A Diffusion MRI Tractography Connectome of the Mouse Brain and Comparison with Neuronal Tracer Data

Abstract

Interest in structural brain connectivity has grown with the understanding that abnormal neural connections may play a role in neurologic and psychiatric diseases. Small animal connectivity mapping techniques are particularly important for identifying aberrant connectivity in disease models. Diffusion magnetic resonance imaging tractography can provide nondestructive, 3D, brain-wide connectivity maps, but has historically been limited by low spatial resolution, low signal-to-noise ratio, and the difficulty in estimating multiple fiber orientations within a single image voxel. Small animal diffusion tractography can be substantially improved through the combination of ex vivo MRI with exogenous contrast agents, advanced diffusion acquisition and reconstruction techniques, and probabilistic fiber tracking. Here, we present a comprehensive, probabilistic tractography connectome of the mouse brain at microscopic resolution, and a comparison of these data with a neuronal tracer-based connectivity data from the Allen Brain Atlas. This work serves as a reference database for future tractography studies in the mouse brain, and demonstrates the fundamental differences between tractography and neuronal tracer data.

Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia

“…Continued research regarding the mechanisms by which ALL and chemotherapy disrupt connectome topology and cognitive function could help identify interventions that will protect against these neurotoxicities without reducing the anticancer efficacy of treatment regimens. Small-world connectomes are highly associated with gene expression networks and also appear to be preserved across species (Calabrese et al, 2015;Fakhry and Ji, 2015). Thus, connectome studies potentially provide unique translational opportunities to identify intervention targets for ALL-related cognitive impairment.…”

Connectome sensitivity or specificity: which is more important?

“…In panel B, red/blue denotes left/right hemispheres and solid/dashed lines denote distinct diffusion imaging data sets. Panels A and B reproduced from Calabrese et al (2015) and Azadbakht et al (2015), respectively, with green lines superimposed.…”

“…Conversely, genuine connections can be overlooked, resulting in false negatives (FNs) and reducing connectome sensitivity. Despite current state of the art, it remains challenging to reconstruct micro-, meso-and macro-scale connectomes that display both high sensitivity and high specificity (Azadbakht et al, 2015;Bastiani et al, 2012;Calabrese et al, 2015;Knosche et al, 2015;Reveley et al, 2015;Thomas et al, 2014).…”

Neural Reorganization Due to Neonatal Amygdala Lesions in the Rhesus Monkey: Changes in Morphology and Network Structure

“…The second possibility is that the diffusion imaging measures (estimated number of streamlines between 2 regions) are relatively insensitive to true white matter effects. Recent work has cast considerable doubt about the sensitivity of diffusion-based tractography and demonstrates sources of artifact that hide the presence of nondominant fiber pathways even with cutting edge acquisition and processing approaches (Thomas et al 2014;Calabrese et al 2015;Reveley al. 2015;Donahue et al 2016).…”