Sharon L. Naismith

Benjamin Sinclair, Lucy Vivash, Jasmine Moses et al.

Perivascular spaces(PVSs) form a central component of the brainś waste clearance system, the glymphatic system. These structures are visible on MRI images, and their morphology is associated with aging and neurological disease. Manual quantification of PVS is time consuming and subjective. Numerous deep learning methods for PVS segmentation have been developed, however the majority have been developed and evaluated on homogenous datasets and high resolution scans, perhaps limiting their applicability for the wide range of image qualities acquired in clinic and research. In this work we train a nnUNet, a top-performing biomedical image segmentation algorithm, on a heterogenous training sample of manually segmented MRI images of a range of different qualities and resolutions from 6 different datasets. These are compared to publicly available deep learning methods for 3D segmentation of PVS. The resulting model, PINGU (Perivascular space Identification Nnunet for Generalised Usage), achieved voxel and cluster level dice scores of 0.50(SD=0.15), 0.63(0.17) in the white matter(WM), and 0.54(0.11), 0.66(0.17) in the basal ganglia(BG). Performance on data from unseen sites was substantially lower for both PINGU(0.20-0.38(WM, voxel), 0.29-0.58(WM, cluster), 0.22-0.36(BG, voxel), 0.46-0.60(BG, cluster)) and the publicly available algorithms(0.18-0.30(WM, voxel), 0.29-0.38(WM cluster), 0.10-0.20(BG, voxel), 0.15-0.37(BG, cluster)), but PINGU strongly outperformed the publicly available algorithms, particularly in the BG. Finally, training PINGU on manual segmentations from a single site with homogenous scan properties gave marginally lower performances on internal cross-validation, but in some cases gave higher performance on external validation. PINGU stands out as broad-use PVS segmentation tool, with particular strength in the BG, an area of PVS related to vascular disease and pathology.

Yifei Sun, James M. Shine, Robert D. Sanders et al.

The white matter of the brain is organised into axonal bundles that support long-range neural communication. Although diffusion MRI (dMRI) enables detailed mapping of these pathways through tractography, how white matter pathways directly facilitate large-scale neural synchronisation remains poorly understood. We developed a data-driven framework that integrates dMRI and functional MRI (fMRI) to model the dynamic coupling supported by white matter tracks. Specifically, we employed track dynamic functional connectivity (Track-DFC) to characterise functional coupling of remote grey matter connected by individual white matter tracks. Using independent component analysis followed by k-medoids clustering, we derived functionally-coherent clusters of white matter tracks from the Human Connectome Project young adult cohort. When applied to the HCP ageing cohort, these clusters exhibited widespread age-related declines in both functional coupling strength and temporal variability. Importantly, specific clusters encompassing pathways linking control, default mode, attention, and visual systems significantly mediated the relationship between age and cognitive performance. Together, these findings depict the functional organisation of white matter tracks and provide a powerful tool to study brain ageing and cognitive decline.

Zhen Xuen Brandon Low, Rory Zhang, Hang Min et al.

Enlarged perivascular spaces (PVS) are increasingly recognized as biomarkers of cerebral small vessel disease, Alzheimer's disease, stroke, and aging-related neurodegeneration. However, manual segmentation of PVS is time-consuming and subject to moderate inter-rater reliability, while existing automated deep learning models have moderate performance and typically fail to generalize across diverse clinical and research MRI datasets. We adapted MedNeXt-L-k5, a Transformer-inspired 3D encoder-decoder convolutional network, for automated PVS segmentation. Two models were trained: one using a homogeneous dataset of 200 T2-weighted (T2w) MRI scans from the Human Connectome Project-Aging (HCP-Aging) dataset and another using 40 heterogeneous T1-weighted (T1w) MRI volumes from seven studies across six scanners. Model performance was evaluated using internal 5-fold cross validation (5FCV) and leave-one-site-out cross validation (LOSOCV). MedNeXt-L-k5 models trained on the T2w images of the HCP-Aging dataset achieved voxel-level Dice scores of 0.88+/-0.06 (white matter, WM), comparable to the reported inter-rater reliability of that dataset, and the highest yet reported in the literature. The same models trained on the T1w images of the HCP-Aging dataset achieved a substantially lower Dice score of 0.58+/-0.09 (WM). Under LOSOCV, the model had voxel-level Dice scores of 0.38+/-0.16 (WM) and 0.35+/-0.12 (BG), and cluster-level Dice scores of 0.61+/-0.19 (WM) and 0.62+/-0.21 (BG). MedNeXt-L-k5 provides an efficient solution for automated PVS segmentation across diverse T1w and T2w MRI datasets. MedNeXt-L-k5 did not outperform the nnU-Net, indicating that the attention-based mechanisms present in transformer-inspired models to provide global context are not required for high accuracy in PVS segmentation.

Yifei Sun, Marshall A. Dalton, Robert D. Sanders et al.

Grey matter loss in the hippocampus is a hallmark of neurobiological aging, yet understanding the corresponding changes in its functional connectivity remains limited. Seed-based functional connectivity (FC) analysis enables voxel-wise mapping of the hippocampus's synchronous activity with cortical regions, offering a window into functional reorganization during aging. In this study, we develop an interpretable deep learning framework to predict brain age from hippocampal FC using a three-dimensional convolutional neural network (3D CNN) combined with LayerCAM saliency mapping. This approach maps key hippocampal-cortical connections, particularly with the precuneus, cuneus, posterior cingulate cortex, parahippocampal cortex, left superior parietal lobule, and right superior temporal sulcus, that are highly sensitive to age. Critically, disaggregating anterior and posterior hippocampal FC reveals distinct mapping aligned with their known functional specializations. These findings provide new insights into the functional mechanisms of hippocampal aging and demonstrate the power of explainable deep learning to uncover biologically meaningful patterns in neuroimaging data.