Quantitative Imaging of Brain Glymphatic Function in Humans

Recent immunological and physiological studies have provided evidence in support of a central nervous system (CNS) lymphatic drainage system in vertebrate animals, and preliminary evidence has suggested that a similar system exists in humans. If operative, this system may have central relevance to many vascular and fluid clearance disorders such as stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease related dementia (ADRD): diseases which represent some of the most pressing healthcare challenges of the 21st century. Evaluating this possibility will require improved, robust imaging methods sensitive to lymphatic drainage dysfunction; as such, the goal of this work is to apply novel magnetic resonance imaging approaches, optimized already for evaluating lymphatic circulation in patients with peripheral lymphatic dysfunction, to quantify relationships between physiological hallmarks of ADRD and CNS lymphatic function in humans.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: [11C]-PIB

Detailed Description

The proposal involves magnetic resonance imaging (MRI) of healthy volunteers and patient volunteers suffering from Parkinson's disease. As part of the research study, volunteers will undergo 1-2 non-invasive MRI scans at a field strength of 3 Tesla. Each scan session will last 60-90 minutes, and will include the time when the volunteers will rehearse the experiment outside of the scanner, time for the volunteers and patients to be comfortably placed in the scanner, scanning, and finally time for the patients to slowly exit the scan room.

All MRI methods are non-invasive and no exogenous contrast agents will be required.

Patient volunteers will also undergo an C-11 PiB PET scan for Aim (2). This procedure utilizes a common radiotracer that is used routinely in clinical PET scans and will be purchased here from PETNET and certified for human use. All PET scans will be performed by a certified PET technologist at the Vanderbilt University Institute of Imaging Science.

Finally, in Aim (3) of this study, measurements of glymphatic function will be performed before and during general anesthesia. Importantly, the general anesthesia will be administered as part of standard-of-care for clinically-indicated MRIs required for deep brain stimulation planning and electrode placement. Therefore, the intervention itself is not a research procedure. Additionally, the scan that will be performed, which is a modified diffusion tensor imaging (DTI) MRI approach, is already performed as part of this clinical protocol. Therefore, it is anticipated that the participant will not be sedated any longer than what would be required for clinical indication for this procedure. As such, while this study qualifies as a clinical trial by NIH criteria, it is expected to pose no more risk than what the participant will receive from their clinical standard-of-care procedure.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• diagnosis of Parkinson's Disease or controls
• willing to participate in PET and MRI imaging

Exclusion Criteria:

• recent stimulant use
• unstable diabetes
• prior stroke
• claustrophobia
• prior cancer treatment with chemotherapy
• history of traumatic brain injury
• any unstable medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parkinson's Disease participants with MCI; Patient volunteers will also undergo a C-11 PiB PET scan. This procedure utilizes a common radiotracer that is used routinely in clinical PET scans and will be purchased here from PETNET and certified for human use. All PET scans will be performed by a certified PET technologist at the Vanderbilt University Institute of Imaging Science.	Drug: [11C]-PIB; [11C]-PIB is a PET radiotracer used to evaluate levels of Αβ burden.; Other Names: N-Methyl-[ 11C]-2-(4'-methylaminophenyl)-6-hydroxybenzothiasole; [11C]-Pittsburgh Compound B; [ 11C]6-OH-BTA-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS)	Using a 3T MRI (body coil transmission and SENSE phased-array 32-channel reception), images will be taken. For analysis, a unitless ratio of diffusion along perivascular space relative to orthogonal to perivascular space at the level of the lateral brain ventricles will be calculated	baseline, under anesthesia

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Manus J Donahue, Ph.D., Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Anti-Inflammatory Agents; 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Other Study ID Numbers: Imaging of Brain Glymphatics

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data may be shared upon request by other researchers.
• IPD Sharing Time Frame: upon request
• IPD Sharing Access Criteria: upon request
• IPD Sharing Supporting Information Type: SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No