Clinical implications of cardiac hyperpolarized magnetic resonance imaging

Abstract

Alterations in cardiac metabolism are now considered a cause, rather than a result, of cardiac disease. Although magnetic resonance spectroscopy has allowed investigation of myocardial energetics, the inherently low sensitivity of the technique has limited its clinical application in the study of cardiac metabolism. The development of a novel hyperpolarization technique, based on the process of dynamic nuclear polarization, when combined with the metabolic tracers [1-(13)C] and [2-(13)C] pyruvate, has resulted in significant advances in the understanding of real time myocardial metabolism in the normal and diseased heart in vivo. This review focuses on the changes in myocardial substrate selection and downstream metabolism of hyperpolarized 13C labelled pyruvate that have been shown in diabetes, ischaemic heart disease, cardiac hypertrophy and heart failure in animal models of disease and how these could translate into clinical practice with the advent of clinical grade hyperpolarizer systems.

Figures

Figure 1

The DNP process. (A) Tracer Sample (13C pyruvate in this example) is placed in a strong magnetic field with a radical source of electrons (B). The sample is cooled to very low temperatures (C) resulting in high electron polarization. Microwaves are used to transfer the spin polarization from electrons to the tracer (D). The tracer is rapidly melted for injection (E).

Figure 2

Metabolic pathways interrogated according to 13C labelled position, blue C2 position, red C1 position. (A) [1-13C]pyruvate spectrum showing conversion to lactate, pyruvate hydrate, alanine and bicarbonate and (B) Example spectra acquired in the first 60s following [2-13C]pyruvate infusion in the in vivo rat heart. [2-13C]pyruvate is observed at 207.8 ppm. Peaks from (1) [5-13C]glutamate, (2) [1-13C]citrate, (3) [1-13C]acetylcarnitine, (4) [1-13C]pyruvate, (5) [2-13C]lactate & (6) [2-13C]alanine can be seen.

Figure 3

Dual-gated short axis images in an animal exhibiting infarcted myocardium following 60-min LAD occlusion. Images are shown at baseline, 45-min post-reperfusion, and 1-week post-reperfusion of the occluded artery. The color scale represents the image intensity, normalized by the maximum LV pyruvate signal intensity. Delayed enhancement revealed an enhancing anteroseptal infarct near the apex (arrows). Anteroseptal akinesis was present at the 45-min time point, persisting at 1 week. Apparent PDH flux in the bicarbonate images was reduced at 45 min, remaining suppressed at 1 week. A defect in myocardial lactate signal was observed in the infarct region (arrows), with elevated lactate in the peri-infarct region. (Reproduced with permission Magn Reson Med. 2013 Apr;69(4 ):1063–71).

Figure 4

Hyperpolarized [1-13C]pyruvate CMR showing alterations to pyruvate dehydrogenase complex (PDC) flux and [13C]lactate production with the pathogenesis of dilated cardiomyopathy (DCM). (A) Representative pyruvate (Pyr, top), bicarbonate (Bic, middle), and lactate (Lac, bottom) 13C CMR images taken from the same pig and at weekly intervals during the pacing protocol, until DCM developed. The images displayed for each metabolite were selected from the same, mid-papillary slice and in the same respiratory cycle. Signal intensity in the pyruvate image was scaled based on 15–100% of the maximum pyruvate signal at week 0, whereas the bicarbonate and lactate signal intensities were scaled based on 15–100% of the maximum bicarbonate signal intensity at week 0. (B) Relative changes to PDC flux with DCM in five pigs.(Reproduced with permission Eur J Heart Fail. 2013 February; 15(2): 130–140).