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

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.

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.

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.

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.