Non-invasive phenotyping of muscle function using multi-nuclear MR

牛津大学生理、解剖和遗传学系（DPAG）和拉德克利夫医学系（RDM） | RAPID Biomedical GmbHBBSRC主题：衰老过程中线粒体功能下降，导致肌肉功能退化、虚弱和晚年残疾，以及由此导致的从疾病和受伤中恢复的能力下降，对老年人的生活质量和寿命构成严重负担。运动项目，特别是那些包括功能训练的项目，经常被推荐用于预防和延缓晚年残疾，但它们往往没有效果，必须尝试几种不同的运动项目/生活方式干预。这种偶发系统通常会让人非常沮丧。提高老年人生活质量的锻炼计划之所以无效，很可能是因为我们对肌肉代谢相关的生活规律的理解有限。利用目前可用的磁共振技术，我们最近能够证明，尽管老年人的总体活动水平与年轻志愿者相似，但运动期间肌肉肌肽水平和代谢通量受到的损害尤其严重。为了评估肌糖原，需要开发一种新的变革性技术。这种专用的三调谐射频（RF）线圈将能够在三个不同的频率（每个核一个）激发和采集MR信号。RAPID Biomedical GmbH是专用非氢射频线圈设计和制造的市场领导者，有几家磁共振制造商提供RAPID射频线圈作为新磁共振系统采购的标准。然而，设计一个三调谐线圈并非易事，因为需要在线圈覆盖、信噪比（SNR）性能和信道耦合之间保持适当的平衡。RAPID射频工程师在设计和测试非氢射频线圈方面的丰富经验对于学生设计高效的三调谐线圈是非常宝贵的。这种培训将特别有助于他们克服多核线圈设计和安全测试的障碍。反过来，一旦构建出具有良好覆盖、无耦合和良好信噪比的高效三调谐线圈，它将用于令人兴奋的代谢研究，该公司也将能够提供三调谐线圈作为潜在的盈利产品。因此，本跨学科项目的目标是：1)设计并构建一个高效的三调谐射频线圈，用于全面的肌肉代谢评估。2)一组参加锻炼计划的老年参与者的肌肉代谢表型，并寻找他们的肌肉表型与干预结果之间的潜在关联。无创定义肌肉代谢表型的能力最终将使我们能够将个体与最有益的生活方式干预相结合，为健康老龄化做出重大贡献。这项工作的受益者包括研究衰老过程中骨骼肌代谢生理变化的更广泛的研究人员。越来越多的研究机构对肌肉代谢的生理和临床研究感兴趣。根据计划，本研究的成果将通过同行评议期刊的出版物、国际研究会议的报告以及学术和非学术机构的内部报告进行交流。

University of Oxford Department of Physiology, Anatomy & Genetics (DPAG) & Radcliffe Department of Medicine (RDM) | RAPID Biomedical GmbHBBSRC themes: Understanding the rules of life / Transformative technologies / Bioscience for an integrated understanding of healthDecline in mitochondrial function during ageing, leading to muscle function deterioration, frailty and late-life disability, as well as associated reduction in the ability to recover from illness and injury, constitutes a severe burden on the quality and length of life of the elderly. Exercise programs, in particular those including functional training, are often recommended for preventing and delaying late-life disability, but they often do not yield benefits, and several different exercise programme/lifestyle interventions have to be tried. This hit-and-miss system is often very discouraging. The ineffectiveness of exercise programmes to improve quality of life in older age is likely caused by our limited understanding of the rules of life connected to muscle metabolism.Using currently available MR technology, we were able to recently show that muscle carnosine levels and metabolic fluxes during exercise are particularly impaired in the elderly population even though their overall activity levels were similar to those of younger volunteers. To assess muscle glycogen as well, a novel transformative technology needs to be developed. Such dedicated triple tuned radio-frequency (RF) coil will be capable of excitation and acquisition of MR signal at three different frequencies (one for each nucleus). RAPID Biomedical GmbH is the market leader for the design and construction of dedicated non-hydrogen RF coils, with several MR manufacturers offering RAPID RF coils as a standard with a new MR system purchase. Still, designing a triple tuned coil is not trivial, as a proper balance between coil coverage, signal-to-noise ratio (SNR) performance and channel coupling needs to be maintained. The rich experience of the RAPID RF engineers with the design and testing of non-hydrogen RF coils will be invaluable for the student when designing an efficient triple tuned coil. This training will particularly help them overcome the obstacles of multi-nuclear coil design and safety testing. In turn, once an efficient triple-tuned coil with good coverage, no coupling and good SNR is constructed, it will be used in an exciting metabolic study, the company will also be able to offer triple tuned coils as a potentially profitable product.Therefore, the objectives of this interdisciplinary project are: 1) Design and construct an efficient triple tuned RF coil for comprehensive muscle metabolism assessment. 2) Phenotype muscle metabolism in a group of elderly participants enrolled to an exercise programme and look for potential association between their muscle phenotype and the intervention outcome.The ability to non-invasively define a muscle metabolism phenotype will ultimately allow us to pair individuals with the most beneficial lifestyle interventions, significantly contributing towards healthy ageing.Beneficiaries of this work include the wider community of researchers investigating the physiological changes of skeletal muscle metabolism during ageing. There is a growing number of research sites interested in physiological and clinical studies of muscle metabolism.It is planned and can be expected that the outcomes of this research will be communicated via publications in peer reviewed journals, through presentations at international research conferences, and through internal presentations within academic and non-academic institutes.