USPIO‐SWI Shows Fingolimod Enhanced Alteplase Action on Angiographic Reperfusion in eMCAO Rats

Background Noninvasive evaluation of the status of cerebral arteriole perfusion remains a practical challenge in murine stroke models, because conventional magnetic resonance imaging (MRI) is no longer capable of capturing these very small vessels. Purpose To investigate the feasibility of ultrasmall superparamagnetic iron oxide particles (USPIO)‐based susceptibility weighted imaging (SWI)‐MRI (USPIO‐SWI) and T2* map‐MRI (USPIO‐T2* map) for monitoring angiographic perfusion in stroke rats. Study Type A preclinical randomized controlled trial. Animal Model Normal rats ( N = 9), embolic middle cerebral artery occlusion (eMCAO) rats ( N = 66). Field Strength/Sequence 7 T; T2* map (multigradient echo), SWI (3D gradient echo). Assessment Experiment 1: To develop a method for angiographic reperfusion evaluation with USPIO‐SWI. Normal rats were used to optimize the USPIO dosage (5.6, 16.8, and 56 mg/kg ferumoxytol) as well as scan time points for cerebral arterioles. Contrast‐to‐noise ratio (CNR) was measured. Stroke rats were further used and the number of visual cortical vessels were counted. Experiment 2: To examine whether fingolimod (lymphocytes inhibitor) enhances the action of tissue plasminogen activator (tPA) in eMCAO rats on cerebral angiographic reperfusion. Statistical Tests Mann–Whitney test and two way‐ANOVA were used. P < 0.05 was considered statistically significant. Results CNR values of cerebral cortical penetrating arteries in normal rats were significantly increased to 4.4 ± 0.5 (5.6 mg/kg), 6.1 ± 0.5 (16.8 mg/kg), and 3.4 ± 0.9 (56 mg/kg) after USPIO injection. The number of visual cortical vessels on USPIO‐SWI images in ischemic regions was significantly less than in control regions (5 ± 2 vs. 56 ± 20) of eMCAO rats. Compared with eMCAO rats who received tPA only, eMCAO rats who received the combination of fingolimod and tPA exhibited significantly higher proportion of complete angiographic reperfusion (69% vs. 17%). Data Conclusion This study supports the feasibility of angiographic perfusion evaluation with USPIO‐SWI in stroke rats. Level of Evidence 2 Technical Efficacy Stage 1