A COMPARISON OF THE EARLY DEVELOPMENT OF ISCHEMIC DAMAGE FOLLOWING PERMANENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS AS ASSESSED USING MAGNETIC-RESONANCE-IMAGING AND HISTOLOGY

Recent developments in diffusion-weighted imaging (DWI) have enabled t he pathological changes that occur during cerebral ischaemia to be stu died. The present studies utilised DWI to investigate the development of early ischaemic changes following permanent middle cerebral artery (MCA) occlusion in the rat, which represents a model of stroke. An inc reased DWI signal was seen in the region of the occluded MCA and this was detectable as early as 1 h postocclusion. DWI images were obtained at nine stereotactic levels throughout the brain, providing a quantif iable measure of the volume of increased signal intensity in each anim al. At 1 h post-MCA occlusion the hyperintense areas were seen in the frontoparietal cortex and lateral caudate nucleus; these areas represe nt the core of the infarct and no protection is seen with any compound s in these areas. There was a progressive increase in the area of hype rintensity up to 4 h post-MCA occlusion, and at this time point the hy perintensity was seen in the dorsolateral cortex and caudate nucleus. At 4 h post-MCA occlusion there was a significant correlation between the volume of hemispheric and cortical ischaemic damage measured using DWI and histology. Thus, it appears that the increased DWI signal see n during the early time points after MCA occlusion was demarcating tis sue that was destined for infarction. The area beyond the hyperintense region at 1 h represents the so-called ''penumbral'' region, because with increasing time (post-MCA occlusion) this area became incorporate d into the infarct. There was also a slight increase in infarct size b etween 4 and 24 h, when assessed using DWI or histology, although two groups of animals were being compared, as opposed to the time-course s tudy, in which just one group of animals was used. At 24 h post-MCA oc clusion there was a good correlation between DWI, histology, and conve ntional T-2 weighted imaging. There was no further increase in size of the infarct between 24 h and 7 days as assessed using histology and T -2-weighted imaging. DWI could not be used to quantify infarct volume at 7 days because there was no uniform signal in the damaged area. At 7 days the area of infarction actually appeared to be darker in the di ffusion-weighted images. The hyperintensity seen in diffusion-weighted images appears to decrease some time between 24 h and 7 days. These d ata provide evidence that DWI can be used to detect early ischaemic ch anges and it appears that the hyperintense areas seen at 1 h delineate s tissue that is destined to become the core of the infarct. Thus, DWI could be used to identify the so-called penumbral areas, which are sa lvageable if treated within the therapeutic window of 2-3 h and may th erefore have an important role in detecting such changes in the clinic al setting.