Synopsis
This is the first study in pediatric subjects investigating the DTI
values and it’s reproducibility along the entire cervical and thoracic spinal
cord (SC). DTI data was acquired from 22 typically developing (TD) children and
15 patients with spinal cord injury (SCI) using an inner field-of-view DTI
sequence. Regions of interest were manually drawn on whole cord at every axial slice along the cervical and thoracic SC. Fractional
anisotropy and radial diffusivity values were significantly different between
TD and SCI suggesting that these appear to be the most sensitive
parameter in assessing the state of SC in chronic phase of SCI. This study
demonstrates that DTI has a potential to be used as an imaging biomarker for
evaluating the extent of injury, which may be useful to prognosticate as well
as monitor patients with SCIBackground
and Objective
Spinal cord injury (SCI) is characterized by loss of motor and
sensory function below the level of injury and affects about 273,000 persons in
the United States
1. Despite the relatively low incidence of
pediatric SCI
2, mortality and cost of life long care are high
3.
Studies of treatment effectiveness are lacking largely due to small clinical
population and lack of valid outcome instruments that yield reliable scores in
children. The precision of the neurological clinical evaluation is poor in children
under 6 years of age
4. In response to the limitations of existing
methods, we have developed and tested an inner field-of-view (FOV) diffusion
tensor imaging (DTI) as a method to evaluate the spinal cord (SC) in typically
developing (TD) and children with SCI. Few studies have examined the utility of
DTI in children
5,6, but none of these studies have examined the
diffusion characteristics along the entire cervical and thoracic SC. The
purpose of this study was to (a) investigate the feasibility of obtaining
reliable DTI parameters along the entire cervical and thoracic SC in TD healthy
children and children with SCI using an inner FOV sequence, (b) examine the
reproducibility of DTI parameters, (c) determine whether microstructural
changes quantified by DTI are associated with clinical neurological deficits.
Methods
Subjects: Twenty-two TD children (mean age, 11.03yrs) without evidence of
SC pathology and 15 patients (mean age, 11.42yrs) with chronic SCI were
recruited. Written informed child assent and parent consent were obtained under
the protocol approved by Institutional review board. The International
Standards for Neurological Classification of SCI (ISNCSCI) were used to define
the clinical level and severity of injury in SCI patients.
Imaging: Subjects underwent 2 identical scans (minimum time between
scans=2h) using 3.0T Verio MR scanner (Siemens, Erlangen, Germany) with
4-channel neck matrix and 8-channel spine matrix coils. The protocol consisted
of conventional T1- and T2-weighted structural scans and axial DTI scans based
on inner FOV sequence described previously
7. Manual shim volume
adjustments were also performed prior to data acquisition. DTI images were
acquired axially using 2 overlapping slabs, to cover the cervical (C1-upper thoracic region) and thoracic
(upper thoracic-L1) SC. The imaging parameters included: 3 averages of 20
diffusion directions, 6 b0 acquisitions, b=800s/mm
2, voxel
size=0.8x0.8x6mm
3, axial slices=40, TR=7900ms, TE=110ms, and
acquisition time=8:49min and no gating.
Data Analysis: A central mask was applied to the raw DTI images to eliminate the
anatomy outside the SC. A mean b0 image was calculated, generated from the
co-registration of all 6 b0 acquisitions. The diffusion weighted images were
corrected for motion using a rigid body correction algorithm
8. After
motion correction, tensor estimation was done on a voxel-by-voxel basis from
the axial DTI images using in-house software developed in MATLAB. For robust
diffusion tensor estimation, a non-linear fitting algorithm using an implementation
of the RESTORE technique was used
9. Regions of interest were
manually drawn on the whole cord on grayscale fractional anisotropy (FA) maps at every axial slice along the cervical and
thoracic SC for both scans. DTI parameters were quantified at each intervertebral disk level and mid-vertebral body
level of the cervical and thoracic SC in all subjects.
Statistical Analysis: Analysis of covariance for repeated measures was performed to
compare data from TD and SCI. Test-retest reliability was calculated
using the intra-class correlation coefficient according
to method of Shrout and Fleiss
10. Association between DTI and
ISNCSCI values were evaluated by Spearman partial correlation coefficients. A p
value ≤ 0.05 was considered statistically significant.
Results
The images obtained with inner FOV sequence
showed excellent delineation of both cervical and thoracic SC with minimal
distortions (Fig. 1). FA values were significantly lower while radial
diffusivity (RD) was significantly higher along the cervical and thoracic SC in
patients with SCI compared to TD, however, mean diffusivity (MD) and axial
diffusivity (AD) values were not statistically significant (Table 1, Fig. 2). There
was a strong reliability for all DTI parameters along the cervical and thoracic
SC in all subjects (Table 2). MD, AD and RD showed the greatest number of correlations
with ISNCSCI followed by FA indicating that better neurological function is
associated with greater unidirectional diffusion (Table 3).
Conclusion
This is the first study in pediatric subjects
investigating the DTI values and it’s reproducibility along the entire cervical
and thoracic SC regions. The observed significant DTI changes between TD and
SCI suggest that FA and RD appears to be the most sensitive parameter in assessing
the state of SC in chronic phase of SCI. This study demonstrates that DTI has a
potential to be used as an imaging biomarker for evaluating the extent of
injury, which may be useful to prognosticate as well as monitor patients with SCI.
Acknowledgements
This work was supported by
National Institute of Neurological Disorders of the National Institutes of
Health under award number R01NS079635.
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