Mapping functional gradients of the striatal circuit using simultaneous microelectric stimulation and ultrahigh-field fMRI in non-human primates.

Advances in functional magnetic resonance imaging (fMRI) have significantly enhanced our understanding of the striatal system of both humans and non-human primates (NHP) over the last few decades. However, its circuit-level functional anatomy remains poorly understood, partly because in-vivo fMRI cannot directly perturb a brain system and map its casual input-output relationship. Also, routine 3T fMRI has an insufficient spatial resolution. We performed electrical microstimulation (EM) of the striatum in lightly-anesthetized NHPs while simultaneously mapping whole-brain activation, using contrast-enhanced fMRI at ultra-high-field 7T. By stimulating multiple positions along the striatum's main (dorsal-to-ventral) axis, we revealed its complex functional circuit concerning mutually connected subsystems in both cortical and subcortical areas. Indeed, within the striatum, there were distinct brain activation patterns across different stimulation sites. Specifically, dorsal stimulation revealed a medial-to-lateral elongated shape of activation in upper caudate and putamen areas, whereas ventral stimulation evoked areas confined to the medial and lower caudate. Such dorsoventral gradients also appeared in neocortical and thalamic activations, indicating consistent embedding profiles of the striatal system across the whole brain. These findings reflect different forms of within-circuit and inter-regional neuronal connectivity between the dorsal and ventromedial striatum. These patterns both shared and contrasted with previous anatomical tract-tracing and in-vivo resting-state fMRI studies. Our approach of combining microstimulation and whole-brain fMRI mapping in NHPs provides a unique opportunity to integrate our understanding of a targeted brain area's meso- and macro-scale functional systems.

Experimental setup for bulk susceptibility effect-minimized, multi-orientation MRI of ex vivo tissue samples.

PURPOSE: Many conventional ex vivo magnetic resonance imaging (MRI) setups utilize cylindrical or other nonspherical tissue containers which can cause static field (B0 ) inhomogeneity affecting the accuracy of the measurements in an orientation-dependent manner. In this work we demonstrate an experimental method to obtain MRI of ex vivo tissue samples held in a spherical container in order to minimize bulk susceptibility-induced B0 inhomogeneity in arbitrary orientations. METHODS: B0 inhomogeneity caused by tissue-air susceptibility mismatch can be theoretically eliminated if the surface of susceptibility discontinuity is spherical. This situation can be approximated by putting a tissue sample in a spherical shell filled with materials with tissue-like magnetic susceptibility. We achieved this on an intact monkey brain by (a) holding the brain with a three-dimensional (3D)-printed holder with tissue-like (within 0.5 ppm) susceptibility, and (b) enclosing the brain and the holder in an acrylic spherical shell filled with diamagnetic liquid. Furthermore, the sphere and the radio-frequency coil for MRI were mounted on a 3D-printed frame designed to reduce B0 inhomogeneity contributions. The sphere could be rotated freely without disturbing the RF coil to facilitate multi-orientation imaging. We verified our setup by mapping B0 in the monkey brain at 13 different orientations in a human 7T scanner, and measuring orientation-dependent R 2 ∗ relaxation rates in the white and gray matters of the brain. The results were then compared with a setup where the brain was held inside a cylindrical container. RESULTS: In all orientations, the B0 standard deviation in the brain in the spherical setup (converted to Larmor frequency offset) was less than about 10 Hz. This corresponds to two-sigma deviation of B0 of <0.07 ppm. The B0 gradient was <9 Hz/mm in 95 % of the brain voxels in all orientations. In high-resolution imaging with e.g. voxel size <0.4 mm, this corresponds to voxel line broadening of <4 Hz (0.013 ppm). R 2 ∗ in the corpus callosum showed distinctly different orientation dependence compared to the gray matter. The B0 uniformity and R 2 ∗ reliability were much reduced in the cylindrical container setup. CONCLUSIONS: We have demonstrated an experimental method to effectively minimize bulk susceptibility-induced B0 perturbation in multi-orientation ex vivo MRI. The method promises to benefit a range of tissue orientation-dependent MR property studies.