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Abstract
Magnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) revealed changes in gray matter volume (GMV) in various disorders. However, the cellular basis of GMV changes has remained largely unclear. We correlated changes in GMV with cellular metrics by imaging mice with MRI and two-photon in vivo microscopy at three time points within 12 weeks, taking advantage of age-dependent changes in brain structure. Imaging fluorescent cell nuclei allowed inferences on (i) physical tissue volume as determined from reference spaces outlined by nuclei, (ii) cell density, (iii) the extent of cell clustering, and (iv) the volume of cell nuclei. Our data indicate that physical tissue volume alterations only account for 13.0% of the variance in GMV change. However, when including comprehensive measurements of nucleus volume and cell density, 35.6% of the GMV variance could be explained, highlighting the influence of distinct cellular mechanisms on VBM results.
Highlights
Magnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) revealed changes in gray matter volume (GMV) in various disorders
While the voxel-based GMV changes during the first week were not significant after correction for multiple comparisons, all shown clusters with changes after 12 weeks were significant after false discovery rate (FDR) corrected threshold free cluster enhancement (TFCE) with 5000 permutations
The general pattern of changes described here was similar to a previous study probing age-dependent GMV changes, with the difference that the mean alteration of volume was more shifted to GMV loss which may be due to the different age range investigated in this study[14]
Summary
Magnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) revealed changes in gray matter volume (GMV) in various disorders. When including comprehensive measurements of nucleus volume and cell density, 35.6% of the GMV variance could be explained, highlighting the influence of distinct cellular mechanisms on VBM results. Magnetic resonance imaging (MRI) has tremendously advanced our understanding of brain structure and function in health and disease. VBM provides an automated quantitative analysis of the distribution of gray and white matter to detect differences in brain tissue concentration for each voxel (e.g. gray matter density, GMD). To include voxel-wise volume changes, the GMD is modulated by multiplication with the Jacobian Determinant (JD). A mechanistic understanding of the physical and cellular basis of GMV changes is pertinent (Fig. 1a)[15,16,17].
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