Hemodynamic alterations in focal cerebral ischemia: temporal correlation analysis for functional imaging

We describe a novel approach for analysing the hemodynamic alterations that result after focal cerebral ischemia. This approach utilizes a temporal correlation analysis of first pass transit data obtained with functional imaging. First pass transits of injected contrast agents are measured with dynamic CT scanning. Normal transit profiles are obtained from contralateral cortical regions to serve as reference profiles. Normalized correlations are then calculated to compare transit profiles from each individual pixel within the brain to the normal reference profile. The normalized correlation coefficient is used as a measure of temporal similarity to quantitatively assess deviations from normal hemodynamics. The method is based on the premise that perturbed hemodynamics are manifested as changes in the shape of the cerebral transit profiles. Correlation maps are produced that display regional alterations in cerebral hemodynamics. Results from rabbit (n=4) and rat (n=4) models of focal ischemia are presented. In the normal contralateral hemisphere, correlation values range from 0.83-0.93 with coefficients of variation of less than 3-4% . The ischemic core is comprised of regions without significant bolus transit. The peripheral zones that lie between normal brain and the ischemic core are composed of intermediate correlation values. By setting statistical thresholds (mean minus 2SD, p < 0.05), we quantitatively define these intermediate zones as the hemodynamic penumbra, i.e. regions where the shape of the first pass transit profile has been altered. The resulting correlation maps clearly image gradients of altered cerebral hemodynamics. Perfusion indices calculated based on transit profile peaks revealed that the penumbral zones possess reduced perfusion on the order of about 40 percent of contralateral values. In summary, we believe that temporal correlation analysis of first pass transit profiles can be used to image the hemodynamic penumbra in focal cerebral ischemia.