Developing Advanced Blood-Brain Barrier Permeability Imaging for Early AD

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Device: GRASP Dynamic Contrast-Enhanced (DCE) MRI
* Device: 3T Brain Scan
* Drug: Gadolinium-based Contrast Agent (GBCA) for MRI


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A<br>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<br>* 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.<br>Device: 3T Brain Scan<br>* Up to 60 minutes, a portion of which uses the GRASP DCE-MRI sequence.<br>Drug: Gadolinium-based Contrast Agent (GBCA) for MRI<br>* 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.<br>* Other names: Gadavist/Gadobutrol;|
| Cohort B<br>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<br>* 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.<br>Device: 3T Brain Scan<br>* Up to 60 minutes, a portion of which uses the GRASP DCE-MRI sequence.<br>Drug: Gadolinium-based Contrast Agent (GBCA) for MRI<br>* 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.<br>* Other names: Gadavist/Gadobutrol;|
| Cohort C<br>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<br>* 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.<br>Device: 3T Brain Scan<br>* Up to 60 minutes, a portion of which uses the GRASP DCE-MRI sequence.<br>Drug: Gadolinium-based Contrast Agent (GBCA) for MRI<br>* 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.<br>* 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 |