Multi-coil multi-nuclear add-on system for clinical field strength NMR-based biomarker detection for Duchenne Muscular Dystrophy

摘要 核磁共振为生物标志物检测提供了既定的优势，但尚未成为 临床标准在很大程度上是由于在临床场强下检测非1H核缺乏敏感性。 阵列线圈提供了一种自然而实用的方法来提高磁共振实验的灵敏度，并且是 几乎所有的成像应用程序。因此，临床扫描仪通常配备有多个接收器通道 对于1H(成像)，但只有一个能够接收第二核信息的单一宽带接收器通道。 因此，非1H数据的收集仅限于每个原子核的系列研究(长实验时间和变化 研究之间的线圈)，并且不能通过使用阵列线圈来实现更高的灵敏度。这个项目 提出了一种解决临床硬件限制的实用方法，并通过 在杜氏肌营养不良症(DMD)中的应用DMD是一种遗传性疾病，影响约1：5,000名新生儿 男童并导致骨骼和心肌退化，导致青少年丧失行走能力 S在20‘年后期出现心脏/呼吸问题，在第三个十年去世。动物模型在中国的价值 DMD(和所有疾病)的研究已经很成熟，但在这个时候对DMD特别重要，因为 实验疗法的爆炸性发展--分子、细胞和药理学。其中一个 世界上大多数患有肌肉营养不良(GRMD)的金毛猎犬栖息在德克萨斯州 A&M大学--一种被证明优于相关治疗评估的动物模型。这个项目将 展示实现基于核磁共振的临床生物标记物检测的可行性 硬件添加，同时允许以无痛、非侵入性和 在德克萨斯临床前科学研究所(TIPS)进行的DMD研究中，最大限度地减少了狗的麻醉时间。目标 1-设计和构建多调谐射频线圈阵列，用于检测1H、31P和23Na。完成这项工作 AIM将导致设计用于SNR增强的活体核磁共振生物标记物检测的射频线圈，具有最小的 对当前GRMD扫描协议的更改。目标2-构建一个附加的多通道频率 翻译系统，在西门子3T扫描仪上提供多通道多核光谱。 完成这一目标将产生一个模块化系统，直接连接到现有的32通道1H 该接收器将允许从另外两个接收器获取最多16个通道的1H数据和最多8个通道数据 原子核--在这种情况下，是31P和23Na。目标3-从已经表征的现有EX中获得1H-31P-23Na数据 活体保存的肌肉样本。完成这一目标将导致对频率进行初步测试 翻译系统，并将验证基于核磁共振的检测的敏感性和特异性。目标4-在体内获得 来自GRMD疾病模型的1H-31P-23Na数据，作为使用 硬件接口，改装3T扫描仪，实现多核多通道采集。完成 这一目标将证实基于体内核磁共振的生物标记物检测作为临床扫描的一种实用选择的实用性。

SUMMARY Nuclear Magnetic Resonance (NMR) offers established advantages for biomarker detection, but has not become clinically standard largely due to a lack of sensitivity in the detection of non-1H nuclei at clinical field strengths. Array coils offer a natural and practical approach to increase sensitivity in MR experiments, and are standard in nearly all imaging applications. As such, clinical scanners are typically equipped with multiple receiver channels for 1H (imaging), but only a single broadband receiver channel capable of receiving second-nuclei information. Collection of non-1H data is therefore limited to serial studies per nucleus (long experiment times and changing of coils between studies) and cannot achieve increased sensitivity through the use of array coils. This project proposes a practical way to address clinical hardware limitations and validates the utility of the approach with application to Duchenne Muscular Dystrophy (DMD). DMD is a genetic disorder that affects ~1:5,000 newborn boys and causes degeneration of skeletal and cardiac muscle, resulting in a loss of ambulation in the teenage years, cardiac/respiratory issues in the late 20’s, and death in the third decade. The value of animal models in the study of DMD (and all diseases) is well established, but is of particular importance to DMD at this time due to the exploding development of experimental therapies – molecular, cellular, and pharmacologic. One of the most established colonies of golden retrievers with muscular dystrophy (GRMD) in the world resides at Texas A&M University – an animal model proven to be superior for relevant assessment of therapies. This project will show the viability of achieving the benefits of clinical NMR-based biomarker detection with a straightforward hardware addition and simultaneously allow for data collection in a manner that is painless, non-invasive, and minimizes anesthesia time for dogs in DMD studies at the Texas Institute for Preclinical Sciences (TIPS). Aim 1- Design and construct multi-tuned RF coil arrays for detection of 1H, 31P, and 23Na. Completion of this aim will result in RF coils designed for SNR-enhanced in vivo NMR-based biomarker detection with minimal changes to the current GRMD scanning protocol. Aim 2- Build an add-on multi-channel frequency translation system to provide multi-channel multinuclear spectroscopy on the Siemens 3T scanner. Completion of this aim will result in a modular system, straightforwardly interfaced to the existing 32-channel 1H receiver that will allow acquisition of up to 16 channels of 1H data and up to eight channel data from two additional nuclei – in this case, 31P and 23Na. Aim 3- Obtain 1H-31P-23Na data from already-characterized existing ex vivo preserved muscle samples. Completion of this aim will result in the initial testing of the frequency translation system and will verify the sensitivity and specificity of NMR-based detection. Aim 4- Obtain in vivo 1H-31P-23Na data from GRMD disease models as an “add on” procedure to current scans using the hardware interface to modify the 3T scanner for multi-nuclear multi-channel acquisition. Completion of this aim will confirm the utility of in vivo NMR-based biomarker detection as a practical option in clinical scanning.