Imaging in Moyamoya Disease - Study to Investigate Different Imaging Technologies for a Better Understanding of Various Imaging Techniques to Evaluate Cerebral Hemodynamics, Disease-activity and Possibly the Etiology in Moyamoya Patients (IMAGINE)

IMAGINE - Imaging in Moyamoya Disease

Aim of this study is to improve patient care in Moyamoya Patients by improving Imaging technologies and aiming to identify factors involved in disease progression.

Main tasks are:

• Analysis of CO2-triggered BOLD fMRI for analysis of cerebral hemodynamics in comparison to H2 15O PET/CT
• Analysis of longitudinal changes of contrast enhancement in vessel-wall imaging and correlation of disease activity with biosampling
• Definition of a standardized recommendation for pre- and postoperative imaging of Moyamoya patients

Study Overview

• Status: Not yet recruiting
• Conditions: Moyamoya Disease; Moyamoya
• Intervention / Treatment: Diagnostic test: MRI; Diagnostic test: H2 15O PET/CT; Other: Biosampling

Detailed Description

Moyamoya Disease (MMD) is a rare disease defined by a bilateral stenosis or occlusion of the terminal internal carotid artery (ICA) and proximal arteries of the circle of willis. The stenosis is usually accompanied by fine collateral vessels appearing as "a puff of smoke" on conventional DSA giving the disease its name (Japanese). The disease is known to progress over time in 20-40% of adult patients, also to initially not affected vessels. To prevent from ischemic or hemorrhagic strokes, most patients need microsurgical revascularization with extracranial-intracranial (EC-IC) bypasses for the affected cerebrovascular territories. The indication for a possible revascularization should always be decided based on functional imaging identifying cerebrovascular territories with an insufficient reserve capacity. The "gold-standard" for measuring the cerebrovascular reserve is H2 15O PET/CT with Acetazolamide challenge (ACZ), whereat also SPECT and different MRI techniques are used but with less sensitivity. Main drawback of H2 15O PET/CT is its very limited availability, high costs, the need to inject ACZ and radiation exposure. Further, the costs of H2 15O PET/CT for Moyamoya patients are not covered by the German health insurance system as no valid high-quality studies are available to prove a possible benefit of this examination.

Throughout the last years the investigators have focused our research on different MRI techniques in Moyamoya patients aiming to find reliable examinations for the evaluation of the cerebral blood flow and to detect and monitor disease progression:

The investigators' newly developed semi-automated algorithms for the evaluation of CO2-triggered BOLD MRI (breathhold fMRI) sequences to identify a reduced vasoreactivity showed a promisingly high correlation to the results of the cerebrovascular reserve measurements as seen in PET/CT. Further, the investigators were able to show that disease progression can be predicted by a temporary contrast enhancement of the vessel wall seen over approximately 24 months as high-resolution vessel-wall imaging was performed consequently in all patients.

Therefore, the main goals of this study are to improve patient care in Moyamoya patients with the following three key elements:

1. Defining the value of CO2 triggered BOLD MRI in the evaluation of cerebral hemodynamics pre- and postoperatively compared to H2 15O PET/CT aiming to possibly prove or reduce the need for PET/CT examinations.
2. Understanding radiographic and pathophysiologic processes causing disease progression as seen by vessel-wall imaging to enable timely revascularization or possibly non-surgical treatment of this disease in the future.
3. Possible new insights in disease-pathophysiology and progression as seen in vessel wall imaging by correlating imaging results with biosampling (peripheral blood
4. Defining a standardized recommendation for pre- and postoperative hemodynamic and MR-morphologic evaluation of Moyamoya patients based on the results of this study.

As secondary objectives the following elements will be analyzed:

1. Neuropsychological impairment in correlation to the hemodynamic and MR-morphologic status of the brain.
2. Feasibility of resting-state fMRI to evaluate cerebral vasoreactivity.

To achieve these goals, the investigators are planning to prospectively include 50 Moyamoya patients in this study with a standardized imaging, neuropsychological testing and biosampling protocol with a two-year follow-up. Under the assumption of a homogenous inclusion of patients, recruitment should be finished after two years with one year of follow-up after the inclusion of the last patient. This cohort will provide reliable information on standardized diagnostic patterns and possibly a broader understanding of pathophysiology causing disease development and progression.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Constantin Roder, Prof. Dr., MD; Phone Number: 0049-7071290; Email: constantin.roder@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with suspicion of Moyamoya Disease
• Patients able to understand the study and to give their informed consent

Exclusion Criteria:

• Cerebral vascular disease caused by atherosclerosis
• Vasculitis
• Contraindications to MRI
• Contraindications to PET/CT
• Pregnancy
• Inability to give informed consent
• Renal insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moyamoya patients; Newly diagnosed Moyamoya patients who will follow a standardized imaging and biosampling protocol. Possible surgical or conservative treatment will not be influenced by this study.	Diagnostic test: MRI; Patients will get special MRI sequences (CO2-triggered BOLD MRI, Vessel-wall imaging, resting state BOLD MRI) to identify cerebral vasoreactivity and disease activity.; Diagnostic test: H2 15O PET/CT; Patients will get H2 15O PET/CT with acetazolamide challenge to define the cerebral vasoreserve for comparison with fMRI Images; Other: Biosampling; Patients do get a venous puncture for blood analysis on circulating endothelial cells and virus PCR analysis
No Intervention: Control group; Healthy patients and patients with intracerebral atherosclerotic disease are used as comparators for the results of biosampling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Value of CO2-triggered BOLD MRI compared to PET/CT	Analysis of comparability of fMRI-based vasoreactivity and PET/CT based vasoreserve (Signal change in percent)	From enrollment until maximum of 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vessel-Wall contrast enhancement	Analysis of vessel-wall contrast enhancement as predictor for disease-activity (Intensity of contrast enhancement relative to reference tissue on MRI)	From enrollment until maximum of 24 months
Circulating endothelial cells	FACS-based analysis of circulating endothelial cells as indicator for disease activity (absolute number of respective circulating endothelial cells subgroup)	From enrollment to a maximum of 24 months
PCR-based virus sampling	Analysis of possible virus infections as indicator for disease etiology (absolute number of Virus DNA based on PCR results)	From enrollment until maximum 24 months

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: University Hospital Freiburg

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Stroke; Moyamoya; EC-IC Bypass
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Moyamoya Disease
• Other Study ID Numbers: IMAGINE Moyamoya; 528291394 (Other Grant/Funding Number: German Research Council (DFG))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be made available anonymized upon reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No