title: Novel MRI detection of the ischemic penumbra: direct assessment of metabolic integrity.
abstract: We describe a novel magnetic resonance imaging technique to directly assess the metabolic integrity of penumbral tissue following stroke. For ischemically stressed tissue to be salvageable, it has to be capable of recovering aerobic metabolism (in place of anaerobic metabolism) on reperfusion. We probed ischemic brain tissue by altering the rate of oxygen delivery using a challenge of 100% oxygen ventilation. Any change from anaerobic to aerobic metabolism should alter the rate of lactate production and hence, levels of tissue lactate. Stroke was induced by permanent middle cerebral artery occlusion in rats. In Series 1 (n = 6), changes in tissue lactate during and following 100% oxygen challenge were monitored using (1)H magnetic resonance spectroscopy (MRS). Diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) were used to locate MRS voxels within the ischemic core, the homotopic contralateral striatum and within PWI/DWI mismatch (i.e. presumed penumbra). After 20  min of oxygen, lactate signal change was -16.1 ± 8.8% (mean ± SD) in PWI/DWI mismatch, +2.8 ± 5.1% in the ischemic core, and -0.6 ± 7.6% in the contralateral striatum. Return to air ventilation for 20  min resulted in a reversal, with lactate increasing by 46 ± 25.3% in the PWI/DWI mismatch, 6.6 ± 6.2% in the ischemic core, and -5 ± 11.4% in the contralateral striatum. In Series 2 (n = 6), a novel form of spectroscopic imaging was used to acquire lactate change maps to spatially identify regions of lactate change within the ischemic brain. This technique has potential clinical utility by identifying tissue that displays anaerobic metabolism capable of recovering aerobic metabolism when oxygen delivery is increased, which could provide a more precise assessment of penumbra.
authors.affiliation: Glasgow Experimental MRI Centre, Division of Clinical Neuroscience, Faculty of Medicine, University of Glasgow, G61 1QH, Scotland, UK. wmh5b@udcf.gla.ac.uk
authors.forename: William M
authors.initials: WM
authors.lastname: Holmes
authors.forename: Maria R
authors.initials: MR
authors.lastname: Lopez-Gonzalez
authors.forename: Lindsay
authors.initials: L
authors.lastname: Gallagher
authors.forename: Graeme A
authors.initials: GA
authors.lastname: Deuchar
authors.forename: I Mhairi
authors.initials: IM
authors.lastname: Macrae
authors.forename: Celestine
authors.initials: C
authors.lastname: Santosh
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D004058:Diffusion / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D019344:Lactic Acid; D010100:Oxygen