Rajakumar Nagarajan1, Youssef Jaber2, Miles Bartlett3, Liam F Fitzgerald3, Julia Miehm3, Frank C Sup IV2, and Jane A Kent1,3
1Human Magnetic Resonance Center, Institute for Applied Life Sciences (IALS), University of Massachusetts, Amherst, MA, United States, 2Department of Mechanical & Industrial Engineering, University of Massachusetts, Amherst, MA, United States, 3Kinesiology, University of Massachusetts, Amherst, MA, United States
Synopsis
The goal of this project was to
develop an MR-compatible, multi-modal ergometer for the reliable measurement of
human skeletal muscle torque, velocity, power and joint angle during 31P
MRS studies of knee extensor muscle energetics.
Intracellular [PCr], [Pi] and pH were determined in the vastus lateralis
with 4-s time resolution during 4 min of maximal voluntary isokinetic
contractions at 240 degrees per second, with a 30 degree range of motion. High S/N for both the MRS and power data
indicate that this tool will be useful in future studies of in vivo muscle bioenergetics.
Introduction
For more than 30 years, phosphorus MR spectroscopy (31P MRS) has been a reliable and robust tool for
noninvasive investigation of human muscle bioenergetics 1. 31P MRS can be used to quantify the concentration and kinetics of
high-energy phosphorus metabolites and pH in resting muscle, as well as during and
following muscular work. For example,
the rate constant for phosphocreatine (PCr) recovery can be used to quantify
the muscle’s capacity for oxidative energy (ATP) production by the mitochondria 2, 3. One advantage of this method is
that measures of muscle torque or work are not necessary. In contrast, accurate determination of the ATP
cost of contraction (work per ATP), including ATP production by the creatine
kinase reaction, nonoxidative glycolysis and oxidative phosphorylation 4-6,
requires precise measures of muscular work.
However, commercial availability of MR-compatible ergometers is very
limited, as are the capabilities of these devices. Therefore, the goal of this project was to
develop and test a new ergometer for measurement of human muscle torque,
velocity, joint angle and power during knee and full-leg extension exercise
during simultaneous measures of 31P MRS in the 3T environment.Materials and Methods
The
ergometer was designed to quantify torque and power during isometric, isotonic
and isokinetic knee and full-leg extension exercise, with the muscle of
interest positioned in the isocenter of a 70-cm bore Skyra 3T system (Siemens Medical
Systems, Germany). Results from pilot studies of a knee
extension protocol are presented here. Required
output variables included position (to determine knee angle), torque and
velocity data with high S/N that would not contribute noise to 31P MRS
signals obtained at rapid (~2s) repetition rates. The test protocol consisted of 4 min of
maximal voluntary isotonic contractions at 240 dps, repeated once every 2 s,
which was designed to induce fatigue 7. Phosphorus spectra were acquired before,
during and for 10 min following the protocol.
Prior
to the exercise study, a 500-ml phosphoric acid phantom was used to determine
the temporal stability of the 6 x 8 cm 31P elliptical loop transmit/receive RF surface coil (J. Smith,
University of Oregon, Eugene OR, USA). Subsequently,
this coil was positioned over the vastus
lateralis muscle and held in place with an elastic wrap and velcro straps. Gradient-echo scout images and T1-weighted
axial images along the femur were used to confirm optimal positioning of the
leg in the isocenter, and correct positioning of the coil over the muscle.
Magnetic
field homogeneity was optimized on water using the body coil, and confirmed on the
PCr peak of the 31P signal to yield width at half-height of ~14 Hz. 31P-MRS data were collected in 3
healthy volunteers (mean age 24.5 years).
Spectra were acquired using a
pulse-and-acquire free induction decay sequence using adiabatic half passage
pulses. The parameters included: 4000 Hz
band width, 2048 complex points, 2s repetition time. Spectra were
averaged as follows: 60s
at rest, 4s during contraction protocol, and 4-30s during recovery. Spectra were processed using jMRUI version 5.2 and quantified using a non-linear
least squares algorithm 8. Resulst and Discussion
Design and testing of the ergometer
resulted in a system well-suited to the 70-cm bore of the 3T (Figures 1 and 2). The system was made MR-compatible by using
non-magnetic materials in the bore and locating all of the powered elements
away from the field (Figure 2). Powered
actuation elements were connected mechanically through a system of low-stretch
cables and pulleys to passive components inside the scanner. The ergometer applies controlled resistive
loads on the lower limb, enabling study of the muscle while it is near its
physical workload limits. A 30 degree
range of motion (ROM), from 105 to 135 degrees, was obtained. The closed-loop force control allowed for isometric,
isotonic and isokinetic contractions; fatigue was produced using the isokinetic
mode.
The
temporal stability of the 31P coil was good, as evidenced by a low
coefficient of variation (0.7%) for signal intensity over the 30-s data
collection period (Figure 3). The
contraction protocol produced substantial changes in [Pi] and pH, two known
inhibitors of contractile function in muscle 9, and the accompanying
decrement in peak power is shown in Figure 4. Conclusion
The
custom engineering and construction approach applied here enables collection of
high S/N 31P metabolites and pH during maximal work of the human knee
extensor muscles. The capacity of this
design to control load and velocity during isotonic and isokinetic contractions
will advance the study of in vivo
muscle energetics by enabling a wide range of contraction protocols. Acknowledgements
No acknowledgement found.References
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