Introduction: Subarachnoid hemorrhage (SAH) is a devastating form of stroke with high rates of mortality and disability. Evidence suggests that acute failure to restore cerebral blood flow (CBF) after SAH may be setting the stage of delayed cerebral ischemia. Despite increasing number of experiments using rodent models, little is known about the effect of CBF and neuro-behavioral profile on ischemic brain injury, vasospasm and neurological outcome for precise grading of this model to mimic clinical severity in humans.
Hypothesis: To investigate the feasibility of MRI-based assessment of clot distribution and CBF for grading SAH severity in a mouse endovascular perforation model.
Methods: SAH was induced by endovascular perforation in adult male C57BL/6 mice. CBF was estimated by MRI continuous arterial spin labeling with short delay after tagging. Neurological deficit and behavioral data were recorded by adhesion removal test and open field test, respectively. MRI and neuro-behavioral performance were assessed immediately after SAH induction and at 24, 72 hours after SAH. The time-course changes of each parameter and their relationships with MRI-based grading score using T2*-weighted image at 24 hours, new ischemic lesion detected by diffusion-weight image (DWI) at 72 hours, day 7 and 14, cortical vasospasm visualized by two-photon laser microscopy (performed between 48-72 hours), and final outcome based on the modified Garcia score at day 21 after SAH were analyzed.
Results: Among a total of 60 mice, the mortality rates at 24 hours and day 21 were 17% and 30%, respectively. There were strong correlations between the CBF value at 72 hours after SAH and MRI grading (24% scored as grade 1, 18% as grade 2, 30% as grade 3, and 28% as grade 4) (r=0.75; P<0.001), incidence of microvasospasm (r=0.68; P<0.001), or functional outcome score at 21 days (r=0.81; P<0.001). Activity as measured by mean daily velocity (mm/sec) (r=0.54; P=0.008) or position rotation ratio (r=0.47; P=0.03) at 24 hours had also moderate correlation with the CBF value.
Conclusions: Non-invasive MRI-based grading that includes both CBF and neuro-behavioral performance at 24 hours enables more accurate in vivo evaluation of SAH severity based on the prevalence of vasospasm and functional outcome.