Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord

Mahdi Alizadeh, Joshua Fisher, Sona Saksena, Yusra Sultan, Chris J. Conklin, Devon M. Middleton, Laura Krisa, Jürgen Finsterbusch, Adam E. Flanders, Scott Faro, M. J. Mulcahey, Feroze B. Mohamed

Research output: Contribution to journalArticle

Abstract

Background and objective: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age. Method: A total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ± 3.26 (mean ± standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6–11 years (n = 11) and age group B = 12–16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters. Results: An increase in FA (group A = 0.42 ± 0.097, group B = 0.49 ± 0.116), white matter tract density (group A = 368.01 ± 236.88, group B = 440.13 ± 245.24) and mean length of fiber tracts (group A = 48.16 ± 20.48 mm, group B = 60.28 ± 23.87 mm) and a decrease in MD (group A = 1.06 ± 0.23 × 10−3 mm2/s, group B = 0.82 ± 0.24 × 10−3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p < 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level. Conclusion: This study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results.

Original languageEnglish (US)
Pages (from-to)784-792
Number of pages9
JournalNeuroImage: Clinical
Volume18
DOIs
StatePublished - Jan 1 2018

Fingerprint

Diffusion Tensor Imaging
Thorax
Pediatrics
Spinal Cord
Anisotropy
Cervical Cord
Age Groups

Keywords

  • Age
  • Diffusion tensor imaging
  • Fiber tractography
  • Pediatric spinal cord

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Alizadeh, M., Fisher, J., Saksena, S., Sultan, Y., Conklin, C. J., Middleton, D. M., ... Mohamed, F. B. (2018). Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord. NeuroImage: Clinical, 18, 784-792. https://doi.org/10.1016/j.nicl.2018.03.014

Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord. / Alizadeh, Mahdi; Fisher, Joshua; Saksena, Sona; Sultan, Yusra; Conklin, Chris J.; Middleton, Devon M.; Krisa, Laura; Finsterbusch, Jürgen; Flanders, Adam E.; Faro, Scott; Mulcahey, M. J.; Mohamed, Feroze B.

In: NeuroImage: Clinical, Vol. 18, 01.01.2018, p. 784-792.

Research output: Contribution to journalArticle

Alizadeh, M, Fisher, J, Saksena, S, Sultan, Y, Conklin, CJ, Middleton, DM, Krisa, L, Finsterbusch, J, Flanders, AE, Faro, S, Mulcahey, MJ & Mohamed, FB 2018, 'Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord', NeuroImage: Clinical, vol. 18, pp. 784-792. https://doi.org/10.1016/j.nicl.2018.03.014
Alizadeh, Mahdi ; Fisher, Joshua ; Saksena, Sona ; Sultan, Yusra ; Conklin, Chris J. ; Middleton, Devon M. ; Krisa, Laura ; Finsterbusch, Jürgen ; Flanders, Adam E. ; Faro, Scott ; Mulcahey, M. J. ; Mohamed, Feroze B. / Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord. In: NeuroImage: Clinical. 2018 ; Vol. 18. pp. 784-792.
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abstract = "Background and objective: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age. Method: A total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ± 3.26 (mean ± standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6–11 years (n = 11) and age group B = 12–16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters. Results: An increase in FA (group A = 0.42 ± 0.097, group B = 0.49 ± 0.116), white matter tract density (group A = 368.01 ± 236.88, group B = 440.13 ± 245.24) and mean length of fiber tracts (group A = 48.16 ± 20.48 mm, group B = 60.28 ± 23.87 mm) and a decrease in MD (group A = 1.06 ± 0.23 × 10−3 mm2/s, group B = 0.82 ± 0.24 × 10−3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p < 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level. Conclusion: This study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results.",
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author = "Mahdi Alizadeh and Joshua Fisher and Sona Saksena and Yusra Sultan and Conklin, {Chris J.} and Middleton, {Devon M.} and Laura Krisa and J{\"u}rgen Finsterbusch and Flanders, {Adam E.} and Scott Faro and Mulcahey, {M. J.} and Mohamed, {Feroze B.}",
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T1 - Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord

AU - Alizadeh, Mahdi

AU - Fisher, Joshua

AU - Saksena, Sona

AU - Sultan, Yusra

AU - Conklin, Chris J.

AU - Middleton, Devon M.

AU - Krisa, Laura

AU - Finsterbusch, Jürgen

AU - Flanders, Adam E.

AU - Faro, Scott

AU - Mulcahey, M. J.

AU - Mohamed, Feroze B.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background and objective: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age. Method: A total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ± 3.26 (mean ± standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6–11 years (n = 11) and age group B = 12–16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters. Results: An increase in FA (group A = 0.42 ± 0.097, group B = 0.49 ± 0.116), white matter tract density (group A = 368.01 ± 236.88, group B = 440.13 ± 245.24) and mean length of fiber tracts (group A = 48.16 ± 20.48 mm, group B = 60.28 ± 23.87 mm) and a decrease in MD (group A = 1.06 ± 0.23 × 10−3 mm2/s, group B = 0.82 ± 0.24 × 10−3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p < 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level. Conclusion: This study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results.

AB - Background and objective: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age. Method: A total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ± 3.26 (mean ± standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6–11 years (n = 11) and age group B = 12–16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters. Results: An increase in FA (group A = 0.42 ± 0.097, group B = 0.49 ± 0.116), white matter tract density (group A = 368.01 ± 236.88, group B = 440.13 ± 245.24) and mean length of fiber tracts (group A = 48.16 ± 20.48 mm, group B = 60.28 ± 23.87 mm) and a decrease in MD (group A = 1.06 ± 0.23 × 10−3 mm2/s, group B = 0.82 ± 0.24 × 10−3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p < 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level. Conclusion: This study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results.

KW - Age

KW - Diffusion tensor imaging

KW - Fiber tractography

KW - Pediatric spinal cord

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