It is believed that early intervention is the key to successful therapeutic outcome in stroke, which is the third most frequent cause of mortality in western society. Therefore the ability to diagnose ischemic brain tissue with a high degree of specificity and sensitivity is critical. Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) hold great promise for noninvasive assessment of brain damage. However, if MR is to become useful for prognosis, it is essential to determine whether reversible or irreversible damage has occurred during and after ischemic periods. MR angiography (MRA) and dynamic contrast imaging assess tissue perfusion and are important for early intervention. However, in many cases tissue is already reperfused ant it is unclear whether any tissue alterations are present and if irreversible damage leading to infarction has occurred or may occur. Conventional spin-density and T2 images are good indicators of edema, but they generally indicate irreversible damage and image changes are often not visible until 5-6 hours or even longer after ischemia. This time lag can be overcome by studying parameters that directly reflect cellular status. MR provides the opportunity for this functional assessment through diffusion imaging or metabolite spectroscopy. Instantaneous (within 1-2 minutes) detection of ischemic brain tissue is possible using water diffusion imaging and/or proton spectroscopic detection of lactate. Also, recent experiments on animals and humans have shown that the brain metabolite N-acetylaspartate (NAA) may undergo large changes in concentration after stroke. The data demonstrate that these NAA changes are irreversible, indicating potential prognostic value for the outcome of the stroke. Our long-term goal is to design a complete MR exam that allows for diagnosis and prognosis of acute stroke in a clinical time frame. To achieve this goal we propose to design improved methods for artifact-free quantitative detection of water diffusion constants and of NAA and lactate. Based on our preliminary data and results in the literature, we hypothesize that water diffusion constants and steady state concentrations of lactate are sensitive indicators of acute ischemia, but that they are not prognostic for outcome with respect to brain damage (hyp. 1, 2). On the other hand, we hypothesize that changes in the concentrations of NAA are indicative of the presence of irreversible brain damage (hyp. 3) and are prognostic for outcome. Based on these hypotheses, our first aim is to optimize our functional MR tissue assessment by designing new MR technology for detection of the above parameters. This design will be performed on the 4.7T animal imager and methods will be tested on two stroke models, first on a global ischemia model and, after the method is optimized, on the more difficult middle cerebral artery occlusion model.
Our second aim i s to transfer the new technology to the 1.5T clinical scanner for use in clinical diagnosis and prognosis of stroke. These methods will be tested on volunteers, automated for efficient use in a clinical setting, and be made available to our clinical collaborators.
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