Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1‐¹³C]pyruvate study

Abstract

Cardiac metabolism has received considerable attention in terms of both diagnostics and prognostics, as well as a novel target for treatment. As human trials involving hyperpolarized magnetic resonance in the heart are imminent, we sought to evaluate the general feasibility of detection of an imposed shift in metabolic substrate utilization during metabolic modulation with glucose-insulin-potassium (GIK) infusion, and thus the limitations associated with this strategy, in a large animal model resembling human physiology. Four [1- C]pyruvate injections did not alter the blood pressure or ejection fraction over 180 min. Hyperpolarized [1- C]pyruvate conversion showed a generally high reproducibility, with intraclass correlation coefficients between the baseline measurements at 0 and 30 min as follows: lactate to pyruvate, 0.85; alanine to pyruvate, 1.00; bicarbonate to pyruvate, 0.83. This study demonstrates that hyperpolarized [1- C]pyruvate imaging is a feasible technique for cardiac studies and shows a generally high reproducibility in fasted large animals. GIK infusion increases the metabolic conversion of pyruvate to its metabolic derivatives lactate, alanine and bicarbonate, but with increased variability.

Overestimation of cardiac lactate production caused by liver metabolism of hyperpolarized [1‐13C]pyruvate

“…Dissolution dynamic nuclear polarization is a promising tool to study cardiac metabolism in vivo and in real time . It has been successfully applied to study cardiac pathologies in preclinical models and is currently being translated to human applications…”

Hyperpolarized [1‐13C]pyruvate MRI can image the metabolic shift in cardiac metabolism between the fasted and fed state in a porcine model

“…Of the 13 fasted pigs, 9 have been presented previously, as well as the 5 fed pigs, to characterize dynamic changes in response to interventions. In the present study, only baseline data are presented.…”

“…Whereas fasting has been used to standardize metabolism between subjects, the fasted state challenges signal‐to‐noise ratio (SNR) because glucose utilization in the heart is minimal, causing low signal intensity and poor image quality in [1‐ 13 C]pyruvate‐reliant studies. Several methods to counteract low SNR have been applied in porcine and human studies, among them an oral glucose load preceding examination and intravenous (IV) infusion of glucose‐insulin‐potassium (GIK) solution . However, although these approaches may help to standardize subjects, they are unphysiological in nature and will not aid in the study of subjects’ habitual metabolism.…”

Acute hypertensive stress imaged by cardiac hyperpolarized [1‐13C]pyruvate magnetic resonance

“…Reconstruction of the 13 C data was conducted as previously described . Data in the form of DICOM images were analyzed in OsiriX MD version 7.0.1 (Pixmeo SARL, Bernex, Switzerland).…”

“…Scan parameters were as follows: 13 C IDEAL spiral sequence 15 : 1 excitation for a spectrum covering the image slice, 11 excitations per image, inter-echo delay 5 1.5 ms, 4 excitations per heart phase, eight frames in total per injection, TE 5 1.1 ms, TR 5 100 ms, bandwidth 5 125,000 Hz, number of spectral points 5 8192, gradient strength 5 40 mT/m, slew rate 5 150 mT/m/ms, flip angle (FA) 5 15 8, matrix 5 60 3 60, FOV 5 150 3 150 mm 2 , in-plane resolution 5 2.5 mm, slice thickness 5 50 mm, total scan time 25-30 s. CINE-LV function: TE 5 1 ms, TR 5 2.9 ms, FA 5 35 8, matrix 5 292 3 292, FOV 5 200 3 200 mm 2 , in-plane resolution 5 0.7 mm and slice thickness 5 8 mm. All scans were electrocardiograph triggered to the diastolic phase and performed during breath-hold, and the single slice was placed mid-ventricular.…”