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- ENLARGED PERIVASCULAR SPACES IN COMMUNITY-BASED OLDER ADULTS
- Javierre Petit, Carles
Enlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function and vascular dementia...
Show moreEnlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function and vascular dementia. Furthermore, recent studies have investigated the links of EPVS with the glymphatic system (GS), since perivascular spaces are thought to play a major role as the main channels for clearance of interstitial solutes from the brain. However, the relationship of EPVS with age-related neuropathologies is not well understood. Therefore, more conclusive studies are needed to elucidate specific relationships between EPVS and neuropathologies. After demonstration of their neuropathologic correlates, detailed assessment of EPVS severity could provide as a potential biomarker for specific neuropathologies.In this dissertation, our focus was twofold: to develop a fully automatic EPVS segmentation model via deep learning with a set of guidelines for model optimization, and to evaluate both manual and automatic assessment of EPVS severity to investigate the neuropathologic correlates of EPVS, and their contribution to cognitive decline, by combining ex-vivo brain magnetic resonance imaging (MRI) and pathology (from autopsy) in a large community-based cohort of older adults. This project was structured as follows. First, a manual approach was used to assess neuropathologic and cognitive correlates of EPVS burden in a large dataset of community-dwelling older adults. MR images from each participant were rated using a semiquantitative 4-level rating scale, and a group of identified EPVS was histologically evaluated. Two groups of participants in descending order of average cognitive impairment were defined based and studied. Elasticnet regularized ordinal logistic regression was used to assess the neuropathologic correlates of EPVS burden in each group, and linear mixed effects models were used to investigate the associations of EPVS burden with cognitive decline. Second, a fully automatic EPVS segmentation model was implemented via deep learning (DL) using a small dataset of 10 manually segmented brain MR images. Multiple techniques were evaluated to optimize performance, mainly by implementing strategies to reduce model overfitting. The final segmentation model was evaluated in an independent test set and the performance was validated with an expert radiologist. Third, the DL segmentation model was used to segment and quantify EPVS. Quantified EPVS (qEPVS) were evaluated by combining ex-vivo MRI, pathology, and longitudinal cognitive evaluation. EPVS quantification allowed to study qEPVS both in the whole brain and regionally. Two different qEPVS metrics were studied. Elastic-net regularized linear regression was used to assess the neuropathologic correlates of qEPVS within each region of interest (ROI) under study, and linear mixed effects models were used to investigate the associations of qEPVS with cognitive decline. Finally, a preliminary study investigated the longitudinal associations of qEPVS with time. The DL segmentation model was re-trained using 4 in-vivo MR images. EPVS were segmented and quantified in a large longitudinal cohort where each participant was imaged at multiple timepoints. Factors that influenced segmentation performance across timepoints were evaluated, and linear mixed effects models controlling for these factors were used to investigate the associations of qEPVS with time.