CORRELATES BETWEEN NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY, DIFFUSION-WEIGHTED IMAGING, AND CA1 MORPHOMETRY FOLLOWING CHRONIC BRAIN ISCHEMIA

Chronic brain ischemia (CBI) was induced in aging (13 month) rats by l igating the left subclavian artery and placing temporary occluders in each common carotid artery [three-vessel occlusion (3-VO)]. Carotid ar tery occluders were removed after 1, 2, or 3 weeks following brain isc hemia or maintained for 9 weeks. Two rats were kept with their occlude rs in place for 25 weeks. On weeks 3 and 9 after CBI, P-31-/H-1-nuclea r magnetic resonance (NMR) spectroscopy and high resolution diffusion weighted imaging were performed in vive, non-invasively for detection of hippocampal high energy phosphates, lactate, intracellular pH, N-ac etyl-aspartate, choline, glutamate, creatine, and structural alteratio ns of the brain following CBI. Brains were histologically processed fo r morphometry of glial fibrillary acidic protein (GFAP) and CA1 damage d neurons 9 weeks after CBI. P-31-/H-1-NMR spectroscopy showed that hi gh energy substrates remained normal in ischemic animals when compared to non-ischemic controls except for an elevation of phosphomonoesters in the hippocampal region. Rats deoccluded 1 and 2 weeks after initia tion of CBI had no NMR spectroscopic or imaging changes. Rats kept isc hemic for 9 weeks showed high signal intensities in the parietal corte x detected by diffusion weighted imaging as well as CA1 damage and inc reased GFAP density but no cortical atrophy or neuronal damage could b e detected histologically. Rats kept ischemic for 25 weeks showed exte nsive cortical atrophy which corresponded to the high signal intensity observed with diffusion weighted imaging in the group kept ischemic f or 9 weeks. These findings indicate that NMR spectroscopy and difussio n weighted imaging can be used to follow the progress of neuronal inju ry in vive and non-invasively. Moreover, diffusion weighted imaging ma y be an excellent predictor of cerebral damage and atrophy prior to hi stopathological detection of such damage. Our present and previous fin dings using our 3-VO model indicate that this aging rat model may be u seful in screening potential therapy for neurodegenerative disorders a ssociated with abnormal aging and memory impairment. (C) 1995 Wiley-Li ss, Inc.