Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophy

Ulrike Bonati; Patricia Hafner; Sabine Schädelin; Maurice Schmid; Arjith Naduvilekoot Devasia; Jonas Schroeder; Stephanie Zuesli; Urs Pohlman; Cornelia Neuhaus; Andrea Klein; Michael Sinnreich; Tanja Haas; Monika Gloor; Oliver Bieri; Arne Fischmann; Dirk Fischer

doi:10.1016/j.nmd.2015.05.006

Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophy

Neuromuscul Disord. 2015 Sep;25(9):679-85. doi: 10.1016/j.nmd.2015.05.006. Epub 2015 Jun 4.

Authors

Ulrike Bonati¹, Patricia Hafner², Sabine Schädelin³, Maurice Schmid⁴, Arjith Naduvilekoot Devasia⁴, Jonas Schroeder⁴, Stephanie Zuesli⁴, Urs Pohlman⁴, Cornelia Neuhaus⁵, Andrea Klein⁶, Michael Sinnreich⁷, Tanja Haas⁸, Monika Gloor⁸, Oliver Bieri⁸, Arne Fischmann⁹, Dirk Fischer¹⁰

Affiliations

¹ 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: [email protected].
² University of Basel Hospital, Department of Neurology, Petersgraben 4, Basel 4031, Switzerland.
³ University of Basel Hospital, Clinical Trial Unit, Petersgraben 4, Basel 4031, Switzerland.
⁴ University of Basel Children's Hospital, Division of Neuropaediatrics, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
⁵ University of Basel Children's Hospital, Therapy Department, Spitalstrasse 33, Postfach, Basel 4031, Switzerland.
⁶ University Children's Hospital Zürich, Department of Paediatric Neurology, Steinwiesstrasse 75, Zürich 8032, Switzerland.
⁷ University of Basel Hospital, Department of Neurology, Petersgraben 4, Basel 4031, Switzerland; University of Basel Hospital, Department of Biomedicine, Hebelstrasse 20, Basel 4031, Switzerland.
⁸ University of Basel Hospital, Division of Radiological Physics, Department of Radiology, Petersgraben 4, Basel 4031, Switzerland.
⁹ University of Basel Hospital, Division of Neuroradiology, Petersgraben 4, 4031 Basel, Switzerland.
¹⁰ 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.

PMID: 26096788
DOI: 10.1016/j.nmd.2015.05.006

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.

Keywords: Duchenne muscular dystrophy; Endpoint; Neuromuscular disorders; Outcome measure; Quantitative MRI.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Child, Preschool
Disease Progression*
Follow-Up Studies
Humans
Magnetic Resonance Imaging / methods*
Male
Muscle, Skeletal / pathology*
Muscular Dystrophy, Duchenne / pathology*
Prospective Studies