title: Hypoxia and Inflammation-Induced Disruptions of the Blood-Brain and Blood-Cerebrospinal Fluid Barriers Assessed Using a Novel T1-Based MRI Method.
abstract: Subtle blood-brain barrier (BBB) disruption is involved in numerous neurological conditions. This disruption is found diffusely in the brain and requires quantitative methods for assessment. We propose a statistical method to identify individual voxels where the BBB is disrupted using T1-weighted MRI. We used models of severe and focal vs. mild and generalized disruption of the BBB to show proof of principle with the cold injury model, hypoxia, and a model of inflammation using low- and high-dose lipopolysaccharide (LPS) treatment. Using voxel-based analysis, we found that mild hypoxia resulted in diffuse disruption of the BBB, whereas more severe hypoxia and high-dose LPS treatment resulted in prominent leakage, particularly in the periventricular area, suggestive of blood-cerebrospinal fluid (CSF) barrier disruption. Our data suggest that the periventricular area may be compromised first in conditions of inflammation and hypoxia. Voxel-based analysis could be used in future studies assessing subtle blood-CSF or BBB disruption.
authors.affiliation: Department of Radiology, University of Calgary, 3330 Hospital Drive, N.W., Calgary, AB, T2N 4N1, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Nabeela
authors.initials: N
authors.lastname: Nathoo
authors.affiliation: Department of Radiology, University of Calgary, 3330 Hospital Drive, N.W., Calgary, AB, T2N 4N1, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Hamza
authors.initials: H
authors.lastname: Jalal
authors.affiliation: Department of Physiology, Umm-Alqura University, Makkah, Saudi Arabia.
authors.forename: Sirajedin S
authors.initials: SS
authors.lastname: Natah
authors.affiliation: General Electric, Beijing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Radiology, University of Calgary, 3330 Hospital Drive, N.W., Calgary, AB, T2N 4N1, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Radiology, University of Calgary, 3330 Hospital Drive, N.W., Calgary, AB, T2N 4N1, Canada. dunnj@ucalgary.ca.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. dunnj@ucalgary.ca.|Experimental Imaging Centre, University of Calgary, Calgary, AB, Canada. dunnj@ucalgary.ca.
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Dunn
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D000067390:Cold Injury / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003287:Contrast Media; D004195:Disease Models, Animal; D005682:Gadolinium; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D008070:Lipopolysaccharides; D005682:Gadolinium
keywords: Blood-brain barrier; Blood-cerebrospinal fluid barrier; Hypoxia; Inflammation; Lipopolysaccharide; MRI; Periventricular; Sodium fluorescein