Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05785598 |
| Other study ID # |
APHP221331 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 30, 2023 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
Elena MESEGUER, Doctor |
| Phone |
140257490 |
| Email |
elena.meseguer[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Transcranial Doppler ultrasonography with injection of contrast agent (intravenously to
enhance the ultrasound signal) is a non-invasive technique that has been used for years to
study intracranial vessels that constitute the polygon of Willis. However, this technique
does not allow good visualization of small vessels, such as perforating arteries.
Ultrasound localization microscopy (ULM) is based on the principle of localizing injected
microbubbles in order to follow their movement to map the microvascular structure. The
concentration of these microbubbles must remain low (in contrast to its classical use in
Doppler ultrasound) in order to isolate and localize them. By using the same images as those
performed in clinical routine by Doppler ultrasound and by processing the data offline, ULM
would increase the resolution by a factor of 10 allowing potential observation of perforating
arteries.
Description:
Transcranial Doppler Ultrasound (TDI) is a non-invasive technique to study the arteries of
the polygon of Willis. Nevertheless, its resolution does not allow visualization of
perforating arteries. Despite the use of a contrast agent that improves the quality of the
signal, perforating arteries are not detectable with the usual techniques because of their
small size.
In recent years, a more powerful ultrasound technique, ultrasound localization microscopy
(ULM), has been described. This technique uses conventional contrast agents and allows for
vascular mapping with up to 10-fold higher resolution than with a conventional ultrasound
method. It is based on the principle of localizing injected and isolated microbubbles in
order to track their movement back to the microvascular structure. Recently, these techniques
have been transferred to the clinical field. One of the recent applications, is 2D
transcranial imaging which has allowed the observation of, among other things, an
intracranial aneurysm using a research ultrasound scanner.
The objective of this project is to apply this technique on routine clinical EDTC images to
visualize perforating arteries in patients with ischemic stroke (in the absence of middle
cerebral artery occlusion and lacunar disease) and in subjects with Moya-Moya syndrome using
a 2D clinical ultrasound scanner.
- Description of the study population and rationale for its selection
In patients with ischemic stroke, visualization of the intracranial arteries can be performed
by Magnetic Resonance Imaging (MRI) Time of Flight (TOF) sequence or by transcranial Doppler
ultrasound (EDTC) with the help of Sonovue contrast medium. These techniques are performed as
part of routine patient care and allow visualization of the arteries of the polygon of Willis
(anterior, middle and posterior cerebral arteries as well as the anterior communicating
artery and posterior communicating arteries). Nevertheless, the perforating arteries are
small arteries (0.34 mm) that are difficult to visualize by standard MRI and EDTC imaging
with the injection of contrast: the exploration of these arteries is therefore complicated by
the techniques available.
Moya-Moya disease is a chronic arteriopathy characterized by a progressive stenosis of the
terminal segment of the internal carotid artery and the proximal segment of the middle and
anterior cerebral arteries. This occlusion will lead to the development of a network of
arterial substitutes by arteries near the carotid termination, the cortex, the leptomeningeal
arteries and the branches of the external carotid artery that irrigate the base of the skull
and the dura mater, and above all a network of anastomotic substitutes between the cortical
arteries and the deep perforating arteries (originating from the M1 segment, proximal to the
middle cerebral artery). The dilation of these deep perforating arteries and their
neo-anastomoses with the cortical arteries gives the deep sylvian territory a radiological
image that the Japanese have described as a "smoke volute" or "Moya Moya" (Moya Moya = smoke
volute in Japanese). This abnormality can also occur in certain situations such as sickle
cell disease, radiation therapy to the brain or Down syndrome. In this case, it is called
Moya-Moya syndrome. In the absence of an underlying cause, it is known as "Moya-Moya
disease".
It is a rare disease. The prevalence is higher in people of Asian descent, but it is also
found in other populations. The incidence is twice as high in women as in men. There are two
peaks of incidence, in children around the age of 5 and in adults around the age of 40. The
incidence in Japan is estimated at 0.35-0.94 per 100,000 population and is 10-20 times lower
in Europe.
The symptoms of this disease are related to the occurrence of thrombotic events related to
occluded arteries (cerebral infarction, transient ischemic attacks, epileptic seizures) or
related to compensatory mechanisms (cerebral hemorrhages related to collateral vessels or
headaches related to dilated collaterals in the dura mater).
This development of the perforating arteries has a typical and pathognomonic image called
Moya-Moya in Japanese, which means "wisps of smoke". Cerebral angiography is the gold
standard for its diagnosis. It allows to define the severity of the lesions of the cerebral
arteries and the visualization of the network of supplements between the perforating arteries
and the pial arteries coming from the cortex. Nevertheless, this is an invasive examination.
Other noninvasive examinations such as MRI or CT can also visualize this suppletive network.
- Description of the feature(s) being investigated
Transcranial Doppler ultrasonography (TDCS) provides hemodynamic information about the status
of the arteries of the polygon of Willis, but it does not allow visualization of the network
of vessels developed in Moya-Moya disease. EDTC images with contrast medium show contrast
medium confluence, but the Moya-Moya network is not well resolved. Otherwise the images of
perforating arteries by MRI have been described the work of T. Matsushige where he proposes a
classification according to its anatomical arrangement.
- Rationale for the duration of the research.
The investigators hypothesize that in the case of ischemic stroke, in the absence of
occlusion or stenosis of the middle cerebral artery and in the absence of lacunar disease, as
well as in patients with Moya-Moya disease or syndrome, the images obtained by EDTC and
interpreted with ULM would allow better detection of perforating arteries by standard
imaging, i.e., the images obtained by MRI TOF sequence and the images obtained by EDTC with
contrast medium This study, whose duration has been established at 1 year, is carried out in
the context of the ERC ResolveStroke project whose final objective is to implement 3D
super-resolution for the diagnosis of stroke in adults.
