Abstract
Healthy ageing coincides with a progressive decline of brain gray matter (GM) ultimately affecting the entire brain. For a long time, manual delineation-based volumetry within predefined regions of interest (ROI) has been the gold standard for assessing such degeneration. Voxel-Based Morphometry (VBM) offers an automated alternative approach that, however, relies critically on the segmentation and spatial normalization of a large collection of images from different subjects. This can be achieved via different algorithms, with SPM5/SPM8, DARTEL of SPM8 and FSL tools (FAST, FNIRT) being three of the most frequently used. We complemented these voxel based measurements with a ROI based approach, whereby the ROIs are defined by transforms of an atlas (containing different tissue probability maps as well as predefined anatomic labels) to the individual subject images in order to obtain volumetric information at the level of the whole brain or within separate ROIs. Comparing GM decline between 21 young subjects (mean age 23) and 18 elderly (mean age 66) revealed that volumetric measurements differed significantly between methods. The unified segmentation/normalization of SPM5/SPM8 revealed the largest age-related differences and DARTEL the smallest, with FSL being more similar to the DARTEL approach. Method specific differences were substantial after segmentation and most pronounced for the cortical structures in close vicinity to major sulci and fissures. Our findings suggest that algorithms that provide only limited degrees of freedom for local deformations (such as the unified segmentation and normalization of SPM5/SPM8) tend to overestimate between-group differences in VBM results when compared to methods providing more flexible warping. This difference seems to be most pronounced if the anatomy of one of the groups deviates from custom templates, a finding that is of particular importance when results are compared across studies using different VBM methods.
Highlights
The human brain undergoes continuous structural changes due to development and aging
Our findings suggest that algorithms that provide only limited degrees of freedom for local deformations tend to overestimate between-group differences in Voxel-Based Morphometry (VBM) results when compared to methods providing more flexible warping
We used the aging brain as a well-known model for structural atrophy and asked whether comparing gray matter (GM) between young and elderly by VBM depends on methodological differences between commonly used software packages, i.e., the unified segmentation/normalization procedure provided by SPM5/SPM8, DARTEL, and FSL
Summary
The human brain undergoes continuous structural changes due to development and aging. Post mortem studies have shown that even healthy aging is accompanied by notable cortical atrophy and loss of brain weight from the sixth life decade onwards (Skullerud, 1985). This brain tissue loss is further accelerated by most neurodegenerative or neuropsychiatric disorders such that magnetic resonance imaging (MRI) in combination with morphometry offers an interesting diagnostic tool for differentiating between healthy and pathological brain changes (for an overview, see Raz and Rodrigue, 2006; Mueller et al, 2012a,b). VBM has been frequently used for investigating GM decline in the context of neurodegenerative pathologies
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