Regional ischemic vulnerability of the brain to hypoperfusion: the need for location specific computed tomography perfusion thresholds in acute stroke patients

Abstract

Background and purpose: To characterize the spatial pattern of cerebral ischemic vulnerability to hypoperfusion in stroke patients.

Methods: We included 90 patients who underwent admission CT perfusion and MRI within 12 hours of ischemic stroke onset. Infarcted brain lesions ("core") were segmented from admission diffusion-weighted imaging and, along with the CT perfusion parameter maps, coregistered onto MNI-152 brain space, which was parcellated into 125 mirror cortical and subcortical regions per hemisphere. We tested the hypothesis that the percent infarction increment per unit of relative cerebral blood flow (rCBF) reduction differs statistically between regions using regression analysis to assess the interaction between regional rCBF and region variables. Next, for each patient, a "vulnerability index" map was constructed with voxel values equaling the product of that voxel's rCBF and infarction probability (derived from the MNI-152-transformed, binary, segmented, diffusion-weighted imaging lesions). Voxel-based rCBF threshold for core was determined within the upper 20th percentile of vulnerability index map voxel values.

Results: Different regions had different percent infarction increase per unit rCBF reduction (P=0.001). The caudate body, putamen, insular ribbon, paracentral lobule, and precentral, middle, and inferior frontal gyri had the highest ischemic vulnerability to hypoperfusion. A voxel-based rCBF threshold of <0.42 optimally distinguished infarct core in the highly-vulnerable regions, whereas rCBF<0.16 distinguished core in the remainder of the brain.

Conclusions: We demonstrated regional ischemic vulnerability of the brain to hypoperfusion in acute stroke patients. Location-specific, rather than whole-brain, rCBF thresholds may provide a more accurate metric for estimating infarct core using CT perfusion maps.

Figure 1

Topographic distribution of infarction in our patients; voxel values reflect the mean probability of infarction for that voxel across all patients. Color scale is based on stratification by quintile groupings.

Figure 2

Mean voxel-based regional ischemic vulnerability of the brain on a color scale for 90 patients. Following non-rigid transformation of the segmented DWI infarct lesion maps to the MNI-152 brain space, each voxel was assigned a 0-to-1 value as the infarction probability. For each patient, “vulnerability index” values in each voxel were calculated as the product of the infarction probability and the relative cerebral blood flow.

Figure 3

Regional ischemic vulnerability of the brain dichotomized into highly vulnerable (green voxels) versus less vulnerable (remainder of the brain) locations. A voxel-based rCBF threshold of <0.42 optimally differentiated infarct core in the highly vulnerable regions (voxels within the upper 20^th percentile of values on the vulnerability map) (area under ROC curve [AUC] 0.72, 54% sensitivity, 80% specificity, p<0.001, bottom left); whereas an rCBF threshold of <0.16 distinguished core in the remainder of the brain, with equal sensitivity and specificity (AUC 0.73, 54% sensitivity, 79% specificity, p<0.001, bottom right).