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

J Magn Reson Imaging. 2022 Apr;55(4):1095-1106. doi: 10.1002/jmri.27914. Epub 2021 Sep 4.

Abstract

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.

Keywords: angiographic reperfusion; inflammation thrombus; lymphocyte's inhibitor; recanalization; vascular protectants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media
  • Dextrans
  • Embolism*
  • Fingolimod Hydrochloride / pharmacology
  • Fingolimod Hydrochloride / therapeutic use
  • Infarction, Middle Cerebral Artery / diagnostic imaging
  • Infarction, Middle Cerebral Artery / drug therapy
  • Magnetic Resonance Imaging / methods
  • Magnetite Nanoparticles*
  • Mice
  • Rats
  • Reperfusion
  • Stroke*
  • Tissue Plasminogen Activator / therapeutic use

Substances

  • Contrast Media
  • Dextrans
  • ferumoxtran-10
  • Fingolimod Hydrochloride
  • Magnetite Nanoparticles
  • Tissue Plasminogen Activator