Jennifer A. Lefeuvre1,2, Wen-Yang Chiang3, Nicholas J. Luciano1, Cecil C. Yen3, Mathieu D. Santin2, Stéphane Lehéricy2, Steve Jacobson4, Afonso C. Silva3, Daniel S. Reich1, and Pascal Sati1
1TNS/NIB/NINDS, National Institutes of Health, Bethesda, MD, United States, 2CENIR, UPMC-Inserm U1127, CNRS 7225, Institut Cerveau Moelle, Paris, France, 3CMS/LFMI/NINDS, National Institutes of Health, Bethesda, MD, United States, 4VIS/NIB/NINDS, National Institutes of Health, Bethesda, MD, United States
Synopsis
When induced to have experimental autoimmune
encephalomyelitis (EAE), marmosets can suffer from motor and sensory
deficits highly suggestive of lesions located in the spinal cord. In this
study, we developed an in vivo spinal cord imaging protocol at 7T for marmosets, and were
able to visualize gray
and white matter as well as focal EAE lesions. Future work will focus on characterizing
the spatiotemporal evolution of spinal cord EAE lesions over the disease course.
Introduction
Experimental autoimmune encephalomyelitis (EAE)
in the common marmoset often involves motor and sensory deficits, similar to MS1.
Previous study using postmortem MRI
on the spinal cord (SC) of marmosets with EAE showed that demyelinated lesions can
be frequently found, and that these lesions are distributed along the entire SC
length2. However, the dynamics of SC lesion development in marmoset
EAE are still unknown. Therefore, the goal of the present study was to develop an in vivo MRI protocol enabling the visualization of normal SC gray
(GM) and white (WM) matter in healthy marmosets, as well as the detection of SC
abnormalities in marmosets with EAE.Methods
Two healthy and one EAE animals were used in
this study. MRI was performed on a 7T/30cm MRI scanner (Bruker). A 3D-printed
cradle was designed to position the anesthetized animals in the supine position
inside the scanner. A custom-built 12-channel phased-array coil was
incorporated inside the plastic cradle to image the entire SC length. A proton density-weighted
(PD-w) fast-spin-echo sequence (2D RARE, TR/TE/Rare factor/NA:3500ms/15ms/2/4)
was acquired at the cervical and thoracic levels in sagittal (0.125×0.125×0.6
mm3) and axial (0.135×0.135×0.6 mm3) planes. Signal-to-noise
ratio (SNR) and contrast-to-noise ratio (CNR) were computed to assess the image
quality.Results
The
3D-printed cradle combined with the custom-built 12-channel phased-array coil
fit the curvature of the entire marmoset spine length. This setup allowed for consistent
alignment of the spine and optimal signal depth for the coil sensitivity. High-quality
sagittal PD-w images showed uniform signal sensitivity along the cord length
(Figure 1). Visualization of the SC was also excellent on axial PD-w images,
partly due to the absence of magnetic susceptibility artifacts (Figure 2). With an SNR>30 for the SC tissues, anatomical structures (GM,
WM, nerve roots, CSF) were clearly identified. Clear delineation between GM and
WM tissues was also possible (CNRGM/WM>11). One focal hyperintense lesion was detected
at the cervical level of an EAE marmoset located within the lateral WM column, possibly
corresponding to an area of demyelination (Figure 3).Conclusion
A
dedicated setup for imaging in vivo
the entire marmoset spinal cord was developed in this study. High-quality images
were acquired at 7T and displayed details of cord anatomy, including GM/WM
tissue contrast. Future work will focus on characterizing aspects of marmoset,
including robust detection of spinal cord lesions with various MRI contrasts
and analysis of the
spatiotemporal evolution of those lesions over the disease course.Acknowledgements
No acknowledgement found.References
1: Villoslada
P, Hauser SL, Bartke I, et al. Human nerve growth factor protects common
marmosets against autoimmune encephalomyelitis by switching the balance of T
helper cell type 1 and 2 cytokines within the central nervous system. J Exp
Med. 2000;191(10):1799-1806.
2: Lefeuvre J. Ultra-high-resolution postmortem imaging of marmoset EAE spinal cords. In
Proceedings of the 24th Annual Meeting of ISMRM, Singapore, 2016. Program
number 4404.