First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism

Brian T Chung; Hsin-Yu Chen; Jeremy Gordon; Daniele Mammoli; Renuka Sriram; Adam W Autry; Lydia M Le Page; Myriam M Chaumeil; Peter Shin; James Slater; Chou T Tan; Chris Suszczynski; Susan Chang; Yan Li; Robert A Bok; Sabrina M Ronen; Peder E Z Larson; John Kurhanewicz; Daniel B Vigneron

doi:10.1016/j.jmr.2019.106617

First hyperpolarized [2-¹³C]pyruvate MR studies of human brain metabolism

J Magn Reson. 2019 Dec:309:106617. doi: 10.1016/j.jmr.2019.106617. Epub 2019 Oct 8.

Authors

Brian T Chung¹, Hsin-Yu Chen², Jeremy Gordon², Daniele Mammoli², Renuka Sriram², Adam W Autry², Lydia M Le Page³, Myriam M Chaumeil³, Peter Shin², James Slater², Chou T Tan⁴, Chris Suszczynski⁴, Susan Chang⁵, Yan Li², Robert A Bok², Sabrina M Ronen², Peder E Z Larson², John Kurhanewicz², Daniel B Vigneron²

Affiliations

¹ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; UCSF - UC Berkeley Graduate Program in Bioengineering, University of California, USA. Electronic address: Brian.Chung@ucsf.edu.
² Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA.
³ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94158, USA.
⁴ ISOTEC Stable Isotope Division, MilliporeSigma, Merck KGaA, Miamisburg, OH 45342, USA.
⁵ Department of Medicine, University of California, San Francisco, CA 94158, USA.

Abstract

We developed methods for the preparation of hyperpolarized (HP) sterile [2-¹³C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-¹³C]pyruvate to [2-¹³C]lactate and [5-¹³C]glutamate in the brain of four healthy volunteers. Metabolite kinetics, signal-to-noise (SNR) and area-under-curve (AUC) ratios, and calculated [2-¹³C]pyruvate to [2-¹³C]lactate conversion rates (k_PL) were measured and showed similar but not identical inter-subject values. The k_PL measurements were equivalent with prior human HP [1-¹³C]pyruvate measurements.

Keywords: Brain metabolism; Hyperpolarized C13; Metabolic imaging.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Area Under Curve
Brain / diagnostic imaging
Brain / metabolism*
Brain Chemistry*
Carbon Isotopes
Energy Metabolism
Feasibility Studies
Glutamic Acid / chemistry
Glutamic Acid / metabolism
Healthy Volunteers
Humans
Lactic Acid / chemistry
Lactic Acid / metabolism
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy / methods*
Pyruvic Acid / chemistry
Pyruvic Acid / metabolism*
Signal-To-Noise Ratio
Sterilization

Substances

Carbon Isotopes
Lactic Acid
Glutamic Acid
Pyruvic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding