Usefulness of magnetite as an MRI contrasting agent in an experimental cerebral ischemic model. Evaluation of lesion detecting time

Abstract

Gd-DTPA has a T1 shortening effect that enhances the contrast in MRI and is widely used for the clinical evaluation of CNS diseases, though it is not suitable for the detection of cerebral ischemic regions during the superacute stage. Superparamagnetic iron oxide particles have a T2 shortening effect on relaxation time, reducing signal intensity on T2- weighted MRI in normal cerebral tissue. From this perspective we tested the feasibility of detecting ischemic lesions during the superacute stage using superparamagnetic iron oxide particles-enhanced MRI. Male Sprague-Dawley rats were anesthetized using pentobarbital and the left middle cerebral artery was permanently occluded (lt.-PMCAO) using a modified version of the Koizumi method. After lt.-PMCAO, 100 μmoles Fe/kg, 1 ml/kg magnetite, superparamagnetic iron oxide particles, (magnetite-injected group, n=9) or physiological saline (vehicle-injected group, n=9) was injected into the femoral vein. T2-weighted MR images were performed at designated time points immediately after injection of magnetite or vehicle on a 6.34 T MR unit. Additionally, in separate animals coronal sections of the brain were stained with 4% 2, 3, 5 triphenyl-tetrazoline-chloride (TTC) to confirm the infarct region. In the magnetite-injected group, a high signal area at the region of lt.-MCA was visible within 20 to 30 min following lt.-PMCAO, whereas in the vehicle-injected group no high signal ischemic area could be confirmed until 3 h after lt.-PMCAO. Infarction was noticed in the TTC staining 3 h following lt.-PMCAO. In this study magnetite injection allowed the detection of ischemia in the occluded MCA area on T2-weighted MRI during the superacute stage. These results suggest that ischemia during the superacute stage can be evaluated using magnetic enhanced MRI.