Methodological considerations for measuring rates of brain atrophy

Purpose: To systematically compare two techniques for measuring brain atrophy rates from serial magnetic resonance imaging (MRI) studies. Materials and 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. Conclusion: 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.