A probabilistic template of human mesopontine tegmental nuclei from in vivo 7T MRI

Abstract

Mesopontine tegmental nuclei such as the cuneiform, pedunculotegmental, oral pontine reticular, paramedian raphe and caudal linear raphe nuclei, are deep brain structures involved in arousal and motor function. Dysfunction of these nuclei is implicated in the pathogenesis of disorders of consciousness and sleep, as well as in neurodegenerative diseases. However, their localization in conventional neuroimages of living humans is difficult due to limited image sensitivity and contrast, and a stereotaxic probabilistic neuroimaging template of these nuclei in humans does not exist. We used semi-automatic segmentation of single-subject 1.1mm-isotropic 7T diffusion-fractional-anisotropy and T₂-weighted images in healthy adults to generate an in vivo probabilistic neuroimaging structural template of these nuclei in standard stereotaxic (Montreal Neurological Institute, MNI) space. The template was validated through independent manual delineation, as well as leave-one-out validation and evaluation of nuclei volumes. This template can enable localization of five mesopontine tegmental nuclei in conventional images (e.g. 1.5T, 3T) in future studies of arousal and motor physiology (e.g. sleep, anesthesia, locomotion) and pathology (e.g. disorders of consciousness, sleep disorders, Parkinson's disease). The 7T magnetic resonance imaging procedure for single-subject delineation of these nuclei may also prove useful for future 7T studies of arousal and motor mechanisms.

Keywords: Ascending arousal and motor systems; Cuneiform/pedunculotegmental/oral pontine reticular/paramedian raphe/caudal linear raphe nuclei; Human mesopontine tegmental nuclei; In vivo neuroimaging template; Multi-contrast 7T MRI.

Figure 1. Probabilistic (n = 12) template labels in MNI space of the left (blue-lightblue) and right (red-yellow) cuneiform nucleus (CnFl, CnFr), pedunculotegmental nucleus (PTgl, PTgr), and oral pontine reticular nucleus (PnOl, PnOr)

Nuclei labels are overlaid on the group average contrast that was used for segmentation (indicated as FA or T₂w). Very good spatial agreement of labels across subjects was observed indicating the feasibility of delineating probabilistic labels of these mesopontine tegmental nuclei.

Figure 2. Probabilistic (n = 12) template labels in MNI space of left (blue-lightblue) and right (red-yellow) paramedian raphe (PMnRl, PMnRr), and caudal linear raphe (CLi, green)

Very good spatial agreement of labels across subjects was observed indicating the feasibility of delineating probabilistic labels of these mesopontine tegmental nuclei.

Figure 3. Template validation and label volumes

We show the spatial overlap (modified Hausdorff distance, bar/errorbar = mean/s.e. across 12 subjects) of semi-automatic labels of CnFl/r, PTgl/r, PnOl/r, PMnRl/r, CLi with: A) manually defined labels; B) the probabilistic atlas label (thresholded at 35%) generated averaging the labels across the other 11 subjects (leave-one-out cross validation). In C) the volume of semi-automatic labels (dark gray, bar/errorbar = mean/s.e. across 12 subjects) and the gold standard label volumes (ligh gray) computed from (Paxinos et al., 2012) is displayed (for PnOl/r, the intermediate bar at ~ 70 mm³ indicates the volume of the superior 9mm-thick part of the gold standard label computed from (Paxinos et al., 2012) Figures 8.42–8.50). Significant differences (p < 0.05) between semi-automatic labels and gold standard labels are indicated with an asterisk (*).