Dataset Information

Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI.

ABSTRACT: RATIONALE:The recent development of hyperpolarized 13C magnetic resonance spectroscopy has made it possible to measure cellular metabolism in vivo, in real time. OBJECTIVE:By comparing participants with and without type 2 diabetes mellitus (T2DM), we report the first case-control study to use this technique to record changes in cardiac metabolism in the healthy and diseased human heart. METHODS AND RESULTS:Thirteen people with T2DM (glycated hemoglobin, 6.9±1.0%) and 12 age-matched healthy controls underwent assessment of cardiac systolic and diastolic function, myocardial energetics (31P-magnetic resonance spectroscopy), and lipid content (1H-magnetic resonance spectroscopy) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1-13C]pyruvate magnetic resonance spectra were also acquired and in 5 of these participants (3 T2DM, 2 controls), this was successfully repeated 45 minutes after a 75 g oral glucose challenge. Downstream metabolism of [1-13C]pyruvate via PDH (pyruvate dehydrogenase, [13C]bicarbonate), lactate dehydrogenase ([1-13C]lactate), and alanine transaminase ([1-13C]alanine) was assessed. Metabolic flux through cardiac PDH was significantly reduced in the people with T2DM (Fasted: 0.0084±0.0067 [Control] versus 0.0016±0.0014 [T2DM], Fed: 0.0184±0.0109 versus 0.0053±0.0041; P=0.013). In addition, a significant increase in metabolic flux through PDH was observed after the oral glucose challenge (P<0.001). As is characteristic of diabetes mellitus, impaired myocardial energetics, myocardial lipid content, and diastolic function were also demonstrated in the wider study cohort. CONCLUSIONS:This work represents the first demonstration of the ability of hyperpolarized 13C magnetic resonance spectroscopy to noninvasively assess physiological and pathological changes in cardiac metabolism in the human heart. In doing so, we highlight the potential of the technique to detect and quantify metabolic alterations in the setting of cardiovascular disease.

SUBMITTER: Rider OJ

PROVIDER: S-EPMC7077975 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized <sup>13</sup>C MRI.

Rider Oliver J OJ Apps Andrew A Miller Jack J J J JJJJ Lau Justin Y C JYC Lewis Andrew J M AJM Peterzan Mark A MA Dodd Michael S MS Lau Angus Z AZ Trumper Claire C Gallagher Ferdia A FA Grist James T JT Brindle Kevin M KM Neubauer Stefan S Tyler Damian J DJ

Circulation research 20200205 6

<h4>Rationale</h4>The recent development of hyperpolarized <sup>13</sup>C magnetic resonance spectroscopy has made it possible to measure cellular metabolism in vivo, in real time.<h4>Objective</h4>By comparing participants with and without type 2 diabetes mellitus (T2DM), we report the first case-control study to use this technique to record changes in cardiac metabolism in the healthy and diseased human heart.<h4>Methods and results</h4>Thirteen people with T2DM (glycated hemoglobin, 6.9±1.0%) ...[more]

PMID: 32078413

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Project description:BackgroundThe heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy.MethodsWe developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load).ResultsWe demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant.ConclusionsWe demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity.

Dataset Information

Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI.

Publications

Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized <sup>13</sup>C MRI.

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