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Right-left asymmetry in the cervical spinal cord using T1 mapping at 7T1Aix Marseille Univ, CNRS, CRMBM, Marseille, France, 2APHM, CHU Timone, Pôle d’Imagerie Médicale, CEMEREM, Marseille, France, 3iLab-Spine, International Associated Laboratory, Marseille-Montreal, France, 4NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montréal, QC, Canada, 5Mila - Quebec AI Institute, Montréal, QC, Canada, 6Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montréal, QC, Canada, 7Centre de Recherche du CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada
Synopsis
Keywords: Spinal Cord, Quantitative Imaging, Spinal cord, T1map, Segmentation, Template, 7T
Motivation: Right-left differences in MR metrics can help identify pathological or specific regions of abnormalities. However, this requires investigating them first on a healthy population
Goal(s): To Investigate whether right-left spinal cord (SC) asymmetry can be identified in vivo and, if yes, determine in which specific regions
Approach: Right-left SC asymmetry was investigated based on cross-sectional area measurements and T1mapping derived from high-resolution 7T MRI and atlas-based segmentation with the AMU7T quantitative template
Results: Right-left T1 asymmetry in the cervical cord was evidenced in one-third of the AMU7T parcels, mostly in motor tracts, but not in lateral corticospinal tracts
Impact: High-resolution quantitative 7T MR imaging and dedicated template may help identify microstructural asymmetry in the spinal cord. Such findings may have to be considered in the future when investigating pathological cohorts
INTRODUCTION
Morphological, structural and functional right-left asymmetry in the brain has been reported, together with the existence of a cerebral asymmetry when comparing right-handed and left-handed subjects [1-3]. In the spinal cord (SC), an unbalance of corticospinal fiber count has been demonstrated postmortem with more fibers on the right and no direct relationship to handedness [4-5]. A morphological asymmetry of the spinal motor neuron cells innervating the upper limbs, with larger cells on the right [6] and a lateralization of motor neuron synaptic activity demonstrated by electromyographic measurements [7] have been reported as well. Handedness and laterality in vivo studies mostly relied on MRI , approached with different imaging modalities in the brain, including 1.5T anatomical [8], 3T functional [9], or 3T diffusion [10-11] MRI. In the SC, right-left asymmetry has been described using 3T fMRI, showing an ipsilateral relationship with handedness [12-13], while other studies relying on quantitative 3T MRI did not observe right-left differences [14-15], possibly because of a lack of sensitivity, or partial volume effect (PVE) contamination. In this context, ultra-high-field (UHF) SC MRI, which provides improved SNR, greater spatial resolution [16-18], and better delineation of gray/white matter (GM/WM) SC substructures [19-20], may open new perspectives, as recently demonstrated using the MP2RAGE sequence [20-21]. Quantitative T1, which is well-suited for in-vivo observation of microstructures [22], may be of particular interest to elucidate the myelin content [23-24]. Combined with AMU7T [25], a 3D quantitative template aligned in the PAM50[26] space recently build from high-resolution 7T images, based on precedent atlases[27-31], new possibilities are thus offered to conduct atlas-based segmentation analyses with refined parcels. The main objective of this study is to take advantage of these methodologies to investigate right-left asymmetry (morphological and/or microstructural) in the SC.MATERIALS AND METHODS
MR protocol:Twenty-three healthy volunteers (10 men, 13 women; age 41.2 ± 13.3 y.o., right-handed) were scanned at 7T using an 8Tx/8Rx neck coil array used in CP mode.A 3D T1-MP2RAGE sequence with high in-plane spatial resolution (0.3x0.3x4 mm3) was acquired as in [20]. (See Fig.1a) . A B1+ map was additionally acquired to correct the quantitative T1map for imperfect radiofrequency excitation [32].
Image processing:
- GM and SC automatic segmentations were performed using the sct_deepseg_sc [33] and sct_deepseg_gm [34] functions of SCT [35]. Masks were manually corrected if required. The WM mask was obtained by subtraction of SC and GM.
- In order to extract metrics in various parcels of WM and GM, the AMU7T template [25] was registered to the subject space, through commands sct_register_to_template and sct_warp_template.
- Left / right T1values and cross-sectional-area (CSA) were calculated per slice in large and refined parcels using the sct_extract_metric command, through its weighted-average (wa) approach.
RESULTS
In the large regions (Fig.2-3), no significant differences were observed for CSA except for hemi-cord*** (p≤0.001), GM*** and WM** (p≤0.01) in C2, and hemi-cord** and GM** in C7, where the left had a higher CSA. For T1, no significant differences were observed except for hemi-cord** and WM* (p≤0.05) in C2 and hemi-cord* and WM* in C6, where the right had a lower T1value.In the refined parcels in lower levels (Fig.4-5), significant differences were observed for CSA in dorsal-intermediate-zone*, fasciculus-gracilis**, and ventral-spinocerebellar**** (p≤0.0001) where the left had a higher CSA, and lateral-corticospinal** and tecto-spinal* where the right had a higher CSA. Significant differences were observed for mean T1 in dorsomarginal-nucleus** and ventral-intermediate-zone** , as well as fasciculus-gracilis** and most of the motor tracts (medial-longitudinal-fasciculus**, medial-reticulospinal* , tecto-spinal*** , ventral-corticospinal***, ventrolateral-reticulospinal**), where the right was associated with lower T1values except for the right lateral-vestibulospinal* which had higher T1.Fig.1b and c summarize the main findings along with the main substructures and their functions.
DISCUSSION & CONCLUSION
In this preliminary study, thanks to high-resolution 7T quantitative T1 MRI and analyses in 23 refined parcels with AMU7T, right-left asymmetry in the cervical cord were evidenced, with lower T1 in 8 right and 1 left parcels on C5-C7 and 4 (and 2 resp.) on C1-C4.Results from some small tracts (1-4 pixels per slice), close to the central canal, may be affected by PVE, and should thus be taken with caution.More importantly, this preliminary study only included right-handed participants so far. Left-handed subjects should now be included to disentangled structural asymmetry (as in [4] from manual laterality (handedness). Larger cohorts should also be considered to study the effect of age and sex.
Acknowledgements
This work was supported by ARSEP (Fondation pour l’Aide à la Recherche sur la Sclérose en Plaques), ANR (Agence Nationale de la Recherche), Fondation Latran, and A*midex.NLM received support from NeuroSchool and Institut Marseille Imaging, Canada Research Chair in Quantitative Magnetic Resonance Imaging [CRC-2020-00179], the Canadian Institute of Health Research [PJT-190258], the Canada Foundation for Innovation [32454, 34824], the Fonds de Recherche du Québec - Santé [322736, 324636], the Natural Sciences and Engineering Research Council of Canada [RGPIN-2019-07244], the Canada First Research Excellence Fund (IVADO and TransMedTech), the Courtois NeuroMod project, the Quebec BioImaging Network [5886, 35450], INSPIRED (Spinal Research, UK; Wings for Life, Austria; Craig H. Neilsen Foundation, USA), Mila - Tech Transfer Funding Program.
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