title: Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers.
abstract: OBJECTIVE
  Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies.
  
  
  METHODS
  Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to three-point Dixon fat-fraction measurement, T₁-relaxometry, T₂-relaxometry and magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks.
  
  
  RESULTS
  Mean between-muscle fat fraction and T₂ differences were small, but significant (p < 0.001). Fat fraction and T 2 correlated positively, and MTR negatively with subject age in both the thigh and calf, with similar significant correlations with weight at thigh level only (p < 0.001 to p < 0.05). Scan-rescan and inter-observer intra-class correlation coefficients ranged between 0.62-0.84 and 0.79-0.99 respectively.
  
  
  CONCLUSIONS
  Quantitative lower-limb muscle MRI using readily implementable methods was sensitive enough to demonstrate inter-muscle differences (small in health), and correlations with subject age and weight. In combination with high reliability, this strongly supports the suitability of these methods to provide longitudinal outcome measures in neuromuscular disease treatment trials.
  
  
  CONCLUSIONS
  • Quantitative lower limb muscle MRI provides potential outcome measures in neuromuscular diseases • Bilateral thigh/calf coverage using sequences sensitive to acute and chronic pathology • Measurements have excellent scan-rescan and interobserver reliability • Measurements show small but significant inter-subject age and weight dependency • Readily implementable sequences suitable for further assessment in patient studies.
authors.affiliation: Medical Research Council Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK, j.morrow@ucl.ac.uk.
authors.forename: Jasper M
authors.initials: JM
authors.lastname: Morrow
authors.forename: Christopher D J
authors.initials: CD
authors.lastname: Sinclair
authors.forename: Arne
authors.initials: A
authors.lastname: Fischmann
authors.forename: Mary M
authors.initials: MM
authors.lastname: Reilly
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Yousry
authors.forename: John S
authors.initials: JS
authors.lastname: Thornton
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001835:Body Weight; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D035002:Lower Extremity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology*; D012372:ROC Curve; D015203:Reproducibility of Results; D012737:Sex Factors; D055815:Young Adult
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