Longitudinal imaging and evaluation of SAH-associated cerebral large artery vasospasm in mice using micro-CT and angiography

Abstract

Longitudinal in vivo imaging studies characterizing subarachnoid hemorrhage (SAH)-induced large artery vasospasm (LAV) in mice are lacking. We developed a SAH-scoring system to assess SAH severity in mice using micro CT and longitudinally analysed LAV by intravenous digital subtraction angiography (i.v. DSA). Thirty female C57Bl/6J-mice (7 sham, 23 SAH) were implanted with central venous ports for repetitive contrast agent administration. SAH was induced by filament perforation. LAV was assessed up to 14 days after induction of SAH by i.v. DSA. SAH-score and neuroscore showed a highly significant positive correlation (r_sp = 0.803, <i>p</i> < 0.001). SAH-score and survival showed a negative significant correlation (r_sp = -0.71, <i>p</i> < 0.001). LAV peaked between days 3-5 and normalized on days 7-15. Most severe LAV was observed in the internal carotid (Δ_max = 30.5%, <i>p</i> < 0.001), anterior cerebral (Δ_max = 21.2%, <i>p</i> = 0.014), middle cerebral (Δ_max = 28.16%, <i>p</i> < 0.001) and basilar artery (Δ_max = 23.49%, <i>p</i> < 0.001). Cerebral perfusion on day 5 correlated negatively with survival time (r_Pe = -0.54, <i>p</i> = 0.04). Arterial diameter of the left MCA correlated negatively with cerebral perfusion on day 3 (r_Pe = -0.72, <i>p</i> = 0.005). In addition, pseudoaneurysms arising from the filament perforation site were visualized in three mice using i.v. DSA. Thus, micro-CT and DSA are valuable tools to assess SAH severity and to longitudinally monitor LAV in living mice.