Critical factors for the management of patients with primary gliomas are the definition of grade and spatial extent of the tumor. While tissue histology is the gold standard for diagnosis of grade, the possibility of sampling error and inability to perform multiple repeat biopsies have meant that the evaluation of tumor extent and the assessment of response to therapy rely heavily upon non-invasive imaging techniques. Although Magnetic Resonance Imaging (MRI) provides data with excellent soft tissue contrast and is widely used for serial evaluation of patients with brain tumors, the observed changes reflect abnormalities in tissue morphology rather than functional characteristics. Distinguishing tumor from edema, inflammation and treatment induced necrosis would be greatly facilitated by obtaining additional information concerning physiological properties of the tissue. Over the past five years we have developed a combined MRI and water suppressed proton spectroscopic imaging (MRSI) examination for the quantitative assessment of tumor extent and response to therapy based upon changes in morphologic abnormalities, hemodyamtic parameters and levels of cellular metabolites. In the current proposal we will apply these techniques to patients with suspected gliomas in order to establish baseline MR parameters for newly diagnosed gliomas, to determine whether there is evidence for these parameters being predictive of outcome and to evaluate response to focal beam radiation therapy. Our hypotheses are (1) that there is a difference between levels of choline, cretaine, N-acetylaspartate and relative cerebral blood volume (rCBV) between gliomas of grades II, III and IV, (2) that there are significant differences between the spatial extent of the Gadolinium enhancing lesion, T2-weighted abnormality, metabolic and hemodynamic abnormalities and (3) that regions which respond positively to focal beam radiation therapy for patients with Grades II and III gliomas display a reduction in choline, creatine, N- acetylaspartate and rCBV, whereas regions corresponding to tumor recurrence exhibit increases in rCBV and choline. It is anticipated that these studies will provide information which will be valuable for tailoring treatment protocols to individual patients, targeting biopsies, surgical resection or focal radiation therapy, evaluating response to therapy and understanding the mechanisms of treatment failure.
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