Rat cerebral ischemia induced with photochemical occlusion of proximal middle cerebral artery: a stroke model for MR imaging research

Abstract

A stroke model in rats with photochemically induced thrombosis (PIT) of proximal cerebral middle artery (MCA) is introduced for magnetic resonance imaging (MRI) study. Thirty-seven rats subjected to surgical and optical procedures for inducing the PIT models were scanned using a 1.5-T scanner with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced perfusion-weighted imaging (PWI) at 1 h and 24 h after MCA occlusion. The penumbra evolution and PWI-derived parameters including relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were monitored; and the relative lesion size (RLS) was compared with the final RLS on the gold standard triphenyl tetrazolium chloride (TTC) staining at 24 h. The results showed that the focal cerebral ischemic lesions were detectable in all rats with different MR approaches. The lesion on PWI at 1 h and on all MR images at 24 h was matched well with that seen on TTC staining; the peri-infarct area decreased from 6.2 +/- 7.2% of the brain volume at 1 h to 0.3 +/- 5.6% at 24 h. Compared to that in the contralateral hemisphere, rCBV in ischemic region was 52.6 +/- 21.4 and 40.0 +/- 15.8% (p > 0.05), and rCBF was 64.6 +/- 11.2 and 47.3 +/- 11.1% (p < 0.05) at 1 h and 24 h respectively. The present PIT model in rats has been successfully adopted for MRI research, which might be feasible for certain stroke studies and should be beneficial for the evaluation on effects of potential diagnostic and therapeutic approaches.

Microplasmin and Tissue Plasminogen Activator: Comparison of Therapeutic Effects in Rat Stroke Model at Multiparametric MR Imaging

“…Body temperature was kept at 37.5°C Ϯ 0.5 (standard deviation) with a heating pad (TR-100; First Sensor Technology, Munich, Germany) during surgery. The middle cerebral artery (MCA) was occluded by using a photothrombotic approach, as described in detail elsewhere (19,20,22). A plastic catheter was placed in the right femoral vein for injection of the photosensitizer rose bengal, test drugs, and contrast agent.…”

“…A 25-mm 2 region of interest containing 49 pixels of 0.72 ϫ 0.72 mm was placed on the region contralateral to the region that contained the lesion, which included the origin of the right MCA to allow measurement of the arterial input function, from which the pixels representing the right MCA branch were selected (20) with consensus of three authors (F.C., Y.N., Y.S. ).…”

“…Chen et al rCBV maps; (c) readouts of rCBF and rCBV were automatically generated by the software; and (d) the percentage of lesional rCBF and rCBV in comparison to those in the contralateral normal sides was calculated (20).…”

“…Results of previous studies have shown that microplasmin reduces brain tissue damage in stroke models of the mouse (14) and the rat (15). However, to our knowledge, direct comparison of tPA and microplasmin for their therapeutic effects in rats, the most commonly used species in cerebral ischemic studies, has not been reported.In the treatment of acute stroke, thrombolytic agents target the brain tissue at risk (or the ischemic penumbra) that has been clinically defined as the ischemic, but still viable and salvageable, tissue if local perfusion is rapidly restored (16,17).Multiparametric magnetic resonance (MR) imaging, including perfusionweighted (PW) and diffusion-weighted (DW) imaging, has been widely applied for guiding and monitoring treatment in hyperacute stroke (2,8,9,11,16,(18)(19)(20). The mismatch between relative lesion volume (rLV) on PW source images and that on apparent diffusion coefficient (ADC) maps (perfusion-diffusion mismatch) provides a practical and approximate measure of the tissue at risk and has been increasingly used for the evaluation of acute stroke.…”

“…Multiparametric magnetic resonance (MR) imaging, including perfusionweighted (PW) and diffusion-weighted (DW) imaging, has been widely applied for guiding and monitoring treatment in hyperacute stroke (2,8,9,11,16,(18)(19)(20). The mismatch between relative lesion volume (rLV) on PW source images and that on apparent diffusion coefficient (ADC) maps (perfusion-diffusion mismatch) provides a practical and approximate measure of the tissue at risk and has been increasingly used for the evaluation of acute stroke.…”