Minhui Ouyang1, Austin Ouyang2, Qiaowen Yu2, Lina Chalak3, and Hao Huang1,4
1Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States, 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 3Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States, 4Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Synopsis
Association white matter tracts connecting different cortical regions underlie
initial brain circuit formation from mid-fetal to normal time of birth. We
examined the microstructure changes of association tracts and compare them to
those of commissural, limbic and projection tracts with high resolution diffusion
MRI of 10 fetal brains specimens at 20 postmenstrual weeks, 19 in vivo preterm brains
at 35 weeks and 17 in vivo brains at 40 weeks. Distinctive microstructural
developmental patterns were found in association tract groups compared to other
tract groups during 35-40 weeks with DTI-derived metrics (including fractional anisotropy,
mean, axial and radial diffusivity measurements). Purpose
Association white matter (WM) tracts connecting different cortical
regions underlie initial brain circuit formation from mid-fetal to normal time
of birth. Valuable insights into microstructural and macrostructural processes
of the WM maturation in this period have been offered by diffusion MRI (dMRI)
of fetal brain specimens [1] and in vivo
preterm and term brains [e.g. 2-4]. Cerebral WM can be categorized into
functional WM tract groups [5], namely association, commissural, limbic and
projection tract groups. In this study, high resolution dMRI of 10 fetal brains
specimens at 20 postmenstrual weeks, 19 in vivo preterm brains at 35 weeks and
17 in vivo brains at 40 weeks were acquired. With establishment of
population-averaged age-specific template at 20, 35 and 40 weeks, WM skeleton
extraction and dMRI tractography of individual tracts categorized into four
tract groups, we examined the microstructure changes of association tracts and
compare them to those of commissural, limbic and projection tracts.
Methods
Ex vivo fetal brain specimens at 20 weeks and in vivo
neonates at 35 and 40 weeks: 46 normal subjects were involved in this
study and divided into three groups according to the postmenstrual age,
including 10
ex vivo fetal brain
specimens (19.5±0.52 weeks), 19 preterm brains (35.1±0.55 weeks) and 17 term
brains (40.7±0.55 weeks).
dMRI
acquisition: dMRI with a high resolution of 0.3x0.3x0.3mm
3 of
ex vivo 20weeks brains were scanned
with a 4.7T Bruker scanner. dMRI of
in
vivo 35 and 40weeks brains was acquired with a 3T Philips Achieva MR system
and parameters were: TR/TE=6850/78 ms, FOV=168x168mm
2,
resolution=1.5x1.5x1.6mm
3, 60 slices, 30 independent diffusion-weighted
directions, b-value = 1000 sec/mm
2, repetition=2. Fractional anisotropy (FA),
axial, radial and mean diffusivity (AD, RD and MD) were calculated for all
subjects using
DTIStudio (mristudio.org).
Identification
of core WM with population-averaged FA maps at 20, 35 and 40 weeks: With the established
age-specific population-averaged templates at 20, 35 and 40 weeks [7], WM skeleton was extracted.
Measurement of
tract-group level DTI-derived metrics at core WM: All major WM tracts
that can be traced at the fetal (20weeks), preterm (35weeks) or term (40weeks)
brain were delineated with DTI tractography [8], following the protocol in the
literature [9]. Binary masks of the individually traced tracts in each tract group
and the WM skeleton were used to compute the tract-group level FA, AD, RD, MD
and the ratio of AD and RD.
Statistical
analysis: Student’s t-tests were performed for group comparison of tract-group level FA, MD,
RD and AD between different ages with Bonferroni correction.
Results
Fig.1 shows the age-specifc population-averaged FA and
color maps at 20, 35 and 40 weeks with WM skeleton shown as green lines. As
shown in the red dashed box in Fig.2a, signficant FA differences between 35 and
40 week can be only found in association tract group, not in commissural,
limbic or projection tract group. However, signficant differences between 35
and 40 week were found in all tract groups with MD, RD and AD measurements
(Fig. 2b-2d). Signficant FA differences were found for all tract groups between
20 and 35 weeks. Distinctive microstructural changes of association tarct group
can be further confirmed by significant increase of the ratio of AD to RD (Fig.
3).
Discussion and
conclusion
Distinctive microstructural
developmental patterns were found in association tract group compared to other
tract groups during 35-40 weeks with DTI-derived metrics (including FA, MD, RD
and AD measurements). It was reported that onset of myelination in the
perinatal brains begins earlier in the commissural and projection tracts than
in association tracts [10-11]. AD, RD and MD decrease may indicate the pre-myelination
stage of all tract groups, which characterized by the proliferation of
oligodendrocytes lineage precursors with a decrease in water content [12-13]. Besides,
we speculate the more prominent RD decrease in association tract group was
caused by an increase of axon density since literature suggests there is a dramatic
development of cortical connections and brain circuit formation during the
perinatal and early postnatal brain development period [10]. However, caution
needs to be taken to interpret results of these DTI-derived metrics which are
used to infer the microstructure, but are not direct measures of axonal
density, axon packing or myelin level [14].
Acknowledgements
This study is funded by NIH MH092535 and MH092535-S1References
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