Magnetic Resonance Imaging-based structural markers of altered fluid dynamics in the paediatric brain

Abstract

Neurofluids encompass a variety of fluids in the central nervous system, including cerebrospinal fluid (CSF), interstitial fluid (ISF), arterial and venous blood. The dynamic exchange of these fluids in the brain parenchyma is essential for delivering nutrients, maintaining homeostasis, and removing metabolic waste. Two primary pathways responsible for waste clearance in the brain are the glymphatic pathway and the intramural periarterial drainage pathway, both of which utilize the perivascular spaces (PVS) surrounding arteries and veins to facilitate the exchange of
CSF and ISF, coordinating with blood flow dynamics. Recent discoveries have identified lymphatic vessels in the dural meningeal layer and associated parasagittal tissue (PSD), revealing additional CSF drainage routes and highlighting novel sites for neuroimmunological surveillance. Impairment of CSF-ISF drainage pathways can
result in the accumulation of toxic waste in the brain, potentially leading to cell death,
neuroinflammation, and neurodegeneration in adults. Although these pathways have been widely researched in animal models and adult humans, the early development of their anatomical structures and pathological significance in infants and young children is poorly understood. PVS and PSD are emerging as potential structural MRI biomarkers for altered CSF and ISF drainage in neurodegenerative and neuroinflammatory disorders in adults but their significance in the developing pediatric brain remains unexplored. The developing pediatric brain is very
different from the adult brain. The anatomical structures such as the meninges, neurons and the glial cells together with fluids such as CSF and ISF develop in different phases in a perfectly orchestrated manner. This supports critical processes such as neurotransmitter signaling, myelination, and neuronal migration. Genetic or environmental toxins can hinder this process and likely affect the development of drainage pathways. Building upon this context, I set out to investigate these biomarkers in a pediatric cohort with autism spectrum disorder (ASD). ASD is a complex condition influenced by a combination of genetic and epigenetic factors. Neuroimaging studies reveal that children with ASD often have enlarged CSF filled subarachnoid spaces, likely due to altered drainage pathways but a thorough
investigation of PVS and PSD has yet to be done. In this study, I present findings from my recently completed research, which has largely been published, where I quantified and analyzed MRI metrics related to PVS and PSD in relation to the severity of ASD symptoms using deep learning methods.

More information

Identifiers

ORCID for Nivedita Agarwal: orcid.org/0000-0002-1387-9566

ORCID for Roxi Carare: orcid.org/0000-0001-6458-3776

ORCID for Chris Kipps: orcid.org/0000-0002-5205-9712

Catalogue record

Export record

Altmetrics