Regional quantification of cardiac metabolism with hyperpolarized [1-13C]-pyruvate MRI evaluated in an oral glucose challenge

Peder E Z Larson; Shuyu Tang; Xiaoxi Liu; Avantika Sinha; Nicholas Dwork; Sanjay Sivalokanathan; Jing Liu; Robert Bok; Karen G Ordovas; James Slater; Jeremy W Gordon; M Roselle Abraham

doi:10.1101/2023.10.16.23297052

Regional quantification of cardiac metabolism with hyperpolarized [1-¹³C]-pyruvate MRI evaluated in an oral glucose challenge

medRxiv [Preprint]. 2023 Oct 19:2023.10.16.23297052. doi: 10.1101/2023.10.16.23297052.

Authors

Peder E Z Larson^{1

2}, Shuyu Tang^{1

2

3}, Xiaoxi Liu¹, Avantika Sinha¹, Nicholas Dwork^{1

4}, Sanjay Sivalokanathan⁵, Jing Liu¹, Robert Bok¹, Karen G Ordovas¹, James Slater¹, Jeremy W Gordon¹, M Roselle Abraham⁶

Affiliations

¹ Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, California, USA.
² UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, California, USA.
³ Vista.ai, Palo Alto, CA, USA.
⁴ Departments of Bioinformatics and Radiology, University of Colorado School of Medicine, Denver, CO, USA.
⁵ Department of Medicine - Division of Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Department of Medicine - Cardiology Division, University of California - San Francisco, San Francisco, California, USA.

Abstract

Background: The heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) ¹³C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP ¹³C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy.

Methods: We developed and applied methods for whole-heart imaging of ¹³C-pyruvate, ¹³C-lactate and ¹³C-bicarbonate, following intravenous administration of [1-¹³C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated ¹³C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load).

Results: We demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6×6×21 mm³ (¹³C-pyruvate) and 12×12×21 mm³ (¹³C-lactate, ¹³C-bicarbonate) . ¹³C-pyruvate and ¹³C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial ¹³C-pyruvate-SNR, ¹³C-lactate-SNR, ¹³C-bicarbonate-SNR, ¹³C-lactate/pyruvate ratio, ¹³C-pyruvate-to-lactate conversion rate, k_PL, and ¹³C-pyruvate-to-bicarbonate conversion rate, k_PB, all had statistically significant increases following oral glucose challenge. k_PB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant.

Conclusions: We demonstrate first-in-human regional quantifications of cardiac metabolism by HP ¹³C-pyruvate MRI that aims to reflect LDH and PDH activity.

Publication types

Preprint

Abstract

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