Posted: July 12th, 2016

Quantifying muscle quality in muscular dystrophy – sensitivity of MRI measures

Quantifying muscle quality in muscular dystrophy – sensitivity of MRI measures
Introduction of the study
The muscular dystrophies are a group of devastating progressive diseases where inherited or novel gene mutations lead to the replacement of functional skeletal muscle by fibrosis and fat, leading ultimately to loss of ambulation. Although there are presently no curative therapies, there are therapeutic options which are undergoing first-in-man trials. MRI quantification of skeletal muscle fat content is becoming more widely used as a trial endpoint. This contrasts with traditional radiological practice, which is mostly qualitative, and insufficiently discriminating to detect longitudinal change in response to natural disease progression or the effects of therapeutic intervention. Traditional methods of assessing physical function are based on physical tests which are dependent on patient motivation and mood. MRI has the potential to be an objective and sensitive endpoint for clinical trials in muscular dystrophy. This is vital, as each individual form of muscular dystrophy is relatively rare, so large numbers of patients cannot be mustered for clinical trials. Trial endpoints must be sensitive and have low variability.
In a pilot project, data on muscle quality has been collected by novel MRI methods. Typically MRI data has been laboriously analyzed by hand, which has limited its applicability, but Dr Kieren Hollingsworth has developed new methods which can acquire the data faster, reducing the burden to the patient.
This project will complete the quantitative analysis of a longitudinal muscular dystrophy dataset looking at the sensitivity of MRI in detecting disease progression compared to traditional function tests.

That it will be possible to detect progressive muscle damage across 6 years in a cohort of LGMD2I patients using a ROI-based analysis.

The muscle MRI protocol can be derived from the papers by Willis Either:
Quantitative Muscle MRI as an Assessment Tool for Monitoring Disease Progression in LGMD2I: A Multicentre Longitudinal Study, Willis TA PLOS One 2013 14;8(8):e70993
Quantitative Magnetic Resonance Imaging in LimbGirdle Muscular Dystrophy 2I: A Multinational Cross-sctional study, Willis TA PLOS One 2014 9:e90377

Interpreting the results from the LGMD2I study
(1) Make a list of any muscle groups where AM and LN readings differ by more than (i) 10% and (ii) 5%. What can we say about the reasons for these differences. Are they due to conservative boundaries, different interpretation of the muscle group or small inclusions of focal fatty areas?
(2) Make a list of any muscle groups where the fat fraction appears to have gone down over time. Does this agree with the visual impression from the respective images. Are there particular muscle groups which are more susceptible to producing negative results than others. Your bar plot suggests that this is the case.
(3) Looking at the muscle groups within the Copenhagen cohort, apply formal non-parametric statistics to find out if the fat fraction has changed over time. Look at SPSS example of this.
(4) Looking at the muscle groups within individuals, have the individuals progressed in a statistically significant way?
(5) Combine the eventual fat-fraction data for each muscle group with the previous Newcastle data (which contains 9 subjects) and calculate the statistics for muscle group progression.
(6) Combined Bland-Altman showing the inter-observer difference between LN and AM for the Copenhagen data.
(7) The patient characteristics (age, gender) for all the subjects to allow you to write up this piece of work can be available in the Patient information.xlxs.

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