Cardiac Metabolism in a Pig Model of Ischemia–Reperfusion by Cardiac Magnetic Resonance with Hyperpolarized 13C-Pyruvate

Abstract

Background: Magnetic resonance (MRI) with hyperpolarized 13 C-pyruvate is a new technique for the assessment of myocardial metabolism. Aims: The aim of this study is to assess the effectiveness of MRI with hyperpolarized 13 C-pyruvate to detect cardiac metabolic changes in a model of ischemia/reperfusion. Methods: A pneumatic occluder was placed around the left anterior descending artery in 7 pigs. A 3 T scanner with a 13 C quadrature birdcage coil was used. Hyperpolarized 13 C-pyruvate was injected intravenously at rest, during coronary occlusion and 5 min after reperfusion. Metabolic images were acquired using a 3D-IDEAL spiral CSI during the injection of 13 C-pyruvate and 3D-parametric maps of 13 C-pyruvate, 13 C-lactate and 13 Cbicarbonate were generated. Metabolic Activity Mismatch (MAM) was defined as the relative change between a) resting state and coronary occlusion or b) resting and reperfusion in all the myocardial segments. Results: During occlusion, a decrease in 13 C-lactate (− 21 ± 26% vs baseline 3 ± 16%, P b 0.0001) and 13 Cbicarbonate (− 29 ± 34% vs 33 ± 52%, P b 0.0001) was found in myocardial segments at risk, as compared with remote segments. In ischemic segments, the 13 C-lactate signal increased during reperfusion (20 ± 42% vs −7 ± 22%, P = 0.0007), while 13 C-bicarbonate was persistently reduced (−38 ± 27% vs 36 ± 51%, p b 0.0001).Conclusions: 13 C-pyruvate MRI is able to detect transient changes in regional metabolism in an in-vivo model of myocardial ischemia-reperfusion.Magnetic resonance (MRI) with hyperpolarized 13C-labeled tracers is an emerging imaging technique for the evaluation of coronary artery anatomy, quantification of myocardial perfusion and a direct assessment of myocardial viability [1]. In particular, MRI with hyperpolarized 13C-pyruvate has allowed, for the first time, to evaluate cardiac metabolism in real time and in vivo [2][3][4]. Relative changes of pyruvate and of its metabolites lactate, alanine and bicarbonate can be monitored under normal conditions, during either acute ischemia or reperfusion, following short-or long-lasting coronary occlusion [5]. Differently from PET where FDG is not metabolized by myocites, the main advantage of hyperpolarized 13C-pyruvate MRI is that the metabolic fate of 13C-pyruvate and its metabolites is directly assessed. A recent study using hyperpolarized 13C-pyruvate showed increased levels of 13C-lactate after 10 min of global ischemia in isolated hearts [6]. Golman et al. combined conventional MRI scan and H13C by a single short-axis slice of chemical shift images (CSI) in a pig model of ischemia-reperfusion, demonstrating decreased 13C-bicarbonate production in stunned viable myocardial segments, after 15-minute coronary occlusion, and decreased 13C-bicarbonate and 13C-alanine production after 45-minute occlusion [7]. Recently, Lau et al. proposed a three-dimensional multislice cardiac-gated spiral 13C imaging approach, permitting wholeheart coverage [8]. A novel fast three-dimensional acquisition (3D IDEAL, Iterative DEcompositio...

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…”

“…Dissolution dynamic nuclear polarization 1 is a promising tool to study cardiac metabolism in vivo and in real time. 2 It has been successfully applied to study cardiac pathologies in preclinical models [3][4][5][6][7][8][9][10] and is currently being translated to human applications. 11 Spectroscopic acquisitions of hyperpolarized signals have been used in several studies [3][4][5]8,10 because of their simple implementation and robustness against frequency offsets.…”

“…Following injection, [1-13 C]pyruvate is processed by three main enzymes-lactate dehydrogenase, alanine transaminase, and pyruvate dehydrogenase-resulting in detectable resonances of [1-13 C]lactate, [1][2][3][4][5][6][7][8][9][10][11][12][13] C]alanine and 13 CO 2 , which is in rapid equilibrium with [ 13 C] bicarbonate. 12,13 The liver has been shown to produce relatively high amounts of [1-13 C]lactate from hyperpolarized [1-13 C]pyruvate.…”

“…The objective of the present work was to study the contribution of liver [1-13 C]lactate to the lactate signal detected in the heart following injection of hyperpolarized [1-13 C]pyruvate. To this end, a presaturation scheme was implemented that enables selective saturation of [1][2][3][4][5][6][7][8][9][10][11][12][13] C]lactate in the liver as part of a sequence that interleaves spectroscopy and metabolic imaging of the heart.…”

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

“…In principle any small molecular probe can be hyperpolarized as long as they contain a nuclear spin, typically 13 C2021. Currently there is an large array of commercial available hyperpolarized of 13 C-labeled molecules which have been utilized in many different animal models of cancer2223, myocardial ischemia242526 and renal diseases27282930, and more recently in patients and healthy volunteers3132 Additionally, [1,4- 13 C]fumarate has been shown to be a reliable imaging biomarker for monitoring cellular necrosis33 in a rat model of xenograft tumors and subsequently in a rat model with folic acid-induced AKI34. These previous results showed an increased 13 C-malate signal in kidneys with progressive tubular necrosis.…”