Andrew Melbourne1, Eliza Orasanu1, Zach Eaton-Rosen1, Manuel J Cardoso1, Joanne Beckmann2, Lorna Smith3, David Atkinson3, Neil Marlow2, and Sebastien Ourselin1
1Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, 2Institute for Women's Health, University College London, London, United Kingdom, 3University College Hospital, London, United Kingdom
Synopsis
This abstract presents an analysis of brain tissue
volume in a cohort of 69 extremely preterm born young adults and 50 term-born
controls at 19 years of age.Introduction
The consequences of extremely preterm birth are a global health concern.
Rates of prematurity are increasing throughout the world and long-term sequelae
range from physical impairments such as cerebral palsy or blindness to social
and executive function impairments such as autism. In the UK, studies have
shown that although survival rates at the lowest gestations are increasing,
rates of disability remain unchanged [1,2]. The long-term impact of these
deficits on adolescence is currently poorly understood and the adolescent brain
phenotype of extreme prematurity is currently unknown. Our work comprises a
study of 69 extremely preterm born 19 year olds and 50 of their age-matched
peers, social-economically matched at 6 years of age. Neuroimaging carried out
on this cohort will enable us to establish the long-term effects of extreme
prematurity on the appearance and structure of the brain. This work
investigates how brain tissue volumes differ in this extremely preterm born
group of young adults.
Methods
Imaging
data were acquired for a cohort of 119 adolescents at 19 years of age. Data for
69 extremely preterm adolescents (F/M=41/28, mean birth gestation=25.0±0.8wks)
and 50 (F/M=30/20) term-born socio-economically matched peers were acquired on
a 3T Phillips Achieva. We acquired 3D T1-weighted MPRAGE (TR/TE=6.93/3.14ms) volumes at
1mm isotropic resolution to obtain a tissue segmentation and region labels
using the Geodesic Information Flows framework [3]. This method produces a state-of-the-art segmentation and regional labeling by voxel-wise voting between several propagated atlases guided by the local image similarity. Region labels
in this routine are specifically defined for the cerebellum (combining both
grey and white matter components). We investigate how these pure tissue volumes vary between
preterm status and by gender and correlate our results with information on height and weight.
Results
Figure 1 shows an example
segmentation of an extremely preterm born adolescent with tissue volumes
labeled. Figure 2 shows tissue volume results grouped by EP/term status and by
gender. Grey and white matter absolute volumes are both significantly reduced
in the EP relative to the term groups.
White matter volume is between
22.4-59.5cm3 (95%ci) lower in preterm females (371cm3±39.2cm3)
than term females (412cm3±37.5cm3); white matter volume
is between 40.0-47.8cm3 lower in preterm males (399cm3±46.4cm3)
than their term-born counterparts (464cm3±36.7cm3) and white
matter volume is also significantly lower in term-born females than term-born
males (-29.8cm3 to -73.3cm3 95%ci).
Grey matter volume is between
13.0-56.2cm3 (95%ci) lower in preterm females (565cm3±42.9cm3)
than term females (600cm3±47.6cm3); grey matter volume is
between 33.6-96.7cm3 lower in preterm males (610cm3±62.7cm3)
than their term-born counterparts (675cm3±37.1cm3) and
grey matter volume is also significantly lower in term-born females than
term-born males (-49.1cm3 to -100cm3 95%ci).
We also investigate the GM to WM
ratio (Figure 2f). The GM/WM ratio is significantly higher (0.03-0.11, p=0.001)
in preterm females (1.52±0.09) than in term females (1.45±0.07). Similarly this
ratio is also higher (0.02-0.13,p=0.006) in preterm males (1.53±0.09) than in
term males (1.46±0.08). Differences between preterm males and preterm females
(p=0.86) and between term males and term females (p=0.97) are not significant,
suggesting that this feature may be representative feature of the preterm brain
summarising differences in an underlying white matter layout independent of
brain size.
Comparable analysis
for cerebellum size suggests a similar significant relationship in volume
between groups. In
addition to investigating the GM/WM ratio, normalisation by brain volume
(including ventricular CSF) illustrates how grey, white and cerebellar volume
are influenced by total brain volume. Differences between grey matter distributions
for each group are reduced such that the results no longer reach significance,
suggesting that the grey matter proportion is not detectably altered.
Differences between normalised cerebellum volumes also do not reach
significance. Differences between normalised white matter volumes do remain
significant, suggesting that it is the white matter component that is affected
most strongly by extremely preterm birth. Carrying out a correction for subject
height does not remove the significant correlations described above, suggesting
a non-linear relationship between height and brain size.
Conclusion
The
analysis in this work has allowed a characterisation of the adolescent preterm
brain to be made. The results suggest that the
white matter component of the preterm brain is more significantly reduced than
the cortical grey and cerebellar volumes. Analysis by both age and gender has
allowed us to separate effects due to natural variability in head size from
those due to extreme prematurity. Across groups, the most variable results are
seen in the EP male group, perhaps suggesting a more variable response to
extremely preterm birth. This might be borne out by future studies of neurocognitive
function [4]. Our future work will investigate how the observation of a relative white
matter reduction reveals itself on microstructural imaging and how these
features manifest in neuropsychological examinations.
Acknowledgements
We would also like to acknowledge the MRC (MR/J01107X/1), the National
Institute for Health Research (NIHR), the EPSRC (EP/H046410/1) and the
National Institute for Health Research University College London
Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact
Initiative- BW.mn.BRC10269). This work is supported by the EPSRC-funded
UCL Centre for Doctoral Training in Medical Imaging (EP/L016478/1).References
[1] Volpe, J. J., 2009. Brain injury in premature infants: a complex
amalgam of destructive and developmental disturbances. Lancet Neurol 8
(1), 110–124.
[2] Moore, T., et al 2012. Neurological and developmental outcome in extremely preterm children born in england in 1995 and 2006: the EPICure studies. BMJ 345, e7961.
[3] Cardoso, M. J. et al. Geodesic Information Flows:
Spatially-Variant Graphs and Their Application to Segmentation and Fusion.IEEE
Trans Med Imaging, 2015, 34, 1976-1988
[4] Northam, G. B. et al. Total brain white matter is a major determinant of IQ in adolescents born preterm. Ann Neurol, 2011, 69, 702-711