Longitudinal diffusion tensor imaging after pediatric traumatic brain injury: Impact of age at injury and time since injury on pathway integrity

Abstract

Following pediatric traumatic brain injury (TBI), longitudinal diffusion tensor imaging may characterize alterations in initial recovery and subsequent trajectory of white matter development. Our primary aim examined effects of age at injury and time since injury on pathway microstructure in children ages 6-15 scanned 3 and 24 months after TBI. Microstructural values generated using tract-based spatial statistics extracted from core association, limbic, and projection pathways were analyzed using general linear mixed models. Relative to children with orthopedic injury, the TBI group had lower fractional anisotropy (FA) bilaterally in all seven pathways. In left-hemisphere association pathways, school-aged children with TBI had the lowest initial pathway integrity and showed the greatest increase in FA over time suggesting continued development despite incomplete recovery. Adolescents showed limited change in FA and radial diffusivity and had the greatest residual deficit suggesting relatively arrested development. Radial diffusivity was persistently elevated in the TBI group, implicating dysmyelination as a core contributor to chronic post-traumatic neurodegenerative changes. The secondary aim compared FA values over time in the total sample, including participants contributing either one or two scans to the analysis, to the longitudinal cases contributing two scans. For each pathway, FA values and effect sizes were very similar and indicated extremely small differences in measurement of change over time in the total and longitudinal samples. Statistical approaches incorporating missing data may reliably estimate the effects of TBI and provide increased power to identify whether pathways show neurodegeneration, arrested development, or continued growth following pediatric TBI. Hum Brain Mapp 37:3929-3945, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: axial diffusivity; children; chronic; dysmyelination; fractional anisotropy; microstructure; neurodegeneration; radial diffusivity; tract-based spatial statistics.

Figure 1

Mean skeletonized FA image with masks corresponding to (a) SLF (blue) and ILF (red); (b) IFOF (blue) and UF (red); (c) cingulum; (d) cingulum hippocampal.

Figure 2

The three‐way interaction of group, age at injury, and time of scanning is plotted for left‐ and right‐hemisphere FA values from the superior longitudinal fasciculus for the total sample. After controlling for age at scan, younger children with TBI had the lowest initial pathway integrity and showed the greatest increase in left hemisphere FA over time. The adolescents with TBI showed the least increase in FA from 3 to 24 months after injury and the greatest deficit at 24 months relative to the OI group. Right hemisphere values showed main effects for group, age, and time but no interactions.

Figure 3

After controlling for age at scan, both radial and axial diffusivities of the left superior longitudinal fasciculus showed more change over time in children than adolescents in both the TBI and OI groups. RD values were significantly elevated in the TBI group suggesting dysmyelination; AD values did not vary by group.