The presence of correlative brain networks between regional gray matter volumes as measured across-subjects in a group of individuals has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI)^1-2. Complementary to well-known brain mapping modalities like functional connectivity and diffusion-weighted imaging, scMRI can provide precious insights into the mutual influence of trophic and plastic processes in health and pathological states³. Despite the emerging use of scMRI to study the brain structural architecture, fundamental questions regarding the genetic and environment contribution to the development of these networks remain largely unanswered. Studies on laboratory mice amenable to genetic and experimental manipulation can complement human research on the emergence of covariance and generate novel hypothesis about the etiopathological origin of aberrant scMRI findings in human brain diseases². To map scMRI networks, we employed high resolution structural MRI coupled with voxel-based morphometry in a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J).High-resolution morpho-anatomical T2-weighted MR imaging of mouse brains was performed in a sample of wild-type (n=53) paraformaldehyde fixed specimens. Local gray matter volumes were mapped using VBM⁴. Briefly, a study-based template was created aligning high-resolution T2W images to a common reference space using affine and diffeomorphic registrations. Individual images of the two groups were then nonlinearly registered to the study-based template using diffeomorphic registration. Gray matter of spatially normalized subjects was then segmented, modulated and smoothed. Neuroanatomical volumes of a parcellated reference atlas were registered to each scan, thus avoiding operator dependent bias in the location of the seed. Networks were investigated using a seed-based approach, hierarchical agglomerative clustering and source based independent component analysis. All experiments were carried out in accordance with the Italian law governing animal welfare and protection.We show that the mouse brain exhibits robust homotopic scMRI networks in both primary and associative cortices (Fig 1-2). Subcortical structures also showed highly symmetric inter-hemispheric correlations (Fig 3), with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Analogous cortical network configurations were also identified using independent component analysis (Fig 4). Hierarchical cluster analysis produced robust antero-cortical, cortico-hippocampal and subcortical-limbic clusters corresponding to previously described neuroanatomical systems (Fig 5). Interestingly, results also show a significant negative correlation between anatomical distance and covariance strength, highlighting the importance of trophic interactions between homotopic distal regions.Our work documents the presence of covarying regional gray matter volumes in a cohort of genetically-homogeneous laboratory mice, defining macroscale correlational networks characterized by high neuroanatomical specificity. Consistent with previous findings in humans, the covariance patterns identified showed strong symmetric correlations among gray matter volumes of homologous brain regions. The use of complementary computational and mapping approaches produced consistent results, thus supporting the robustness of our findings. Importantly, the lack of anatomical covariance in antero-posterior midline regions exhibiting robust white matter connectivity supports the emerging view that scMRI only partially reflect underlying fiber connections, and, as such, scMRI should not be simply considered as a proxy for white matter connectivity.We provide the first evidence of robust inter-hemispheric anatomical covariance networks in the laboratory mouse, thus paving the way to the investigation of genetic underpinnings of scMRI alterations described in neuropsychiatric populations. Our finding of robust homotopic networks in inbred mice suggests that population-based scMRI can emerge also in genetically homogeneous population, probably as a result of plastic and environmental stimuli.