Development of Novel Radiofrequency coils for Hyperpolarized 13C Magnetic Resonance Imaging

磁共振成像和光谱学（MRI和MRS）通常用于监测心脏结构、功能和能量学，在重复的时间和疾病的进展阶段。MRS非常适合于新陈代谢的研究，因为它可以检测到广泛的化合物，使用碳（13C）和磷（31P）等原子核。然而，MRS在代谢测量中的应用受到固有的低灵敏度的限制。在标准MRI中，水中的高质子浓度（110M）弥补了这种低灵敏度，但对于低浓度和有限天然丰度的原子核，如13C，情况并非如此。使用一种称为超极化磁共振（MR）的新技术可以将MRS检测富含13c的示踪剂的体内灵敏度提高10,000倍以上。通过这种方式，超极化MR能够前所未有地可视化正常和异常代谢，允许实时测量体内瞬时底物摄取和酶转化。牛津大学是世界上第一个开发和使用超极化磁共振来测量啮齿动物心脏病模型体内代谢的学术机构。例如，在糖尿病心脏病的体内模型中，超极化[1-13C]丙酮酸通过心肌丙酮酸脱氢酶的通量的改变，通过13c -碳酸氢盐的产生来评估，已被证明与疾病严重程度相关。这项临床前工作也已转化为临床研究，我们最近获得了人类心脏的第一个动态13C MRS数据。超极化磁共振领域的技术发展已经扩展了该技术，允许从测量信号中生成代谢图像，从而可以识别患病心脏中发生的代谢过程中的空间不均匀性。获取此类代谢图像的最大挑战之一是设计合适的射频（RF）线圈以敏感和均匀地获取数据。该项目的目的是与Pulseteq有限公司合作，开发适用于啮齿动物和人类心脏超极化磁共振成像研究的合适射频线圈。目标是开发合适的发射线圈，以确保射频能量均匀地传递到胸部，并开发敏感的接收线圈，以确保从快速跳动的心脏获得最佳的信号接收。Pulseteq Ltd是一家成熟的射频线圈供应商，用于临床前和临床磁共振应用。他们在设计和制造适用于磁共振成像和多核（即非质子）磁共振光谱应用的线圈方面拥有丰富的经验。他们还拥有将这些线圈与所有主要制造商（例如西门子，飞利浦，GE医疗，安捷伦，布鲁克）制造的MRI系统集成的经验。因此，他们可以很好地为线圈的设计提供适当的指导和输入，以满足超极化磁共振成像在啮齿动物和人类心脏中的应用所带来的独特挑战。心脏成像的独特要求也将为临床前和临床水平的心脏生理学（特别是代谢和灌注）提供坚实的基础。

Magnetic resonance imaging and spectroscopy (MRI and MRS) are routinely used to monitor cardiac structure, function and energetics, at repeated times and progressive stages of disease. MRS is ideally suited to the study of metabolism due to the extensive range of compounds it can detect, using nuclei such as carbon (13C) and phosphorus (31P). However, the application of MRS in the measurement of metabolism is limited by an intrinsically low sensitivity. In standard MRI, the high proton concentration in water (110M) compensates for this low sensitivity, but this is not the case for low concentration and limited natural abundance nuclei, such as 13C.The use of a novel technique called hyperpolarized magnetic resonance (MR) can increase the in vivo sensitivity of MRS to detect 13C-enriched tracers by more than 10,000-fold. In this way, hyperpolarized MR enables unprecedented visualization of normal and abnormal metabolism, allowing real-time measurement of instantaneous substrate uptake and enzymatic transformation in vivo. The University of Oxford was the first academic institution in the world to develop and use hyperpolarized MR to measure in vivo metabolism in rodent models of cardiac disease. For example, alterations in the flux of hyperpolarized [1-13C]pyruvate through myocardial pyruvate dehydrogenase, assessed by the production of 13C-bicarbonate, have been shown to correlate with disease severity in an in vivo model of diabetic heart disease. This preclinical work has also been translated into clinical studies and we have recently acquired the first dynamic 13C MRS data from the human heart.Technical developments in the field of hyperpolarized MR have expanded the technology to allow the generation of metabolic images from the measured signals, which allows the identification the spatial inhomogeneities in the metabolic processes that occur in the diseased heart. One of the greatest challenges in the acquisition of such metabolic images in the design of suitable radio-frequency (RF) coils to sensitively and homogeneously acquire the data. The aim of this project is, in collaboration with Pulseteq Ltd, to develop suitable RF coils for use in both rodent and human hyperpolarized MR imaging studies of the heart. The goal would be to develop appropriate transmit coils to ensure the homogeneous delivery of RF energy over the chest and sensitive receive coils to ensure optimal reception of signals from the rapidly beating heart.Pulseteq Ltd are a well-established supplier of RF coils for both pre-clinical and clinical magnetic resonance applications. They have a wealth of experience in the design and manufacture of coils suitable for both MR imaging and multi-nuclear (i.e. non-proton) MR spectroscopy applications. They also have experience in the integration of such coils with MRI systems made by all the main manufacturers (e.g. Siemens, Philips, GE Healthcare, Agilent, Bruker). They are therefore well placed to provide suitable guidance and input into the design of coils to meet the unique challenges raised by the application of hyperpolarized MR imaging in the rodent and human heart. The unique requirements of imaging the heart will also provide a solid grounding in cardiac physiology (especially metabolism and perfusion) at both the pre-clinical and clinical levels.