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A comparison of altered white matter microstructure in youth born with congenital heart disease or born preterm
Kaitlyn Easson1,2, May Khairy3, Charles V Rohlicek4
1Advances in Brain and Child Development (ABCD) Research Laboratory, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Insights
Youth born with congenital heart disease (CHD) or preterm both show white matter deficits in myelination and axon density. However, preterm individuals uniquely exhibit altered axon orientation, suggesting distinct developmental pathways.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Pediatric Cardiology
Background:
- White matter microstructure alterations are observed in individuals with congenital heart disease (CHD) and those born preterm.
- The underlying causes of these microstructural disruptions in CHD and preterm populations remain unclear.
- This study investigates common and distinct white matter alterations in these groups.
Purpose of the Study:
- To compare white matter microstructural elements—myelination, axon density, and axon orientation—in youth with CHD and preterm youth.
- To elucidate shared and unique neurodevelopmental impacts of CHD and preterm birth on white matter.
- To inform potential therapeutic strategies for these populations.
Main Methods:
- Utilized multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) on brain MRIs.
- Included participants aged 16-26 years with operated CHD, preterm-born (≤33 weeks GA), and healthy controls.
- Analyzed myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) in 30 white matter bundles using tractometry and bundle profiling.
Main Results:
- Both CHD and preterm groups showed reduced MWF and some instances of lower NDI compared to controls.
- No significant differences in orientation dispersion index (ODI) were found between the CHD and control groups.
- The preterm group exhibited altered ODI (both higher and lower) compared to controls, and lower ODI compared to the CHD group.
Conclusions:
- Youth with CHD and preterm youth share deficits in white matter myelination and axon density.
- Preterm birth is associated with a distinct pattern of altered axonal organization not observed in the CHD group.
- Further longitudinal research is needed to understand the emergence of these microstructural differences and guide therapeutic development.
Introduction:
Alterations to white matter microstructure as detected by diffusion tensor imaging have been documented in both individuals born with congenital heart disease (CHD) and individuals born preterm. However, it remains unclear if these disturbances are the consequence of similar underlying microstructural disruptions. This study used multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) to characterize and compare alterations to three specific microstructural elements of white matter - myelination, axon density, and axon orientation - in youth born with CHD or born preterm.
Methods:
Participants aged 16 to 26 years with operated CHD or born ≤33 weeks gestational age and a group of healthy peers of the same age underwent a brain MRI including mcDESPOT and high angular resolution diffusion imaging acquisitions. Using tractometry, average values of myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) were first calculated and compared between groups for 30 white matter bundles. Afterwards, bundle profiling was performed to further characterize the topology of the detected microstructural alterations.
Results:
The CHD and preterm groups both presented with widespread bundles and bundle segments with lower MWF, accompanied by some occurrences of lower NDI, relative to controls. While there were no differences in ODI between the CHD and control groups, the preterm group presented with both higher and lower ODI compared to the control group and lower ODI compared to the CHD group.
Discussion:
While youth born with CHD or born preterm both presented with apparent deficits in white matter myelination and axon density, youth born preterm presented with a unique profile of altered axonal organization. Future longitudinal studies should aim to better understand the emergence of these common and distinct microstructural alterations, which could orient the development of novel therapeutic approaches.
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