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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 ...

A role for calciferol in zinc homeostasis was investigated by radioisotope uptake and compartmental analysis techniques. Cholecalciferol was injected into rats 4–5 days prior to radioisotopic study of rapidly exchangeable pools ( < 4 h). Kidney, liver, and duodenum had significant increases in zinc uptake rates. Bone and skeletal muscle had significant decreases. No other tissues had significant differences. Compartmental analysis models generated by the SAAM-25 digital computer program suggested a decrease in the fractional tissue to plasma coefficient to be the mechanism for the observed changes in the serum zinc concentration and tissue zinc accumulation rates. It is not clear whether this is a specific effect of calciferol on zinc homeostasis or is a nonspecific response which may reflect some role for zinc in calciferol metabolism.