Prostate cancer is presently the second leading cause of cancer death in American men. Several variables in the occurrence and natural history of prostate cancer make it especially difficult to treat. Statistics indicate that less than 1 percent of prostate cancers cause clinical disease. Yet when they do, the average survival time of patients with metastases is less than two years. Currently there is no reliable way of predicting which cancers will be indolent versus those that will metastasize and result in death. Also as screening for these diseases improves, more and earlier stage tumors will be detected increasing the difficulties in managing these patients. A variety of treatment options exist and no consensus has been reached on what constitutes the best therapy and how to assess early treatment response, which is only poorly addressed by conventional imaging techniques. A noninvasive method such as Magnetic Resonance Spectroscopic Imaging (MRSI) to characterize prostate cancers based on cellular function and metabolism would be an extremely valuable tool for the clinical management of prostate cancer. In this project, we will develop new techniques to greatly improve prostate MRSI studies. They include: 1) New endorectal coils with a 2+fold improvement in sensitivity allowing increased spectral and spatial resolution, reduced motion artifacts, and improved Bo homogeneity over prostate (reduced magnetic susceptibility effects; 2) New rf pulses for better controlled water/lipid suppression, improved conformal spatial selection with 2.7 fold improvement in selectivity; 3) Absolute quantitation using electronic referencing to provide accurate measurements of metabolite levels (especially critical following hormonal therapy). 4) New 2d J-resolved MRS sequences for detection of additional metabolites (polyamines, lipid, lactate) and accurate T2 information; 5) MRI/MRSI guided tissue sample collection for accurate correlation of high resolution magic angle spinning (HR MAS) NMR spectra with outstanding spectral resolution from small (5-lOmg) tissue samples which then will be correlated to conventional histology and new molecular marker assays of the same sample. In this renewal research project, we will apply these new techniques to characterize the metabolic differences between prostate cancers with varying biologic aggressiveness and hormone responsiveness. While these technical developments are specifically designed for this research project, they will greatly improve the quality, reliability, applicability of this method for future clinical studies both at our institution and others.
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