Longitudinal Dixon Magnetic Resonance Imaging in dysferlinopathy patients can provide a powerful tool in assessing outcomes of therapeutic interventions.

Fat replacement in muscles measured by Dixon MRI provides an excellent marker for disease progression in dysferlinopathy patients. Although no specific therapies exist for dysferlinopathies, these disorders entail multiple pathways to muscle cell death, each of which is potentially a target for intervention; therefore, developing methods to measure therapeutic outcomes of novel drug trials is extremely important. In this study, we looked at a cohort of 11 patients from the JAIN COS natural history study who had been scanned at least 6 times over a 10-year period. Fat fraction analysis to measure the quantity of fat in muscles was carried out for seven muscles in the lower leg and nine muscles in the thigh. In both lower legs and thighs, percentage fat fraction showed a steady increase over the years with lower legs regressing slightly faster (slope = 3.24 % per year, SD = 0.85, range 1.62-4.74) than thighs (slope = 2.16 % per year, SD = 1.21, range 0.42-4.57), this difference was significant (p=0.015). The R2 fit was almost linear with a mean of 0.94 (range 0.81 to 0.99); there was no sign of sigmoidal behaviour which is commonly seen in other muscular dystrophies. Furthermore, certain muscles undergo disease progression early with gastrocnemius medialis and soleus in the lower leg, semimembranosus and adductor magnus in the thighs being most likely to show fatty transformation before other muscles. Linear regression analysis may predict the clinical direction a patient may take and time to lose ambulation as well as mapping the disease progression of individual muscles. In conclusion, Dixon MRI provides a valuable tool to capture any changes in disease progression following therapeutic drug intervention by measuring deviations in the slope of fat fraction percentage progression. Fat replacement in muscles measured by Dixon MRI provides an excellent marker for disease progression in dysferlinopathy patients. Although no specific therapies exist for dysferlinopathies, these disorders entail multiple pathways to muscle cell death, each of which is potentially a target for intervention; therefore, developing methods to measure therapeutic outcomes of novel drug trials is extremely important. In this study, we looked at a cohort of 11 patients from the JAIN COS natural history study who had been scanned at least 6 times over a 10-year period. Fat fraction analysis to measure the quantity of fat in muscles was carried out for seven muscles in the lower leg and nine muscles in the thigh. In both lower legs and thighs, percentage fat fraction showed a steady increase over the years with lower legs regressing slightly faster (slope = 3.24 % per year, SD = 0.85, range 1.62-4.74) than thighs (slope = 2.16 % per year, SD = 1.21, range 0.42-4.57), this difference was significant (p=0.015). The R2 fit was almost linear with a mean of 0.94 (range 0.81 to 0.99); there was no sign of sigmoidal behaviour which is commonly seen in other muscular dystrophies. Furthermore, certain muscles undergo disease progression early with gastrocnemius medialis and soleus in the lower leg, semimembranosus and adductor magnus in the thighs being most likely to show fatty transformation before other muscles. Linear regression analysis may predict the clinical direction a patient may take and time to lose ambulation as well as mapping the disease progression of individual muscles. In conclusion, Dixon MRI provides a valuable tool to capture any changes in disease progression following therapeutic drug intervention by measuring deviations in the slope of fat fraction percentage progression.