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John Kurhanewicz
Prostate Cancer Imaging Research Program The accurate characterization of prostate cancer is a major problem in the management of individual prostate cancer patients and in monitoring treatment effects. To address this pressing need, we (Drs. Kurhanewicz, Vigneron and Nelson) have developed over the past 15 years a large research program at UCSF to develop new anatomic and metabolic (MR spectroscopic imaging, MRSI) methods to provide an improved assessment of human prostate cancer. I have directed the UCSF Prostate Imaging Program over the last ten years and we have applied these advanced imaging techniques in over 4700 research and clinical exams. This has been a truly translational, multidisciplinary research project that has ranged from basic MR development to now routine clinical usage of these magnetic resonance imaging tools in the clinic. In conjunction with GE Healthcare we have developed a commercial MRI/MRSI staging exam (“PROSE”) for prostate cancer patients, and have provided the leadership and training for a NIH funded multi-center trial of this commercial exam (ACRIN 6659). In a number of ongoing grants, we are investigating the ability of combined MRI/MRSI to detect and characterize the extent and aggressiveness of prostate cancer prior to therapy, to improve radiation treatment planning, and to determine it’s ability to detect residual disease early after therapy and predict clinical outcome. Another focus of the UCSF prostate imaging program is the investigation of other imaging sequences that can provide additional functional information within the same MR staging exam. Currently, single-shot fast spin echo diffusion weighted imaging and dynamic contrast enhanced imaging techniques are being optimized and incorporated into a multi-parametric 1 hour prostate MRI/MRSI exam in order to provide the most accurate diagnosis and characterization of prostate cancer in individual patients. We are also currently using multi-parametric in vivo imaging data to target cancer tissues in prostate cancer patients who undergo biopsy and/or radical prostatectomy for prostate cancer. 1H HR-MAS is a non-destructive ex vivo technique that can enhance spectral resolution in spectroscopic examinations of intact biological tissues prior to the pathologic, immunohistochemical and gene micro-array analysis of the same tissue sample. As part of two ongoing NIH grants we are establishing a database correlating metabolic profiles associated with specific prostate tissue types, grades of prostate cancer, response to therapy and to begin correlating pre- and post-therapy metabolic profiles with gene expression profiles. The initial success of this project has resulted in the establishment of the Biomedical NMR lab that I direct. The laboratory houses the 11.7T HR-MAS NMR spectrometer and other equipment necessary to perform the subsequent pathologic and genetic analysis of the ex vivo tissues. This facility has resulted in the expansion of my research program beyond prostate cancer to include; (1) the identification of chemical changes associated with disc degeneration, (2) the identification of metabolic profiles associated with dense breast and breast cancer, and (3) the metabolic profiles associated varying types and grades of brain tumors. A new direction for the UCSF Prostate Imaging Program is the development of high field MR imaging and multi-nuclear (31P and 13C) spectroscopy techniques. One project involves the translation of the 1.5T PROSE package to 3T scanners. There are also several studies investigating the possibilities of multinuclear MRS using the higher sensitivity and spectral resolution associated with the higher field MR scanners (3 and 7T) and the increased sensitivity gained by hyperpolarized NMR spectroscopy of 13C labeled substrates. Specifically, we are using human prostate cell lines cultured with 13C labeled substrates, and transgenic mice injected with 13C labeled substrate to; (1) determine the key 13C labeled metabolites that best identify the presence of prostate cancer and characterize its aggressiveness, and (2) determine the kinetics of incorporation of 13C labels into the key metabolites as well as the T1 and T2 relaxation times of the 13C labeled metabolites. This data will be combined with specialized rf detectors, fast 13C spectroscopic imaging pulse sequences, and data reconstruction and analysis protocols to detect hyperpolarized 13C labeled metabolites in the first clinical trial of the use of hyperpolarized 13C labeled pyruvate to image prostate cancer patients (collaborative effort with GE healthcare).
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