Measuring Fluid Flow in the Brain Using Alcohol and MRI in Healthy Participants

Summary

Intracranial interstitial fluid (ISF) flow is crucial for adequate clearance of extracellular waste products from the brain parenchyma. Recent demonstrations have shown that a deficiency in flow leads to the accumulation of such waste products in neurodegenerative disorders. Unfortunately, no clinical investigation that gives a quantitative measure of ISF flow exists. Such a test could prove very useful in the clinical setting for multiple neurologic disorders by providing a measure of potential diagnostic importance, as well as yielding a means to monitor response to treatment.

The investigators hypothesize that such an investigation can be developed using magnetic resonance spectroscopy to give a quantitative measure of ISF flow, using spectroscopy of ethanol as a dynamic marker of interstitial fluid. Beneficially, the approach is non-invasive. This pilot project aims to develop this technique with proof of concept in healthy volunteers (males in the age range of 20-75).

This pilot project aims to develop the technique, demonstrating its ability to detect ISF flow and potential differences in rates among healthy volunteers. Success at this stage will give rise to this technique being extended to studies involving individuals with various forms of intracranial pathology for comparison with values seen in healthy individuals, with the ultimate goal of it providing a measure of diagnostic significance in multiple clinical scenarios.

Conditions

• Diagnostic Technics, Neurological

Interventions

DIAGNOSTIC_TEST

Single-voxel MRS

Diagnostic test is a single voxel MRS scan

DIAGNOSTIC_TEST

Multi-voxel MRSI

Diagnostic test is a multi-voxel MRS imaging scan

DIAGNOSTIC_TEST

Magnetization Transfer Imaging

Diagnostic test is a set of magnetic transfer weighted images

OTHER

Alcohol ingestion

Participants will ingest an ethanol-containing beverage of approximately 0.5g/kg of ethanol mixed in 355 mL of a non-caffeinated, sugar-free carbonated drink which must be consumed in 5 minutes

DEVICE

ClearMate

Participants will breathe through the ClearMate, an MR-compatible non-rebreathing circuit which provides oxygen and carbon dioxide that quickly decreases a person's blood alcohol level.

DIAGNOSTIC_TEST

Blood sampling

Participants will have a peripheral arterial and peripheral venous line inserted and periodic arterial and venous blood samples will be measured for blood alcohol content.

Sponsors & Collaborators

• University Health Network, Toronto

  collaborator OTHER

• Sunnybrook Health Sciences Centre

  lead OTHER

Principal Investigators

• Greg J Stanisz, PhD · Sunnybrook Research Institute

• David Mikulis, MD · Krembil Research Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

20 Years

Max Age

75 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-01-31

Primary Completion

2027-01-31

Completion

2028-01-31

Countries

• Canada

Study Locations