Nonlinear registration of longitudinal images and measurement of change in regions of interest.

We describe here a method, Quarc, for accurately quantifying structural changes in organs, based on serial MRI scans. The procedure can be used to measure deformations globally or in regions of interest (ROIs), including large-scale changes in the whole organ, and subtle changes in small-scale structures. We validate the method with model studies, and provide an illustrative analysis using the brain. We apply the method to the large, publicly available ADNI database of serial brain scans, and calculate Cohen's d effect sizes for several ROIs. Using publicly available derived-data, we directly compare effect sizes from Quarc with those from four existing methods that quantify cerebral structural change. Quarc produced a slightly improved, though not significantly different, whole brain effect size compared with the standard KN-BSI method, but in all other cases it produced significantly larger effect sizes.