Perfusion and diffusion in the extremely preterm young adult thalamus
Andrew Melbourne1, Zach Eaton-Rosen1, Eliza Orasanu1, Joanne Beckmann2, Alexandra Saborowska3, 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 work investigates the appearance of the thalamus using multiple MR imaging contrasts between a population of extremely-preterm born adolescents and their term-born peers.

Introduction

Infants born in extreme prematurity (less than 28 weeeks completed gestation) are at increased risk of adverse neurodevelopmental outcome [1]. The long-term impact of extreme prematurity on long term brain development is currently poorly understood. Neuroimaging studies of young adult survivors are now available and the measurement of tissue composition and structure with MRI can now be correlated with neurocognitive performance. Previous work in preterm neonates [2,3] has repeatedly shown developmental differences in the thalamus and here, through the use of multi-contrast MRI we investigate the long-term structural and perfusion changes in the thalamus of survivors of extreme prematurity at 19 years of age.

Data

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 socioeconomically matched peers were acquired on a 3T Phillips Achieva. Diffusion weighted data was acquired across four b-values at b = {0,300,700,2000}s.mm−2 with n={4,8,16,32} directions respectively at TE=70ms (2.5x2.5x3.0mm). T2 weighted data was acquired in the same space as the diffusion imaging with ten echo times at TE={13,16,19,25,30,40,50,85,100,150}ms (2.5x2.5x3.0mm). We acquired Pseudo-Continuous ASL (PCASL) for 30 control-label pairs with PLD=1800ms+41ms/slice, label duration τ=1650ms (resolution 3x3x5mm) [4]. PCASL Acquisition was carried out using 2D EPI in the same geometry as the DWI ensuring similar levels of distortion. In addition we acquired 3D T1-weighted (TR/TE=6.93/3.14ms) volume at 1mm isotropic resolution.

Methods

Diffusion weighted data were fitted using the Neurite Orientation Dispersion and Density Imaging model to calculate a neurite density estimate [6]. The thalamic T2 is estimated by fitting a mono-exponential decay to the echo time data greater than 40ms whilst myelin density can be estimated from the short component of a three-compartment multi-exponential fit to the multi-echo T2 imaging data with T2s of {20,80,200}. Cerebral blood flow maps are estimated from the PCASL data [4]. Additionally, we obtain a multi-class tissue segmentation and corresponding region labels from the T1-weighted data [5]. Example parameter maps and a thalamic segmentation are shown in Figure 1.

Results

Figure 2 shows the differences in thalamus volume, average neurite and myelin densities, Fractional Anisotropy (FA), T2 and thalamic blood flow for this cohort. For the entire cohort, thalamus volume is reduced from an average 13.3±1.3cm3 to 11.4±1.3cm3 (ci: -(1.42 to 2.38)cm3, p<0.001), NODDI imaging suggests that the non-significant lowering of thalamic FA (p=0.60) in EPs has a significant component associated with a reduced neurite density (ci: -(0.006-0.028), p=0.004). There is no observable significant difference in the estimated myelin content (ci: -0.01 to 0.02, p=0.71), although the average thalamus T2 is reduced from 61.3ms to 59.7ms (ci: 0.05 to 3.0ms, p=0.04). Thalamus blood flow is reduced on average from 31.5ml/100g/min to 29.7ml/100g/min (ci: -(0.07 to 3.58)ml/100g/min, p=0.04).

Discussion

Using multi-parametric MRI we have compared the phenotypes of the EP and term-born adolescent thalamus. We have shown that the thalamus of extremely preterm survivors shows structural alteration even at 19 years of age. In addition to having a lower volume, the measured neurite density is lower in the EP group, whilst myelin density is not measurably different which may have implications for the functional properties of the tissue. Average thalamus blood flow per voxel and T2 also appear to be reduced. Given the importance of the thalamus as a central relay of information, these features are likely to have strong implications for the social and developmental outcomes of these young adults. Our future work will increase the size of the current cohort and investigate to what extent structural and functional measurement differences in the thalamus are linked to external physiological and psychological factors.

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] Ball, G., et al, 2015. Thalamocortical connectivity predicts cognition in children born preterm. Cereb Cortex. 25(11):4310-8

[3] Eaton-Rosen, Z., et al, 2015. Longitudinal measurement of the developing grey matter in preterm subjects using multi-modal mri. Neuroimage 111, 580–589.

[4] Alsop, D. C. et al (2014). Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the european consortium for ASL in dementia. MRM; 73(1):102-16

[5] 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

[6] Zhang, H. et al. 2012. NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. Neuroimage 61 (4), 1000–1016.

Figures

Thalamic imaging data. A) Thalamus parcellation, B) Neurite density, C) colour-coded FA, D) T2 map, E) Cerebral Blood Flow map.

Distributions of imaging parameters for A) Thalamus volume, B) Neurite Density, C) Myelin density, D) Blood Flow, E) FA, F) T2.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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