Study the Longitudinal in vivo and Cross-Sectional ex vivo Brain Volume Difference for Disease Progression and Treatment Effect on Mouse Model of Tauopathy Using Automated MRI Structural Parcellation

Abstract

Brain volume measurements extracted from structural MRI data sets are a widely accepted neuroimaging biomarker to study mouse models of neurodegeneration. Whether to acquire and analyze data in vivo or ex vivo is a crucial decision during the phase of experimental designs, as well as data analysis. In this work, we extracted the brain structures for both longitudinal in vivo and single-time-point ex vivo MRI acquired from the same animals using accurate automatic multi-atlas structural parcellation, and compared the corresponding statistical and classification analysis. We found that most gray matter structures volumes decrease from in vivo to ex vivo, while most white matter structures volume increase. The level of structural volume change also varies between different genetic strains and treatment. In addition, we showed superior statistical and classification power of ex vivo data compared to the in vivo data, even after resampled to the same level of resolution. We further demonstrated that the classification power of the in vivo data can be improved by incorporating longitudinal information, which is not possible for ex vivo data. In conclusion, this paper demonstrates the tissue-specific changes, as well as the difference in statistical and classification power, between the volumetric analysis based on the in vivo and ex vivo structural MRI data. Our results emphasize the importance of longitudinal analysis for in vivo data analysis.

Preliminary evidence that maternal immune activation specifically increases diagonal domain volume in the rat brain during early postnatal development

“…This is relevant as in vivo studies in MIA rat models do show differences in ventricular volume [20, 24]. Total brain volume and that of most grey matter structures also shrinks post-perfusion [16, 41, 46]. Prior work however, including our own, suggests that major group-level differences in grey matter volumes are preserved despite this shrinkage from in vivo to ex vivo and can be confirmed post-mortem [16, 41].…”

“…Third, we chose to collect ex vivo MR images, as opposed to in vivo MR images. The enhanced image quality available with ex vivo data increases the statistical power to detect subtle volume changes when performing cross-sectional comparisons of two groups [13, 41]. Therefore, if the study objective is detection of a neuroanatomical phenotype, without attention to its time course, then ex vivo imaging is preferable, hence our decision to opt for this approach [13].…”

“…Total brain volume and that of most grey matter structures also shrinks post-perfusion [16, 41, 46]. Prior work however, including our own, suggests that major group-level differences in grey matter volumes are preserved despite this shrinkage from in vivo to ex vivo and can be confirmed post-mortem [16, 41]. Taken together, the choice of ex vivo MR imaging is consistent with the aims of the current study, but the case for longitudinal in vivo studies is also reinforced.…”

“…For the MR image analysis, group-level differences in volume, FA (unit less) and MD (mm 2 s −1 ) were assessed using atlas-based segmentation (ABS) [20], taking advantage of a publicly available high resolution MRI atlas of the Wistar rat brain at PD18 that is parcellated into 26 regions of interest (ROI) [39]. We analysed relative volumes since total brain volume accounts for the majority of inter-animal variation in the volume of individual brain structures [13, 41]. Volume data for each atlas ROI was therefore expressed as a percentage of total brain volume [20].…”

ViceCT and whiceCT for simultaneous high-resolution visualization of craniofacial, brain and ventricular anatomy from micro-computed tomography

“…Nevertheless, a limitation of such ex vivo imaging techniques is the need to dissect the brain from the skull and/or to section the tissue, which disrupts their original 3D structure. Moreover, all ex vivo techniques have the common drawback that the ventricles significantly shrink or collapse after euthanasia 14 – 16 , precluding evaluation of ventricular anatomy.…”