Mapping Caudolenticular Gray Matter Bridges in the Human Brain Striatum Through Diffusion Magnetic Resonance Imaging and Tractography

Abstract

In primates, the putamen and the caudate nucleus are connected by ~1 mm-thick caudolenticular gray matter bridges (CLGBs) interspersed between the white matter bundles of the internal capsule. Little is understood about the functional or microstructural properties of the CLGBs. In studies proposing high resolution diffusion magnetic resonance imaging (dMRI) techniques, CLGBs have been qualitatively identified as an example of superior imaging quality; however, the microstructural properties of these structures have yet to be examined. In this study, it is demonstrated for the first time that dMRI is sensitive to an organized anisotropic signal oriented in the direction parallel to the CLGBs, suggesting that dMRI could be a useful imaging method for probing the microstructure of the CLGBs. To demonstrate the anisotropic diffusion signal is coherently organized along the extent of the CLGBs and to enable a subsequent CLGB microstructural measurement, a customized tractography seeding and filtering method is proposed that utilizes the shape of the human striatum (putamen + caudate nucleus) to reconstruct the CLGBs in 3D. The proposed seeding strategy seeds tractography streamlines outward and normal to the surface of a 3D model of the striatum such that reconstructed streamlines are more likely to follow the diffusion signal peaks aligned parallel to the CLGBs. The method is applied to three different diffusion datasets, namely a high resolution 760 μm isotropic diffusion dataset acquired on a single subject, the test–retest cohort included as part of the human connectome project (N = 44) with diffusion data acquired at 1.25 mm isotropic, and a locally acquired “clinical” test–retest dataset acquired at 2.0 mm isotropic (N = 24). Reconstructed CLGBs directly overlap expected gray matter regions in the human brain for all three datasets. In addition, the method is shown to accurately reconstruct CLGBs repeatedly across multiple test–retest cohorts. The tractography CLGB reconstructions are then used to extract a quantitative measurement of microstructure from a local model of the diffusion signal along the CLGBs themselves. This is the first work to comprehensively study the CLGBs in vivo using dMRI and presents techniques suitable for future human neuroscience studies targeting these structures.