Motor Unit Magnetic Resonance Imaging (MUMRI) to Assess Age Related Changes in Skeletal Muscle

Abstract

Motor units are the smallest functional unit of skeletal muscle, containing: the nerve cell body, myelinated axon and all muscle fibres which are innervated by the singular axon. Motor units generate muscle contraction and relaxation and hence movement. Sarcopenia is a muscle disease in which there is a generalised loss of muscle strength and mass which is commonly associated with ageing. One of the underlying components in the pathophysiology of sarcopenia are degenerative changes to motor units including: a selective denervation of fast twitch type II motor units, an increase in the size of the territories which surviving motor units innervate preceding a generalised loss of muscle strength and mass. Current techniques used to measure motor unit activity such as electromyography provide information about the function of motor units. However, they are invasive and restricted to certain muscle groups. This work presents a novel magnetic resonance imaging technique called motor unit MRI (MUMRI). Applied both at rest and in conjunction with in-scanner electrical stimulation, MUMRI offers a novel way to study motor unit activity and morphology in-vivo. In this work MUMRI has been applied in a healthy ageing cohort study to further understand changes to motor unit activity with healthy ageing. Motor unit activity presents as transient signal voids on MUMRI images, due to the re-ordering of water molecules during muscle fibre contraction and relaxation. The first study performed was to simulate the MUMRI experiment to further investigate the mechanisms which contribute to the observed signal changes. Theoretical simulations of two gradient schemes representing the two MUMRI sequences: pulsed gradient spin echo and phase contrast, were performed to assess the effects of altering the type and relative strengths of simulated muscle fibre contraction on the observed signal. These simulations were then related to real world data acquired in a small number of healthy volunteers in a retrospective analysis. A second pilot study was performed in 10 healthy volunteers of different ages, to measure single motor unit morphology of lower limb muscles (size and shape of territories innervated by single motor units) in conjunction with in-scanner electrical stimulation. This study presents the first ever imaging assessment of single motor unit activity in-vivo. Finally, a study applying three different MUMRI techniques in a cohort of 60 healthy volunteers aged 25 – 85 years was carried out. The first experiment examined how whole muscle and single motor unit twitch profiles varied with age. The second experiment measured the morphology of single motor unit territories in the large ageing cohort to further explore how this changes with age. Finally changes to the fasciculation rate (spontaneous activity) of motor units within lower limb muscles was examined using the MUMRI technique.