一个多腔动态单一酶幻影超极化磁共振剂研究的用途
Summary
A multi-compartment dynamic phantom is used to simulate some biology of interest for metabolic studies using hyperpolarized magnet resonance agents.
Abstract
磁共振超极化底物的影像显示在实时关键的生化过程的评估重要的临床前景。由于受超极化状态施加限制的根本，充满异国情调的成像和重建技术是常用的。对于动态的，多光谱成像方法表征一个实用的系统迫切需要。这样的系统必须可重复复述正常和病理组织的相关化学动力学。最广泛使用的基材日期是超极化[1- 13 C]丙酮酸癌症代谢的评估。我们描述了介导丙酮酸至乳酸的转化基于酶的幻象系统。反应通过超极化剂的注入开始到虚线内的多个腔室，其中每一个包含不同的是控制反应速率的试剂的浓度。多个隔室是必要的，以确保伊马蔓茎序列忠实捕获组织的空间和代谢异质性。该系统将通过提供化学动力学所不具备与传统幻影，以及控制和再现那是不可能在体内帮助的先进影像战略的制定和验证。
Introduction
的13 C标记的化合物的超极化的磁共振成像（MRI）的临床影响主要取决于其测量流经实时磁共振光谱学和光谱成像1-5化学转化率的能力。期间顺序开发和验证，动态化学转化一般是通过在体内或体外模型6-9，提供有限的控制和再现性来实现的。对于稳健的测试和质量保证，它保留了化学转化特有的这种测量更多的控制系统将是首选。我们概述实现使用动态单一酶虚线可重复的方式这种转换的方法。
与超极化13 C制剂的研究大多集中于一个正常运作的生物环境成像超极化基板。这是显而易见的选择，如果目标是研究生物人处理或确定在临床护理潜在影响。然而，如果一些测量系统或数据处理算法的表征是期望的，生物模型有许多缺点，如固有的空间和时间变化10。然而，传统的静态幻影缺乏化学转化驱动在超极化基底的MRI主要临床利益，并且不能用于表征转化率或其他动态参数11的检测。使用单一酶系统，我们可以提供可控的和可重复的化学转化，从而实现动态显像策略严格的审查。
该系统是针对谁正在开发的成像策略超极化基板，并希望反对其他方法相比性能特征调查。如果静态测量所需的终结点，然后静13 C-标有代谢幻影无线会足够了11。在另一端，如果更复杂的生物特征是该方法（交货，蜂窝密度等 ）则实际的生物模型，将需要12-14的关键。该系统非常适合的，旨在提供明显的化学转化率的定量测量成像战略评估。
Protocol
Representative Results
Discussion
超极化的代谢物实时成像具有序列设计，验证和质量控制许多独特的挑战。解决时空和光谱异质性的能力提供大量的临床潜力，但是排除了与常规MRI相关的质量保证和验证方法。复杂的成像序列或重建算法可能会有细微的依赖使得它们难以定性或验证成像实验之外。生物的异质性和其它实际问题限制使用的在体内和体外模型来表征或验证序列，硬件或数据处理算法。
<p class…Disclosures
The authors have nothing to disclose.
Acknowledgements
这项工作是由CPRIT补助（RP140021-P5）和朱莉娅·琼斯马修斯癌症研究学者CPRIT研究培训奖（RP140106，CMW）的支持。
Materials
| BioSpect 7T | Bruker | BioSpec 70/30 USR | 7 Tesla Pre-Clinical MRI Scanner |
| HyperSense | Oxford Instruments | Hypersense DNP Polarizer | Dynamic Nuclear Polarizer for MRI agents |
| 1-13C-Pyrvic Acid | Sigma Aldrich | 677175 | Carbon 13 labled neat pyruvic acid |
| Trityl Radical | GE Healthcare | OX063 | Free radical used in Dynamic Nuclear Polarization |
| NaOH | Sigma Aldrich | S8045 | |
| EDTA | Sigma Aldrich | E6758 | Ethylenediaminetetraacetic acid |
| LDH | Worthingthon | LS002755 | Lactate Dehydrogenase from rabbit muscle |
| NADH | Sigma Aldrich | N4505 | β-Nicotinamide adenine dinucleotide, reduced dipotassium salt |
| Trizma | Sigma Aldrich | T7943 | Trizma® Pre-set crystals |
| NaCl | Sigma Aldrich | S7653 |
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