Magnetic resonance imaging investigations of ischemic stroke, intracerebral hemorrhage and blood-brain barrier pathology

In this dissertation, magnetic resonance imaging (MRI) was used as the primary tool for studies of therapeutic interventions on ischemic stroke and intracerebral hemorrhage (ICH), and blood-brain barrier (BBB) pathology in rats. In a study, rats subjected to 2-h of transient middle cerebral artery occlusion (MCAO) were studied over 1-year period using multiparametric MRI, behavioral tests, and histology. MRI detectable changes of ischemia-damaged brain-tissues appeared to continue for at least 1-year post-ischemia. In another study, the effects of statin treatment on experimental ICH were investigated using behavioral, histological, and MRI measures of recovery. Atorvastatin and simvastatin significantly improved neurological outcome, decreased tissue loss, decreased hematoma volume and increased neurogenesis when administered at 2 mg/kg daily for 1-week post-ICH.;In one of the BBB pathology studies, MRI was performed on rats at 24-h after 3-h of MCAO using first Gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) and then 'Gd-DTPA linked to bovine serum albumin and Evans blue' (Gdv I BSA-EB). The variations in enhancing areas for the contrast agents (CAs) were reflected by T1sat variations. In another study, arterial input functions (AIFs) measured using MRI by DeltaR1 (=Delta[1/T1]) after a bolus injection of Gd-DTPA were compared to those measured by direct arterial blood sampling after an injection of 'radio-labeled Gd-DTPA' (Gd-[14C]DTPA). MRI-DeltaR1 underestimated the peak blood CA level that was captured by blood sampling. The original AIF, reconstructed individual AIFs from blood sampling and cohort-averaged AIF were employed to estimate blood-to-brain influx constant (Ki), and combined fractional volume of plasma and rapidly equilibrating non-plasma space (Vp+Vo) in a MCAO model. All Ki estimates showed good agreement. The original AIF overestimated Vp+Vo. Very good correlation of the influx constants between the MRI and quantitative autoradiography (QAR) methods with spatial agreement demonstrated the efficacy of Patlak method. In another study, a step-down infusion procedure was used in a MCAO model. Both extravascular enhancement of Gd-DTPA on MRI and Gd-[14C]DTPA on QAR were identical in size and location. The terminal tissue:plasma distribution ratios of Gd-[14C]DTPA tended to be slightly higher in these areas. The MRI derived Ki values for Gd-DTPA closely agreed and correlated well with those obtained for Gd-[14C]DTPA.