title: Autoradiographic imaging of cerebral ischaemia using a combination of blood flow and hypoxic markers in an animal model.
abstract: Current routine clinical techniques, including angiography and perfusional single-photon emission tomography, can be used to indicate problems in cerebral vascular supply and areas of cerebral hypoperfusion following a stroke, but cannot distinguish between ischaemic core and penumbra. In order to image specifically the penumbra, a method or indicator should be able to define areas with reduced blood flow, and a degree of metabolic compromise. In this context, the tissue could be regarded as hypoxic rather than ischaemic, and we have therefore chosen to investigate the potential of radio-labelled hypoxic markers in the study of ischaemia. In order to combine a hypoxic marker with a blood flow marker we used technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and iodine-125 iodoazomycin arabinoside (125I-IAZA), during cerebral ischaemia in the rat middle cerebral artery occlusion model. 99mTc-HMPAO and 125I-IAZA were injected simultaneously 2 h following occlusion of the middle cerebral artery, and 5 h before decapitation. Paired autoradiograms were produced and compared. Three distinct patterns emerged from the autoradiograms: slightly decreased perfusion with no uptake of the hypoxic marker indicating an area of misery perfusion; moderately decreased perfusion with concomitant uptake of iodoazomycin arabinoside, a region of hypoxia; and severely decreased perfusion with no retention of the hypoxic tracer. In conclusion, we present a new use for an imaging agent in the investigation of cerebral hypoxia. This agent, IAZA together with HMPAO, provides a means of separating the penumbra into regions of misery perfusion and hypoxia. The potential impact of this may be important in the clinical investigation of stroke.
authors.affiliation: The Royal College of Surgeons Unit of Biophysics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: M F
authors.initials: MF
authors.lastname: Lythgoe
authors.forename: S R
authors.initials: SR
authors.lastname: Williams
authors.forename: L I
authors.initials: LI
authors.lastname: Wiebe
authors.forename: A J
authors.initials: AJ
authors.lastname: McEwan
authors.forename: I
authors.initials: I
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002545:Brain Ischemia / Q000000981:diagnostic imaging*; D015687:Cell Hypoxia; D002560:Cerebrovascular Circulation; D007457:Iodine Radioisotopes; D008297:Male; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D010091:Oximes; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D019690:Technetium Tc 99m Exametazime
chemical_list: D007457:Iodine Radioisotopes; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D010091:Oximes; C070588:iodoazomycin arabinoside; D019690:Technetium Tc 99m Exametazime