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）|HBBSRC主题：了解生命规则/变革性技术/生物科学促进对健康的综合理解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，以及从疾病和伤害中恢复的能力下降，对老年人的生活质量和寿命构成严重负担。运动计划，特别是那些包括功能训练，经常被推荐用于预防和延迟晚年残疾，但它们往往不会产生好处，必须尝试几种不同的运动计划/生活方式干预。这种打不中的制度往往令人沮丧。运动计划对提高老年人生活质量的无效性可能是由于我们对与肌肉代谢有关的生活规则的了解有限，我们最近利用现有的MR技术证明，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尤其受损。为了评估肌肉糖原，需要开发一种新的变革技术。这种专用的三重调谐射频（RF）线圈将能够在三个不同频率（每个核一个）下激励和采集MR信号。RAPID Biomedical GmbH是专用非氢RF线圈设计和制造的市场领导者，多家MR制造商提供RAPID RF线圈作为新MR系统采购的标准。尽管如此，设计三重调谐线圈并不简单，因为需要保持线圈覆盖范围、信噪比（SNR）性能和通道耦合之间的适当平衡。RAPID RF工程师在设计和测试非氢RF线圈方面的丰富经验对于设计高效三重调谐线圈的学生来说是非常宝贵的。该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，一旦一个有效的三调谐线圈具有良好的覆盖范围，无耦合和良好的SNR构建，它将被用于一个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一个潜在的有利可图的产品。因此，这个跨学科项目的目标是：1）设计和构建一个有效的三调谐RF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关联。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体与最有益的生活方式干预配对，这项工作的受益者包括更广泛的研究人员社区，他们调查了骨骼肌代谢的生理变化，老化越来越多的研究机构对肌肉代谢的生理学和临床研究感兴趣。计划并可以预期，这项研究的结果将通过同行评审期刊上的出版物，通过国际研究会议上的演讲以及通过学术和非学术机构的内部演讲进行交流。

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.