Three-Dimensional Metabolic and Hemodynamic Imaging of the Normal and Ischemic Rat Brain

Abstract

Unique insights into the topography of local metabolism/blood flow interrelationships in focal cerebral ischemia have been afforded by the recent development of powerful image-processing techniques permitting three-dimensional (3D) autoradiographic image-averaging and analysis of replicate studies by a novel method termed "disparity analysis". This method, based upon a linear affine transformation model, directly estimates scaling, translation and rotation parameters simultaneously. The method was validated in awake Wister rats studied for local cerebral glucose metabolism (1CMRgl) with 14C-2-deoxyglucose. Brains were subserially sectioned, aligned by disparity analysis, and mapped into a common template so as to generate aggregate 3D data sets of the mean and standard deviation of the entire series (n=9). Internal anatomic architecture was faithfully represented in the average image, and Fourier analysis revealed satisfactory retention of low-frequency information. The method was then applied to study metabolism/blood flow relationships in the acute focal ischemic penumbra of Sprague-Dawley rats subjected to distal photothrombotic middle cerebral artery (MCA) occlusion, coupled with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Matched series were studied for 1CBF at 1.5 h and for 1CMRgl at 1.25-2 h post-occlusion. The averaged 1CBF image revealed the ischemic penumbra (defined as 1CBF 20-40% of control) to form a "shell" around the cortical ischemic core and a confluent aggregate at the anterior and posterior poles of the corezone. 1CMRgl in the penumbra was heterogeneous, ranging from near-normal to markedly increased. An average 1CMRgl/1CBF ratio data set revealed marked metabolism-flow uncoupling in penumbral pixels, averaging nearly live-fold above control ratio values. Sustained deflections of the DC potential were recorded in the penumbra, the site of marked uncoupling. This analysis defined for the first time the 3D topography of the ischemic penumbra and substantiated marked metabolism/flow dissociation, which is believed to be a metabolic consequence of the energy demand imposed by repeated peri-infarct depolarizations.