Astrocytomas, the most common type of brain tumors, are primarily diagnosed by the histopathological evaluation of cellular morphological changes in biopsy samples. In addition to changes in cell morphology, tumors also display altered cellular biochemistry. Tumor metabolic alterations may provide valuable information for clinical grading, biology-based prognosis, and therapeutic monitoring of astrocytomas. Conventional ex vivo 1HMRS has been used to study tumor samples; however, it is hampered by the need for the often destructive chemical extraction of tissue. We propose to evaluate the diagnostic potential of the newly developed high-resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy (1HMRS) on intact specimens of human astrocytomas. We plan to quantify HRMAS metabolites and measure histopathological features on the same tumor specimens, to select tumor metabolic markers, and to establish biochemical databases for astrocytoma diagnosis and prognosis.
Our specific aims are: 1) To quantify metabolic concentrations with HRMAS 1HMRS in different regions of normal human brain; 2) To quantify metabolic alterations in newly diagnosed, adult supratentorial, diffuse fibrillary astrocytomas, and to use these measures to identify and define HRMAS 1HMRS markers able to type and grade these tumors; 3) To evaluate the capability of HRMAS spectroscopic markers in predicting the histological grade of adult cerebral hemisphere astrocytomas; and 4) To evaluate the usefulness of HRMAS metabolic markers as independent indicators of tumor behavior and predictors of 2 year survival for patients with glioblastoma multiforme (GBM). If successful, our study will establish astrocytoma HRMAS metabolic databases and objective parameters to serve as an adjunct modality for predicting tumor development, progression and patient outcome. We expect that current diagnostic sensitivity and specificity will be improved by utilizing HRMAS 1HMRS tumor markers. The results from this study will also further current understanding of tumor neurobiology and provide new linkages among fields such as clinical pathology, clinical radiology, tumor biology and molecular genetics. Astrocytoma metabolic markers obtained from this study will have important implications on the future development of magnetic resonance spectroscopic imaging (MRSI) and localized in vivo MR spectroscopy for non-invasive diagnosis and therapeutic monitoring of these neoplasms.
