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Abstract:
The human hippocampal formation can be divided into a set of
cytoarchitecturally and functionally distinct subregions, involved in
different aspects of memory formation. Neuroanatomical disruptions
within these subregions are associated with several debilitating brain
disorders including Alzheimer's disease, major depression,
schizophrenia, and bipolar disorder. Multi-center brain imaging
consortia, such as the Enhancing Neuro Imaging Genetics through
Meta-Analysis (ENIGMA) consortium, are interested in studying disease
effects on these subregions, and in the genetic factors that affect
them. For large-scale studies, automated extraction and subsequent
genomic association studies of these hippocampal subregion measures may
provide additional insight. Here, we evaluated the test-retest
reliability and transplatform reliability (1.5 T versus 3 T) of the
subregion segmentation module in the FreeSurfer software package using
three independent cohorts of healthy adults, one young (Queensland Twins
Imaging Study, N=39), another elderly (Alzheimer's Disease Neuroimaging
Initiative, ADNI-2, N=163) and another mixed cohort of healthy and
depressed participants (Max Planck Institute, MPIP, N=598). We also
investigated agreement between the most recent version of this algorithm
(v6.0) and an older version (v5.3), again using the ADNI-2 and MPIP
cohorts in addition to a sample from the Netherlands Study for
Depression and Anxiety (NESDA) (N=221). Finally, we estimated the
heritability (h(2)) of the segmented subregion volumes using the full
sample of young, healthy QTIM twins (N=728). Test-retest reliability was
high for all twelve subregions in the 3 T ADNI-2 sample (intraclass
correlation coefficient (ICC)=0.70-0.97) and moderate-to-high in the 4
TQTIM sample (ICC=0.5-0.89). Transplatform reliability was strong for
eleven of the twelve subregions (ICC=0.66-0.96); however, the
hippocampal fissure was not consistently reconstructed across 1.5 T and
3 T field strengths (ICC=0.47-0.57). Between-version agreement was
moderate for the hippocampal tail, subiculum and presubiculum
(ICC=0.78-0.84; Dice Similarity Coefficient (DSC)=0.55-0.70), and poor
for all other subregions (ICC=0.34-0.81; DSC=0.28-0.51). All hippocampal
subregion volumes were highly heritable (h(2)=0.67-0.91). Our findings
indicate that eleven of the twelve human hippocampal subregions
segmented using FreeSurfer version 6.0 may serve as reliable and
informative quantitative phenotypes for future multi-site imaging
genetics initiatives such as those of the ENIGMA consortium. (C) 2016
The Authors. Published by Elsevier Inc.
