Monday, May 14, 2018

Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience

Dissolution DNP has come a long way.


Cunningham, C.H., et al., Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience. Circ Res, 2016. 119(11): p. 1177-1182.


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 (13)C metabolic magnetic resonance imaging of the human heart. METHODS AND RESULTS: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by (13)C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-(13)C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported </=1 month post procedure. The [1-(13)C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed (13)C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-(13)C]lactate signal appeared both within the chambers and in the myocardium. The mean (13)C image signal:noise ratio was 115 for [1-(13)C]pyruvate, 56 for (13)C-bicarbonate, and 53 for [1-(13)C]lactate. CONCLUSIONS: These results represent the first (13)C images of the human heart. The appearance of (13)C-bicarbonate signal after administration of hyperpolarized [1-(13)C]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.