MRI-visible Enlarged Perivascular Spaces and the Alteration of Lymphatic Drainage System in CAA

  • STATUS
    Recruiting
  • End date
    Jul 31, 2023
  • participants needed
    120
  • sponsor
    National Taiwan University Hospital
Updated on 26 January 2021
MRI
amyloid deposition

Summary

In this three-year proposal, we will explore the MRI-visible EPVS in CAA and investigate its pathophysiology using animal models. Our specific aims include: (1) Establish the relationship of MRI-visible enlarged perivascular space and CAA, (2) Determine whether vascular amyloid clearance in CAA is associated with lymphatic drainage system, (3) Establish longitudinal data for MRI-visible enlarged perivascular space and cerebral amyloid angiopathy progression.

Description

Cerebral amyloid angiopathy (CAA) involves amyloid deposition in the vessel walls in the cerebral cortex and overlying leptomeninges, causing symptomatic intracerebral lobar intracerebral hemorrhage (ICH) in the elderly. CAA is considered as a form of cerebral small vessel disease, which refers to a group of vascular pathologies that affect the small vessels of the brain. In addition to lobar ICH, patients may present with other parenchymal injuries that can be detected on blood-sensitive MRI, such as multiple strictly lobar cerebral microbleeds, cortical superficial siderosis and leukoariosis. Recently, CAA has been suggested in association with MRI-visible enlarged perivascular space (EPVS) in centrum-semiovale (CSO), contrary to more severe MRI-visible EPVS in basal ganglia that is frequently found in chronic hypertension. The dilated perivascular space in CAA is suggestive of chronic poor perivascular drainage of the leptomeningeal arteries, predisposing individuals to impaired or altered meningeal lymphatic drainage and causing defect in amyloid clearance and subsequent CAA development. Nevertheless, it is unknown whether lymphatic drainage are the main routes for vascular amyloid clearance, and its relationship to the long-term outcome has not been clearly investigated in clinical patients yet.

In this three-year proposal, we will explore the MRI-visible EPVS in CAA and investigate its pathophysiology using animal models. Our specific aims include: (1) Establish the relationship of MRI-visible enlarged perivascular space and CAA, (2) Determine whether vascular amyloid clearance in CAA is associated with lymphatic drainage system, (3) Establish longitudinal data for MRI-visible enlarged perivascular space and cerebral amyloid angiopathy progression. In the first year, we will recruit spontaneous ICH patients for brain MRI, in vivo amyloid imaging and measuring their plasma A40/42 levels. We aim to confirm EPVS in CSO as a specific marker for CAA, and to provide direct evidence that dilated perivascular space is worse with more advanced CAA; For the second year, we plan to use transgenic CAA mouse models to confirm that meningeal lymphatic drainage routes are crucial for clearance of vascular amyloid-. We will manipulate the lymphatic drainage routes by either blockage or enhancement of the lymphatic vessels, to see if the vascular amyloid clearance is affected; For the third year, the main research focus will on be establishing the longitudinal data on amyloid and tau deposition in clinical ICH patients. We plan to repeat in vivo amyloid imaging in 2 years, for the purpose of validating our hypothesis in human that baseline worse lymphatic drainage function is associated with quicker cerebral vascular amyloid progression or prediction of future CAA development. We will also recruit patients for in vivo tau imaging to investigate long-term neuronal injury and neurodegeneration, namely tau-mediated neurofibrillary tangle, in relation to the impaired perivascular drainage in CAA.

Details
Condition Cerebral Amyloid Angiopathy, Cerebral Hemorrhage, Amyloidosis, Amyloidosis, intracerebral hemorrhage, intracerebral haemorrhage, hemorrhage cerebral, intracerebral hemorrhage (ich), cerebral bleeding
Treatment 1. amyloid PET;2. T807 PET
Clinical Study IdentifierNCT04604587
SponsorNational Taiwan University Hospital
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Ageabove 20 years old
Evidence of intraparenchymal hemorrhage on CT or MRI
Patient agrees to participate in the study and receive neurophsychological examinations, genetic and biochemical markers test, MRI and PET imaging

Exclusion Criteria

patients with potential causes of hemorrhage including trauma, structural lesion, brain tumor, or coagulopathy due to systemic disease or medication
Patients could not receive the PET and MRI studies, including but not limited to poor cooperative agitation impeding adequate study, allergy to contrast medium, hemodynamic instability, implantation of cardiac pacemaker, past history of receiving aneurysm clipping, panic mood to MRI study, impaired kidney function
Patients with pregnancy or recently having a plan for pregnancy
Patients with breast feeding or recently having a plan for breast feeding
Patients with history of allergy to 11C-PiB and 18F-T807, or severe allergy history
Patient or family who does not agree to participate in the study
patient with high risk by doctor evaluate
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