title: Simple and effective exercise design for assessing in vivo mitochondrial function in clinical applications using (31)P magnetic resonance spectroscopy.
abstract: 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.
authors.affiliation: Wolfson Brain Imaging Centre, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.|National Institute for Health Research/Wellcome Trust Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Sleigh
authors.affiliation: Wolfson Brain Imaging Centre, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Lupson
authors.affiliation: Department of Paediatrics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
authors.forename: Ajay
authors.initials: A
authors.lastname: Thankamony
authors.affiliation: Department of Paediatrics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, CB2 0QQ, UK.
authors.forename: David B
authors.initials: DB
authors.lastname: Savage
authors.affiliation: Wolfson Brain Imaging Centre, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
authors.forename: T Adrian
authors.initials: TA
authors.lastname: Carpenter
authors.affiliation: Magnetic Resonance &Image Analysis Research Centre, Department of Musculoskeletal Biology and MRC - Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing, University of Liverpool, Liverpool, L69 3GE, UK.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Kemp
mesh_terms: D000328:Adult; D000842:Ankle / Q000502:physiology; D019992:Databases as Topic; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008060:Lipodystrophy / Q000175:diagnosis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D010725:Phosphocreatine; D010758:Phosphorus