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CHAPTER 3
Image analysis
Manual measures of global volume and shape analysis of the hippocampus
After preprocessing the MR images the hippocampi were manually traced using MultiTracer by a single rater (SC), who was blind to all demographical variables and was trained by an expert (JHC) according to an established protocol (Thompson et al. 2004) (details in supplementary material S3.1). Hippocampal global volumes obtained from these tracings were statistically analyzed. To assess the shape deformations of different hippocampal subfields, an anatomical surface mesh modeling method was applied according to standard procedures (Thompson et al. 2004). In brief: Localized gray matter contractions and expansions of the hippocampal surface were established corresponding to the CA1, CA2-3 and subiculum. In each individual, the medial core, a central 3D curve threading down the long axis of the structure, was computed and from each point on the hippocampal surface, a radial distance measure was derived to the medial core. Statistical comparisons were made at each hippocampal surface point between the groups to index contrasts on a local scale. Probability values from these statistical comparisons were mapped onto an average hippocampal shape for the entire sample to generate a 3D representation of the structural differences between the groups. The approximate overlay of the hippocampal subfields was defined based on the Duvernoy atlas (Duvernoy 1988) (Figure 3.1a).
Automated extraction of hippocampal global and subfield volumes
We used FreeSurfer v5.1 (http://surfer.nmr.mgh.harvard.edu) to segment all images into tissue classes and to extract estimates of hippocampal subfield volumes (CA1, CA2-CA3, CA4-DG, subiculum, presubiculum and fimbria) (Van Leemput et al. 2009). An estimate of parenchymal volume (total gray matter (GM) + total white matter (WM)) was also obtained using FreeSurfer and was used in subsequent statistical analyses to correct for whole-brain size.
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