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

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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.