Reversible Focal Ischemic Injury Demonstrated by Diffusion‐Weighted Magnetic Resonance Imaging in Rats

Background and Purpose: Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively display focal brain abnormalities within minutes after the onset of ischemia. We performed the present study to determine the effects of 1 and 2 hours of temporary ischemia on DWI. Methods: We examined DWI and T2-weighted magnetic resonance images (T2WI) during and after 1 and 2 hours of temporary middle cerebral artery occlusion in rats (n=10 for each group). In a subgroup of four animals from each group, we employed perfusion magnetic resonance imaging to monitor cerebral perfusion. Neurological outcome and infarct size after survival for 24 hours were compared between the groups and correlated with DWI and T2WI studies. Results: Perfusion studies qualitatively documented hypoperfusion and reperfusion during and after temporary occlusion. Lesion size on DWI during reperfusion was significantly less than that during ischemia for 1 (55% decline, p<0.02) but not 2 hours of occlusion. The DWI signal intensity ratio (intensity compared with that in the contralateral homologous area) just before withdrawal of the occluder was significantly less in regions where the hyperintensity disappeared after withdrawal than in regions with persistent hyperintensity (p<0.002). The T2WI studies revealed few or no abnormalities, except after 2 hours of occlusion. The neurological outcome was significantly better in the 1-hour than in the 2-hour group (p<0.05). Postmortem infarct volume was significantly smaller in the 1-hour group than in the 2-hour group (p<0.05). The postwithdrawal DWI accurately predicted infarct size (R=0.96, p<0.0001). Conclusions: The present study indicates that DWI can rapidly display not only irreversible but also reversible ischemic brain damage and enhances the importance of DWI as a diagnostic modality for stroke.

[1]  R. Ojemann,et al.  Thresholds of focal cerebral ischemia in awake monkeys. , 1981, Journal of neurosurgery.

[2]  L. Pitts,et al.  Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. , 1986, Stroke.

[3]  Yoji Yoshida,et al.  Experimental studies of ischemic brain edema , 1986 .

[4]  M Brant-Zawadzki,et al.  MR imaging of acute experimental ischemia in cats. , 1986, AJNR. American journal of neuroradiology.

[5]  D. LeBihan,et al.  Molecular diffusion nuclear magnetic resonance imaging. , 1991 .

[6]  K Minematsu,et al.  Diffusion‐weighted magnetic resonance imaging , 1992, Neurology.

[7]  D. Bihan,et al.  4809701 Method to measure the molecular diffusion and/or perfusion parameters of live tissue , 1991 .

[8]  T. Sundt,et al.  Restoration of middle cerebral artery flow in experimental infarction. , 1969, Journal of neurosurgery.

[9]  J. Ryu,et al.  Reevaluation of transient ischemic attacks as a risk factor for early mortality. , 1991, Stroke.

[10]  B. Siesjö,et al.  Thresholds in cerebral ischemia - the ischemic penumbra. , 1981, Stroke.

[11]  M. Moseley,et al.  Detection with echo‐planar MR imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia , 1991, Journal of magnetic resonance imaging : JMRI.

[12]  N M Branston,et al.  Cortical Evoked Potential and Extracellular K+ and H+ at Critical Levels of Brain Ischemia , 1977, Stroke.

[13]  K. Kogure,et al.  Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. , 1989, Stroke.

[14]  C. Sotak,et al.  New magnetic resonance techniques for evaluating cerebrovascular disease , 1992, Annals of neurology.

[15]  K. Hossmann,et al.  Cation Activities in Reversible Ischemia of the Cat Brain , 1977, Stroke.

[16]  A. Tamura,et al.  Correlation Between rCBF and Histological Changes Following Temporary Middle Cerebral Artery Occlusion , 1980, Stroke.

[17]  R. Auer,et al.  Biological differences between ischemia, hypoglycemia, and epilepsy , 1988, Annals of neurology.

[18]  Wei Li,et al.  Fast magnetic resonance diffusion‐weighted imaging of acute human stroke , 1992, Neurology.

[19]  B. Rosen,et al.  Perfusion imaging with NMR contrast agents , 1990, Magnetic resonance in medicine.

[20]  D. Graham,et al.  Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema. , 1985, Journal of neurosurgery.

[21]  M. Scully,et al.  Thrombolytic therapy. , 1968, British medical bulletin.

[22]  U. Degirolami,et al.  Tissue plasminogen activator reduces neurological damage after cerebral embolism. , 1985, Science.

[23]  R. Turner,et al.  Echo-planar imaging: magnetic resonance imaging in a fraction of a second. , 1991, Science.

[24]  M. Ginsberg,et al.  Diffuse cerebral ischemia in the cat: I. Local blood flow during severe ischemia and recirculation , 1978, Annals of neurology.

[25]  H. Zeumer,et al.  Thrombolytic therapy in stroke: possibilities and hazards. , 1986, Stroke.

[26]  F J Schuier,et al.  Experimental Brain Infarcts in Cats: II. Ischemic Brain Edema , 1980, Stroke.

[27]  P. Grenier,et al.  MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. , 1986, Radiology.

[28]  D. Le Bihan Molecular diffusion nuclear magnetic resonance imaging. , 1991, Magnetic resonance quarterly.

[29]  M E Moseley,et al.  Comparison of diffusion‐ and T2‐weighted MRI for the early detection of cerebral ischemia and reperfusion in rats , 1991, Magnetic resonance in medicine.

[30]  J. LaManna,et al.  Impairment of metabolic recovery with increasing periods of middle cerebral artery occlusion in rats. , 1990, Stroke.

[31]  R A Knight,et al.  Temporal evolution of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging. , 1991, Stroke.

[32]  T. Olsen,et al.  Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke. , 1983, Stroke.

[33]  W. Yuh,et al.  MR imaging of cerebral ischemia: findings in the first 24 hours. , 1991, AJNR. American journal of neuroradiology.

[34]  P. Mansfield Multi-planar image formation using NMR spin echoes , 1977 .

[35]  J. Koizumi,et al.  Experimental studies of ischemic brain edema. Effect of recirculation of the blood flow after ischemia on post-ischemic brain edema. , 1989 .

[36]  W. Powers Cerebral hemodynamics in ischemic cerebrovascular disease , 1991, Annals of neurology.

[37]  W D Heiss,et al.  Functional recovery of cortical neurons as related to degree and duration of ischemia , 1983, Annals of neurology.

[38]  M. Kowada,et al.  Cerebral ischemia. II. The no-reflow phenomenon. , 1968, The American journal of pathology.

[39]  P. Weinstein,et al.  Reversible middle cerebral artery occlusion without craniectomy in rats. , 1989, Stroke.

[40]  D. Le Bihan,et al.  Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. , 1988, Radiology.

[41]  J. Kurhanewicz,et al.  Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats. , 1990, AJNR. American journal of neuroradiology.

[42]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[43]  P. Weinstein,et al.  Neurological deficit and cerebral infarction after temporary middle cerebral artery occlusion in unanesthetized cats. , 1986, Stroke.

[44]  J. Kucharczyk,et al.  Early detection of regional cerebral ischemia in cats: Comparison of diffusion‐ and T2‐weighted MRI and spectroscopy , 1990, Magnetic resonance in medicine.

[45]  W. Pulsinelli,et al.  Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. , 1991, Stroke.