Figure 1.
(Top row) Axial high-resolution susceptibility-weighted images (SWI) in three subjects, at the level of the globus pallidus (GP), putamen and thalamus. 7T SWI provides high contrast between structures such as the external (GPe) and internal (GPi) segments of GP, as can be seen in each inset in the uppermost row. The white arrows indicate the border between GPe and GPi, known as the lamina pallidi medialis (uppermost insets). Axial high-resolution T2-weighted images in three subjects at the level of the substantia nigra (SN) and red nucleus (RN) are presented in the middle row. Coronal T2-weighted images in three subjects at the level of the subthalamic nucleus (STN) and SN (bottom row). Coronal images provide good contrast enabling differentiation between SN and STN along the lateral-medial axis, as indicated by the white arrow in each inset. SWI and T2-weighted images were co-registered and both used to segment GPe, GPi, SN, and STN. More details on the advantages of 7T SWI and T2-weighted imaging can be found in [33].
Figure 2.
Volumes of segmented basal ganglia and thalamus.
This graph summarizes statistics (mean and standard deviation over the five datasets) of the volume of the seven structures of interest in this study. Volumes were found to be in agreement with values reported in the literature. No statistical difference was detected between left and right hemispheres. Average agreement index (see Materials and Methods) was 0.94 for two datasets of the same subject acquired on different days. (Blue: left hemisphere, Red: right hemisphere).
Figure 3.
Segmentation and reconstruction of fiber pathways of the basal ganglia and thalamus.
(Panel A) Three-dimensional visualization of manual segmentations of basal ganglia and thalamus from high-resolution SWI, T2-weighted images and fractional anisotropy maps. Segmentations are superimposed on T2-weighted images. (Panel B) White matter pathways identified using diffusion MRI probabilistic tractography. The white wireframe volumes represent white matter tracts identified as pathways of interest (see Materials and Methods). From left to right: (1) nigrostriatal, (2) nigropallidal, (3) subthalamopallidal and (4) pallidothalamic pathways with AL: ansa lenticularis and TF: thalamic fasciculus. Background images are 7T T2-weighted MR images. (Top right inset) Yellow lines depict the orientation and location of T2-weighted images in each panel. (A1) Axial image at the level of SN; (A2) Coronal image at the level of the posterior Tha; (B1) Axial image at the level of SN, caudo-rostral orientation; (B2) Coronal image at the level of the anterior GPi; (B3) Axial image slightly inferior to STN to avoid obscuring portions of the tract; (B4) Coronal image at the level of the posterior Tha, rostro-caudal orientation. Color code: Caudate nucleus, CN: light blue; Putamen, Pu: red; External globus pallidus, GPe: dark blue; Internal globus pallidus, GPi: green; Substantia nigra, SN: yellow; subthalamic nucleus, STN: magenta; Thalamus, Tha: orange.
Figure 4.
Reconstruction of fiber pathways of the basal ganglia and thalamus.
White matter pathways identified using diffusion MRI probabilistic tractography. The white wireframe volumes represent white matter tracts identified as pathways of interest (see Materials and Methods). From left to right: (Panel A) nigrothalamic pathway, (Panel B) and (Panel C) pallidostriatal pathway, (Panel D) thalamostriatal pathway, (Panel E) thalamopallidal pathway. (Bottom right inset) Yellow lines depict the orientation and location of T2-weighted images in each panel. (Panels A, B, C) Axial images at the level of SN; (Panel D) Coronal image at the level of the posterior Tha; (Panel E, left) Coronal image at the level of the anterior thalamus; (Panel E, middle and right) Axial images at the level of the inferior GP. Color code: Caudate nucleus, CN: light blue; Putamen, Pu: red; External globus pallidus, GPe: dark blue; Internal globus pallidus, GPi: green; Substantia nigra, SN: yellow; Thalamus, Tha: orange.
Figure 5.
Parcellation of the basal ganglia and thalamus based on their white matter projections.
Various sub-territories identified in the basal ganglia and thalamus by exploiting the fact that these divisions exhibit distinctively stronger connectivity with other structures. Within each of the seven regions-of-interest, voxels presenting a high probability of connection with another structure are categorized according to the color of that very structure. (Bottom right inset) The yellow lines depict the location of axial T2-weighted images in each panel. (Panel A) Inferior SN; (Panel B, C, D, F) Inferior GP; (Panel E) Superior GP; (Panel G) Superior Tha, inferior-superior view. Color code: Caudate nucleus, CN: light blue; Putamen, Pu: red; External globus pallidus, GPe: dark blue; Internal globus pallidus, GPi: green; Substantia nigra, SN: yellow; subthalamic nucleus, STN: magenta; Thalamus, Tha: orange.
Figure 6.
Probability of connection between basal ganglia and thalamus.
This chart summarizes statistics (mean and standard deviation over the five datasets) of the proportion of probabilistic streamlines starting from each voxel of a given structure and reaching a specific target region, by comparison with the total number of streamlines reaching the entire basal ganglia area or thalamus. For a given subject, structure and target region, the proportion of probabilistic streamlines is defined as the average proportion over all voxels of the sub-territory of the structure connected to a specific target region. The sub-territory is defined as the area with proportion of streamline greater or equal to 50% of the maximum proportion. Color code: Caudate nucleus, CN: light blue; Putamen, Pu: red; External globus pallidus, GPe: dark blue; Internal globus pallidus, GPi: green; Substantia nigra, SN: yellow; subthalamic nucleus, STN: magenta; Thalamus, Tha: orange.
Figure 7.
Spatial agreement between functional and anatomical connectivity maps.
The figure demonstrates spatial overlap, within the putamen or thalamus, between the areas reached by white matter nigral projections and the resting-state functional activations of the substantia nigra. The white wireframe volumes represent reconstructions of the nigrostriatal (A) and nigrothalamic (B) pathways. R-fMRI activation maps of the substantia nigra were obtained using FDR (see Materials and Methods). They are represented using isolines of equal p-values, with blue lines corresponding to p = 0.01 and red lines to p≪0.01. Spatial agreement between anatomical and functional connectivity maps is visible in the dorsal part of the putamen (A) and in thalamus, within the putative Vc nucleus (B). Orientation in (A) is caudo-rostral with T2-weighted image at the level of the substantia nigra. Inset in (A) is a magnified view of the overlap area between anatomical and functional connectivity. The red surface representing putamen was clipped in its upper part to reveal the R-fMRI activation (isolines) and endpoint of the nigrostriatal projections. Orientation in (B) is oblique caudo-rostral with SWI images at the level of the inferior and anterior thalamus.
Table 1.
White matter pathways identified in-vivo in individual human subjects, and previous studies.
Figure 8.
Basal ganglia and thalamus circuits, and newly identified pathways in-vivo in individual human subjects.
The diagram, adapted from [7], summarizes known pathways of the basal ganglia and thalamus connectome, from histology and recent MRI population studies. The lines outlined in red indicate pathways uniquely identified in-vivo in individual human subjects in this study using 7T MRI. Although the directionality (afferent/efferent) of these pathways is known from histology, diffusion MRI tractography is unable to recover this information, hence the absence of polarity for the pathways identified in this study.
Figure 9.
Subject-specific analysis pipeline.
This diagram summarizes the pre-processing, registration, and segmentation steps that were required to identify the seven regions-of-interest used in this work: caudate nucleus (CN), putamen (Pu), external and internal globus pallidus (GPe and GPi), substantia nigra (SN), subthalamic nucleus (STN), and thalamus (Tha). Axial SWI and T2-weighted images were linearly registered using nine degrees-of-freedom (DOF), and used to delineate GPe and GPi. Coronal SWI and T2-weighted images were also linearly registered using nine DOF, and used to delineate SN and STN. The purple arrows indicate spatial relations between structures, exploited to segment them (i.e. GPe and GPi are adjacent and simultaneously segmented). Diffusion-weighted images were corrected for motion, eddy-current, and susceptibility-induced distortions, and were then used to estimate fractional anisotropy (FA) and averaged b0 images. Subsequently, axial and coronal high-resolution T2-weighted images were aligned with the averaged b0 in order to resample segmentations of GPe, GPi, SN, and STN into diffusion native space, and then used for tractography seeding. CN, Pu and Tha were segmented from the FA image. Finally, resting-state fMRI (R-fMRI) data were corrected for motion and susceptibility-induced distortions. An average R-fMRI image was created and used as a template to register axial and coronal T2-weighted images, and b0, in order to resample all regions-of-interest into R-fMRI native space and then to generate R-fMRI activation maps.