A Comprehensive Framework for Automated Segmentation of Perivascular Spaces in Brain MRI with the nnU-Net

Background: Enlargement of perivascular spaces (PVS) is common in neurodegenerative disorders including cerebral small vessel disease, Alzheimer's disease, and Parkinson's disease. PVS enlargement may indicate impaired clearance pathways and there is a need for reliable PVS detection methods which are currently lacking. Aim: To optimise a widely used deep learning model, the no-new-UNet (nnU-Net), for PVS segmentation. Methods: In 30 healthy participants (mean$\pm$SD age: 50$\pm$18.9 years; 13 females), T1-weighted MRI images were acquired using three different protocols on three MRI scanners (3T Siemens Tim Trio, 3T Philips Achieva, and 7T Siemens Magnetom). PVS were manually segmented across ten axial slices in each participant. Segmentations were completed using a sparse annotation strategy. In total, 11 models were compared using various strategies for image handling, preprocessing and semi-supervised learning with pseudo-labels. Model performance was evaluated using 5-fold cross validation (5FCV). The main performance metric was the Dice Similarity Coefficient (DSC). Results: The voxel-spacing agnostic model (mean$\pm$SD DSC=64.3$\pm$3.3%) outperformed models which resampled images to a common resolution (DSC=40.5-55%). Model performance improved substantially following iterative label cleaning (DSC=85.7$\pm$1.2%). Semi-supervised learning with pseudo-labels (n=12,740) from 18 additional datasets improved the agreement between raw and predicted PVS cluster counts (Lin's concordance correlation coefficient=0.89, 95%CI=0.82-0.94). We extended the model to enable PVS segmentation in the midbrain (DSC=64.3$\pm$6.5%) and hippocampus (DSC=67.8$\pm$5%). Conclusions: Our deep learning models provide a robust and holistic framework for the automated quantification of PVS in brain MRI.

Perivascular space Identification Nnunet for Generalised Usage (PINGU)

Perivascular spaces(PVSs) form a central component of the brain\'s 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.