Rapid sequential injections of hyperpolarized [1-13C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer
Rapid sequential injections of hyperpolarized [1-13C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer
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DOI：
10.1016/j.mri.2012.09.002
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发表时间：
2013-05-01
影响因子：
2.5
通讯作者：
Vigneron, Daniel B.
中科院分区：
文献类型：
--
作者：
Hu, Simon;Larson, Peder E. Z.;Vigneron, Daniel B.
利用动态核极化(DNP)的超极化技术的发展使得在体内以很高的信噪比快速测量C-13代谢成为可能。然而，使用传统的DNP设备，在动物体内连续注射超极化化合物受到极化建立时间控制的实际最短注射间隔时间的限制，对于[1-C-13]丙酮酸来说，该时间约为一小时。这排除了对在更快的时间尺度上发生的代谢变化的监测。在这项研究中，我们展示了在正常大鼠注射超极化[1-C-13]丙酮酸盐之间间隔5分钟的情况下，使用能够同时极化多达4个样品并快速连续溶解它们的原型亚开尔文动态核偏振器，能够获得体内动态磁共振波谱(MRS)和3D磁共振波谱成像(MRSI)数据。由于多次注射，超极化光谱中的扰动很小，这表明这种方法不会混淆在这个时间尺度上发生的新陈代谢研究。作为应用这项技术和方法监测生理干预后代谢快速变化的初步示范，我们研究了抗癌剂二氯乙酸酯(DCA)的药效学，收集了DCA给药前、给药后1分钟和给药后6分钟的超极化数据。DCA给药后仅1分钟(以及6分钟)，C-13-碳酸氢盐显著增加。(C)2013 Elsevier Inc.保留所有权利。
The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of C-13 metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-C-13]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-C-13]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in C-13-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration. (C) 2013 Elsevier Inc. All rights reserved.