Developing Advanced Blood-Brain Barrier Permeability Imaging for Early AD

Developing Advanced Blood-Brain Barrier Permeability Imaging for Early Alzheimer's Disease

Aging is the primary risk factor in aging-related dementia. An important initiating factor for the development and progression of cognitive impairment is disruption of the blood-brain barrier (BBB). BBB plays an important role in maintaining normal brain homeostasis and protecting neural tissues from toxins. It is hypothesized that such changes known to be common in aging and can be an early process that precedes Alzheimer's Disease (AD). The microvascular changes related to subtle BBB disruption can be measured with permeability-surface area (PS) derived from GRASP DCE-MRI acquired less than 10 minutes, and the patterns of increased PS in normal and abnormal aging are different.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: GRASP Dynamic Contrast-Enhanced (DCE) MRI; Device: 3T Brain Scan; Drug: Gadolinium-based Contrast Agent (GBCA) for MRI

• Study Type: Observational
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy cognitively normal control subjects of both age cohorts will be recruited by the study coordinator from (i) a pool of established volunteer subjects at NYU Langone Health who previously participated in research and who have agreed to be contacted about future research, (ii) Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant databases such as RedCap and DataCore, and (iii) individuals who have contacted NYU to express interest in participating in research as a healthy volunteer.

Subjects with aMCI will be recruited by Dr. Wisniewski from an ongoing NIH-funded large grant at NYU Barlow Center.

Description

Inclusion Criteria:

• Subjects that have been diagnosed with aMCI ages 65-85

Exclusion Criteria:

• Pregnant, planning to get pregnant, or nursing.
• Claustrophobia
• Cardiac pacemaker
• Intracranial clips, metal implants, unremovable jewelries, metal in eyes.
• History or presence of any other major medical, neurologic or psychiatric conditions, such as Alzheimer's diseases, Parkinson's diseases, and stroke.
• Renal or liver disease as this may cause concerns related to Gad-based contrast agent
• Allergy to the contrast agent Gadolinium

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; Cognitively normal control participants aged 20 - 40 years. Participants will undergo a 3T brain scan that will last up to 60 minutes using the GRASP DCE-MRI sequence performed during the first 21 minutes of scan time.	Device: GRASP Dynamic Contrast-Enhanced (DCE) MRI; Golden-angle Radial Sparse Parallel (GRASP) DCE MRI is an MRI sequence designed to improve spatial and temporal resolution while enabling retrospective reconstruction with flexible temporal resolution.; Device: 3T Brain Scan; Up to 60 minutes, a portion of which uses the GRASP DCE-MRI sequence.; Drug: Gadolinium-based Contrast Agent (GBCA) for MRI; Gadavist/Gadobutrol is a gadolinium-based contrast agent indicated for intravenous use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system.; Other Names: Gadavist/Gadobutrol
Cohort B; Cognitively normal control participants aged 65 - 85 years. Participants will undergo a 3T brain scan that will last up to 60 minutes using the GRASP DCE-MRI sequence performed during the first 21 minutes of scan time.	Device: GRASP Dynamic Contrast-Enhanced (DCE) MRI; Golden-angle Radial Sparse Parallel (GRASP) DCE MRI is an MRI sequence designed to improve spatial and temporal resolution while enabling retrospective reconstruction with flexible temporal resolution.; Device: 3T Brain Scan; Up to 60 minutes, a portion of which uses the GRASP DCE-MRI sequence.; Drug: Gadolinium-based Contrast Agent (GBCA) for MRI; Gadavist/Gadobutrol is a gadolinium-based contrast agent indicated for intravenous use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system.; Other Names: Gadavist/Gadobutrol
Cohort C; Amnestic mild cognitive impairment (aMCI) patients aged 65 and older. Participants in Cohort C will be matched by age and gender to participants in Cohort B. Participants in Cohort C will undergo a 3T brain scan that will last up to 60 minutes using the GRASP DCE-MRI sequence performed during the first 9 minutes of scan time.	Device: GRASP Dynamic Contrast-Enhanced (DCE) MRI; Golden-angle Radial Sparse Parallel (GRASP) DCE MRI is an MRI sequence designed to improve spatial and temporal resolution while enabling retrospective reconstruction with flexible temporal resolution.; Device: 3T Brain Scan; Up to 60 minutes, a portion of which uses the GRASP DCE-MRI sequence.; Drug: Gadolinium-based Contrast Agent (GBCA) for MRI; Gadavist/Gadobutrol is a gadolinium-based contrast agent indicated for intravenous use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system.; Other Names: Gadavist/Gadobutrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Permeability Surface Area (PS) as Measured by GRASP DCE-MRI Sequence	PS is measured by quantifying the contrast agent flow through blood vessel walls per unit volume of brain while accounting for the blood flow rate in the vessel.	Up to 21 Minutes
Blood-Brain Barrier (BBB) Permeability as Measured by GRASP DCE-MRI Sequence	Golden-angle Radial Sparse Parallel (GRASP) dynamic contrast-enhanced (DCE) MRI sequence will be collected for the quantification of subtle BBB leakage throughout the brain.	Up to 21 Minutes

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Yulin Ge, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2018
• Primary Completion (Actual): January 28, 2022
• Study Completion (Actual): July 11, 2023

Study Registration Dates

• First Submitted: December 26, 2017
• First Submitted That Met QC Criteria: December 26, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 17-01336

Drug and device information, study documents

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