UCSF researchers test out new scanning technology - ABC news
The accurate characterization of prostate cancer is a major problem in the management of individual prostate cancer patients and in monitoring treatment effects. The UCSF Prostate Imaging Program was established by John Kurhanewicz, PhD and Daniel Vigneron, PhD to address this pressing need. The Prostate Imaging Program is a research program that develops new magnetic resonance imaging methods to improve the assessment of prostate cancer. Kurhanewicz has directed the UCSF prostate imaging program since 1998; the group has applied their advanced imaging techniques in over 6,500 research and clinical exams.
Utilizing Cutting Edge Magnetic Resonance Imaging (MRI) In Patient Care
The Program's translational multidisciplinary research projects range from basic MR development to the implementation of what are now routine usages of magnetic resonance imaging tools in the clinic. The program has developed a commercial multiparametric (MP) magnetic resonance imaging MR staging exam for prostate cancer patients, and with NIH funding is optimizing and clinically validating this exam. This FDA approved non-invasive exam involves a combination of anatomic, metabolic, diffusion and perfusion imaging in order to better detect and characterize prostate cancer in individual patients. Program members are investigating the ability of multiparametric MR: to detect and characterize the extent and aggressiveness of prostate cancer prior to therapy, to improve radiation treatment planning, to detect residual disease early after therapy and to predict clinical outcome.
Developing new Biomarkers of Prostate Cancer presence, aggressiveness and response to therapy
The NIH defines a biomarker as biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. There is a growing amount of published data demonstrating that metabolic biomarkers can significantly improve the clinical assessment of cancer in patients and the development of new biomarkers is a focus of the Prostate Imaging Program. The program uses MP MR data to locate cancer tissues in prostate cancer patients who undergo a biopsy and/or radical prostatectomy. The resulting prostate tissue is then analyzed using a non-destructive spectroscopic technique (1H HR-MAS) that enhances spectral resolution and provide the concentrations of all of the metabolic biomarkers in the prostate tissue. The same tissue can then undergo pathologic, genomic and proteomic analysis providing a unique platform for new biomarker discovery. With NIH funding the program is interested in establishing new biomarkers of cancer aggressiveness and androgen sensitivity as well as companion biomarkers for new therapies. The success of the above biomarker discovery projects has resulted in the establishment of the UCSF Biomedical Nuclear Magnetic Resonance Facility, directed by Dr. Kurhanewicz, dedicated to biomarker discovery and clinical translation.
The Future of MRI of Prostate Cancer
A new direction for the program is the development and clinical translation of an extraordinary new molecular imaging technique utilizing hyperpolarized 13C labeled metabolic substrates that has the potential to revolutionize the way we use MR imaging in the risk assessment of prostate cancer patients. Hyperpolarized (HP) 13C MR is a new molecular imaging technique that allows rapid (seconds) and noninvasive monitoring of dynamic pathway-specific metabolic and physiologic processes. Hyperpolarization, achieved through the dynamic nuclear polarization (DNP) technique, can provide unprecedented gain in sensitivity (10,000 – 100,000 fold increase) for imaging 13C-labeled bio-molecules that are endogenous, nontoxic, and nonradioactive. Metabolically active HP 13C -labeled compounds can be delivered to living systems where the substrate is metabolized and the products can be imaged in real time. The ability to detect down-stream metabolism, specifically the metabolic flux of HP 13C-pyruvate to lactate catalyzed by lactate dehydrogenase (LDH), has shown great potential for not only detecting prostate cancer, but for also assessing the aggressiveness (pathologic grade) of the cancer and response to therapy. The first DNP polarizer for human studies has been sited at UCSF and we have successfully completed the first clinical trial of 13C MR metabolic imaging in patients with prostate cancer. Future trials clinical studies of HP 13C MR in patients with advanced prostate cancer are planned to investigate the clinical value of this technique and new technical developments are underway to allow the assessment of metastatic prostate cancer.
Figure 1. Combined MRI/DTI/3D-MRSI of the prostate at 1.5 T. (A) Axial T2 weighted image and 3D-MRSI spectral grid. The black arrows indicate a region of prostate cancer. (B) Corresponding 3D-MRSI spectral array showing the presence of an aggressive appearing tumor (very elevated choline and reduced citrate) on the left side of the gland (right side of the image). (C) An image of the mean diffusional coefficient of water also demonstrating a region of prostate cancer (black arrows) in the same location as the T2 weighted image and MRSI. Representative spectra taken from the region of healthy prostate tissue and prostate cancer.
We are investigating the role MR imaging, including diffusion weighted imaging and MR spectroscopy, can play in noninvasive assessment of nonalcoholic fatty liver disease (NAFLD) and in changes in the liver and in metabolism due to diet. In particular, we are looking at assessing grades of steatosis and inflammation and the stage of fibrosis in the liver. We have several ongoing studies that include in vivo MR imaging of patients who are going on for a biopsy. In addition to the in vivo MR data, we have clinical and pathological information on these patients, many of whom are part of the UCSF site of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), an NIH, NIDDK funded, multicenter study. We are also obtaining high resolution magic angle spinning (HRMAS) spectroscopy from liver tissue samples to help guide our in vivo efforts. Currently, fatty liver disease is definitively diagnosed and assessed using invasive biopsies. In view of the high population prevalence of NAFLD, a non-invasive mode of distinguishing the relatively benign condition of simple fatty liver (or steatosis) from the more progressive form, Non Alcoholic Steatohepatitis (NASH) would be preferable and very broadly applicable. Our preliminary data shows striking MR differences between normal and diseased patients and among the different grades of steatosis, demonstrating the potential promise of MR for the noninvasive evaluation of fatty liver disease.