Acute Changes in MRI Diffusion, Perfusion, T 1 , and T 2 in a Rat Model of Oligemia Produced by Partial Occlusion of the Middle Cerebral Artery Mark F. Lythgoe, 1 * David L. Thomas, 1,2 Fernando Calamante, 1 Gaby S. Pell, 2 Martin D. King, 1 Albert L. Busza, 1 Christopher H. Sotak, 3 Stephen R. Williams, 1 Roger J. Ordidge, 2 and David G. Gadian 1 Oligemic regions, in which the cerebral blood flow is reduced without impaired energy metabolism, have the potential to evolve toward infarction and remain a target for therapy. The aim of this study was to investigate this oligemic region using various MRI parameters in a rat model of focal oligemia. This model has been designed specifically for remote-controlled occlusion from out- side an MRI scanner. Wistar rats underwent remote partial MCAO using an undersize 0.2 mm nylon monofilament with a bullet- shaped tip. Cerebral blood flow (CBF ASL ), using an arterial spin labeling technique, the apparent diffusion coefficient of water (ADC), and the relaxation times T 1 and T 2 were acquired using an 8.5 T vertical magnet. Following occlusion there was a decrease in CBF ASL to 35  5% of baseline throughout the middle cerebral artery territory. During the entire period of the study there were no observed changes in the ADC. On occlusion, T 2 rapidly decreased in both cortex and basal ganglia and then normalized to the pre- occlusion values. T 1 values rapidly increased (within approxi- mately 7 min) on occlusion. In conclusion, this study demonstrates the feasibility of partially occluding the middle cerebral artery to produce a large area of oligemia within the MRI scanner. In this region of oligemic flow we detect a rapid increase in T 1 and decrease in T 2 . These changes occur before the onset of vaso- genic edema. We attribute the acute change in T 2 to increased amounts of deoxyhemoglobin; the mechanisms underlying the change in T 1 require further investigation. Magn Reson Med 44: 706 –712, 2000. © 2000 Wiley-Liss, Inc. Key words: cerebral ischemia; middle cerebral artery occlusion; magnetic resonance imaging; penumbra During the past 20 years middle cerebral artery occlusion (MCAO) in rats has been extensively used to model human stroke. This technique produces a focal area of cerebral ischemia, which may be achieved in a variety of ways, most commonly: permanent or reversible intraluminal MCAO (1,2); coagulation or ligation of the middle cerebral artery (MCA) after craniotomy (3). Diffusion-weighted magnetic resonance imaging (DWI) and measurements of the apparent diffusion coefficient (ADC) of water have found increasing use in the investi- gation of cerebral ischemia, providing the opportunity to identify acute changes (4). The early ADC changes follow- ing a stroke are thought to reflect cytotoxic edema and impaired energy metabolism (5). Numerous DWI investi- gations of cerebral ischemia in the rat have been performed by occluding the MCA, with the animal outside the mag- net, using the intraluminal approach (6). Although this technique allows reperfusion of the MCA, the acute phase of the insult is lost during the time taken to introduce the animal into the magnet. This limitation has been overcome by remote-controlled occlusion of the MCA, in which oc- clusion is performed remotely from outside the bore of the imaging magnet (7–9). Improvements such as this have allowed investigation of the pathological consequences of stroke immediately following occlusion and have permit- ted direct comparison with control images without the need for image registration. When occluding the MCA using an intraluminal ap- proach, the area of decreased cerebral blood flow (CBF) is inhomogeneous (10,11). There are broadly two territories of decreased perfusion: an area of ischemia, and a region of oligemia. The region that is most familiar is the territory of ischemia, which is produced in the conventionally oc- cluded MCA studies and is distinguished by a severely reduced CBF below the ischemic threshold, in which tis- sue hypoxia develops and CBF values are too low to sus- tain the tissues metabolic needs. The territory of oligemia, which is less apparent after MCAO, is characterized by a moderate reduction in flow, yet sufficient to maintain ionic homeostasis (12). This regional classification has been further character- ized using PET data. Regions which exhibit an increase in oxygen extraction fraction (OEF) with a decrease in CBF are known as areas of misery perfusion. This territory may be further divided into a region of oligemic misery perfu- sion which is characterized by a reduced CBF, increased OEF, yet normal oxygen consumption (CMRO 2 ) and a re- gion of ischemic misery perfusion with reduced CBF, in- creased OEF, yet decreased CMRO 2 (13). The definitions of ischemia and oligemia are also rele- vant to other imaging techniques such as MRI and autora- diography (10,14). In previous studies using MCAO in the rat, small regions of oligemia have been differentiated within the area of perfusion deficit using combinations of CBF and autoradiographic images of hypoxia (14), MRI T * 2 and ADC maps (10), and MRI CBF and ADC images (15). The uncoupling between flow and metabolism in re- gions of oligemia has been demonstrated using PET (16). PET studies in humans have indicated that, up to 17 hr 1 Royal College of Surgeons Unit of Biophysics, Institute of Child Health, University College London, London, UK. 2 Department of Medical Physics and Bioengineering, University College Lon- don, London, UK. 3 Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester and Department of Radiology, University of Massachusetts Med- ical School, Worcester, MA. Grant sponsor: Wellcome Trust. *Correspondence to: Dr. Mark F. Lythgoe, RCS Unit of Biophysics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. E-mail: mlythgoe@ich.ucl.ac.uk Received 24 April 2000; revised 12 June 2000; accepted 20 June 2000. Magnetic Resonance in Medicine 44:706 –712 (2000) © 2000 Wiley-Liss, Inc. 706