Differences in Ischemic Lesion Evolution in Different Rat Strains Using Diffusion and Perfusion Imaging

Abstract

Background and Purpose-Interstrain differences in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. We investigated, in 2 commonly used rat strains (Sprague-Dawley [SD] and Wistar-Kyoto [WK]), the spatiotemporal evolution of ischemia after permanent suture MCAO using diffusion and perfusion imaging. Methods-Serial measurements of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were performed up to 210 min after MCAO. Lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after MCAO. Results-While the ADC-derived lesion volume increased rapidly during the first 120 min after MCAO and essentially stopped growing after 3 hours in SD rats, ADC lesion in WK rats increased progressively during the entire 210-min period and was significantly smaller at all time points (PϽ0.05). The abnormal perfusion volume correlated highly with the TTC-defined infarct size in both groups. In WK rats, the abnormal perfusion volume was significantly larger than the abnormal diffusion volume up to 90 min after MCAO (PϽ0.001), whereas the diffusion/perfusion mismatch was significant (PϽ0.001) only at 45 min in SD rats. ADC-CBF scatterplots analysis revealed a slower and less robust ADC decline over time in WK rats in pixels with severe (Ͻ20% of normal) and moderate (21 to 40% of normal) CBF reduction. Conclusions-This study demonstrated substantial differences in acute ischemic lesion evolution between SD and WK rats. These interstrain variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

“…This approach has been shown to provide equivalent information on the perfusion deficit as quantified through the use of continuous arterial spin labeling (Bråtane et al, 2010). The volume of initially hypoperfused tissue remained essentially stable over time after ischemia in normotensive animals (ANOVA repeated measures, time effect: P = 0.44) as has been previously described (Legos et al, 2008;Bardutzky et al, 2005). However in SHR, hypoperfusion expanded with time (ANOVA repeated measures, time effect: P < 0.05) and was greater than that of WKY at 240 minutes after the occlusion, suggesting a failure of collateral circulation in SHR.…”

Evolution of the Neurochemical Profile after Transient Focal Cerebral Ischemia in the Mouse Brain

“…This suggests that a knowledge of the additional metabolic information attainable as shown in this study likely provides a complementary insight into various stroke models (Bardutzky et al, 2005).…”

Identification of hyperacute ischemic stroke with a more homogenous nature

“…While rats 3 and 9 (group 2) presented early rapid changes within half an hour of the characteristic in the ischemic lesions, lesion volumes and abnormal ADC values in seven rats (group 1) were stable in a narrow range over time from the first diffusion MRI. Though there have been several studies on murine focal ischemic stroke models using prospective serial MRI [10,11,[13][14][15]21,22], those spatiotemporal changes observed in our seven rats (group 1) had not been reported to our knowledge. In previous studies, two different patterns of temporal changes of the ADC values after MCAO have been described: one is a gradual ADC decline pattern over time [14,15] and the other is acute ADC decline, which remained in a stable pattern thereafter [11,22].…”

“…A rat brain is very small and it is thus difficult to define ischemic core and growing infarction respectively, so the whole ischemic area in an animal was outlined as a region of interest as in our study and the previous studies [10,37] and we then analyzed its MRI characteristics. However, temporal evolution of the infarction could also be evaluated by the voxel-by-voxel technique to measure different regional ADC values [15,23].…”

“…location and volume of the ischemic lesions, temporal evolution of the stroke, and complication rate with the use of either sutures or macrospheres [9][10][11][12][13][14]. This diversity in rat MCAO models is caused by several variables, including shape and size of thread tips, mode of arterial obstruction, characteristics of the rats (such as strain, weight and vascular anatomy) [6][7][8]12,15].…”