title: Methodological considerations for measuring rates of brain atrophy.
abstract: OBJECTIVE
  To systematically compare two techniques for measuring brain atrophy rates from serial magnetic resonance imaging (MRI) studies.
  
  
  METHODS
  Using the separation in atrophy rate between cohorts of cognitively normal elderly subjects and patients with Alzheimer's disease (AD) as the gold standard, we evaluated 1) different methods of computing volume change; 2) different methods for steps in image preprocessing-intensity normalization, alignment mask used, and bias field correction; 3) the effect of MRI acquisition hardware changes; and 4) the sensitivity of the method to variations in initial manual volume editing. For each of the preceding evaluations, measurements of whole-brain and ventricular atrophy rates were calculated.
  
  
  RESULTS
  In general, greater separation between the clinical groups was seen with ventricular rather than whole-brain measures. Surprisingly, neither the use of bias field correction nor a major hardware change between the scan pairs affected group separation.
  
  
  CONCLUSIONS
  Atrophy rate measurements from serial MRI are candidates for use as surrogate markers of disease progression in AD and other dementing neurodegenerative disorders. The final method has excellent precision and accurately captures the expected biology of AD-arguably the two most important features if this technique is to be used as a biomarker of disease progression.
authors.affiliation: Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. gunter.jeffrey@mayo.edu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.forename: Maria M
authors.initials: MM
authors.lastname: Shiung
authors.forename: Armando
authors.initials: A
authors.lastname: Manduca
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results