Supplemental Material for:
Genetic Dissection of the Mouse Brain Using High-Field Magnetic Resonance Microscopy
A. Badea1, G.A. Johnson1, R.W. Williams2
Submitted to NeuroImage, December 2008
1Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC, USA
2Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA
Magnetic resonance (MR) imaging has demonstrated that variation in brain structure
is associated with differences in behavior and disease state. However, it has rarely
been practical to prospectively test causal models that link anatomical and
functional differences in humans. In the present study we have combined classical
mouse genetics with high-field MR to systematically explore and test such
structure-functional relations across multiple brain regions. We segmented
33 regions in two parental strains -- C57BL/6J (B) and DBA/2J (D) -- and in
nine BXD recombinant inbred strains. All strains have been studied extensively
for more than 20 years using a battery of genetic, functional, anatomical,
and behavioral assays. We compared levels of variation within and between
strains and sexes, by region, and by system. Average within-strain variation
had a coefficient of variation (CV) of 1.6% for the whole brain; while the
CV ranged from 2.3 -- 3.6% for olfactory bulbs, cortex and cerebellum, and
up to ~18% for septum and laterodorsal thalamic nucleus. Variation among
strains averages ranged from 6.7% for cerebellum, 7.6% for whole brain,
9.0% for cortex, up to ~26% for the ventricles, laterodorsal thalamic
nucleus, and the interpeduncular nucleus. Heritabilities averaged 0.60 +/- 0.18.
Sex differences were not significant with the possible (and unexpected) exception
of the pons (~20% larger in males). A correlation matrix of regional volumes
revealed high correlations among functionally related parts of the CNS (e.g.,
components of the limbic system), and several high correlations between regions
that are not anatomically connected, but that may nonetheless be functionally
or genetically coupled.
Files in This Data Supplement
All datasets associated with this publication are available from CIVMSpace, our
Web-based data portal.
The datasets represent a collection of 22 brains, one male and one female
from each of 11 strains : C57BL/6, DBA2, and 9 BXD strains selected for
large hippocampal volume variations.
The images are high resolution three-dimensional (3D) MR data acquired at
21.5-micron isotropic resolution (T1) and matched 43-micron resolution
MEFIC processed scans (T2). The results of automated segmentation into
33 structures are also provided.
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This work was made possible through collaborations with the
Mouse Biomedical Informatics Research Network (MBIRN),
NIH/NCRR grant U24 RR021760 (A. W. Toga).
All experiments were
conducted at the Duke Center for In Vivo Microscopy,
an NCRR/NCI National Biomedical Technology Resource Center,
under grants P41-RR005959 and R24-CA092656 (G. A. Johnson).