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Investigating Cardiac Metabolism in the Isolated Perfused Mouse Heart with Hyperpolarized [1-13C]Pyruvate and 13C/31P NMR Spectroscopy
Published on: April 21, 2023
Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience
Charles H Cunningham1, Justin Y C Lau2, Albert P Chen2
1From the Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada (C.H.C., J.Y.C.L., B.J.G., G.A.W.); Medical Biophysics, University of Toronto, ON, Canada (C.H.C., J.Y.C.L., B.J.G., G.A.W.); GE Healthcare, Toronto, ON, Canada (A.P.C.); Pharmacy (W.J.P.) and Schulich Heart Program (I.R., G.A.W.), Sunnybrook Health Sciences Centre, Toronto, ON, Canada; and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada (K.A.C). chuck@sri.utoronto.ca.
Rationale:
Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism.
Objective:
To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart.
Methods And Results:
Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1-13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1-13C]lactate.
Conclusions:
These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1-13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology.
Clinical Trial Registration:
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.
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