The University of Pennsylvania seeks to acquire a HyperSense instrument for enhancing the magnetization of heteronuclei. HyperSense, manufactured by Oxford Instruments, is an instrument which uses Dynamic Nuclear Polarization (DNP) to increase the magnetization of a sample prior to a magnetic resonance experiment. Using this system, it is possible to amplify the signal-to-noise ratio of 1D NMR spectra by a factor of up to 10,000. Due to this extraordinary signal-to-noise enhancement, this product opens up qualitatively new areas of research, potentially revolutionizing the field of routine NMR spectroscopy. Furthermore, it is straightforward to extrapolate this concept and its potential to MR imaging. This unique and modular instrument may be used with any current conventional NMR system to produce polarization-enhanced samples for liquid state NMR. The samples obtained in this fashion are then portable to MRI applications. A variety of target molecules with central energy metabolism, signaling, and biosynthesis roles have been successfully hyperpolarized through the DNP technique. The proposed instrument will facilitate basic research in physiology, cancer, and diabetes. The HyperSense polarizer is a general purpose instrument and could be used to polarize many other important compounds such as fatty acids and amino acids. The proposed instrument is dedicated 100% to research, and it will be used by investigators from the University of Pennsylvania, Children's Hospital of Philadelphia, Fox Chase Cancer Center, and Thomas Jefferson University. It will significantly enhance ten major user programs with Principal Investigators who are supported by twenty-three NIH grants. The ten programs include (i) evaluation of 15N-labeled compounds as tracers of pulmonary perfusion and inflammation, (ii) a study of metabolism of phenylacetate and phenylbutyrate in cancer cells aimed at understanding how these two compounds inhibit cancer proliferation, (iii) a study of pancreatic beta cells to further understand their role in diabetes, (iv) in vitro measurements of metabolic pathways in human glioma cells with the goal of understanding the changes which enable rapid cell proliferation, (v) a study of the potential of hyperpolarized ammonium as a probe of glutamine synthetase activity, (vi) a feasibility study concerning the use of hyperpolarized tracers to detect ovarian cancer in a murine model, (vii) evaluation of whether hyperpolarized tracers may be used to identify pancreatic cancer xenografts in mice, (viii) measurements of the TCA cycle flux in healthy and defective murine and human islet cells, (ix) a study, using a rat model, of methods for sensitizing human melanoma to hyperthermia and chemotherapy, and (x) the initiatives supported by the Small-Animal Imaging Resource (SAIR) at the University of Pennsylvania.
Hyperpolarized carbon-13 MR imaging and spectroscopy have the potential to reveal metabolic processes in healthy and diseased organs with an unprecedented sensitivity. Important clinical applications include diagnosis of tumors and other cancer cells, more rapid monitoring of response to therapy, and research into diabetes and other physiological disorders.
