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 (P<0.05). 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 (P<0.001), whereas the diffusion/perfusion mismatch was significant (P<0.001) 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 (<20% 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.

Figure 1

Representative ADC and CBF maps from one WK and one SD rat. Three of 8 maps are shown at 45, 90, 120, 180, and 210 min after occlusion for ADC maps and at 210 min for CBF maps.

Figure 2

Temporal evolution of ADC- and CBF-derived lesion volumes (mean±standard deviation) by using previously established viability thresholds in permanently occluded rats. SD: open triangles indicate CBF lesion; closed triangles, ADC lesion; WK: open circles indicate CBF lesion; closed circles, ADC lesion. *P<0.05, **P<0.01 for differences in ADC lesion volumes at the same time points.

Figure 3

Temporal evolution of the diffusion/perfusion mismatch (mean±standard deviation). Triangles indicate SD; circles, WK. *P<0.05, **P<0.01 for differences in diffusion/perfusion mismatch volumes at the same time points.

Figure 4

Time course of quantitative cerebral blood flow (A) and ADC (B) in the total right hemisphere (RH), the lateral caudoputamen (Cp), and the parietal cortex (Cortex). SD: closed circles indicate RH; closed diamonds, lateral caudoputamen; closed triangles, parietal cortex; WK: open circles indicate RH; open diamonds, lateral caudoputamen; open triangles, parietal cortex. *P<0.05, **P<0.01 for differences in the same region of interest at the same time points.

Figure 5

Temporal evolution of ADC values (mean±standard deviation) for pixels with severe (<20% of normal left hemisphere [LH]), moderate (21–40% of LH), and modest (41–55% of LH) cerebral blood flow reduction. Gray columns indicate SD; black columns, WK. *P<0.05, **P<0.005 for differences in ADC at the same time points.