Middle cerebral artery occlusion in rats studied by magnetic resonance imaging.

Abstract

Ischemia due to middle cerebral artery occlusion was studied in 29 rats from 1 to 24 hours after occlusion using magnetic resonance imaging. Images were made before and after the injection of a superparamagnetic iron oxide compound, AMI-25. Subtraction images demonstrated the region of perfusion deficit as early as 1 hour after occlusion, earlier than conventional T 2 -weighted images. A major problem in the study of animal models of stroke is variability in the size and loca-L. tion of the ischemic lesions. This problem complicates experiments requiring serial in vivo measurements of the metabolic status of the involved brain. Since magnetic resonance spectroscopy can serially define these metabolic changes, 1 -3 the study of focal ischemia would be aided by magnetic resonance imaging (MRI) methods that could also serially define the volume of ischemic brain with precision yet without elaborate or time-consuming techniques. Although this problem obviously does not concern studies of global ischemia, it is important to develop magnetic resonance methodology to study focal lesions that will complement studies of global ischemia since it is focal lesions that are most often encountered clinically. We are addressing this issue using MRI with contrast agents in a model of focal ischemia, middle cerebral artery occlusion in rats. Paramagnetic compounds enhance proton relaxation times, thereby altering the intensity of the images. Paramagnetic compounds that are retained Received October 27, 1988; accepted March 1, 1989. in the intravascular space for adequate lengths of time can thus be used to image volumes of altered perfusion. We have previously demonstrated hemispheric differences in perfusion in a rat three-vessel occlusion model using gadolinium-diethylenetriaminepentaacetic acid complexed to albumin. 4 In our current experiments, we employed a superparamagnetic iron oxide formulation, AMI-25 (Advanced Magnetics Inc., Cambridge, Massachusetts) more potent than gadolinium. AMI-25 has been used to image the liver 5 but has not been used to study the brain. The effects of AMI-25 are readily visualized with T 2 -weighted spin-echo imaging. Using middle cerebral artery occlusion in rats and intravenous injection of AMI-25, we can detect focal ischemia early. Materials and MethodsTwenty-nine adult Sprague-Dawley rats (200-300 g) that had been allowed free access to food and water were anesthetized with a 90 : 10 mg/kg i.m. ketamine: xylazine mixture. Arterial and venous access via femoral catheters was established, and blood pressure and arterial blood gases were monitored. Core body temperature was maintained using a circulating water bath (K-module, Hamilton, Cincinnati, Ohio). Ipsilateral common carotid and middle cerebral arteries were occluded permanently according to the method described by Brint et al. 6 After shaving and providone-iodine preparation of the ventral neck and the region of the right zygoma, the right common carotid artery was dissected via a midline cervical incision and ligated. The rat was ...

Cerebral Blood Volume in Acute Brain Infarction

“…A number of experimental [7][8][9][10][11] and clinical MR studies [12][13][14][15] have demonstrated a reduction in the signal change during the passage of contrast medium in the ischemic core distal to the occluded cerebral arteries. In accordance with these results, our study indicated that both relCBF and relCBV are severely reduced in the ischemic core within 6 hours after the onset of cerebral infarction in humans.…”

“…5,6 Because the MRI contrast medium is an intravascular tracer, the DSC-MRI provides a measure of cerebral blood volume (CBV) as the area under the concentration-time curve of the contrast agent. Studies of animal ischemia model [7][8][9][10][11] and human acute infarction [12][13][14][15] have shown a decrease in CBV in the vascular territory of steno-occlusive lesions. Although CBV is a fundamental factor in hemodynamic studies of ischemic brain disorder, few studies have reported the relationship between CBV and cerebral blood flow (CBF) in acute stroke patients.…”

Noninvasive determination of regional cerebral blood flow in rats using dynamic imaging with Gd(DTPA)

“…The extent of the signal reduction depends on the magnetic moment of the lanthanide ion, the partial blood volume per tissue unit mass, and the tissue perfusion rate. Using this principle, Belliveau et al ( I 1 ) and Bradley et al ( 12) found differences in MR signal attenuation in animal models of brain ischemia, qualitatively describing the reduced cerebral blood flow (CBF) to the affected brain areas.…”

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

“…As a result of systematic further development of SPIO, in particular size variation and coating modifications, numerous additional areas of application in preclinical and clinical MR diagnostics have been tested in the last two decades. Therefore, SPIO have been frequently tested in preclinical feasibility studies as a T1 contrast agent for MR angiography in vascular diagnostics [10], as a T2 or T2* contrast agent for the detection of atherosclerotic plaques [11] and vascular thrombi [12], in perfusion diagnosis of tumors [13], myocardium [14], renal parenchyma [15], vital brain [16], cerebral ischemia [17], and the placenta [18], and in the diagnosis of synovial structures, e. g. in the knee [19]. Newer applications in the primarily still preclinical experimental field of molecular imaging describe on a cellular level the in vitro labeling of cell types (e. g. macrophages, lymphocytes, progenitor/stem cells) with SPIO (cell labeling) and their diagnostic in vivo MR imaging and migration tracking (tracking/migration monitoring) [20,21].…”