The goal of this research is to optimize and validate a novel magnetic resonance (MR) imaging technique for in vivo assessment of cell density. If successful, the approach would provide timely assessment of tumor response during therapy of individual patients, a measurement that is not available currently. We propose to test a method for deriving tissue cell volume fraction (CVF) from tissue sodium concentration (TSH) measured by noninvasive multi-nuclear Na/hD MR imaging (MRI). Preliminary data suggest that change in tissue CVFis a direct measure of cell kill, and may be a clinically important parameter for following tumor response during interventions. The absence of change in CVF may suggest that therapy should be altered to avoid toxic effects of ineffective therapy early in the course of treatment. Given that multiple measurements can be made during therapy, the rate of change in CVF may be a measure of tumor responsiveness. As CVF is a regional parameter, response in heterogeneous tumors can be followed regionally rather that globally as assessed by total tumor volume. The measurement of tissue CVF exploits a soluble-resonance radiofrequency coil for quantification of 23Na single intensity as a tissue sodium concentration that is independent of instrument response, coil and sample geometry. As sodium is largely an extra-cellular ion, the tissue sodium concentration reflects the extra-cellular volume and can be inversely related to CVF in a simple two compartment model. Animal models of glioma C6 in rat and human sarcoma in nude mouse will be used to follow changes in CVF as measured by MRI before and after photon external beam radiation. The accuracy and precision of the MR measurement of radiation-induced changes in TSH, and its derived parameter CVF, are to be determined in these models by comparison to radiotracer dilution assays. Tumor volume by conventional MRI and histopathology of the MR method of TSH and CVF mapping will be established under the controlled conditions of the animal models prior to human studies.
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