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Simple and effective exercise design for assessing in vivo mitochondrial function in clinical applications using (31)P magnetic resonance spectroscopy.

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Sleigh, Alison 
Lupson, Victoria 
Thankamony, Ajay 
Dunger, David B 
Savage, David B 


The growing recognition of diseases associated with dysfunction of mitochondria poses an urgent need for simple measures of mitochondrial function. Assessment of the kinetics of replenishment of the phosphocreatine pool after exercise using (31)P magnetic resonance spectroscopy can provide an in vivo measure of mitochondrial function; however, the wider application of this technique appears limited by complex or expensive MR-compatible exercise equipment and protocols not easily tolerated by frail participants or those with reduced mental capacity. Here we describe a novel in-scanner exercise method which is patient-focused, inexpensive, remarkably simple and highly portable. The device exploits an MR-compatible high-density material (BaSO4) to form a weight which is attached directly to the ankle, and a one-minute dynamic knee extension protocol produced highly reproducible measurements of post-exercise PCr recovery kinetics in both healthy subjects and patients. As sophisticated exercise equipment is unnecessary for this measurement, our extremely simple design provides an effective and easy-to-implement apparatus that is readily translatable across sites. Its design, being tailored to the needs of the patient, makes it particularly well suited to clinical applications, and we argue the potential of this method for investigating in vivo mitochondrial function in new cohorts of growing clinical interest.



Adult, Ankle, Databases as Topic, Exercise, Female, Humans, Hydrogen-Ion Concentration, Lipodystrophy, Magnetic Resonance Spectroscopy, Male, Mitochondria, Phosphocreatine, Phosphorus, Reproducibility of Results

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Springer Science and Business Media LLC
Medical Research Council (G0701532)
Medical Research Council (G0600717)
Wellcome Trust (091551/Z/10/A)
Wellcome Trust (107064/Z/15/Z)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0600717/1)
We are grateful to all the participants. This work was funded by the Clinical Research Infrastructure Grant. We thank the National Institute for Health Research (NIHR) Cambridge BioResource and S. Nutland, for facilitating the recruitment of the 24 BioResource volunteers. We thank the NIHR Cambridge Biomedical Research Centre for funding the BioResource and we also acknowledge research grants from Addenbrooke's Charitable Trust and the British Society for Pediatric Endocrinology and Diabetes. D.B.S. is supported by the Wellcome Trust [091551] and the U.K. National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. A.S. and the Siemens MAGNETOM 3T Verio scanner are funded by the NIHR via an award to the Cambridge NIHR/Wellcome Trust Clinical Research Facility. A.T. and D.B.D. are supported by the U.K. NIHR Cambridge Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.