deep neural network models have only been utilized in limited ways.