A critical issue for the treatment of malignant brain tumors is the definition of spatial extent and functional activity of the tumor. These parameters are important in predicting whether a patient will benefit from focal rather than more widespread therapy and in tailoring the most appropriate volume for targeted radiation therapy. In the current application, the applicants proposed to determine whether the serial MRI and water suppressed proton spectroscopic imaging (MRSI) can be used in directing focal radiation therapy for patients with brain tumors. The population which was chosen as a model system comprises 80 patients with malignant gliomas who have shown an increase in the size of the lesion on Gadolinium enhanced MRI and are being treated for tumor recurrence with Gamma Knife (GK) radiosurgery. The questions being addressed are: (1) how often would MRSI define a different target region for GK radiosurgery than the contrast enhancing lesion; (2) is treatment with GK radiosurgery effective within the treated region; and (3) do portions of the MRSI lesion which are outside the GK target correspond to sites of recurrence? In addition to evaluating serial changes in tissue metabolism, applicants proposed to add dynamic perfusion weighted echo planar imaging to the MRI/MRSI examinations in order to determine whether changes in hemodynamic parameters will contribute information which is valuable in the assessment of brain tumors. The first three years of prior funding were described to have shown that MRSI has great potential for distinguishing active tumor from normal brain tissue, edema and treatment induced necrosis. The applicants described having identified the metabolic characteristics of these tissue types and developed technology for the quantitative assessment of response to therapy based upon changes in the volume of the contrast enhancing lesion, the region of abnormality on the T2-weighted images, the distributions of choline, creatine, and N-acetylaspartate. The applicants have used these serial MRI/MRSI examinations to follow patients with primary and metastatic brain tumors, compared the results of MRSI examinations with FDG PET correlated metabolic parameters and histologic analysis of tissue samples obtained using image guided surgery. The preliminary data obtained from these studies provide compelling evidence that MRSI can make a contribution to the clinical evaluation of patients with brain tumors. The goal of the proposed study is to establish whether these results hold up in a well controlled population of patients being treated in a uniform manner.
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