Cellular correlates of gray matter volume changes in magnetic resonance morphometry identified by two-photon microscopy

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.

Structural aberrations of the brain associated with migraine: A narrative review

“…The mechanisms leading to gray matter structural aberrations and longitudinal changes need to be further investigated. It is likely that differences in the density, size, or number of neurons, glial cells, and synaptic connections that occur with neurodegeneration or brain development contribute to measured changes 31 . However, it is also likely that factors such as hydration status, blood volume, and patient motion in the scanner impact gray matter structural measurements 32‐34 .…”

Neurogenic-dependent changes in hippocampal circuitry underlie the procognitive effect of exercise in aging mice

“…Furthermore, in a study of auditory fear conditioning, a higher spine density could explain 20% of the increased volume in the auditory cortex of mice ( Keifer et al., 2015 ). These local changes would also contribute to the macroscopic volume change promoted by neurogenesis ( Asan et al, 2021 ; Biedermann et al., 2012 ; Keifer et al., 2015 ).…”

The Aged Striatum: Evidence of Molecular and Structural Changes Using a Longitudinal Multimodal Approach in Mice

“…The resulting TPMs were used to segment images from each individual at 12, 18, and 24 months of age into gray matter, white matter, and cerebrospinal fluid (GM, WM, CSF, respectively) and used for voxel-based morphometric analysis. A second measurement of structural changes was performed using tensor-based morphometry (TBM) as described elsewhere ( Asan et al, 2021 ), to determine local morphometric changes of brain structure with time.…”