Basic Evaluation of Experimental Mouse Subarachnoid Hemorrhage by 7.0T Small Animal Scanner

Abstract

Aim: Mice are becoming increasingly popular as animal models to elucidate the molecular pathogenesis of neuronal injury after subarachnoid hemorrhage (SAH). The purpose of this study was to undertake a basic evaluation of experimental mouse SAH using a 7T MRI. Methods: A total of 28 male C57Bl/6J mice were used. In 17 animals, SAH was induced by the filament perforation model. In two animals, transient focal cerebral ischemia by middle cerebral artery occlusion (MCAo) was induced for comparison. Nine mice were used as controls. T1-weighted images (T1WI), T2-weighted images (T2WI), T2*-weighted images (T2*WI), and apparent diffusion coefficient (ADC) maps were acquired at day 0 and at various time points for follow-up (range: day 1–6 after SAH). Semiquantitative cerebral blood flow (CBF) analysis by 14C-iodoamphetamine (IMP) autoradiography was added in nine animals. Results: Subarachnoid blood could be best seen in T2*WI. The degree of hemorrhage varied. Due to the very small size of the cerebrospinal compartments, the interpretation was difficult in mild SAH. All animals evaluated ≥2 d showed signs of hydrocephalus, which was best seen in T2WI. T2 hyperintensity of the corpus callosum and external capsule, indicating white matter injury, could be observed after SAH. Measured ventricle and white matter injury volumes were significantly higher at day 3 after SAH compared with day 0 (p = 0.001 and 0.003). SAH did not lead to visible “territorial ischemia” in contrast to MCAo. Markedly hypointense cortical veins were visible in the peracute (≤30 minute) and delayed (≥3 d) phase after SAH in T2*WI. This phenomenon might reflect an increased oxygen extraction fraction due to reduced CBF. The 14C-IMP analysis indicated a decreased global CBF after SAH, compared with control animals. Conclusions: MRI is feasible and valuable in evaluating various pathophysiological changes in the brain of mice after SAH. T2*WI seems best for SAH detection and grading its severity. The occurrence of hydrocephalus and white matter injury could be quantitatively analyzed by T2WI. T2*WI illustrated a specific change of “markedly hypointense cortical veins,” a possible sign for altered CBF after SAH. Thus, further CBF studies by MRI seem warranted with using arterial spin labeling technique in this model.