Diffusion Tensor Imaging of the Cervical and Thoracic Spinal Cord in Pediatric Subjects using an inner FOV 2D RF pulse sequence.
Sona Saksena1, Devon M Middleton2, Laura Krisa3, Pallav Shah2, Scott H Faro2, Rebecca Sinko3, John Gaughan4, J├╝rgen Finsterbusch5, M J Mulcahey3, and Feroze B Mohamed1

1Department of Radiology, Thomas Jefferson University, Philadelphia, PA, United States, 2Department of Radiology, Temple University, Philadelphia, PA, United States, 3Department of Occupational Therapy, Thomas Jefferson University, Philadelphia, PA, United States, 4Biostatistics Consulting Center, Temple University School of Medicine, Philadelphia, PA, United States, 5Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

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 SCI

Background 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 States1. Despite the relatively low incidence of pediatric SCI2, mortality and cost of life long care are high3. 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 age4. 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 children5,6, 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 previously7. 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/mm2, voxel size=0.8x0.8x6mm3, 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 algorithm8. 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 used9. 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 Fleiss10. 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.

References

1. Jones LL, Oudega M, Bunge MB, Tuszynski MH. 2001. Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury. J. Physiol. 533(Pt 1), 83-89. 2. Piatt JH Jr. 2015. Pediatric spinal injury in the US: epidemiology and disparities. J. Neurosurg. Pediatr. 26, 1-9. 3. Parent S, Mac-Thiong JM, Roy-Beaudry M, Sosa JF, Labelle H. 2011. Spinal cord injury in the pediatric population: a systematic review of the literature. J. Neurotrauma. 28(8), 1515-1524. 4. Mulcahey MJ, Gaughan JP, Chafetz RS, Vogel LC, Samdani AF, Betz RR. 2011. The international standards for neurological classification of spinal cord injury: psychometric evaluation and guidelines for use with children and youth. Phys. Med. Rehabil. 92, 1264-1269. 5. Mohamed FB, Hunter LN, Barakat N, Liu CS, Sair H, Samdani AF, Betz RR, Faro SH, Gaughan J, Mulcahey MJ. 2011. Diffusion tensor imaging of the pediatric spinal cord at 1.5T: preliminary results. AJNR Am. J. Neuroradiol. 32(2), 339-345. 6. Mulcahey MJ, Samdani AF, Gaughan JP, Barakat N, Faro S, Shah P, Betz RR, Mohamed FB. 2013. Diagnostic accuracy of diffusion tensor imaging for pediatric cervical spinal cord injury. Spinal Cord 51(7), 532-537. 7. Finsterbusch J. 2012. Improving the performance of diffusion-weighted inner field-of-view echo-planar imaging based on 2D-selective radiofrequency excitations by tilting the excitation plane. J. Magn. Reson. Imaging 35(4), 984–992. 8. Middleton DM, Mohamed FB, Barakat N, Hunter LN, Shellikeri S, Finsterbusch J, Faro SH, Shah P, Samdani A, Mulcahey MJ. 2014. An investigation of motion correction algorithms for pediatric spinal cord DTI in healthy subjects and patients with spinal cord injury. Magn. Reson. Imaging 32(5), 433-439. 9. Chang L, Jones DK, Pierpaoli C. 2005. RESTORE: Robust Estimation of Tensors by Outlier Rejection Magn. Reson. Med. 53(5), 1088-1095. 10. Shrout PE, Fleiss JL. 1979. Intraclass Correlations: Uses in Assessing Rater Reliability. Psychological Bulletin 86(2), 420-428.

Figures

Table 1: Mean and standard deviation of FA, MD, AD and RD along the cervical and thoracic SC in TD and patients with SCI.

FA, fractional anisotropy; MD, mean diffusivity; AD, axial diffusivity; RD, radial diffusivity; SC, spinal cord; TD, typically developing; SCI, spinal cord injury


Table 2: ICC [95% CI] for repeatability of each DTI parameter across all levels of cervical and thoracic SC.

ICC, intra-class correlation coefficient; CI, confidence interval; DTI, diffusion tensor imaging; LCL, lower confidence limit; UCL, upper confidence limit


Table 3: Spearman correlation coefficients (rs) of DTI values* and ISNCSCI values.

*Bold areas reflect fair association.

† P ≤ 0.05

DTI, diffusion tensor imaging; ISNCSCI, International Standards for Neurological Classification of spinal cord injury; UETMS, upper extremity total motor score; LETMS, lower extremity total motor score; TPPS, total pinprick score; TLTS, total light touch score; AC, anal contraction; AS, anal sensation


Fig. 1: Reconstructed sagittal FA color maps of the C1-T5-T6 (a1) and T4-T5-Mid-L1 (a2) SC of a representative TD and C1-Mid-T10 (a3) and T5-T6-Mid-L2 (a4) SC of a SCI patient. Arrow represents the level of injury.

Fig. 2: Boxplots of average FA, MD, AD and RD values for the TD (n=22) and SCI patients (n=15) along the entire cervical and thoracic SC.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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