Perfusion and diffusion-weighted MR imaging for in vivo evaluation of treatment with U74389G in a rat stroke model.

BACKGROUND AND PURPOSE The present study was performed to examine the potential of diffusion-weighted (DW) imaging and dynamic first-passage bolus tracking of susceptibility contrast agents (perfusion imaging) for early in vivo evaluation of the effects of treatment with the free radical scavenger U74389G in a rat model of temporary focal ischemia. METHODS After 45 minutes of middle cerebral artery occlusion, the treatment group (n = 9) received an infusion of U74389G, and the control group (n = 9) received the identical volume of the vehicle. Reperfusion was instituted in both groups after 120 minutes of middle cerebral artery occlusion. The DW images were collected during middle cerebral artery occlusion and reperfusion and were compared with histologically assessed areas of tissue injury after 2 hours of reperfusion. The dynamic perfusion series were processed on a pixel-to-pixel basis to produce parametric maps reflecting the maximum reduction in the signal obtained during the first passage of the contrast agent and the time delay between the arrival of the bolus and the point of maximum contrast-agent effect. RESULTS The area of ischemic injury, as assessed from the DW imaging at 60 minutes of reperfusion, was significantly smaller in the treatment group: 9 +/- 8% of ipsilateral hemisphere compared with 19 +/- 8% in the control group. The histological examination after 2 hours of reperfusion demonstrated an area of ischemic injury of 10 +/- 8% for the treatment group compared to 25 +/- 10% in the control group. In the treatment group, the perfusion imaging showed a reduction in time delay to maximum effect of the contrast agent in the ischemic hemisphere compared with the control group. CONCLUSIONS The DW imaging during early reperfusion showed a protective effect of postocclusion treatment with the free radical scavenger U74389G. The improvement of time delay to maximum effect of the contrast agent observed in the perfusion imaging of the treatment group may reflect an improvement in the collateral flow to the ischemic tissue.

[1]  F. Godtliebsen,et al.  Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion. , 1995, Stroke.

[2]  D. Gadian,et al.  Monitoring the initial expansion of focal ischaemic changes by diffusion‐weighted MRI using a remote controlled method of occlusion , 1994, NMR in biomedicine.

[3]  H. B. Verheul,et al.  Comparison of diffusion‐weighted MRI with changes in cell volume in a rat model of brain injury , 1994, NMR in biomedicine.

[4]  B. Dardzinski,et al.  Apparent diffusion coefficient mapping of experimental focal cerebral ischemia using diffusion‐weighted echo‐planar imaging , 1993, Magnetic resonance in medicine.

[5]  H. B. Verheul,et al.  Temporal evolution of NMDA-induced excitoxicity in the neonatal rat brain measured with 1H nuclear magnetic resonance imaging , 1993, Brain Research.

[6]  O. Haraldseth,et al.  K‐space substitution: A novel dynamic imaging technique , 1993, Magnetic resonance in medicine.

[7]  S. Majumdar,et al.  Cerebral perfusion in children: detection with dynamic contrast-enhanced T2*-weighted MR images. , 1993, Radiology.

[8]  B. Rosen,et al.  Pitfalls in MR measurement of tissue blood flow with intravascular tracers: Which mean transit time? , 1993, Magnetic resonance in medicine.

[9]  J W Belliveau,et al.  Measurement of Cerebrovascular Changes in Cats After Transient Ischemia Using Dynamic Magnetic Resonance Imaging , 1993, Stroke.

[10]  C. Sotak,et al.  Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion‐weighted MRI , 1993, Neurology.

[11]  R A Knight,et al.  Histopathological correlations of nuclear magnetic resonance imaging parameters in experimental cerebral ischemia. , 1993, Magnetic resonance imaging.

[12]  N C Huang,et al.  The evolution of acute stroke recorded by multimodal magnetic resonance imaging. , 1993, Magnetic resonance imaging.

[13]  J. Tsuruda,et al.  Cytotoxic brain edema: assessment with diffusion-weighted MR imaging. , 1992, Radiology.

[14]  S. Williams,et al.  Diffusion‐Weighted Imaging Studies of Cerebral Ischemia in Gerbils: Potential Relevance to Energy Failure , 1992, Stroke.

[15]  R. Koehler,et al.  Tirilazad Mesylate Does Not Improve Early Cerebral Metabolic Recovery Following Compression Ischemia in Dogs , 1992, Stroke.

[16]  K Minematsu,et al.  Reversible Focal Ischemic Injury Demonstrated by Diffusion‐Weighted Magnetic Resonance Imaging in Rats , 1992, Stroke.

[17]  A. Buchan,et al.  Tirilazad Reduces Cortical Infarction After Transient but Not Permanent Focal Cerebral Ischemia in Rats , 1992, Stroke.

[18]  L. Hedlund,et al.  Mechanism of Detection of Acute Cerebral Ischemia in Rats by Diffusion‐Weighted Magnetic Resonance Microscopy , 1992, Stroke.

[19]  B. Siesjö,et al.  Penumbral Tissues Salvaged by Reperfusion Following Middle Cerebral Artery Occlusion in Rats , 1992, Stroke.

[20]  Wei Li,et al.  Acute cerebral ischemia: evaluation with dynamic contrast-enhanced MR imaging and MR angiography. , 1992, Radiology.

[21]  O. Haraldseth,et al.  Quicker metabolic recovery after forebrain ischemia in rats treated with the antioxidant U74006F. , 1991, Stroke.

[22]  P van Gelderen,et al.  Restricted and anisotropic displacement of water in healthy cat brain and in stroke studied by NMR diffusion imaging , 1991, Magnetic resonance in medicine.

[23]  Mark S. Cohen,et al.  Contrast agents and cerebral hemodynamics , 1991, Magnetic resonance in medicine.

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

[25]  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.

[26]  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.

[27]  E. Hall,et al.  Effects of tirilazad mesylate on postischemic brain lipid peroxidation and recovery of extracellular calcium in gerbils. , 1991, Stroke.

[28]  R R Edelman,et al.  Cerebral blood flow: assessment with dynamic contrast-enhanced T2*-weighted MR imaging at 1.5 T. , 1990, Radiology.

[29]  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.

[30]  A. Betz,et al.  Dimethylthiourea Reduces Ischemic Brain Edema without Affecting Cerebral Blood Flow , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[31]  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.

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

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

[34]  A. Betz,et al.  Allopurinol and dimethylthiourea reduce brain infarction following middle cerebral artery occlusion in rats. , 1989, Stroke.

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

[36]  W. Young,et al.  21-Aminosteroid reduces ion shifts and edema in the rat middle cerebral artery occlusion model of regional ischemia. , 1988, Stroke.

[37]  E. Hall,et al.  Attenuation of postischemic cerebral hypoperfusion by the 21-aminosteroid U74006F. , 1988, Stroke.

[38]  N. Lassen,et al.  Cerebral Transit of an Intravascular Tracer May Allow Measurement of Regional Blood Volume but Not Regional Blood Flow , 1984, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.