and Purpose Diffusion-weighted nuclear magnetic resonance imaging has been shown to detect early ischemia-related alterations in experimental stroke. This raises the question of whether the observed increase in signal intensity is correlated with changes in cerebral metabolism. After middle cerebral artery occlusion, nuclear magnetic resonance diffusion images were recorded and compared with the regional concentration of cerebral metabolites and with histology of identical planes. Methods Seven

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... anesthetized Fischer rats were subjected to permanent occlusion of the middle cerebral artery. T" T 2 , and diffusion images (b factors ranging from 0 to 1500 s/mm 2 ) were measured in three to five planes after 7 hours. Thereafter, brains were frozen in situ for histology and quantitative bioluminescence imaging of ATP, glucose, lactate, and for fluorescence imaging of tissue pH. Results Seven hours after middle cerebral artery occlusion, the apparent diffusion coefficient was reduced from 615±97xl0" 6 -mm 2 -s-' (contralateral brain) to 359±42x 10~6-mm 2 -s~' (ischemic brain; mean±SD, f<.01). A precise topical coincidence was demonstrated between changes in nuclear magnetic resonance diffusion images, pattern of histological damage, ATP-depleted areas, and local tissue acidosis, the lesion area amounting to between 24.1% and 27.6% of the hemisphere at the level of the caudateputamen. The area of elevated brain lactate clearly exceeded the acidic core of the infarct and included the slightly alkaline border zone. Conclusions The data demonstrate that after 7-hour middle cerebral artery occlusion, the reduction of the apparent diffusion coefficient in nuclear magnetic resonance diffusion images reflects precisely the region of histological injury, breakdown of energy metabolism, and tissue acidosis. (Stroke. 1994;25:494-500.)