Target Audience

This talk is intended for a multi-disciplinary audience of MR physicists with expertise in hardware and software development, alongside biologists and clinicians who seek advanced treatments for diseases that involve energy metabolism.

Outcome/Objectives

The audience of this talk to gain an understanding of the outstanding challenges in the diagnosis and management of metabolic diseases alongside state-of-the-art hyperpolarization methods that may help address these challenges. Hopefully, this multi-disciplinary awareness can spark new collaborations that apply hyperpolarization techniques to help solve clinical problems.

Purpose

An expanding body of research has implicated abnormal energy metabolism as a cause or consequence of heart disease. The purpose of this review is to critically examine how hyperpolarized contrast media, used in combination with MR data acquisition methods, may advance our ability to assess energy metabolism non-invasively and thus improve management of clinical disease. While a wide variety of relevant clinical fields will be mentioned, particular attention will be paid to cardio-renal diseases of oxidative metabolism [1].

Methods

The previous speaker in this session, Dr. Peder Larson, will discuss in detail methods for developing hyperpolarized contrast media and the spectroscopic and imaging approaches necessary to acquire non-invasive, dynamic MR data following the infusion of hyperpolarized tracers. As such, this talk will begin where he left off and discuss the clinical applications for which these techniques may be useful. This talk will introduce how imaging studies of energy metabolism are commonly performed, and analyze how incorporating hyperpolarized contrast media could enable realization of unmet technical needs in clinical practice in the near future.

Results

The talk will first introduce the studies using hyperpolarized 13C-pyruvate and MR that have been published, to illustrate what is necessary for a successful human trial using this technology [2, 3]. We will then discuss clinical trials that are underway and being planned across the globe, and the pre-clinical data that has underpinned the design of these studies. Here, we will focus on 13C-pyruvate as a clinical tracer and also introduce work demonstrating the value of 13C-fumarate [4]. Finally, we will introduce several clinical conditions whose diagnosis or treatment could particularly benefit from the introduction of hyperpolarized 13C MRS and MRI [5, 6]. Thus, the structure of the talk will progress through time, from past to present and future, and shift from emphasis on technical considerations to potential medical application.

Discussion & Conclusions

The maturation of hyperpolarized MR has provided the foundation for new non-invasive methods to measure tissue oxygen metabolism as part of a ‘one-stop shop’ evaluation of organ structure and function. Pre-clinical studies have indicated that by using hyperpolarized tracers with advanced MRI and MRS pulse sequences, it may be possible to measure blood supply and mechanisms of oxidative metabolism rapidly and robustly, with high signal generated by safe contrast. The recent translation of hyperpolarized MR methods into the clinic will hasten the technological refinements and patient research required to cement its role as a clinical tool for assessment of energy metabolism.

Acknowledgements

No acknowledgement found.

References

1. Schroeder, M. and C. Laustsen, Imaging oxygen metabolism with hyperpolarized magnetic resonance: a novel approach for the examination of cardiac and renal function. Biosci Rep, 2017. 37(1). 2. Cunningham, C.H., et al., Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience. Circ Res, 2016. 3. Nelson, S.J., et al., Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate. Sci Transl Med, 2013. 5(198): p. 198ra108. 4. Gallagher, F.A., et al., Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors. Proc Natl Acad Sci U S A, 2009. 106(47): p. 19801-6. 5. Shah, S.J., et al., Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap. Circulation, 2016. 134(1): p. 73-90. 6. Lee, B.K., et al., Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease. Circulation, 2015. 131(12): p. 1054-60.