title: Measuring brain volume by MR imaging: impact of measurement precision and natural variation on sample size requirements.
abstract: OBJECTIVE
  To determine the sample size needed to provide adequate statistical power in studies of brain volume by MR imaging, we examined the precision and variability of measurements in healthy controls.
  
  
  METHODS
  A cohort of 52 people (mean age, 25.1 years) was examined at weeks 0 and 12 at 1.5 T. We used an axial multisection T1-weighted sequence and a contiguous proton-attenuation/T2-weighted sequence. Data were registered to a probabilistic brain atlas, and an automated atlas-based program was used to segment brain tissue by type and by lobe. We assumed that there were no changes in volume because there were no intervening neurologic events. Sample sizes required to yield 80% statistical power in detecting a significant difference in volume were calculated for various experimental designs, assuming a patient-control volume difference of 5% or 2%.
  
  
  RESULTS
  The precision of most measurements was excellent, but required sample sizes were larger than anticipated. If the goal was to detect a 5% difference in whole brain volume in a 2-sample cross-sectional study, the required sample was 73 patients and 73 controls because brain volume varies between individuals in a way that is not informative about disease effects. For a similar 2-sample longitudinal study, the required sample size was just 5 patients and 5 controls.
  
  
  CONCLUSIONS
  Our results argue strongly for longitudinal studies in preference to cross-sectional studies, especially as research budgets decline. Our findings also suggest that there may be more uncertainty than expected in published MR imaging brain volume studies.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7160, USA. Grant_Steen@med.unc.edu
authors.forename: R G
authors.initials: RG
authors.lastname: Steen
authors.forename: R M
authors.initials: RM
authors.lastname: Hamer
authors.forename: J A
authors.initials: JA
authors.lastname: Lieberman
mesh_terms: D000328:Adult; D000465:Algorithms; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009929:Organ Size / Q000502:physiology; D015203:Reproducibility of Results; D018401:Sample Size; D012680:Sensitivity and Specificity