The overall goal of this P41 center is to disseminate optimal new hyperpolarized (HP) 13C MR technologies with optimal training/documentation to advance significantly this emerging molecular imaging method. Through our HP MR studies to date, it has become clear both that hyperpolarized 13C MR has outstanding research and clinical value, but also that virtually all aspects of this technology (instrumentation, agent chemistry, DNP/dissolution methodology, MR acquisition, and data analysis) are currently suboptimal and require focused technological development to realize their full potential. This center includes three Technology Research & Development (TR&D) projects led by experienced hyperpolarized MR researchers. All TR&D developments are driven in a push-pull manner by 10 independently NIH-funded Collaborative Projects (CP's) and the technology resources of the center will be utilized by 8 Service Projects (SP's) and disseminated to all interested investigators through hands-on workshops, visits, email, and via the HMTRC website. TR&D1, led by the PI Dr. Vigneron, is focused on DNP polarizer and MR acquisition development for pre-clinical animal studies and their translation for future human studies. TR&D2 led by Dr. Kurhanewicz focuses on the development of new robust and realistic pre-clinical models for HP MR studies, optimization of current HP probes & investigation of new HP probes, and the development of methods that provide appropriate correlative pathologic, biologic and other imaging data for understanding and validating HP MR findings. TR&D3 led by Dr. Nelson focuses on enhancing a free open-source specialized software platform for HP MR data reconstruction and visualization. In its first four years, the HMTRC has developed new polarization, MR acquisition, bioreactor, and analysis techniques driven by close interactions with the CP projects resulting in 70 publications and over 150 conference presentations. This BTRC has also spawned/supports currently more than 15 NIH grants including new ones for all 10 proposed CP's. Guided by an exceptional EAC, the HMTRC has created an extensive infrastructure that extends nationally and internationally to support the SP's and other collaborators, a new website, highly successful hands-on workshops, and other focused training and dissemination activities. Since the submission of the current P41, the first Phase 1 clinical trial in prostate cancer patients was conducted and demonstrated safety and feasibility of this emerging molecular imaging technique. Now, four of the Collaborative Projects include future human studies. Therefore we are modifying the structure and goals of the center to not only advance preclinical HP MR, but also to include new technology development, administrative infrastructure, training and dissemination to support and advance future human studies at UCSF and other institutions.

Public Health Relevance

Hyperpolarized MR is a new molecular imaging method to monitor enzymatic conversions through key, previously-inaccessible biochemical pathways. Therefore this center project aims to collaboratively develop new technology to advance this field in order to better identify and understand human disease and ultimately to translate and disseminate these techniques for improved patient care.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB013598-09
Application #
9696830
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Liu, Guoying
Project Start
2011-07-01
Project End
2021-05-31
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
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
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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