Abstract
Voxel-based morphometry (VBM) and tensor-based morphometry (TBM) both rely on spatial normalization to a template and yet have different requirements for the level of registration accuracy. VBM requires only global alignment of brain structures, with limited degrees of freedom in transformation, whereas TBM performs best when the registration is highly deformable and can achieve higher registration accuracy. In addition, the registration accuracy varies over the whole brain, with higher accuracy typically observed in subcortical areas and lower accuracy seen in cortical areas. Hence, even the determinant of Jacobian of registration maps is spatially varying in their accuracy, and combining these with VBM by direct multiplication introduces errors in VBM maps where the registration is inaccurate. We propose a unified approach to combining these 2 morphometry methods that is motivated by these differing requirements for registration and our interest in harnessing the advantages of both. Our novel method uses local estimates of registration confidence to determine how to weight the influence of VBM- and TBM-like approaches. Results are shown on healthy and mild Alzheimer's subjects (N = 150) investigating age and group differences, and potential of differential diagnosis is shown on a set of Alzheimer's disease (N = 34) and frontotemporal dementia (N = 30) patients compared against controls (N = 14). These show that the group differences detected by our proposed approach are more descriptive than those detected from VBM, Jacobian-modulated VBM, and TBM separately, hence leveraging the advantages of both approaches in a unified framework.