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John Kurhanewicz, PhD
Research Interests
UCSF Prostate Cancer Imaging Program
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, Daniel Vigneron, PhD
and Sarah Nelson, MD to address this pressing need. The Prostate
Imaging Program is a research program that develops new anatomic
and metabolic (MR spectroscopic imaging, MRSI) 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 5,500 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. With GE Healthcare
the Program developed a commercial MRI/MRSI staging exam
(PROSE) for prostate cancer patients, and provided the leadership
and training for a NIH funded multi-center trial to use this
exam (ACRIN 3359) commercialy on patients. Program members
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,
to detect residual disease early after therapy and to predict
clinical outcome. Another focus of the Program is to investigate
imaging sequences that may provide additonal information
during already established MR staging exams. One such example
is the development of single-shot fast spin echo diffusion
weighted imaging and dynamic contrast enhanced imaging techniques
for incorporation into an one-hour multi-parametric prostate
MRI/MRSI exam. If successful the enhanced test will provide
increased accuracy and characterization in diagnosis of prostate
cancer in individual patients.
Developing new Biomarkers of Prostate Cancer presence, aggressiveness
and response to therapy
The NIH
definesa 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 multi parameter imaging 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 establishing a database
of resulting data to correlate metabolic biomarkers with specific: prostate tissue
types, grades of prostate cancer and responses to therapy. The database also
begins correlating pre- and post-therapy metabolic biomarkers with ggenomic and
proteomic biomarkers.
The Future of MRI of Prostate Cancer
New
directions for the UCSF Prostate Imaging Program is the development
of high field MR imaging and multi-nuclear and hyperpolarized
13C spectroscopy techniques. One such research project involves
the translation of the 1.5T PROSE package to 3T scanners. Several
studies are investigating multinuclear MRS using the higher sensitivity
and spectral resolution associated with the higher field MR scanners
(3 and 7T). Another project involves the development and clinical
translation of an extraordinary new 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. 13C labeled substrates have been recently polarized
using dynamic nuclear polarization (DNP) techniques to obtain
tens of thousands fold enhancement of the 13C NMR signals of
the substrate as well as subsequent metabolic products. Through
collaboration with GE Healthcare, the first DNP polarizer for
human studies has been installed at UCSF along with two additional
DNP polarizers for preclinical animal and cell culture studies,
and we have been actively involved in preclinical studies focused
on translating this exciting technology into the clinic.
UCSF High Field Hyperpolarized Nuclear Magnetic
Resonance (NMR) Facility
The initial success
of the above biomarker discovery projects has resulted in
the establishment of the UCSF High Field Hyperpolarized Nuclear
Magnetic Resonance (NMR) Facility. The High Field Hyperpolarized
NMR Facility is located within the UCSF NMR Lab on the Mission
Bay Campus at UCSF occupies 1660 sq. ft. and houses a high
field 500MHz spectrometer and 600MHz imaging NMR spectrometers
that are uniquely integrated with a HyperSense™ (Oxford
Instruments) DNP polarizer. These instruments are dedicated
to running biomedical samples and have complimentary features,
including; high-resolution magic angle spinning (HR-MAS)
spectroscopy, multi-nuclear and hyperpolarized 13C spectroscopy
and micro-imaging capabilities. These instruments will
provide a platform for biomarker discovery and model systems
to better understand the the mechanisms involved in cancer
evolution, progression and response to therapy.
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