ASSESSING TUMOR MALIGNANCY IN VIVO USING SODIUM MRI

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

Normal brain cells maintain a relatively low intra-cellular sodium concentration (10-20mM) against a large sodium pool in the extra-cellular space (120-150mM concentration). The large concentration gradient that develops across the cell membrane is critically important for maintenance of basic cellular functions and it is severely disrupted during the course of many pathological conditions. Measurement of intracellular sodium content by invasive means in a variety of cancer types has demonstrated a positive correlation between intra-cellular sodium content and mitotic activity. As mitotic activity constitutes an important prognostic factor used in the design of a therapeutic plan, a non-invasive means to assess the intracellular sodium content in neoplastic tissue could prove to be a valuable tool for the clinical evaluation of brain tumors. Sodium MRI represents an attractive approach for the non-invasive monitoring of changes in sodium content in vivo. The sodium MRI methods demonstrated up to now can only provide quantitative maps of total tissue sodium concentration in vivo. The more demanding goal of producing in vivo maps of the intra-cellular tissue sodium concentration in humans is a challenging application, with exciting benefits, for which practical solutions can now be formulated using triple quantum (TQ) sodium imaging schemes. This exploratory proposal is written in response to program announcement PA-98-008 (Exploratory/Developmental Grants for Diagnostic Cancer Imaging) and is aimed at exploring the relationship between triple-quantum filtered sodium signal intensity and tumor mitotic activity in vivo using a pool of glioma patients undergoing treatment at the Pittsburgh Cancer Institute. Our aims are to characterize the TQF NMR signal in normal and neoplastic brain tissue, and to study is correlation with mitotic activity in low and high grade gliomas. The underlying hypothesis driving these studies is that TQF NMR signal exhibits a positive correlation with mitotic activity in human gliomas. If this hypothesis is proven true a more comprehensive study aimed at fully characterizing this correlation will be assembled and submitted for consideration under the traditional RO1 mechanism.