Background and Purpose
No studies have determined the effect of differences in pial collateral extent (number and diameter), independent of differences in environmental factors and unknown genetic factors, on severity of stroke. We examined ischemic tissue evolution during acute stroke, as measured by magnetic resonance imaging (MRI) and histology, by comparing 2 congenic (CNG) mouse strains with otherwise identical genetic backgrounds but with different alleles of the Determinant of collateral extent-1 (Dce1) genetic locus. We also optimized magnetic resonance (MR) perfusion and diffusion deficit thresholds by using histological measures of ischemic tissue.
Methods
Perfusion, diffusion, and T2-weighted MRI were performed on collateral-poor (CNG-Bc) and collateral-rich (CNG-B6) mice at 1, 5 and 24h after permanent middle cerebral artery occlusion (pMCAo). MRI-derived penumbra and ischemic core volumes were confirmed by histology in a subset of mice at 5 and 24h after pMCAo.
Results
Although perfusion deficit volumes were similar between strains 1h after pMCAo, diffusion deficit volumes were 32% smaller in collateral-rich mice. At 5h, collateral-rich mice had markedly restored perfusion patterns showing reduced perfusion deficit volumes, smaller infarct volumes, and smaller perfusion-diffusion mismatch volumes compared with the collateral-poor mice (p<0.05). At 24h, collateral-rich mice had 45% smaller T2-weighted lesion volumes (p<0.005) than collateral-poor mice, with no difference in perfusion-diffusion mismatch volumes because of penumbral death occurring 5 to 24h after pMCAo in collateral-poor mice.
Conclusions
Variation in collateral extent significantly alters infarct volume expansion, transiently affects perfusion and diffusion MRI signatures, and impacts salvage of ischemic penumbra after stroke onset.