Asymmetry analysis in rodent cerebral ischemia models

Rationale and Objectives. An automated method for identification and segmentation of acute/subacute ischemic stroke, using the inherent bi-fold symmetry in brain images, is presented. An accurate and automated method for localization of acute ischemic stroke could provide physicians with a mechanism for early detection and potentially faster delivery of effective stroke therapy. Materials and Methods. Segmentation of ischemic stroke was performed on magnetic resonance (MR) images of subacute rodent cerebral ischemia. Eight adult male Wistar rats weighing 225-300 g were anesthetized with halothane in a mix of 70% nitrous oxide/30% oxygen. Animal core temperature was maintained at 37 degrees C during the entire surgical procedure. including occlusion of the middle cerebral artery (MCA) and the 90-minute post-reperfusion period. To confirm cerebral ischemia. transcranial measurements of cerebral blood flow were performed with laser-Doppler flowmetry, using 15-mm flexible fiberoptic Doppler probes attached to the skull over the MCA territory. Animal MR scans were performed at 1.5 T using a knee coil. Three experts performed manual tracing of the stroke regions for each rat, using the histologic-stained slices to guide delineation of stroke regions. A strict tracing protocol was followed that included multiple (three) tracings of each stroke region. The volumetric MR image data were processed for each rat by computing the axis of symmetry and extracting statistical dissimilarities. A nonparametric Wilcoxon rank sum test operating on paired windows in opposing hemispheres identified seeds in the pixels exhibiting statistically significant bi-fold mirror asymmetry. Two brain reference maps were used for analysis: an absolute difference map (ADM) and a statistical difference map (SDM). Although an ADM simply displays the absolute difference by subtracting one brain hemisphere from its reflection, SDM highlights regions by labeling pixels exhibiting statistically significant asymmetry. Results. To assess the accuracy of the proposed segmentation method, the surrogate ground truth (the stroke tracing data) was compared to the results of our proposed automated segmentation algorithm. Three accuracy segmentation metrics were utilized: true-positive volume fraction (TPVF), false-positive volume fraction (FPVF), and false-negative volume fraction (FNVF). The mean value of the TPVF for our segmentation method was 0.8877; 95% CI 0.7254 to 1.0500; the mean FPVF was 0.3370, 95% CI -0.0893 to 0.7633; the mean FNVF was 0.1122, 95% CI -0.0502 to 0.2747. Conclusions. Unlike most segmentation methods that require some degree of manual intervention, our segmentation algorithm is fully automated and highly accurate in identifying regions of brain asymmetry. This approach is attractive for numerous neurologic applications where the operator's intervention should be minimal or null.