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Voxel-based morphometry analyses of in vivo MRI in the aging mouse lemur primate
Stephen J Sawiak1, Jean-Luc Picq2, Marc Dhenain3
1Wolfson Brain Imaging Centre, University of Cambridge, Addenbrooke's Hospital Cambridge, UK ; Behavioural and Clinical Neuroscience Institute, University of Cambridge Cambridge, UK.
Abstract:
Cerebral atrophy is one of the most widely brain alterations associated to aging. A clear relationship has been established between age-associated cognitive impairments and cerebral atrophy. The mouse lemur (Microcebus murinus) is a small primate used as a model of age-related neurodegenerative processes. It is the first non-human primate in which cerebral atrophy has been correlated with cognitive deficits. Previous studies of cerebral atrophy in this model were based on time consuming manual delineation or measurement of selected brain regions from magnetic resonance images (MRI). These measures could not be used to analyse regions that cannot be easily outlined such as the nucleus basalis of Meynert or the subiculum. In humans, morphometric assessment of structural changes with age is generally performed with automated procedures such as voxel-based morphometry (VBM). The objective of our work was to perform user-independent assessment of age-related morphological changes in the whole brain of large mouse lemur populations thanks to VBM. The study was based on the SPMMouse toolbox of SPM 8 and involved thirty mouse lemurs aged from 1.9 to 11.3 years. The automatic method revealed for the first time atrophy in regions where manual delineation is prohibitive (nucleus basalis of Meynert, subiculum, prepiriform cortex, Brodmann areas 13-16, hypothalamus, putamen, thalamus, corpus callosum). Some of these regions are described as particularly sensitive to age-associated alterations in humans. The method revealed also age-associated atrophy in cortical regions (cingulate, occipital, parietal), nucleus septalis, and the caudate. Manual measures performed in some of these regions were in good agreement with results from automatic measures. The templates generated in this study as well as the toolbox for SPM8 can be downloaded. These tools will be valuable for future evaluation of various treatments that are tested to modulate cerebral aging in lemurs.
Insights
This study introduces an automated method for assessing age-related brain atrophy in mouse lemurs, a primate model for aging. The new technique accurately identifies brain regions previously difficult to measure, aiding future research on cognitive decline.
Area of Science:
- Neuroscience
- Primate Aging Research
- Neuroimaging
Background:
- Cerebral atrophy is a key brain change associated with aging and cognitive decline.
- Mouse lemurs (Microcebus murinus) are valuable non-human primate models for studying age-related neurodegeneration.
- Previous manual MRI analysis methods for cerebral atrophy were time-consuming and limited to easily delineated brain regions.
Purpose of the Study:
- To implement an automated, user-independent method for assessing age-related morphological changes across the entire brain in mouse lemurs.
- To overcome limitations of manual delineation for analyzing difficult-to-measure brain regions.
Main Methods:
- Voxel-Based Morphometry (VBM) using the SPMMouse toolbox within SPM 8.
- Analysis of magnetic resonance images (MRI) from thirty mouse lemurs aged 1.9 to 11.3 years.
- Comparison of automated VBM results with manual measurements in selected regions.
Main Results:
- Automated VBM successfully identified age-associated atrophy in numerous brain regions, including those previously inaccessible to manual analysis (e.g., nucleus basalis of Meynert, subiculum, hypothalamus).
- Atrophy was also detected in cortical areas (cingulate, occipital, parietal), nucleus septalis, and the caudate.
- Automated findings showed good agreement with manual measurements in comparable regions.
Conclusions:
- Automated VBM provides a robust and efficient method for assessing whole-brain age-related changes in mouse lemurs.
- The developed tools and templates facilitate future research on aging and neurodegenerative treatments in this primate model.
- This approach enables the study of age-associated atrophy in critical brain regions relevant to human aging.
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