Imaging - Clinical Evaluation of Altered Nervous System Drainage — I-CLEANED  

Autism Spectrum Disorder Clinical Trial

Official title: Multi-signal Analysis of the Composition and Movement of Fluid in Various Cerebral Compartments in Healthy Subjects and Subjects With White Matter Pathology

Status Recruiting

Clinical Trial Summary

The current study aims to evaluate the aspects of perfusion, fluid diffusivity in the interstitium and the T1 and T2 signal of the PVS and WMH. The current study has the following objectives: a) evaluate the perfusion aspects using the gadolinium-based contrast medium of brain tissues in the short term; b) the direction of flow of fluids at very low speed in the white matter using the DTI sequences configured for this purpose; c) T1-mapping of the lesions of interest.

The expected results will help us understand two aspects of neurofluid dynamics: a) how the fluid moves within the central nervous system in the first minutes after the injection of the tracer (in our case the gadolinium-based contrast medium) and b) what is the composition of the fluid within the PVS and WMH and how can investigators characterize them more accurately.

Clinical Trial Description

Among the various indirect markers of altered drainage of neuroglial waste metabolites, there is the widening of the perivascular spaces (PVS) and the presence of white matter signal alterations.

An increase in the number of PVS and their enlargement could represent an indirect marker of obstruction to the drainage of fluids and solutes along the arterial wall at the level of the white matter. This obstruction would also be the basis of tissue hypoxia resulting in the formation of areas of signal hyperintensity in the white matter (White Matter Hyperintensities, WMH) often observed in patients with neurodegenerative diseases and small vessel disease.

It is currently unclear what the main drainage route of brain waste metabolites is. Surely there are at least two.

The glymphatic theory proposes the entry of the cerebrospinal fluid (CSF) from the subarachnoid space towards the brain parenchyma in a centripetal direction and exit of the metabolic waste along the perivenous spaces. The drainage of metabolic waste could also be explained by the more recent "intramural periarterial drainage" (IPAD) theory which shows elimination along the arterial walls in a centrifugal direction.

In magnetic resonance imaging (MRI), the study of solute drainage requires a dynamic evaluation, which is able to evaluate the temporal movement of a tracer. There are several MRI techniques, already described in the literature, which can be used to obtain information relating to perfusion processes and the coupling of neuronal and vascular activity in different brain areas.

The circulation of CSF is well known, which is produced largely at the level of the choroid plexuses and is then partly reabsorbed by the arachnoid granulations at the level of the subarachnoid space. Recent studies demonstrate that the CSF re-enters the brain parenchyma in a centripetal manner, crossing the thickness of the gray matter and then the white matter. This movement is regulated by various factors, and in particular by the activity of the smooth muscle cells of the arterial walls, the aquaporin 4 receptors (water channels) and by the chemical-physical properties of the extracellular matrix in the extracellular space. ;

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Neuroinflammation

• NCT number: NCT06432023
• Study type: Observational
• Source: IRCCS Eugenio Medea
• Status: Recruiting
• Start date: October 1, 2023
• Completion date: January 31, 2026