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MRI vastus lateralis fat fraction predicts loss of ambulation in Duchenne muscular dystrophy
Objective
We studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchenne
muscular dystrophy by assessing the additive predictive value of vastus lateralis (VL) fat fraction
(FF) to age on loss of ambulation (LoA).
Methods
VL FFs were determined on longitudinal Dixon MRI scans from 2 natural history studies in
Leiden University Medical Center (LUMC) and Cincinnati Children’s Hospital Medical
Center (CCHMC). CCHMC included ambulant patients, while LUMC included a mixed
ambulant and nonambulant population. We fitted longitudinal VL FF values to a sigmoidal
curve using a mixed model with random slope to predict individual trajectories. The additive
value of VL FF over age to predict LoA was calculated from a Cox model, yielding a hazard ratio.
Results
Eighty-nine MRIs of 19 LUMC and 15 CCHMC patients were included. At similar age,
6-minute walking test distances were smaller and VL FFs were...
Objective
We studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchenne
muscular dystrophy by assessing the additive predictive value of vastus lateralis (VL) fat fraction
(FF) to age on loss of ambulation (LoA).
Methods
VL FFs were determined on longitudinal Dixon MRI scans from 2 natural history studies in
Leiden University Medical Center (LUMC) and Cincinnati Children’s Hospital Medical
Center (CCHMC). CCHMC included ambulant patients, while LUMC included a mixed
ambulant and nonambulant population. We fitted longitudinal VL FF values to a sigmoidal
curve using a mixed model with random slope to predict individual trajectories. The additive
value of VL FF over age to predict LoA was calculated from a Cox model, yielding a hazard ratio.
Results
Eighty-nine MRIs of 19 LUMC and 15 CCHMC patients were included. At similar age,
6-minute walking test distances were smaller and VL FFs were correspondingly higher in
LUMC compared to CCHMC patients. Hazard ratio of a percent-point increase in VL FF for
the time to LoA was 1.15 for LUMC (95% confidence interval [CI] 1.05–1.26; p = 0.003) and
0.96 for CCHMC (95% CI 0.84–1.10; p = 0.569).
Conclusions
The hazard ratio of 1.15 corresponds to a 4.11-fold increase of the instantaneous risk of LoA in
patients with a 10% higher VL FF at any age. Although results should be confirmed in a larger
cohort with prospective determination of the clinical endpoint, this added predictive value of
VL FF to age on LoA supports the use of qMRI FF as an endpoint or stratification tool in
clinical trials.
- All authors
- Naarding, K.J.; Reyngoudt, H.; Zwet, E.W. van; Hooijmans, M.T.; Tian, C.X.; Rybalsky, I.; Shellenbarger, K.C.; Louer, J. le; Wong, B.L.; Carlier, P.G.; Kan, H.E.; Niks, E.H.
- Date
- 2020-01-14
- Journal
- Neurology
- Volume
- 94
- Issue
- 13
- Pages
- e1386 - e1394