Abstract

ISODATA using MRI parameter-weighted images has been previously employed to characterize ischemic cell damage after stroke in rats. In an effort to increase the objectivity and to further automate the ISODATA, MRI parameter maps were now employed. Male Wistar rats were subjected to embolic stroke and received treatment via a femoral vein at 4 h post-stroke. The control rats received saline and were sacrificed at 6, 24 and 48 h after stroke, respectively. Treated rats received rtPA alone or were treated with a combination of rtPA and an antibody, 7E3 F(ab′) 2, against the glycoprotein receptor that binds the platelet to fibrin. These rats were sacrificed at 24, or 48, h post-stroke. T 1, T 2 and diffusion maps were employed for map ISODATA analysis. H&E histological analysis of coronal sections of tissue was performed and compared with map ISODATA from the corresponding sections. ISODATA signatures were highly correlated ( R ∼ 0.80, P < 0.0001) with the ischemic cell damage analyzed at 6, 24 and 48 h post-stroke. At 24 and 48 h after stroke, ISODATA lesion sizes were highly correlated ( R > 0.97, P < 0.001) with lesion sizes measured histologically. The combination treatment of rtPA and 7E3 F(ab′) 2 reduced both infarction size ( P < 0.002) and average signature ( P < 0.03) at 48 h after stroke, compared to saline-treated animals. No significant difference was found between saline and rtPA-alone-treated rats. The map ISODATA successfully provides objective and automated quantitation of the ischemic damage in both size and severity in an embolic stroke model of rat with and without a therapeutic intervention.

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