Simple and effective exercise design for assessing in vivo mitochondrial function in clinical applications using 31P 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 31P 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.

A low-cost Mr compatible ergometer to assess post-exercise phosphocreatine recovery kinetics

“…These values are comparable with those reported in the literature [23, 35–39]. The power output showed high reliability with intra- and inter-exam coefficient of variation of 4.4% and 3.6%, respectively.…”

Impaired skeletal muscle mitochondrial bioenergetics and physical performance in chronic kidney disease

“…All MRS was performed on a Bruker 4.7-T magnet with Biospin console. The within-patient reproducibility of 31 P MRS leg ATPmax, our principal measure of muscle energetics, was less than 10%, in agreement with that of other investigators (5%-8% within-person day-to-day coefficient of variation) (48,49), while, for the hand, the coefficient of variation was 13%. The within-patient coefficient of variation for ATPflux was 14%.…”

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders

“…However, to address this potential source of variance in τCr measurements, percentage CrCEST was included in statistical models as a covariate. Additional studies would be further strengthened by setting exercise parameters in accordance with individual work capacity, and including the work performed by each subject as a covariate (33,34). In addition, it will be useful to validate techniques for individualizing exercise intensity so as to standardize percentage change in CrCEST across participants of different abilities and levels of fitness when τCr is prioritized as the main outcome.…”