Genxia He1,2 and Junchao Qian1
1High Magnetic Field Lab of Chinese Academy of Sciences, Hefei, People's Republic of China, 2Department of Neurology, Anhui Medical University, Hefei, People's Republic of China
Synopsis
Spinal cord injury (SCI) leads to neuronal cell death,
axonal damage and demyelination. Brain undergo anatomical changes following SCI.
Recently MR phase imaging has shown promising application in
visualizing demyelination. In this study we explored the possibility to investigate integrity of
cranial corticospinal tract in SCI using phase imaging. Diffusion tensor
imaging was also used to verify the axonal integrity. The results showed phase
contrast decreased along with axial diffusivity did not significantly change in
contralateral pyramid two weeks post-injury compared to pre-injury levels. Thus,
phase imaging is a potential endogenous biomarker for brain axonal integrity
after SCI.
INTRODUCTION
Spinal cord injury (SCI) leads to neuronal cell death,
axonal damage and demyelination. Both spinal cord 1 and brain 2 undergo anatomical changes following SCI. Recently MR phase imaging has
shown promising application in visualizing demyelination 3 or axonal
damage 4. Therefore, in this study we explored the possibility to investigate integrity of cranial
corticospinal tract (CST) in SCI using phase imaging. Diffusion tensor imaging
(DTI), and its metrics, e.g. axial diffusivity (λ∥) were also used to verify the axonal integrity and preclude
the potential contribution of axonal injury to the observed decrease in
frequency contrast. We also correlated the MRI findings to immunohistochemistry.MATERIALS and METHODS
These studies were performed on eight Sprague-Dawley rats
weighing from 300–350 g. A T9 spinal cord hemisection was performed as
described previously 5. MR scans were carried out on day 0 (pre-injury) and 2
weeks post-injury. All MR studies were performed on an Agilent 9.4 T/400
mm spectrometer. For in vivo MR studies, rats
were anesthetized with a mixture of 2% isoflurane, 30% oxygen and air. A standard 2D gradient echo sequence was used
to acquire the phase images with TR/TE = 1500/15 ms, flip angle = 60o, matrix size 192 × 192,
FOV = 25 mm × 25 mm, 48 slices with slice thickness of 0.5 mm, a spectral width
of 10'000 Hz, 2 averages and a total scan time 9 minutes and 36 seconds. Diffusions
images were acquired using a multi-shot spin-echo echo planar imaging (EPI)
sequence with TR/TE = 3000/24 ms, 8 shots, matrix size 128 × 128, FOV = 25 mm ×
25 mm, 24 slices with slice thickness = 1 mm, 2 averages. A total of thirty
diffusion encoding directions were used at a b-value of 800 s/mm2. Phase
images were obtained as described previously 6. The DTI metrics,
i.e. λ∥ and radial
diffusivity (λ⊥) were
then calculated using several steps within the FSL 5.0.
To quantify CST changes, each MR dataset was analyzed
using ImageJ. Statistical comparisons made between the pre-injury and
post-injury levels were carried out by two tailed Student’s unpaired t tests.RESULTS
Fig.2 shows that the phase contrast decreased mainly in contralateral
pyramid by 46% two weeks post-injury compared to pre-injury levels. Significant reduction of 39% in
contralateral pyramid (p < 0.05) two
weeks post-injury compared to pre-injury levels when quantified λ⊥ values. The λ∥ in all those regions did
not significantly change 2 weeks post-injury compared to pre-injury levels.DISCUSSION
The reduction of frequency contrast along with no significant
changed λ∥ were observed in the contralateral pyramids in this study, suggestive of
loss of myelin or demyelination without obvious axonal damage in the CST white
matter. These MRI findings were confirmed by immunohistological
results, i.e. myelin basic protein staining lost but without obvious reduction
in neurofilament staining after two weeks after injury. The reduced λ⊥in the contralateral pyramids, which may be associated
with activated astrocytes according to the increased expression of GFAP in
those regions. In conclusion, phase imaging is a potential endogenous biomarker
for brain axonal integrity after spinal cord injury.Acknowledgements
This work was supported by the National Natural Science
Foundation of China (http://www.nsfc.gov.cn/) grant 81201068.References
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