title: Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. Validation using [14C]2-deoxyglucose autoradiography.
abstract: Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T(2)(*) MRI (T(2)(*) OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T(2)(*) signal change during OC. [(14)C]2-deoxyglucose (2-DG) autoradiography was combined with T(2)(*) OC to determine metabolic status of T(2)(*)-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T(2)(*) signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T(2)(*)-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T(2)(*) signal increase of 9.22% ± 3.9% (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T(2)(*) signal change was negligible in ischemic core, 3.2% ± 0.78% in contralateral regions, and 1.41% ± 0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.
authors.affiliation: Glasgow Experimental MRI Centre, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. c.robertson.1@research.gla.ac.uk
authors.forename: Craig A
authors.initials: CA
authors.lastname: Robertson
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.forename: Lindsay
authors.initials: L
authors.lastname: Gallagher
authors.forename: Maria del Rosario
authors.initials: Mdel R
authors.lastname: Lopez-Gonzalez
authors.forename: William M
authors.initials: WM
authors.lastname: Holmes
authors.forename: Barrie
authors.initials: B
authors.lastname: Condon
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
authors.forename: Celestine
authors.initials: C
authors.lastname: Santosh
authors.forename: I Mhairi
authors.initials: IM
authors.lastname: Macrae
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D003847:Deoxyglucose; D006019:Glycolysis; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D008297:Male; D008660:Metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D003847:Deoxyglucose; D010100:Oxygen