title: Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases.
abstract: Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases.
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5. joelr@sri.utoronto.ca.|Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre (SHSC), Toronto, ON, Canada. joelr@sri.utoronto.ca.
authors.forename: Joel
authors.identifier: http://orcid.org/0000-0002-5582-1776
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5.|Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre (SHSC), Toronto, ON, Canada.
authors.forename: Courtney
authors.initials: C
authors.lastname: Berezuk
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5.|Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre (SHSC), Toronto, ON, Canada.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McNeely
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5.|Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre (SHSC), Toronto, ON, Canada.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: JoAnne
authors.initials: J
authors.lastname: McLaurin
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5.|Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre (SHSC), Toronto, ON, Canada.|Department of Medicine, Neurology (SHSC), Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
mesh_terms: D000818:Animals; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008208:Lymphatic System / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology*; D059906:Neuroimaging / Q000379:methods*; D057170:Translational Research, Biomedical
keywords: Alzheimer’s disease; Cerebrovascular disease; Dementia; Interstitial fluid drainage; Perivascular metabolic clearance; Perivascular space; Virchow–Robin space