Vessel wall imaging in moymoya vasculopathy using intracranial MRI at 7.0 tesla

Moyamoya vasculopathy (MMV) is a cerebrovascular disease in which a progressive
bilateral occlusion of the supraclinoid internal carotid artery (ICA) and its
proximal branches predisposes patients to stroke. The etiology is still
unknown, and histopathological analyses of affected vessels show a combination
of hyperplasia of smooth-muscle cells and luminal thrombosis. We propose a
prospective study to investigate the intracranial vessel wall in moyamoya
patients using a 7.0 tesla MR system. Based upon the intracranial vessel wall
sequence, developed by the 7T group and used in an ongoing study (IVI study), a
7.0 tesla MR protocol will be developed and optimized for the visualization of
the intracranial arterial wall in patients with MMV. With these results, we
will gain insight in the underlying pathological vessel wall changes in MMV,
which has not been reported on 7.0 tesla yet.

Primary Objective: To study arterial vessel wall abnormalities of the
intracranial vessels (circle of Willis and its main branches and the moyamoya
vessels) in patients with MMV in comparison with age- and sex-matched subjects
without known intracranial vessel wall disease, using 7T MRI.

Secondary Objective: To investigate differences in the vessel walls between the
symptomatic and asymptomatic hemisphere in each individual patient and between
children and adults.

Third Objective: To investigate the blood flow through the major arteries
(circle of Willis and its main branches) and the moyamoya vessels
(lenticulostriatal and leptomeningeal collaterals) and correlate this to the
severity of the disease according to the Suzuki grading system with cerebral
angiography. This will be achieved by bolus tracking after the administration
of a Gadolinium-based contrast agent.

Fourth objective: To characterize the intracranial vessel wall, by evaluating
the signal characteristics on multiple MRI sequences.

This study is designed as a single-center case-control observational
non-therapeutic study. Intracranial vessel wall imaging will be performed with
a 7T MRI scanner in patients with MMV, combined with standard clinical imaging
of the brain. Results will be compared with the results of age- and sex-matched
subjects. High resolution pre- and post-contrast (gadolinium) images of the
arterial vessel wall will be obtained using a dedicated intracranial vessel
wall sequence at 7.0 tesla MRI. In addition to the vessel wall images,
ultra-high resolution MR angiography of the intracranial vasculature (lumen)
will be acquired. Furthermore, the MRA sequence will easily discriminate
arteries from veins with opposite flow directions. The duration of the protocol
will be approximately 60 minutes. The results of our study may enable
characterization of the intracranial vessel wall pathology of MMV and help us
to further investigate the etiology of MMV.

Baseline characteristics of all patients and control subjects will be collected
during inclusion into our study.
Blood samples of all patients are already taken after first presentation for
clinical purposes to verify the absence of renal dysfunction.
Healthy volunteers will be asked for known renal impairment. All patients will
have their regular clinical work-up and treatment, independent of this study or
its results.

We aim at an inclusion of 20 moyamoya patients, 10 children and 10 adults, in 4
years. A small group needs anesthesia during an MRI examination. Anesthesisized
patients cannot be handled in the 7T scanner and will therefore not be included
into this study. Since a similar MRI protocol is used in patients with
suspected pituitary adenoma scanned in the context of clinical care, we will
retrospectively include 20 of these patients after matching for age and sex.
Furthermore, since we used a similar scanning protocol as in the included
control groups in the *IVI* or *DIVA* studies, we would like to include these
subjects in case we do not have a sufficient number of matches. In case we
cannot find suitable matches from the aforementioned studies, we will include
up to 10 healthy adult volunteers by asking the caregivers / partners of the
patients to participate.

During the total scan, children can watch a movie or cartoon to have some
distraction from the scanner noise. This might comfort the patient during the
scan and may contribute to less motion artifacts.

The project will be performed in close collaboration with the department of
Neurology and Neurosurgery and the department of Radiology (especially the 7T
MR group) of the UMCU.

During the MRI, patients are exposed to strong magnetic fields and radio waves.
In normal clinical practice, MRI is very
often used. There are no harmful effects on the human body determined. In some
cases, people experience flashes of light, tingling and transient dizziness.
These are always during the scan and disappear immediately after scanning.
Implanted medical devices might become disturbed by the magnetic field. People
with medical implants are therefore not considered for the study.

The gadolinium contrast agent is widely used for MR imaging exams in the
clinical setting, and as such it is
administered to thousands of patients every year in our hospital. In some
cases, an allergic reaction may occur. This
creates itching and nausea with possible red bumps on the skin. Almost always,
these symptoms disappear after the
examination. It is seldom that medical treatment is necessary. At all times,
there will be a doctor present as the contrast
agent is administered. Patients with a known allergy to the contrast agent
gadolinium can not participate in this study.
If patients have renal problems, they can not participate in this study.

This is a group-related research: our patient population predominantly consists
of children. Furthermore, MMV has a different course in children then in
adults, with amongst others a higher progression rate. It is important to
investigate differences in vessel walls between children and adults. The low
risks of undergoing a MRI make the risk and burden for the subjects in
proportion to the value of the research.