Development of regional cortical GM and WM volumes in utero in fetuses with Trisomy 21.
Poster No:
875
Submission Type:
Abstract Submission
Authors:
Abi Fukami - Gartner1, Alena Uus1, Vanessa Kyriakopoulou1, Helena Sousa1, Roos Bos1, Daniel Cromb1, Megan Hall1, Joseph Hajnal1, Maria Deprez1, Jana Hutter1, Lisa Story1, Jonathan O'Muircheartaigh1, Mary Rutherford1
Institutions:
1Centre for the Developing Brain, King’s College London, London, United Kingdom
First Author:
Co-Author(s):
Vanessa Kyriakopoulou, Dr
Centre for the Developing Brain, King’s College London
London, United Kingdom
Centre for the Developing Brain, King’s College London
London, United Kingdom
Jonathan O'Muircheartaigh
Centre for the Developing Brain, King’s College London
London, United Kingdom
Centre for the Developing Brain, King’s College London
London, United Kingdom
Introduction:
Trisomy 21 (T21, i.e., Down syndrome) is the most common cause of intellectual disability with a known genetic aetiology affecting approximately 1 in 1000 live births (De Graaf 2021). Most individuals with T21 are classified as having mild to moderate intellectual disability, although a wide and largely unexplained range of neurodevelopmental outcomes are observed (Chapman 2000). There is still a gap in knowledge about detailed structural brain development in utero in T21. We have recently published a comprehensive volumetric phenotyping of the neonatal brain in T21 (Fukami-Gartner, 2023). Here, we investigate the timing and differences in the development of regional cortical grey matter (GM) and white matter (WM) volumes in utero in fetuses with T21.
Methods:
Typically developing controls (TDC) were comprised of n=397 fetal participants (gestational age, GA, range=19.86 to 38.29 weeks) from 3 studies: the 'developing Human Connectome Project' (dHCP, REC 14/LO/1169, n=257); the 'Placental Imaging Project' (PiP, REC 16/LO/1573, n=78); and, the 'individualised risk prediction [..] in pregnancies that deliver preterm' study (PRESTO, REC 21/SS/0082, n=62). T2-weighted (T2w) MRI were acquired on a 3T Philips Achieva system at TE=250ms (for dHCP) or TE=180ms (for PiP and PRESTO) as detailed in (Uus 2023). 25 fetuses with confirmed T21 (GA=24.00 to 35.71) from the 'early brain imaging in DS' (eBiDS, REC 19/LO/0667) were imaged with the above protocols at either TE=180ms (n=20) or 250ms (n=5). All T2w images were motion-corrected and 3D SVR reconstructed to 0.5mm isotropic pixel resolution. Total tissue volume, total cortical GM and WM were initially segmented using the BOUNTI pipeline (Uus 2023). These were sub-divided into frontal, parietal, occipital, temporal, insular and cingulate regions in atlas space (Fig 1A) and propagated into subjects using classical registration methods. Non-linear regressions of volumes against GA were fitted and compared using the extra-sum-of-squares F-test in Graphpad Prism v9.0.
Results:
Total tissue volume had a significantly different non-linear fit from 24 to 36 weeks GA for fetuses with T21 (F-test, pFDR < 0.0001) with reduced volumes particularly after 30 GA. As such, total GM volume and total WM volume (both pFDR < 0.0001) also showed significantly different non-linear fits throughout gestation. Total WM volumes were more markedly reduced than total GM volumes after 30 GA in T21 (Fig.1B). A breakdown into frontal, parietal, occipital and temporal segments provided details of regional volumetric differences between T21 and TDC. Frontal and occipital GM had a significantly different non-linear fit (both pFDR < 0.0001) with reduced volumes in T21, whilst parietal (pFDR = 0.42) and temporal GM volumes (pFDR = 0.18) did not show any difference in non-linear fit across gestation. All WM regional volumes had a significantly different non-linear fit (all pFDR < 0.0001) with reduced volumes in T21. Volumetric reductions after 30 GA were more marked in frontal, occipital and temporal WM than in parietal WM (Fig.2A-B).
Conclusions:
To the best of our knowledge, the detailed development of regional cortical GM and WM volumes has never been studied in utero in T21 (Hamner 2018, Tarui 2020). With regards to cortical GM, this analysis showed that frontal and occipital GM volumes deviated from TDC, with particularly reduced volumes after 30 GA, whilst parietal and temporal GM volumes did not show any significant difference across gestation. All WM regions deviated from TDC, although parietal WM volumes did not have a marked reduction in volume after 30 GA, as per other WM regions. This analysis corroborates our findings in neonates with T21 following delivery (Fukami-Gartner 2023) and further elucidates the timings of volumetric deviations in utero. These volumetric results may be associated with brachycephaly, as identified in unpublished craniofacial biometry in this cohort, and evidenced in ex vivo fetal examinations (Guihard-Costa 2006).
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Genetics:
Neurogenetic Syndromes 1
Modeling and Analysis Methods:
Segmentation and Parcellation 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping
Keywords:
Congenital
Cortex
Development
DISORDERS
Neurological
Pediatric Disorders
Segmentation
STRUCTURAL MRI
White Matter
Other - Down syndrome
1|2Indicates the priority used for review
Provide references using author date format
de Graaf G. 2021. Estimation of the number of people with Down syndrome in Europe. Eur J Hum Genet. 29:402–410.
Fukami-Gartner A. 2023. Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome. Cereb Cortex. 33:8921–8941.
Guihard-Costa AM. 2006. Biometry of face and brain in fetuses with trisomy 21. Pediatr Res. 59:33–38.
Hamner T. 2018. Pediatric Brain Development in Down Syndrome: A Field in Its Infancy. J Int Neuropsychol Soc. 24:966–976.
Tarui T. 2020. Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome. Cereb Cortex. 30:382–390.
Uus AU. 2023. BOUNTI: Brain vOlumetry and aUtomated parcellatioN for 3D feTal MRI. Elife. 12:RP88818.