MRI of motor units in ALS - version 1.0 June 2019
Research type
Research Study
Full title
Motor unit assessment with magnetic resonance imaging. A new way to measure and understand the pathophysiology of amyotrophic lateral sclerosis
IRAS ID
268280
Contact name
Linda Heskamp
Contact email
Sponsor organisation
Newcastle Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 11 months, 31 days
Research summary
Summary of Research
Amyotrophic lateral sclerosis (ALS) is a rapid, progressive neuromuscular disorder caused by damage to the motor nerves which connect the brain, via the spinal cord, to the muscles. Each motor nerve connects with many separate fibres within the same muscle which allows the brain to cause the muscle to contract and move. The collections of fibres connected to each nerve are known as motor units.
In ALS, motor units in some muscles are more often affected than motor units in other muscles. Understanding this selective vulnerability could direct new diagnostic approaches and lead to identification of new treatments. We aim to investigate this selective vulnerability in ALS by studying their muscle composition (motor unit type and distribution) and function in two ways. For this, we will use a new type of magnetic resonance imaging (MRI) scan called “Motor Unit MRI” (MUMRI) which takes pictures of the motor units.
First, we will use MUMRI to study the number of motor units, and motor unit size and composition in the leg muscles by assessing muscle twitch dynamics. We will combine this with in-scanner force measurements and muscle oxidative capacity measurements acquired by phosphorus magnetic resonance spectroscopy. Second, we will apply a ‘whole-body’ MUMRI approach to study fasciculation, i.e. spontaneous muscle contractions, in a larger subset of muscles. This is because fasciculation is the first abnormality observed in ALS. Finally, we will apply both MUMRI techniques over a 6 month period to track the disease progression and spread through multiple muscles in ALS. This project will lead to new information about the pathophysiological mechanisms behind motor neuron degeneration in ALS. Furthermore, ‘whole-body’ MUMRI could become a new diagnostic tool in ALS.Summary of Results
The research study investigated whether a new type of MRI scan called “motor unit MRI” (MUMRI) could detect spontaneous twitching of small parts of muscles in different body regions. These twitches are known as fasciculation and are a recognised feature of motor neuron disease (MND, also known as amyotrophic lateral sclerosis). Our objective was to use the MUMRI scan for the first time in MND patients to examine if there was potential for the method to help diagnose the disease. We recruited 10 patients with MND and collected MUMRI scans in the calf muscles, the back muscles, one forearm and the tongue. The scan in each body area collected 60 images over a 1 minute time period. As a measure of disease activity, we counted the number of times we observed a fasciculation (twitch) in any of the muscles seen in the image. We repeated the scans in 9 of the patients 6 months later to investigate if we could see changes over time, since MND is progressive and currently untreatable. We compared our data with scans collected in healthy volunteers. We found that the number of fasciculation in each body area was much greater (and statistically significantly greater) in the MND patients than in the healthy volunteers, although in the individual patient not all body areas were affected to the same degree. Combining our measurements across all body areas, we found that in 8 of the MND patients the total number of fasciculation counted was greater than in any of our healthy volunteers. (As a group the counts in the 10 healthy volunteers ranged from 9 to 127 fasciculation, while in the patients the numbers ranged from 89 to 1339 fasciculation). There did not appear to be a difference in number of fasciculation over time in the patients, but new computer analysis methods are now being developed which may be able to identify more subtle changes. The data from this study indicate that MUMRI detects a high frequency of fasciculation in MND patients which should be studied further as a potentially new and non-invasive diagnostic test for MND.REC name
Wales REC 5
REC reference
19/WA/0279
Date of REC Opinion
27 Sep 2019
REC opinion
Favourable Opinion