Using nine degrees-of-freedom registration to correct for changes in voxel size in serial MRI studies

Quantitative longitudinal brain magnetic resonance (MR) studies may be confounded by scanner-related drifts in voxel sizes. Total intracranial volume (TIV) normalisation is commonly used to correct serial cerebral volumetric measurements for these drifts. We hypothesised that automated rigid-body registration of whole brain incorporating automatic scaling correction might also correct for such fluctuations, and might be a more practical alternative. Twenty-three subjects (12 patients with Alzheimer's disease [AD] and 11 controls) had at least two serial T1-weighted volumetric brain MR scans. Ten scans from the control subjects were artificially scaled (stretched) by 1.5, 3.0, 4.6 and 6.1%. A 9-degrees-of-freedom (9dof) registration was used to register the scaled scans back onto the original scans and corresponding scaling factors compared to TIV measurements. A further nine 1-year repeat scans from the AD subjects were artificially scaled and registered (9dof) to baseline. The two correction methods were further assessed using multiple serial scans for each of the 23 subjects (resulting in 49 scan pairs). All serial scans were registered (9dof) to baseline. TIV was measured on all scans. It was found that the 9dof registration successfully recovered the artificially generated scaling changes. Scaling correction using 9dof registration did not alter the amount of brain atrophy measured over the 1-year period in the AD subjects. The 9dof volume scaling factors were very similar to the TIV ratios (repeat TIV over baseline TIV), but less variable (p < 0.001), in both artificial and 'real' scenarios. In the latter, the volume scaling factors allowed identification of two time-points in which a 3% change in voxel size had occurred. Both the 9dof brain registration and TIV correction were successfully able to correct for these fluctuations. Significant shifts in voxel size are a problem in longitudinal brain imaging studies. It is important that such changes are adjusted for: 9dof registration, which is automated and computationally inexpensive, may be superior to the more labour-intensive TIV correction for this purpose.