? The main thrust for this project is the validation of single and triple quantum sodium MRI as a non-invasive novel means for the detection of neoplastic changes associated with the development of malignant tumors in the human brain. Because neoplastic changes precede the development of angiogenesis and blood brain barrier breakdown, the proposed technique could provide with an independent imaging approach for detecting non-enhancing tissue that would otherwise develop into a malignant tumor and/or tumor tissue that remains viable after resection. The proposed approach relies on the use of triple and single quantum sodium MRI for the detection of the increase in the intracellular sodium content that precedes cell depolarization prior to mitosis. As increased mitotic activity is a necessary condition for neoplastic changes, the development of tumor tissue is usually accompanied by large (400%) changes in the intracellular sodium content. These, in turn lead to changes in the total tissue sodium concentration that are clearly visible, but potentially nonspecific, in the total tissue sodium concentration maps (single quantum sodium MRI). The proposed use of triple quantum sodium filtration, removes this constraint by neglecting most of the signal contributions arising in the extra-cellular space. Triple quantum sodium NMR techniques have been used for many years for the assessment of the changes in sodium content in the intracellular space. Imaging extensions of these techniques have been recently introduced by our laboratory and explored in the context of the proposed pathology under the auspices of an exploratory grant from the National Institutes of Health. In this application, we proposed to further the development of this application in the context of specific hypotheses that have been supported by several observations made during the execution of the aforementioned exploratory grant. All the proposed studies will be carried out in conjunction with the Departments of Neurooncology and Neurosurgery at the University of Pittsburgh Medical Center using a pool of treatment-naive brain tumor patients available through the Pittsburgh Cancer Institute. ? ?
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