PHYSIOLOGIC IMAGING OF HUMAN BRAIN TUMORS

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Recent advances in radiologic imaging techniques provide detailed pictures of the gross anatomy of brain tumors; the impact of this structural information on clinical outcome, however, has been limited. A major reason for the inability to directly translate anatomic findings into improved treatment is that the relationship between static anatomy and the dynamic biologic behavior of tumors is not straightforward. The pathobiology of a tumor is a function of numerous non-anatomic factors, of which one -- cell division -- is physiologically crucial. Cell division and the requisite DNA synthesis are directly related to tumor growth behavior, including response to treatment. Thus, the long term objective of this research is to develop in vivo physiologic imaging techniques which correlate highly with DNA synthesis and cell division. Furthermore, we will document that these techniques are the histopathologic grade of gliomas. It is anticipated that this physiologic information will be complementary to anatomic imaging in aiding the treatment of human brain tumors. Three in vivo methods will be evaluated for their correlation with DNA synthesis in primary and secondary brain tumors: 1) 11C thymidine incorporation into DNA was detected by PET, (2 glucose utilization as measured by PET 18Fdeoxyglucose uptake, and 3) bioenergetic state of tumor tissue as reflected by 1H31P magnetic resonance spectroscopy (MRS). The first method is postulated to be a direct measure of NA synthesis while the latter two methods are indirect reflections of cell division and therefore DNA synthesis. For each method, correlation with DNA synthesis as measured by BUDR incorporation, mitotic index, and the histopathologic grade of the tumor will be performed. Based on the results of the in vivo correlations with DNA synthesis (Years 1-3), the method or methods which best reflect tumor cell division and DNA synthesis will be applied to brain tumor patients pre and post radiation therapy. Post treatment in vivo physiologic imaging results will be correlated with 3D MR volumetric measurements of tumor growth in order to evaluate their ability to monitor acute treatment response.