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Clinical Trial
. 2016 Nov 11;119(11):1177-1182.
doi: 10.1161/CIRCRESAHA.116.309769. Epub 2016 Sep 15.

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

Charles H Cunningham  1 , Justin Y C Lau  2 , Albert P Chen  2 , Benjamin J Geraghty  2 , William J Perks  2 , Idan Roifman  2 , Graham A Wright  2 , Kim A Connelly  2
Affiliations
Clinical Trial

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

Charles H Cunningham et al. Circ Res. .

Abstract

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.

Keywords: heart failure; magnetic resonance imaging; metabolic imaging; metabolism; mitochondria.

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Figures

Figure 1.
Figure 1.
Representative 13C images displayed as color overlays on top of grayscale anatomic images in a midleft ventricle (LV) slice from subject 01(A–C) and subject 03(D–F). The [1-13C]pyruvate substrate was seen mainly in the blood pool within the cardiac chambers (A and D). Flux of pyruvate through the pyruvate dehydrogenase complex is reflected in the 13C-bicarbonate images (B and E), with signal predominantly in the wall of the LV. The [1-13C]lactate signal (C and F) appeared with a diffuse distribution covering the muscle and chambers.
Figure 2.
Figure 2.
Grayscale anatomic (A) and 13C images(B–D) from subject 01 are shown separately with the calculated maximum signal:noise ratio (SNR). A summary of maximum image SNR across the different subjects is shown on the right (E).
Figure 3.
Figure 3.
Representative dynamic 13C spectra acquired using a nonselective excitation pulse from one of the subjects are shown in A and B. The spectrum in B is the sum of the 5 consecutive time points shown in A. Lactate and bicarbonate to pyruvate ratios from the spectroscopic data are shown in C and D, respectively. For the 3 subjects with cardiac-gated spectroscopic acquisitions, the lactate:pyruvate ratios increased over time, whereas the bicarbonate:pyruvate ratios remained relatively stable during the time before the signal:noise ratio became too low for quantification.
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