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

Abstract

BACKGROUND\nNoninvasive 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.\n\n\nPURPOSE\nTo 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.\n\n\nSTUDY TYPE\nA preclinical randomized controlled trial.\n\n\nANIMAL MODEL\nNormal rats (N\xa0=\u20099), embolic middle cerebral artery occlusion (eMCAO) rats (N\xa0=\u200966).\n\n\nFIELD STRENGTH/SEQUENCE\n7\u2009T; T2* map (multigradient echo), SWI (3D gradient echo).\n\n\nASSESSMENT\nExperiment 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\u2009mg/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.\n\n\nSTATISTICAL TESTS\nMann-Whitney test and two way-ANOVA were used. P\xa0<\u20090.05 was considered statistically significant.\n\n\nRESULTS\nCNR values of cerebral cortical penetrating arteries in normal rats were significantly increased to 4.4\u2009±\u20090.5 (5.6\u2009mg/kg), 6.1\u2009±\u20090.5 (16.8\u2009mg/kg), and 3.4\u2009±\u20090.9 (56\u2009mg/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\u2009±\u20092 vs. 56\u2009±\u200920) 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%).\n\n\nDATA CONCLUSION\nThis study supports the feasibility of angiographic perfusion evaluation with USPIO-SWI in stroke rats.\n\n\nLEVEL OF EVIDENCE\n2 TECHNICAL EFFICACY STAGE: 1.