P.69 Minimum clinically important difference in magnetic resonance biomarkers in DMD

Magnetic resonance (MR) biomarkers that quantify increases in intramuscular fat are highly sensitive to disease progression and predictive of meaningful functional milestones in DMD. However, the minimum clinically important difference (MCID), defined as "the smallest change that is important to patients" has not been established. The purpose of this investigation was to estimate the MCID for both muscle fat fraction measured using MR spectroscopy and bulk muscle T2 measured using MRI. As part of the multicenter ImagingDMD study, localized 1H-MR spectra (TE=108 ms; TR=3000 ms) and multi-echo T2 weighted images were collected longitudinally in 180 males with DMD, with 0-8 annual follow up visits. Spectra from the vastus lateralis and soleus muscles were integrated and relaxation-corrected then used to estimate fat fraction (fat:(fat+water)). Spin-echo images were used to calculate T2 maps, which were manually segmented to obtain T2 measurements for 7 leg muscles. Ambulatory function groups were defined as: able to rise from the floor - Group I; able to walk - Group II; nonambulatory - Group III. MCID was estimated using 1) the standard error of measurement method, incorporating the group variance and day-to-day reproducibility of the measurement from 111 study participants, 2) the 1/3 standard deviation method, and 3) a survey of experts. Combining results from the three estimation methods, ranges for MCID for fat fraction were 0.02-0.05 in the vastus lateralis and 0.01-0.05 in the soleus. For MRI T2, MCID ranged between 1.9 and 3.0 ms for the vastus lateralis and 0.9 and 2.4 ms for the soleus. The average annual change in fat fraction or T2 exceeds the MCID in Groups I, II, and III for vastus lateralis fat fraction, Groups I and II for vastus lateralis T2, Groups II and III for soleus fat fraction, and Group II for soleus T2. Expected change, expected variability, and estimated MCID in the target population should all be considered when selecting a primary MR measure to use in clinical trials.