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. Thus, 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 occured during and after ischemic periods. In addition to assessing large- and small-vessel perfusion using MR angiography (MRA) and dynamic contrast imaging, it is essential to have access to MR parameters that reflect reversible and irreversible tissue damage during and after ischemic periods. Spin-Density/T2-weighted imaging is a good indicator of edema (hyperintensity), but is not sensitive in the acute phase. It is therefore important to develop new functional imaging methods that can quantitatively assess tissue status when neurologic recovery is still possible. Diffusion imaging can detect ischemic tissue within minutes post-onset, but contrary to early expectations based on animal studies, clinical results generally show that regions of reduced diffusion proceed to infarction at follow-up. In addition, perfusion images generally show an area of reduced flow larger than the region of compromised diffusion, the so-called perfusion-diffusion mismatch. Because it is essential to assess the risk of infarction in this region, which often evolves to reduced diffusion, there is a need for new functional modalities to diagnose this mismatch area at the time of clinical evaluation. Based on recent results obtained by us, we have designed the following hypotheses: (1) quantification of oxygen extraction ratio (OER) can predict the risk for tissue infarction based on the principle of flow thresholds; (2) changes in protein synthesis are reflected in the proton magnetization transfer rate between proteins and water, which can be imaged through the MRI relaxation rate T1rho; (3) It is possible to measure pH using proton MRS, which will provide an additional tissue parameter for stroke evaluation on a standard clinical scanner (proton only). Our corresponding three aims are to develop new methodologies to measure OER, T1rho, and pH, and to subsequently test our three hypothesis on cat brain models of reduced blood flow and of transient global and focal ischemia. Our fourth and final aim is to implement the new technologies on the clinical scanner and to optimize their use for a fast and specific clinical stroke exam.
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