Impact of inconsistent resolution on VBM studies João M.S. Pereira, ⁎ Peter J. Nestor, and Guy B. Williams Department of Clinical Neurosciences, University of Cambridge School of Clinical Medicine, Cambridge, UK Received 13 September 2007; revised 16 January 2008; accepted 22 January 2008 Available online 1 February 2008 This paper considers the effects of using magnetic resonance scans with different voxel dimensions in voxel-based morphometry studies. This is of potential relevance to many longitudinal studies or any ad-hoc study that relies on pre-existing databases of subjects. In order to study this effect, a group of controls were contrasted with a group of semantic dementia as well as with a group of Alzheimer's disease patients using a mixture of different voxel dimensions scans on each side of the sta- tistical test. Scans were interpolated using a sinc function in order to obtain a different voxel depth. The effects were measured by com- paring the output of each analysis to the benchmark in which all scans had the original depth (and highest resolution), both visually and through the computation of the root–mean–square error difference between the resulting t-maps. It was shown that the impact is highly dependent on the scan itself, with some images showing more ro- bustness to the interpolation process, and hence yielding fewer differences. A measure of robustness is proposed, which may be used in order to understand the impact of mixing different dimensions or adjusting them for each scan. Indiscriminate use of voxel dimensions on both groups was found to produce more errors (false positives/false negatives) than does an approach involving the use of balanced groups and a voxel dimension nuisance covariate. © 2008 Elsevier Inc. All rights reserved. Keywords: VBM; Voxel dimensions; Interpolation; Degradation Introduction Voxel based morphometry (VBM) is a popular tool for com- parison of structural changes, such as regional grey matter density, in patient cohorts. Ideally, raw data for VBM processing should be as coherent as possible, i.e., scans should be acquired in the same scanner with the same imaging parameters (Good et al., 2001). In general, studies only use consistently acquired data (Mechelli et al., 2005; Gitelman et al., 2001) but this may be an issue for longitudinal or multi-centre studies. For instance, it is conceivable that in rare diseases, acquisition of a cohort may take several years, spanning scanner upgrades or changes to acquisition protocols. In such circumstances, it would be potentially advantageous to include such mixed scans in a single analysis. Since the usual VBM method involves reslicing the data to a lower resolution and application of a smoothing kernel, it is feasible that such an analysis might be unbiased. The following experiments explore the impact of one source of scan heterogeneity—variation in slice thickness. This paper addressed the impact of interpolation on results. The modelling of voxel differences through a nuisance covariate was also explored. Methods Subjects Subjects were chosen from two different diseased cohorts with different patterns of atrophy: Alzheimer ’ s disease (AD—mild diffuse atrophy) and semantic dementia (SD—severe focal atrophy). Each cohort had 14 subjects and was contrasted with a sample of 14 normal controls. Demographic details are provided in the Supplementary material. These dementia cohorts present very distinct atrophic patterns: SD is characterised by severe, typically asymmetric, atrophy of the anterior temporal lobes (Williams et al., 2005), whereas AD shows a more diffuse pattern of cortical atrophy – more so posteriorly – as well as an atrophic hippocampal region (Nestor et al., 2006; Lerch et al., 2005). Imaging Subjects were scanned using a 1.5-T GE MRI scanner. The images were acquired using a coronal T1-weighted 3D spoiled gradient echo sequence with echo time of 4.2 ms, inversion time of 650 ms and flip angle of 20°. All scans had original voxel dimensions of 0.86 × 0.86 × 1.5 mm 3 and number of slices 256 × 256 × FoV in which FoV is the field of view on the coronal direction, in this case ranging from 110 to 124. Two additional T1 3D MPRAGE scans were acquired from a single healthy volunteer using a Siemens Trio 3-T MRI scanner, with voxel dimensions 1×1×1 mm 3 (matrix size 240 × 256 × 176) and 1 × 1 × 1.5 mm 3 (matrix size 240 × 256 × 256) with echo time 5.9 ms, inversion time 900 ms and flip angle 9°. www.elsevier.com/locate/ynimg NeuroImage 40 (2008) 1711 – 1717 ⁎ Corresponding author. E-mail address: jmsp2@wbic.cam.ac.uk (J.M.S. Pereira). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2008.01.031