Synopsis
By
using a surface-based method (FreeSurfer), the cortical thickness measurement was
performed on young adolescents born preterm with very low birth weight (n = 15,
birth weight < 1500 g) and age-matched term born controls (n = 17). The preterms, who present no brain injuries,
showed a thicker cortex in parietal, occipital, and temporal regions compared
to the controls, suggesting the delay of cortical thinning.Purpose
Preterm born neonates with very low birth weight
(VLBW, birth weight < 1500g) have a high risk of brain injury, and the
encephalopathy of prematurity could influence the process of cortical
maturation during childhood and affect brain function. To investigate the abnormality of gray
matter, the cerebral cortical thickness is considered as an important biomarker
of neuroanatomical development. The
growth pattern of healthy children, which could vary at different cortical
regions, is generally composed of an initial increase that reaches to the peak
at around 8 to 10 years, followed by a decrease due to pruning of inefficient
synaptic connection.
1 In comparison with age-matched controls, both
regional cortical thinning and thickening in preterms have been reported in several
MRI-based studies,
2-6 and diverse results are found at different
scan ages. For example, regions with
thinner cortex is more prominent in preterm born teenagers with VLBW
2-3
while a thicker cortex is found at more regions in school-aged children.
4-6
Also, the presence of focal brain injury, such as periventricular leukomalacia
and intraventricular hemorrhage, may lead to a distinct pattern of cortical
thickness.
4 To our knowledge, previous investigations in preterm
born adolescents did not exclude those preterms with brain injuries.
2-3
Therefore, the aim of this study is to explore the cortical development by
comparing the cortical thickness between young adolescents born preterm with VLBW
and age-matched controls.
Methods
The
MPRAGE sequence (TE/TR = 2.07/2000 ms, TI = 900 ms, flip angle = 9°, FOV = 256 mm, voxel size = 1mm
3)
is performed on a 3-T scanner (Magnetom Skyra, Siemens, Erlangen, Germany) to
obtain three-dimensional T1-weighted MRI of 15 young adolescents born preterm
(mean age = 12.8 years, SD = 1.4, five females) and 17 term born controls (mean
age = 13.8 years, SD = 1.7, six females).
Neither periventricular leukomalacia nor neonatal cerebral lesion was
found in the preterm group. The cortical
thickness is estimated by using a fully-automated surface-based method
7
(FreeSurfer software package, version 5.3.0), which is one of the most widely
used techniques at its field.
2, 4-6 In brief, this method reconstructs the white
matter surface (white matter-gray matter interface) and the pial surface (gray
matter-CSF interface) by a topological mesh model, and the cortical thickness
is calcualted as the average of the distance from a given point on gray/white
boundary to the closest point on pial surface and from that point back to the
closest point on white matter surface again.
All values of cortical thickness can be mapped the inflated cortex, and
the global or regional statistics of thickness can be computed. To reduce noise-induced error in segmentation
and registration, a Gaussian kernel with a full width at half maximum of 30 mm
is used for smoothing. Unpaired two-sample
t-test is used for group comparison between preterms and controls. A two-tailed p value less than 0.05 is
considered statistically significant.
Results
The pretem group shows significantly thicker
cortex at parietal (post central gyrus, superior parietal lobule, and
precuneus), temporal (superior temporal gyrus), and occipital lobes (lateral
occipital cortex) compared to the normal control (Figure 1, Table 1). No region indicates that the preterm group
has thinner cortical thickness than control.
In addition, no significant difference is found on global thickness
between groups.
Discussion
Previous studies examing cortical thickness in school-aged
children with no
6 or possibly mild
5 brain injuries report
a thicker cortex at frontal, occipital, and parietal regions and a thinner
cortex at a more limited area in preterm born subjects. Besides, age is found correlated negatively
with global and regional cortical thickness in preterms, but not in controls, suggesting
the delay of cortical thinning in children born preterm.
5 In this
study, data were acquired at early adolescence when the growth of cortical
thickness has already reached its peak and pruning is taking place in healthy term
born subjects. As a result, our finding of
a thicker cortex in preterms is consistent with the hypothesis of delayed
maturation,
5, 6 yet the possibility of permenant cortical change
can not be ruled out. The main limitation
of this study is the small number of participants, limiting the statistical
power. Further longitudinal
investigation is required to provide more insight of cortical maturation in
preterm born survivors.
Acknowledgements
This work was funded by Ministry of Science and Technology at Taiwan (MOST 104-2221-E-110-039).References
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