Fasciculation IN Amyotrophic Lateral Sclerosis Using MUMRI (FINALSUM)
Lead Research Organisation:
Newcastle University
Department Name: Translational and Clinical Res Institute
Abstract
New and better therapies are transforming the outlook for patients with Motor Neuron Disease (MND). To be effective these must be given as early as possible, but patients still typically wait 12 months between symptom onset and diagnosis. The critical factor is the time to see a neurologist; at this point the diagnosis can be made, life-prolonging therapy started, and patients recruited to clinical trials. What is needed is a quick, accurate and widely available screening test sensitive to the earliest stages of the disease so that the correct patients can be fast-tracked to see a neurologist without overwhelming this limited resource. The vast majority of patients have an MRI scan at some point prior to seeing a neurologist, so improving the ability of MRI to detect key features of early MND would be an important advancement for patient stratification.
We have developed a rapid and entirely pain-free MRI based method which is exquisitely sensitive to muscle twitching called fasciculation. Fasciculation is a useful screen for MND since it occurs early in the disease and in the context of progressive motor weakness is highly suggestive of the disease.
We call this technique motor unit MRI, or MUMRI. MUMRI uses a variation of a type of imaging available on any modern MRI scanner. MUMRI requires only that the subject lies relaxed in the scanner, adds only 1 minute extra scanning time per body region, and needs no additional scanner software or hardware to perform. Current methods of detecting fasciculation are either invasive (needle electromyography), time consuming (ultrasound) or sample only superficial muscles (surface electromyography).
In a pilot study of 4 MND patients we detected a greater than 10-fold increase in fasciculation in the lower limbs compared to controls. More recently, we have developed a 'whole-body' version which images the head, upper limbs, thorax and lower limbs in a single scan session. We showed MUMRI detected significantly increased fasciculation rates in at least one body region in 9 out of 9 patients with typical MND compared to controls.
To be a useful screening test, MUMRI must be applicable on as wide a range of MRI scanners as possible. We developed MUMRI on a Philips MRI scanner, and have successfully implemented it on our local NHS Trust's Siemens scanners. However, we need to test whether MUMRI can be rolled out to MRI scanners throughout the NHS. To do this we will: 1) test whether MUMRI can be implemented on the 3 most common makes of MRI scanner, and; 2) compare the sensitivity of MUMRI in detecting fasciculation on scanners with different magnetic strengths.
To do this we have partnered with 4 major ALS centres around the UK; Leeds, Sheffield, Oxford and King's College London which together see over 1,000 MND patients per year. These centres use the 3 major MRI scan vendors (Philips, GE and Siemens) with both 3T and 1.5T magnet strengths. Phase 1 of the project is to visit each centre and implement the MUMRI protocol on their local scanners. Phase 2 is to recruit 12 patients with recently diagnosed ALS in each centre and invite them to undergo MUMRI scanning during their routine clinical imaging. Phase 3 is to compare fasciculation detection rates between each type of scanner to establish whether or not MUMRI can successfully be rolled-out throughout the NHS and beyond. The aim of this project is to determine;
1) Whether MUMRI can be applied on any make, model, and magnet strength of MRI scanner.
2) To establish the diagnostic accuracy of the technique in patients with ALS.
We have developed a rapid and entirely pain-free MRI based method which is exquisitely sensitive to muscle twitching called fasciculation. Fasciculation is a useful screen for MND since it occurs early in the disease and in the context of progressive motor weakness is highly suggestive of the disease.
We call this technique motor unit MRI, or MUMRI. MUMRI uses a variation of a type of imaging available on any modern MRI scanner. MUMRI requires only that the subject lies relaxed in the scanner, adds only 1 minute extra scanning time per body region, and needs no additional scanner software or hardware to perform. Current methods of detecting fasciculation are either invasive (needle electromyography), time consuming (ultrasound) or sample only superficial muscles (surface electromyography).
In a pilot study of 4 MND patients we detected a greater than 10-fold increase in fasciculation in the lower limbs compared to controls. More recently, we have developed a 'whole-body' version which images the head, upper limbs, thorax and lower limbs in a single scan session. We showed MUMRI detected significantly increased fasciculation rates in at least one body region in 9 out of 9 patients with typical MND compared to controls.
To be a useful screening test, MUMRI must be applicable on as wide a range of MRI scanners as possible. We developed MUMRI on a Philips MRI scanner, and have successfully implemented it on our local NHS Trust's Siemens scanners. However, we need to test whether MUMRI can be rolled out to MRI scanners throughout the NHS. To do this we will: 1) test whether MUMRI can be implemented on the 3 most common makes of MRI scanner, and; 2) compare the sensitivity of MUMRI in detecting fasciculation on scanners with different magnetic strengths.
To do this we have partnered with 4 major ALS centres around the UK; Leeds, Sheffield, Oxford and King's College London which together see over 1,000 MND patients per year. These centres use the 3 major MRI scan vendors (Philips, GE and Siemens) with both 3T and 1.5T magnet strengths. Phase 1 of the project is to visit each centre and implement the MUMRI protocol on their local scanners. Phase 2 is to recruit 12 patients with recently diagnosed ALS in each centre and invite them to undergo MUMRI scanning during their routine clinical imaging. Phase 3 is to compare fasciculation detection rates between each type of scanner to establish whether or not MUMRI can successfully be rolled-out throughout the NHS and beyond. The aim of this project is to determine;
1) Whether MUMRI can be applied on any make, model, and magnet strength of MRI scanner.
2) To establish the diagnostic accuracy of the technique in patients with ALS.
