Identifying latent disease factors differently expressed in patient subgroups using group factor analysis

In this study, we propose a novel approach to uncover subgroup-specific and subgroup-common latent factors addressing the challenges posed by the heterogeneity of neurological and mental disorders, which hinder disease understanding, treatment development, and outcome prediction. The proposed approach, sparse Group Factor Analysis (GFA) with regularised horseshoe priors, was implemented with probabilistic programming and can uncover associations (or latent factors) among multiple data modalities differentially expressed in sample subgroups. Synthetic data experiments showed the robustness of our sparse GFA by correctly inferring latent factors and model parameters. When applied to the Genetic Frontotemporal Dementia Initiative (GENFI) dataset, which comprises patients with frontotemporal dementia (FTD) with genetically defined subgroups, the sparse GFA identified latent disease factors differentially expressed across the subgroups, distinguishing between "subgroup-specific" latent factors within homogeneous groups and "subgroup common" latent factors shared across subgroups. The latent disease factors captured associations between brain structure and non-imaging variables (i.e., questionnaires assessing behaviour and disease severity) across the different genetic subgroups, offering insights into disease profiles. Importantly, two latent factors were more pronounced in the two more homogeneous FTD patient subgroups (progranulin (GRN) and microtubule-associated protein tau (MAPT) mutation), showcasing the method's ability to reveal subgroup-specific characteristics. These findings underscore the potential of sparse GFA for integrating multiple data modalities and identifying interpretable latent disease factors that can improve the characterization and stratification of patients with neurological and mental health disorders.

Domain-agnostic segmentation of thalamic nuclei from joint structural and diffusion MRI

The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI.