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

多线圈多核附加系统，用于杜氏肌营养不良症临床场强 NMR 生物标志物检测

• 批准号: 10552836
• 负责人: Mary Preston McDougall
• 金额: $ 6.84万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10552836
• 关键词: Address; Affect; Anesthesia procedures; Animal Model; Animals; Biological Markers; Biomedical Engineering; Canis familiaris; Cardiac; Cell Nucleus; Cessation of life; Chemicals; Clinical; Collection; Data; Data Collection; Detection; Development; Diagnosis; Disease; Disease model; Duchenne muscular dystrophy; Dystrophin; Electrical Engineering; Engineering; Environment; FDA approved; Frequencies; Genetic Diseases; Image; Institutes; Investigational Therapies; Lead; Link; MRI Scans; Magnetic Resonance Imaging; Metabolic; Modeling; Modification; Molecular; Muscle; Muscular Dystrophies; Myocardium; Newborn Infant; Nuclear Magnetic Resonance; Painless; Patients; Pharmacology; Physiologic pulse; Physiology; Play; Procedures; Proteins; Protocols documentation; RF coil; Reproducibility; Role; Sampling; Scanning; Science; Sensitivity and Specificity; Skeletal Muscle; Spectrum Analysis; System; Techniques; Technology; Teenagers; Testing; Texas; Time; Translations; Universities; Work; base; biomarker identification; boys; clinical imaging; design; design and construction; experience; experimental study; human male; in vivo; instrumentation; magnetic field; mdx mouse; metabolomics; mouse model; muscle metabolism; pre-clinical; preservation; prevent; respiratory; spectroscopic imaging; treatment response

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.

概括 核磁共振（NMR）为生物标志物检测提供了确定的优势，但尚未成为 临床上标准的主要是由于在临床场优势下检测非1H核的敏感性缺乏敏感性。 阵列线圈提供了一种自然而实用的方法来提高MR实验的灵敏度，并且是标准的 几乎所有成像应用。因此，临床扫描仪通常等效于多个接收器通道 对于1H（成像），但只有一个宽带接收器通道能够接收第二核信息。 因此，非1H数据的收集仅限于每个核的串行研究（长实验时间和变化 研究之间的线圈）并且无法通过使用阵列线圈来提高灵敏度。这个项目 提案是一种解决临床硬件限制并通过使用该方法验证方法的实用方法 应用于Duchenne肌肉营养不良（DMD）。 DMD是一种影响〜1：5,000新生儿的遗传疾病 男孩并导致骨骼和心脏肌肉的变性，导致少年失去野蛮 多年来，20年代后期的心脏/呼吸道问题以及第三个十年的死亡。动物模型在 DMD（和所有疾病）的研究已经确定，但此时尤其重要 实验疗法的爆炸开发 - 分子，细胞和药物学。中的一个 德克萨斯州世界住宅中，最成熟的黄金猎犬殖民地具有肌肉营养不良（GRMD） A＆M大学 - 一种动物模型被证明是对疗法的相关评估的优越性。这个项目将 展示实现基于NMR的生物标志物检测的好处的生存能力 增加硬件，只是允许以痛苦，无创和的方式收集数据 在德克萨斯临床前科学研究所的DMD研究中，狗的麻醉时间最小化（TIPS）。目的 1-设计和构造多调整的RF线圈阵列，用于检测1H，31p和23na。完成此操作 AIM将导致RF线圈设计用于基于Vivo NMR的SNR增强的生物标志物检测 更改当前的GRMD扫描协议。目标2-构建附加多通道频率 翻译系统可在西门子3T扫描仪上提供多通道多核光谱。 该目标的完成将导致模块化系统，直接干扰现有的32通道1H 接收器将允许从两个附加的两个渠道获得多达16个渠道的1H数据和多达8个频道数据 核 - 在这种情况下，31p和23na。 AIM 3-从现有的EX获得1H-31P-23NA数据 体内保留的肌肉样品。此目标的完成将导致频率的初始测试 翻译系统，并将验证基于NMR的检测的灵敏度和特异性。目标4-获取体内 GRMD疾病模型的1H-31P-23NA数据是使用该扫描的“添加”程序 硬件接口可修改3T扫描仪以进行多核多渠道采集。完成 该目标将确认基于体内NMR的生物标志物检测的实用性，作为临床扫描中的实际选择。