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Published on: January 31, 2019
Cellular correlates of gray matter volume changes in magnetic resonance morphometry identified by two-photon
Livia Asan1, Claudia Falfán-Melgoza2, Carlo A Beretta1,3
1Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
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.
Insights
Changes in brain gray matter volume (GMV) are linked to cellular changes, not just tissue volume. This study used MRI and microscopy in mice to reveal how cell density and nucleus size influence GMV in brain imaging.
Area of Science:
- Neuroimaging
- Cellular Biology
- Quantitative Anatomy
Background:
- Voxel-based morphometry (VBM) using magnetic resonance imaging (MRI) detects gray matter volume (GMV) changes in neurological disorders.
- The underlying cellular mechanisms driving these GMV alterations remain poorly understood.
Purpose of the Study:
- To investigate the cellular basis of GMV changes observed in brain MRI.
- To correlate macroscopic GMV changes with microscopic cellular metrics in vivo.
Main Methods:
- Longitudinal in vivo imaging of mice using MRI and two-photon microscopy over 12 weeks.
- Quantification of cellular metrics including physical tissue volume, cell density, cell clustering, and cell nucleus volume.
- Analysis of age-dependent structural brain changes.
Main Results:
- Physical tissue volume changes accounted for only 13.0% of the variance in GMV.
- Incorporating cell nucleus volume and cell density explained 35.6% of the GMV variance.
- Demonstrated that cellular composition significantly influences VBM-derived GMV.
Conclusions:
- GMV changes detected by VBM are influenced by cellular-level alterations, including cell density and nucleus size.
- Understanding these cellular mechanisms is crucial for accurate interpretation of VBM findings in various brain conditions.
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