Lower diffusivity along the perivascular spaces in preterm-born adults
Poster No:
306
Submission Type:
Abstract Submission
Authors:
Aurore Menegaux1, Maria Mora Alvarez2, Benita Schmitz-Koep3, Jil Wendt3, Dennis Hedderich3, Marcel Daamen4, Henning Boecker5, Claus Zimmer6, Dieter Wolke7, Peter Bartmann8, Christian Sorg3
Institutions:
1TUM University Hospital, Technical University of Munich, Munich, Bavaria, 2Developing Brain Institute, Children’s National Hospital, Washington, DC, 3TUM University Hospital, Technical University of Munich, School of Medicine and Health, Munich, Bavaria, 4University Hospital Bonn, Bonn, NRW, 5Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, NRW, 6Institute for Neuroradiology, TUM University Hospital, Munich, Bavaria, 7Department of Psychology, University of Warwick, Warwick, CV4 7AL, 8Department of Neonatology, University Hospital Bonn, Bonn, NRW
First Author:
Co-Author(s):
Benita Schmitz-Koep
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
Jil Wendt
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
Dennis Hedderich
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
Henning Boecker
Department of Diagnostic and Interventional Radiology, University Hospital Bonn
Bonn, NRW
Department of Diagnostic and Interventional Radiology, University Hospital Bonn
Bonn, NRW
Christian Sorg
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
TUM University Hospital, Technical University of Munich, School of Medicine and Health
Munich, Bavaria
Introduction:
The glymphatic system is a newly identified waste clearance system in the brain (Hladky et al. 2022). It promotes the elimination of toxic substances and maintains homeostasis in the brain through cerebrospinal fluid and interstitial fluid dynamics along the perivascular spaces (Iliff et al., 2012).
Several methodologies have been proposed to investigate the glymphatic system using magnetic resonance imaging, the main one being injection of gadolinium-based contrast agent (Iliff et al., 2013). However, studies in human subjects are limited due to the invasive nature of contrast agent administration. Recently, a non-invasive method based on diffusion weighted imaging (DWI) named diffusion tensor imaging along the perivascular spaces (DTI-ALPS) has been proposed (Taoka et al. 2017). The ALPS index measures the diffusivity within the perivascular spaces around the medullary veins at the level of the lateral ventricle bodies. Using DTI-ALPS, a previous study reported lower ALPS index in preterm compared to term-born neonates suggesting delayed maturation of the glymphatic system (Lin et al., 2024). However, whether glymphatic system function is altered in adulthood after preterm birth remains unclear.
Several methodologies have been proposed to investigate the glymphatic system using magnetic resonance imaging, the main one being injection of gadolinium-based contrast agent (Iliff et al., 2013). However, studies in human subjects are limited due to the invasive nature of contrast agent administration. Recently, a non-invasive method based on diffusion weighted imaging (DWI) named diffusion tensor imaging along the perivascular spaces (DTI-ALPS) has been proposed (Taoka et al. 2017). The ALPS index measures the diffusivity within the perivascular spaces around the medullary veins at the level of the lateral ventricle bodies. Using DTI-ALPS, a previous study reported lower ALPS index in preterm compared to term-born neonates suggesting delayed maturation of the glymphatic system (Lin et al., 2024). However, whether glymphatic system function is altered in adulthood after preterm birth remains unclear.
Methods:
We investigated brain clearance in 81 full-term (FT) and 63 very preterm (<32 weeks of gestation and/or birth weight <1500g, VP/VLBW) adults aged 26 years from the Bavarian longitudinal study (Wolke & Meyer 1999). DWI data were preprocessed using the PreQual pipeline which included denoising, inter-scan normalization, generation of a synthetic undistorted b0 for distortion correction as well as susceptibility-induced distortion, motion and eddy currents correction using FSL top-up and EDDY with replacement of outliers (Cai et al., 2021; Andersson et al., 2017). A tensor model was applied using the DTIFIT tool implemented in FSL. Finally, the ALPS index was calculated for the projection and association fibers at the level of the lateral ventricles, specifically for the left and right superior corona radiata and the left and right superior longitudinal fasciculus. This was done by computing the diffusion along the x, y, and z axes (Dxx, Dyy, Dzz) using the following formula (Liu et al., 2023): ALPS index = mean(ProjectionDxx, AssociationDxx)/ mean (ProjectionDyy,AssociationDzz)
General linear models were used to investigate differences in bilateral, left and right ALPS index between groups including sex and scanner as covariates. In order to investigate the link between ALPS index and the degree of prematurity, Pearson partial correlations between ALPS index and birth variables (gestational age, birth weight) or duration of mechanical ventilation were performed in the VP/VLBW group controlling for sex and scanner. All statistical analyses were performed using IBM SPSS (v27; IBM Corp., Armonk, NY, USA).
General linear models were used to investigate differences in bilateral, left and right ALPS index between groups including sex and scanner as covariates. In order to investigate the link between ALPS index and the degree of prematurity, Pearson partial correlations between ALPS index and birth variables (gestational age, birth weight) or duration of mechanical ventilation were performed in the VP/VLBW group controlling for sex and scanner. All statistical analyses were performed using IBM SPSS (v27; IBM Corp., Armonk, NY, USA).
Results:
We found significantly lower ALPS index (p<0.001, Figure 1) in VP/VLBW compared to FT adults. In addition, the ALPS index was also lower in VP/VLBW adults compared to FT born individuals in both hemispheres separately (ALPS left (p<0.001) and ALPS right (p=0.003), Figure 1). Finally lower ALPS index in VP/VLBW adults was significantly negatively associated with the duration of mechanical ventilation (r=-0.33, p=0.010, Figure 2) and showed a trend towards significance for gestational age (r=0.23, p = 0,077). We found no significant association with birth weight (r=-0.01, p=0.98).
·Figure 1: Lower ALPS index in VP/VLBW adults compared to term-born controls. * indicates p < 0.005
·Figure 2: Higher ALPS index is associated with lower ventilation in VP/VLBW adults
Conclusions:
We found lower ALPS index in VP/VLBW compared to FT born adults which was associated with the duration of mechanical ventilation at birth and might be indicative of impaired brain clearance. However, DTI ALPS presents several limitations and the use of additional methodologies in combination with DTI-ALPS is necessary to infer long-term impaired brain clearance after preterm birth (Ringstad 2024).
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Novel Imaging Acquisition Methods:
Diffusion MRI
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other
Keywords:
Development
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Preterm birth; Glymphatic system
1|2Indicates the priority used for review
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2. Iliff, J.J. et al. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med., 4(147):147ra11.
3. Iliff, J.J. et al. (2013). Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest. 123(3):1299–309.
4. Taoka, T. et al. (2017). Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTIALPS) in Alzheimer’s disease cases. Jpn J Radiol. 35:172–178.
5. Lin, S. et al. (2024). Evaluation of Glymphatic System Development in Neonatal Brain via Diffusion Analysis along the Perivascular Space Index. Annals of Neurology, 96(5), 970-980.
6. Wolke, D. et al. (1999). Cognitive status, language attainment, and prereading skills of 6-year-old very preterm children and their peers: The Bavarian Longitudinal Study. Developmental Medicine and Child Neurology, 41(2), 94–109.
7. Cai, L.Y. et al. (2021). Prequal: An automated pipeline for integrated preprocessing and quality assurance of diffusion weighted MRI images. Magnetic Resonance in Medicine, 86(1), 456–470.
8. Andersson, J.L. et al. (2017). Towards a comprehensive framework for movement and distortion correction of diffusion MR images: Within volume movement. Neuroimage 152: 450-466.
9. Liu, X. et al. (2023). Cross-Vendor Test-Retest Validation of Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) for Evaluating Glymphatic System Function, Aging and Disease. Aging and Disease. 15(4), 1885-1898 DOI: https://doi.org/10.14336/AD.2023.0321-2
10. Ringstad, G. (2024). Glymphatic imaging: a critical look at the DTI-ALPS index. Neuroradiology, 66 (2), 157-160