TR&D1 is responsible for the polarizer instrumentation and the MRI acquisition hardware/software required for all hyperpolarized 13C MRI studies performed in this P41 Center housing five dissolution DNP polarizers. All technology developments are driven by the 10 Collaborative Projects with iterative push-pull optimization and user training. These technology resources are then utilized by the 8 Service Projects (6 extramural) and the general scientific community with feedback on performance, quality of training, and ease of dissemination. In the inaugural funding cycle, TR&D1 oversaw new polarizer installation/development to enable and improve the hyperpolarizations required for all CP's and TR&D's, developed new MR sequences for preclinical studies driven by CP's and TR&D2 needs, and facilitated the first human clinical trial with recent preliminary translation work driven by the new CP's that include future clinical research (CP3,6,9,10). We have also worked closely with TR&D3 personnel to create and test new analysis methods to reconstruct, analyze and visualize the new HP 13C MRI techniques through this project. Also a major focus in the current and proposed renewal project is the training of new users (both intra- & extramural and facilitating the dissemination and widespread use of TR&D1 technology.
Aim 1 : Polarizer Instrumentation Development and Testing. In this aim new DNP/dissolution hardware and methods will be developed for Oxford Instruments HyperSense DNP polarizers, HyperSense Testbed polarizer, the POC polarizer used in the first Phase 1 Clinical Trial, and the GE SpinLab multi-sample polarizer.
Aim 2 : Preclinical HP 13C MRI Technology Development. In vivo hyperpolarized 13C MRI requires specialized hardware and MR sequences for optimal animal studies. Based on extensive preliminary work, Drs. Vigneron's and Larson's groups will develop specialized HP MR sequences optimized for performance, reliability, and ease of use in collaboration with preclinical CP1-8 investigators and Dr. Nelson TR&D3 analysis technique development group.
Aim 3 : New Acquisition Technology for Clinical Translation of HP 13C MRI. Driven by CP projects proposing human studies and with the input of the Translation Advisory Committee, new hardware/software will be developed to enable future novel HP 13C MRI clinical research studies with push-pull iterative optimization.
This aim will also include training, dissemination, and input/feedback from SP3 and other sites proposing future patient HP 13C MRI.

Public Health Relevance

Hyperpolarized MRI using Dynamic Nuclear Polarization (DNP) is a powerful new imaging technique which uses specialized instrumentation to provide signal enhancements of over 5-orders of magnitude for carbon-13 enriched compounds. This project is designed to develop new hardware and acquisition software technology to advance this new imaging method.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB013598-09
Application #
9696833
Study Section
Special Emphasis Panel (ZEB1)
Project Start
Project End
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
9
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Zhu, Xucheng; Gordon, Jeremy W; Bok, Robert A et al. (2018) Dynamic diffusion-weighted hyperpolarized 13 C imaging based on a slice-selective double spin echo sequence for measurements of cellular transport. Magn Reson Med :
Larson, Peder E Z; Chen, Hsin-Yu; Gordon, Jeremy W et al. (2018) Investigation of analysis methods for hyperpolarized 13C-pyruvate metabolic MRI in prostate cancer patients. NMR Biomed 31:e3997
Chen, Hsin-Yu; Larson, Peder E Z; Gordon, Jeremy W et al. (2018) Technique development of 3D dynamic CS-EPSI for hyperpolarized 13 C pyruvate MR molecular imaging of human prostate cancer. Magn Reson Med 80:2062-2072
Milshteyn, Eugene; von Morze, Cornelius; Reed, Galen D et al. (2018) Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized 13C imaging using the bSSFP sequence. J Magn Reson 290:46-59
Milshteyn, Eugene; von Morze, Cornelius; Gordon, Jeremy W et al. (2018) High spatiotemporal resolution bSSFP imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate with spectral suppression of alanine and pyruvate-hydrate. Magn Reson Med 80:1048-1060
von Morze, Cornelius; Reed, Galen D; Larson, Peder E et al. (2018) In vivo hyperpolarization transfer in a clinical MRI scanner. Magn Reson Med 80:480-487
Taglang, CĂ©line; Korenchan, David E; von Morze, Cornelius et al. (2018) Late-stage deuteration of 13C-enriched substrates for T1 prolongation in hyperpolarized 13C MRI. Chem Commun (Camb) 54:5233-5236
Gordon, Jeremy W; Hansen, Rie B; Shin, Peter J et al. (2018) 3D hyperpolarized C-13 EPI with calibrationless parallel imaging. J Magn Reson 289:92-99
Maidens, John; Gordon, Jeremy W; Chen, Hsin-Yu et al. (2018) Spatio-Temporally Constrained Reconstruction for Hyperpolarized Carbon-13 MRI Using Kinetic Models. IEEE Trans Med Imaging 37:2603-2612
Qin, Hecong; Carroll, Valerie N; Sriram, Renuka et al. (2018) Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes. Sci Rep 8:7928

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