Abstract
Age-specific resources in human MRI mitigate processing biases that arise from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue's relative contribution to total brain volume would change with age in the adult rat. Data from a longitudinal study of rats at 3, 5, 11, and 17 months old were used to test this hypothesis. Tissue volume was estimated from high resolution structural images using a priori information from tissue probability maps. However, existing tissue probability maps generated inaccurate gray matter probabilities in subcortical structures, particularly the thalamus. To address this issue, gray matter, white matter, and CSF tissue probability maps were generated by combining anatomical and signal intensity information. The effects of age on volumetric estimations were then assessed with mixed-effects models. Results showed that herein estimation of gray matter volumes better matched histological evidence, as compared to existing resources. All tissue volumes increased with age, and the tissue proportions relative to total brain volume varied across adulthood. Consequently, a set of rat brain templates and tissue probability maps from across the adult lifespan is released to expand the preclinical MRI community's fundamental resources.
Highlights
Animal models of aging are valuable for understanding age-related brain changes
Thalamic gray matter (GM) estimates derived from the RESILIENT Tissue Probability Map (TPM) had greater means and standard deviations than those from either existing TPM (Figure 2E)
Since the spatial distribution of T1 map values is similar to that of T2w images (i.e., cerebrospinal fluid (CSF) has high, white matter (WM) has low, and GM has intermediate values), we suggest these can be used as pseudo-T2w templates
Summary
Animal models of aging are valuable for understanding age-related brain changes. The process of physiological and cognitive decline with increasing age is near-universal in mammals (Morrison and Baxter, 2012); for example, during their lifespan, rodents spontaneously demonstrate age-related cellular changes in regions susceptible to aging in humans (Gallagher and Nicolle, 1993). Age-Specific Adult Rat MRI Resources environmental confounds can be robustly controlled compared to human studies. This control over experimental settings affords findings which are expected to generalize across species (e.g., to humans) when using homologous methods. Prior information can take the form of, e.g., reference images, which are often the average of a representative sample and known as templates; and tissue probability maps (TPMs), which use probabilistic classifications of voxels to extract biologically meaningful classes. Such information is population-specific and does not generalize across species. Compared to human brains, rodent brains are elongated along the coronal axis, have a smaller proportion of white matter (WM), and do not have cortical folding
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