PROJECT SUMMARY/ABSTRACT The overall goal of this Hyperpolarized MRI Technology Resource Center (HMTRC) renewal project is to develop and disseminate optimal new hyperpolarized (HP) 13C MR technologies with requisite training/documentation to advance significantly this emerging molecular imaging method driven push-pull by 13 Collaborative Projects (10 extramural). Through numerous preclinical and clinical research studies to date, it has become clear both that HP 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) require specialized developments to realize their full potential. These new technologies, driven “push-pull” by the CPs, will be developed through three Technology Research & Development (TRD) projects and provided to 12 Service Projects (10 extramural) to benefit their funded research and disseminated widely to the general scientific community. TRD1 focuses on technology development for polarizer and RF detector/exciter instrumentation. TRD2 will develop novel HP MR molecular imaging probes tested in realistic preclinical models and correlative science studies. TRD3 will develop new HP C-13 MR acquisition and free, open-source analysis software for the reconstruction, analysis, and visualization of HP MR data specialized for CP and SP needs. This proposed P41 renewal project was recently reviewed by our External Advisory Committee that is comprised of experts in HP 13C MRI, clinical translation, and CP & SP PI’s. Their report states: “The EAC…is unanimous in their assessment that the HMTRC is high functioning as an NCBIB. The HMTRC has led the nation (and the world) in the development and translation of HP MRI through a unique combination of skills, expertise, instrumentation, environment, clinical engagement, and industry engagement, which simply does not exist elsewhere. The HMTRC will continue to serve as a critical national resource through the next funding cycle as the field of HP MRI expands and matures, particularly with the clinical translation of new HP agents, and more sites engaging in research involving human subjects. The restructured Center benefits from clear and enhanced synergy between all TR&Ds and Collaborative Projects that are more broadly geographically distributed. HMTRC programs for training and dissemination remain outstanding. Progress in the engagement and stimulation of clinical interest is nothing short of remarkable, and crucial for the continuing growth and development of this field.” The current P41 project was designed 5 years ago to focus on preclinical HP 13C MR research, since at that time, human studies were only being conducted at UCSF. However, now that many different sites are conducting clinical research studies with the support of this NCBIB, the new renewal P41 is redesigned to facilitate widespread future clinical trials of HP 13C MRI to address unmet clinical needs.

PROJECT NARRATIVE Hyperpolarized MR is an emerging molecular imaging method to monitor enzymatic conversions through key, previously-inaccessible biochemical pathways. In this renewal project, this center aims to collaboratively develop new technology with broad geographic and scientific diversity to advance this field in order to better identify and understand human disease and to translate and disseminate these techniques for new clinical trials and ultimately improved patient care.