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

牛津大学生理学、解剖学和遗传学系(DPAG)和拉德克利夫医学系(RDM)|RAPID Biomedical GmbHBBSRC主题：了解生命规则/变革技术/生物科学以综合了解健康状况，衰老过程中线粒体功能下降，导致肌肉功能恶化、虚弱和晚年残疾，以及相关的疾病和损伤恢复能力下降，对老年人的生活质量和寿命构成严重负担。运动方案，特别是包括功能训练在内的运动方案，经常被推荐用于预防和延缓晚年残疾，但它们往往不能产生好处，必须尝试几种不同的运动方案/生活方式干预措施。这种三思而后行的系统往往非常令人沮丧。运动计划对提高老年人生活质量的效果不佳，可能是因为我们对与肌肉新陈代谢有关的生命规则的了解有限。利用目前可用的磁共振技术，我们最近能够证明，在运动过程中，老年人的肌肉肌肽水平和代谢流尤其受损，尽管他们的整体活动水平与年轻志愿者相似。为了同样评估肌肉糖原，需要开发一种新的变革性技术。这种专用的三重调谐射频(RF)线圈将能够以三种不同的频率(每个原子核一个)激励和获取MR信号。Rapid Biomedical GmbH是设计和制造专用非氢射频线圈的市场领先者，有几家磁共振制造商购买了新的磁共振系统，将快速射频线圈作为标准提供。尽管如此，设计三重调谐线圈并不是一件容易的事，因为需要在线圈覆盖、信噪比(SNR)性能和通道耦合之间保持适当的平衡。快速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在设计高效的三重调谐线圈时将是无价的。这次培训将特别帮助他们克服多核线圈设计和安全测试的障碍。反过来，一旦一个具有良好覆盖率、无耦合和良好信噪比的高效三调谐线圈被构建出来，它将被用于令人兴奋的代谢研究，该公司还将能够提供三调谐线圈作为潜在的有利可图的产品。因此，这个跨学科项目的目标是：1)设计和构建一个用于全面肌肉代谢评估的高效三调谐射频线圈。2)参加锻炼计划的一组老年参与者的表型肌肉代谢，并寻找他们的肌肉表型和干预结果之间的潜在联系。非侵入性定义肌肉代谢表型的能力最终将使我们能够将个人与最有益的生活方式干预配对，对健康老龄化做出显著贡献。这项工作的好处包括更广泛的研究人员社区，他们调查衰老期间骨骼肌代谢的生理变化。越来越多的研究站点对肌肉代谢的生理和临床研究感兴趣。计划并可以预期的是，这项研究的结果将通过同行评议期刊上的出版物、国际研究会议上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.