Novel MRI Biomarkers in Neuromuscular Disease

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More than 2,000 people a year die of motor neuron disease (MND). In this relentlessly progressive condition, the motor nerve fibres that control the muscles die off, resulting in weakness and eventually paralysis. Early diagnosis allows patients to receive life-prolonging treatment, but current clinical tests are only sensitive to the later stages of the disease by which time it may be too late for these to work.We have recently developed an entirely new way to detect early changes in the muscles of patients with MND. This uses a type of MRI scanning that can detect characteristic twitches in tiny regions of the muscles (called fasciculation) that occur before the nerve fibres have died. These regions are called motor units. We were able to show that our new technique, which we call Motor Unit MRI (MUMRI), detected hundreds of fasciculations in the leg muscles of patients with MND but not in healthy subjects. This is very exciting as it is the first time that fasciculation has been detected using MRI, and it potentially offers a sensitive, quick, and entirely pain-free way to diagnose and monitor patients with MND and other diseases.The aims of this project are: to take these promising early results and develop them into a tool that can be used to study the same muscle region repeatedly; to then use the refined technique to answer fundamental questions about how the disease develops; and to produce a 'whole-body' version that can be used to study patients in the clinic.We will ask patients with MND to undergo several scans over a two-year period. As well as taking the MUMRI images, we will also perform currently used tests such as muscle MRI, ultrasound, and electrical muscle tests. This will allow us to see when the changes seen on MUMRI first appear, whether these occur earlier in the disease than currently available tests, and how the changes develop as the disease progresses.A great strength of MUMRI is that it detects activity at the level of individual motor nerve fibres. This has never before been possible in humans, and it allows us to answer some fundamental questions about how MND develops. For example, we do not know if motor units that start to show fasciculation are about to die, or whether in fact these are the healthy ones doing their best to compensate for the damage occuring around them. We also do not know if the disease starts throughout the muscle, or start in just a few motor units before spreading. Since we can repeatedly image the same motor units with MUMRI we can begin to answer these questions, and in turn learn more about the disease itself.Finally, we will develop new ways to use MUMRI in muscles other than the legs. This is important since MND can affect anywhere in the body, and this is an essential step to MUMRI being used in the clinical setting. It will also allow us to study how fasciculation spreads throughout the body in MND, complimenting the earlier work on understanding how the disease originates.Our team includes research physicists, neurophysiologists, radiologists and neurologists. This gives us the ability to bring together a broad range of techniques to study MND. It also helps us to engage with a wide range of stakeholders from people involved in basic science into new imaging techniques, clinicians who apply these to diagnose and treat patients, and patients themselves. This gives us the best opportunity to translate this promising new technique into the clinic, whilst ensuring that our results are relevant and acceptable.