Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease

Abstract

Voxel-based morphometry (VBM) is a popular method for probing inter-group differences in brain morphology. Variation in the detailed implementation of the algorithm, however, will affect the apparent results of VBM analyses and in turn the inferences drawn about the anatomic expression of specific disease states. We qualitatively assessed group comparisons of 43 normal elderly control subjects and 51 patients with probable Alzheimer's disease, using five different VBM variations. Based on the known pathologic expression of the disease, we evaluated the biological plausibility of each. The use of a custom template and custom tissue class prior probability images (priors) produced inter-group comparison maps with greater biological plausibility than the use of the Montreal Neurological Institute (MNI) template and priors. We present a method for initializing the normalization to a custom template, and conclude that, when incorporated into the VBM processing chain, it yields the most biologically plausible inter-group differences of the five methods presented.

Fig. 1

shows a schematic flow diagram of Method 1.

Fig. 2

shows schematic flow diagrams of Methods 2–4. Method 2 used the MNI template and priors. Methods 3–4 used the custom template and priors. The brain mask was used only for Method 4.

Fig. 3

shows a schematic flow diagram for creation of the custom template and priors. Note the registration and normalization parameters are saved for future use in Method 5.

Fig. 4

shows sagittal views of the MNI GM prior (left), and our customized GM prior (right). Note the morphological differences, especially the difference in ventricle size.

Fig. 5

shows a schematic of Method 5.

Fig 6

(Method 1) Group effect analysis with standard VBM before (left), and after (right) family-wise error correction.

Fig 7

(Method 2) Group effect analysis with optimized VBM using MNI template and priors before (left), and after (right) FWE correction.

Fig 8

(Method 3) Group effect analysis with optimized VBM using custom template and priors before (left), and after (right) FWE correction.

Fig 9

(Method 4) Group effect analysis with optimized VBM using custom template and priors, plus hand-edited brain masks before (left), and after (right) FWE correction.

Fig 10

(Method 5) Group effect analysis with optimized VBM using custom template and priors, plus the re-initialization scheme described in the text, before (left), and after (right) FWE correction.