title: Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophy.
abstract: In muscular dystrophies quantitative muscle MRI (qMRI) detects disease progression more sensitively than clinical scores. This prospective one year observational study compared qMRI with clinical scores in Duchenne muscular dystrophy (DMD) to investigate if qMRI can serve as a surrogate outcome measure in clinical trials. In 20 DMD patients the motor function measure (MFM) total and subscores (D1-D3) were done for physical examination, and the fat fraction (MFF) of thigh muscle qMRI was obtained using the two-point Dixon method. Effect sizes (ES) were calculated for all measures. Sample size estimation (SS) was done modelling assumed treatment effects. Ambulant patients <7 years at inclusion improved in the MFM total and D1 score (ES 1.1 and 1.0). Ambulant patients >7 years (highest ES in the MFM D1 subscore (1.2)), and non-ambulant patients (highest ES in the total MFM score (0.7)) worsened. In comparison the ES of QMRI was much larger, e.g. SS estimations for qMRI data were up to 17 fold smaller compared to the MFM total score and up to 7 fold to the D1 subscore, respectively. QMRI shows pathophysiological changes in DMD and might serve as a surrogate outcome measure in clinical trials.
authors.affiliation: University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland; University of Basel Hospital, Department of Neurology, Petersgraben 4, Basel 4031, Switzerland. Electronic address: ulrike.bonati@ukbb.ch.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bonati
authors.affiliation: University of Basel Hospital, Department of Neurology, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hafner
authors.affiliation: University of Basel Hospital, Clinical Trial Unit, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schädelin
authors.affiliation: University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
authors.forename: Maurice
authors.initials: M
authors.lastname: Schmid
authors.affiliation: University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
authors.forename: Arjith
authors.initials: A
authors.lastname: Naduvilekoot Devasia
authors.affiliation: University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schroeder
authors.affiliation: University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zuesli
authors.affiliation: University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Pohlman
authors.affiliation: University of Basel Children's Hospital, Therapy Department, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Neuhaus
authors.affiliation: University Children's Hospital Zürich, Department of Paediatric Neurology, Steinwiesstrasse 75, Zürich 8032, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Klein
authors.affiliation: University of Basel Hospital, Department of Neurology, Petersgraben 4, Basel 4031, Switzerland; University of Basel Hospital, Department of Biomedicine, Hebelstrasse 20, Basel 4031, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Sinnreich
authors.affiliation: University of Basel Hospital, Division of Radiological Physics, Department of Radiology, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Haas
authors.affiliation: University of Basel Hospital, Division of Radiological Physics, Department of Radiology, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Gloor
authors.affiliation: University of Basel Hospital, Division of Radiological Physics, Department of Radiology, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bieri
authors.affiliation: University of Basel Hospital, Division of Neuroradiology, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Arne
authors.initials: A
authors.lastname: Fischmann
authors.affiliation: University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland; University of Basel Hospital, Department of Neurology, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Fischer
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology*; D011446:Prospective Studies
keywords: Duchenne muscular dystrophy; Endpoint; Neuromuscular disorders; Outcome measure; Quantitative MRI