Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals.

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals.
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DOI:
10.1002/mrm.27122
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发表时间:
2018-05
影响因子:
3.3
通讯作者:
Comment A
Comment A
中科院分区:
医学3区
文献类型:
--
作者:
Bastiaansen JAM;Yoshihara HAI;Capozzi A;Schwitter J;Gruetter R;Merritt ME;Comment A

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在注射使用光诱导非持久性自由基制备的超极化13 C标记底物混合物后,在体内同时探测碳水化合物和短链脂肪酸的心脏代谢。将混合的[1- 13 C]丁酸和[1- 13 C]丁酸的液滴在液氮中冷冻成玻璃状珠。研究了乙醇添加作为增加极化水平的手段。用紫外(UV)光照射珠粒,并通过ESR光谱测量自由基浓度。在7 T极化器中进行动态核极化(DNP)后,珠子溶解,并将无自由基的超极化溶液迅速转移到位于9.4 T扫描仪内的注射泵中。将超极化溶液注射到健康大鼠体内以测量心脏代谢。紫外线照射产生的非持久性自由基的混合物中含有13 C-标记的维生素C和丁酸,并使超极化的两个基板由DNP。乙醇的加入增加了自由基浓度从16至26 mM。液态13 C极化是3%内的泵在注射时,并增加到5%,通过添加乙醇的基板混合物之前,UV照射。在大鼠心脏中,在体内的13 C信号从乳酸,丙氨酸,碳酸氢盐和乙酰肉毒碱被检测到以下的代谢注射底物混合物。两个13 C-标记的底物和检测他们的心肌代谢在体内的共极化,而不使用持久的自由基。在含有超极化13 C-底物的溶液中不存在自由基可以简化临床应用的转化,因为在注射之前不需要过滤。
To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13C-labeled substrate mixture prepared using photo-induced non-persistent radicals. Droplets of mixed [1-13C]pyruvic and [1-13C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet (UV) light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization (DNP) in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. UV-irradiation created non-persistent radicals in a mixture containing 13C-labeled pyruvic and butyric acids and enabled the hyperpolarization of both substrates by DNP. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to UV irradiation. In the rat heart, the in vivo 13C signals from lactate, alanine, bicarbonate and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Co-polarization of two 13C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13C-substrates may simplify the translation to clinical use because no filtration is required prior to injection.
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发表时间: 2015-10-01
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