Skeletal muscle water T2 in DMD across the fat-fraction range and disease progression

Topic:

Clinical Trials

Poster Number: 31 S

Author(s):

Eric Baetscher, Oregon Health & Science University, Sean Forbes, PhD, University of Florida, Rebecca Wilcocks, PhD, University of Florida, Kelly Rock, PhD, University of Florida, William Triplett, BS, University of Florida, Alison Barnard, PhD, University of Florida, Prathyusha Bellam, PT, University of Florida, Shakeel Ahmed, PhD, University of Florida, Pratiksha Awale, PT, University of Florida, Claudia Senesac, PhD, University of Florida, Donovan Lott, PhD, University of Florida, Glenn Walter, PhD, University of Florida, Krista H Elvire Vandenborne, PhD, University of Florida, William D Rooney, PhD, Oregan Health and Science University

Background: Skeletal muscle water T2 measured by magnetic resonance spectroscopy (MRS) is elevated in early stages of Duchenne muscular dystrophy (DMD), a finding that has been attributed to inflammation-associated edema. We examined highly sampled cross sectional MRS data to determine whether elevated water T2 is present at very low fat fraction (FF) values and if the relationship between FF and water T2 is associated with disease progression.

Objectives: To investigate muscle water T2 trajectories and disease progression in DMD.

Methods: Motivated by an overestimate of muscle water T2 at low FF by linear regression, we constructed a growth + linear function [T2 (FF;scale,k1,k2,k3) = scale×(1-exp⁡([-k1*FF])+(k2*FF)+k3)] to model the relationship between water T2 and FF from a dataset of 1999 T2 and FF observations from 226 unique subjects. These data were obtained from MRS examinations of the vastus lateralis (VL) muscle in the upper leg and soleus (Sol) muscle in the lower leg. The range of ages included was 4.0–21.8 years (mean age: 11.0 years).

Results: We found an initial increase in muscle water T2 with FF<0.12 that peaks at lower FF in VL (0.06) than in Sol (0.12), with a water T2 value of 23.5ms in VL and 28.7ms in Sol at FF=0. These water T2 values at very low FF are not elevated compared to the mean water T2 for unaffected control participants, which we found to be 28.4ms (standard deviation 0.96ms). At the group level, after the initial increase, water T2 decreases for FF>0.12 in both Sol and VL. At the group and individual level, a steeper negative decline in muscle water T2 with FF portends more rapid disease progression.

Conclusions: Although skeletal muscle inflammation and associated edema is known to be a factor in DMD, these results indicate that edema does not precede measurable increases in FF. The behavior of water T2 with increasing FF (k2 from equation in Methods) is associated with disease progression: A more progressive disease course is observed when water T2 values decrease markedly with increasing FF. A more benign disease course is observed when water T2 remains high and does not decline with increasing FF. The consistently high water T2 observed in slower progression may be associated with prolonged inflammatory processes that preserve muscle.