Rationale: The recent development of hyperpolarized 13C Magnetic Resonance Spectroscopy (MRS) has made it possible to measure cellular metabolism in vivo, in real time. Objective: By comparing participants with and without type 2 diabetes (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 type 2 diabetes (HbA1c 6.9{plus minus}1.0%) and 12 age-matched healthy controls underwent assessment of cardiac systolic and diastolic function, myocardial energetics (31P-MRS) and lipid content (1H-MRS) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1-13C]pyruvate MR spectra were also acquired and in five of these participants (3 T2DM, 2 controls), this was successfully repeated 45 minutes after a 75g oral glucose challenge. Downstream metabolism of [1-13C]pyruvate via pyruvate dehydrogenase (PDH, [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 type 2 diabetes (Fasted:0.0084{plus minus}0.0067[Control] vs. 0.0016{plus minus}0.0014[T2DM], Fed:0.0184{plus minus}0.0109 vs. 0.0053{plus minus}0.0041, p=.013). In addition, a significant increase in metabolic flux through PDH was observed after the oral glucose challenge (p<.001). As is characteristic of diabetes, 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 MRS to non-invasively 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.

中文翻译：

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使用超极化 13C MRI 对健康和糖尿病人心脏的心脏代谢进行无创体内评估。


理由：超极化 13C 磁共振波谱 (MRS) 的最新发展使得实时测量体内细胞代谢成为可能。目的：通过比较患有和不患有 2 型糖尿病 (T2DM) 的参与者，我们报告了第一项病例对照研究，利用该技术记录健康和患病人类心脏的心脏代谢变化。方法和结果：13 名 2 型糖尿病患者（HbA1c 6.9{+/-}1.0%）和 12 名年龄匹配的健康对照者接受了心脏收缩和舒张功能、心肌能量学 (31P-MRS) 和脂质含量 (1H-MRS) 的评估）在禁食状态下。在一个子集中（5名T2DM，5名对照）中，还获得了超极化[1-13C]丙酮酸MR光谱，并且在其中5名参与者（3名T2DM，2名对照）中，在75克口服葡萄糖挑战后45分钟成功重复了这一过程。评估了[1-13C]丙酮酸通过丙酮酸脱氢酶（PDH，[13C]碳酸氢盐）、乳酸脱氢酶（[1-13C]乳酸）和丙氨酸转氨酶（[1-13C]丙氨酸）的下游代谢。 2 型糖尿病患者通过心脏 PDH 的代谢通量显着降低（空腹：0.0084{plus minus}0.0067[对照] vs. 0.0016{plus minus}0.0014[T2DM]，进食：0.0184{plus minus}0.0109 vs. 0.0053 {加减}0.0041，p=.013)。此外，口服葡萄糖挑战后观察到通过 PDH 的代谢通量显着增加 (p<.001)。作为糖尿病的特征，在更广泛的研究队列中也证实了心肌能量、心肌脂质含量和舒张功能受损。 结论：这项工作首次证明了超极化 13C MRS 无创评估人类心脏代谢生理和病理变化的能力。在此过程中，我们强调了该技术在检测和量化心血管疾病中代谢变化的潜力。