PROJECT SUMMARY Perivascular spaces are a critical component of the glia-lymphatic circuit, facilitating the clearance of soluble waste. The role of perivascular spaces and changes in the brain’s clearance system in normal development, aging, and cognition is not fully understood, mainly due to lack of neuroimaging capabilities. However, noninvasive in vivo mapping of the perivascular space fluid with high accuracy and reliability is now made possible with our recent analytical developments, using human connectome project (HCP) data. The objective of this project is to map structural and diffusion features of perivascular space fluid across lifespan. PVS features include PVS presence (e.g., count and volume fraction) and diffusion (e.g., diffusivity and anisotropy). These features will be extracted regionally and globally across the brain. Structural MRI will provide information regarding localization and extent of the PVS and diffusion MRI will be used to investigate biophysical properties of the PVS fluid and surrounding tissue. The central hypothesis is that the perivascular space fluid increases across lifespan. We also hypothesize that individual differences exist in perivascular spaces as a function of demographic, general health and lifestyle health choices, such as body mass index, blood pressure, tobacco use and sleep quality. The central hypothesis will be tested by characterizing the normative map of the perivascular space fluid across the lifespan and in relation to various demographic, cognitive measures, and health factors. We will also examine whether subjects neuro-behavioral performances can be predicted by perivascular space features. We will pursue these aims by applying innovative MRI-based computational techniques that we recently developed and optimized on HCP data. We will also use Adolescent Brain Cognitive Development (ABCD) Studies to build first normative template of PVS in neurodevelopment. Together, our findings will ultimately allow for a better understanding of the human brain clearance system, and our shared perivascular space mapping workflow can provide a resource for researchers to study a wide range of neurological conditions.