Hyperpolarized MRI Technology Resource Center: New MRI Technology to Advance Patient Care

Hyperpolarized [1-13C] pyruvate MRI for metabolic assessment of prostate cancer osseous metastases following immune therapy.With funding from the National Institutes for Health, the Hyperpolarized MRI Technology Resource Center (HMTRC) develops and disseminates hyperpolarized (HP) 13C MR techniques and instrumentation, specialized data acquisition methodology and analysis software for biomedical research. Hyperpolarized 13C MRI is an emerging molecular imaging technique that provides unprecedented tissue metabolic information. The overarching goal of the HMTRC is to advance precision molecular imaging and address unmet clinical needs in cancers and various other diseases. Established in 2011, the HMTRC is the quintessential example of our department's vision of Leading Imaging Innovation to Improve Health, and its strategic pillar of Team Science and Moonshot.

Hyperpolarized 13C MRI – a paradigm-shifting molecular imaging technology

Hyperpolarized 13C MRI is an emerging powerful molecular imaging strategy that allows safe, non-radioactive, real time and pathway-specific investigation of dynamic metabolic and physiological processes that were previously inaccessible by imaging. This has been made possible by the recent development of the dynamic nuclear polarization (DNP) technique that can dramatically increase the signal of 13C labeled biomolecules by more than 50,000-fold. This technique has enabled rapid in vivo investigation of metabolism that is central to a variety of diseases, including cancer, cardiovascular disease and metabolic disease of the liver and kidney.

One key advantage of HP 13C technology is the diverse array of probes that can be polarized. The most widely studied HP probe to date is 13C pyruvate, a highly biologically relevant probe as pyruvate lies at a critical branch point of multiple metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle and amino acid biosynthesis. This is the first HP probe that has been translated for clinical metabolic investigations here at UCSF and has been shown to be safe and feasible. There are numerous other HP 13C probes, mainly comprised of endogenous biomolecules, that have shown great promise for investigating physiology and metabolism relevant to human diseases. Examples include probes to measure perfusion, pH, tissue necrosis and redox capacity.

Clinical translation of hyperpolarized 13C MRI to address unmet needs

The Center investigators pioneered many new HP 13C MRI techniques including the first-in-human clinical trial of HP 13C pyruvate MRI showing not only safety and feasibility, but also the ability to detect occult prostate cancer not visualized on standard-of-care MRI. These human studies, reported in 60 publications thus far, have demonstrated the value of this powerful molecular imaging technology to risk stratify disease and monitor response to therapy in cancers as well as other diseases (Figs 1 and 2). For example, quantitative HP 13C pyruvate measures of cellular energy metabolites are significantly increased in aggressive prostate, breast, brain, renal and pancreatic cancers, and decreased with response to therapy.

Looking ahead, a key focus of the HMTRC in the next five years is accelerating the clinical translation of this emerging molecular imaging technology through a close collaboration between basic scientists and clinicians and through strong partnership with industry and government agencies. The projects are designed to have major scientific and clinical impact through novel HP technology development and new multi-site collaborations.

Additionally, a Radiologist Leadership Committee with Robert Flavell, MD, PhD; Michael Ohliger, MD; Javier Villanueva-Meyer, MD; Zhen Jane Wang, MD; and David Wilson, MD, PhD, has been established to lead clinical translation efforts and guide technology development to address unmet clinical needs for cancers of the prostate, brain, kidney and pancreas; traumatic brain injury; liver disease; and cardiac disease. For example, HMTRC investigators are studying HP 13C pyruvate MRI for early response monitoring of prostate cancer metastases following immune therapy (Figure 2), and for evaluating brain metabolism (Figure 3), the alteration of which is implicated in various degenerative brain diseases.

Training and dissemination to increase impact

The HMTRC training and dissemination program already has and will continue to create a national and global impact on the advancement of this technology. This is accomplished through several different approaches. To date, the Center has provided focused hands-on training in equipment, acquisition techniques and analysis software to over 150 individuals including graduate students, post-doctoral fellows, radiology residents and researchers from the Collaborative and Service Projects. Nineteen of these trainees thus far have become faculty at UCSF or at other institutions. Over 60 sites to date have visited the HMTRC to receive hands-on training in the technologies and resources developed by the Center. The training that takes place at the annual HMTRC Workshop (Figure 4) is particularly valuable to the push-pull development of these technologies as they provide training and interactions focused on the technical aspects of HP 13C MR preclinical and translational research and analysis. In addition, protocols, software, regulatory, clinical trial set-up and support are disseminated at these Workshops to provide experience on how this technology is implemented for clinical research.

To enable a broader dissemination of the HP 13C technology developed by the HMTRC, several web-based initiatives have been developed to benefit other researchers, and to enable multi-site studies. For example, despite the COVID-19 pandemic, the Center continues its dissemination effort virtually via the launch of a successful and well-received Hyperpolarized MRI Seminar Series in 2021-22.

In the last year, the Center has also launched a new website (http://hyperpolarizedmri.ucsf.edu) which is a key component in the training and dissemination of tools, resources and technologies developed by the Center. Content on the website includes over 100 "How-to" tutorials and training modules, recorded workshop and HP 13C seminar presentations, with over 12,400 total website views in the year of website launch. This platform for online resources accompanies the dissemination of Center-developed technologies including analysis software, MRI sequences and HP probe preparations. These resources have shown a broad reach in the research community, for example, with over 23,000 software downloads to date.

HMTRC — looking back and looking forward 

The HMTRC was recently reviewed by the External Advisory Committee comprised of experts in the technology. Their review has concluded the following:

"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."

Just as MRI advanced medical imaging by providing information beyond that from CT/X-ray, HP 13C MRI can provide clinically needed metabolic biomarker information beyond what PET and SPECT can, and in a safe, non-radioactive two-minute addition to current MRI exams. Looking forward, the faculty, staff and trainees in the HMTRC are energized by their work in advancing this innovative and powerful technology for improving disease diagnosis and response monitoring, and ultimately advancing patient care.