Unruptured Cerebral Aneurysm: prediction of evolution: a prospective multi-centre study

Unruptured intracranial aneurysms (UIAs) have a prevalence of 3.2% in the
general population. UIAs usually remain asymptomatic, but if they subsequently
rupture there are often severe clinical consequences. In selected groups, the
risk of rupture may be <1% per year. Those risks associated with the natural
history have to be balanced against the well-known treatment-related mortality
and morbidity in seeking to secure a UIA, as the overall treatment-associated
mortality and morbidity ranges from 0.5% to 0.7% and 3% to 17%, respectively.
Past and current studies have suggested that UIAs may be classified as
presenting a high or low rupture risk based on their location and size.
However, the majority of UIAs is small. Additionally, the impact of any
management strategy on health-related quality of life or cognition remains
poorly investigated. Clinical decision making thus mainly relies on general
risk factors organized in prognostic scores, such as the PHASES score. The
balance between risk and benefit makes the identification of a specific,
individual-based marker for higher risk of rupture a valuable addition to
therapeutic decision-making processes.

There is strong evidence to suggest that growing aneurysms are at higher risk
of rupture. A systematic review of the literature reveals an estimation of a
yearly growth probability of 3.85% (95% CI 3.4% to 4.3%) with a total follow-up
of 7799 patient-years and 300 growth events observed in 3079 patients and 3855
UIAs. Several studies having suggested that growing UIAs have an increased risk
of rupture, hence follow-up imaging of untreated UIAs is recommended. However,
guidelines from the American Heart Association and European Stroke Organization
lack recommendations on which patients should be considered for follow-up
imaging and at what time interval it should be performed.

Preliminary studies have demonstrated that aneurysmal wall enhancement (AWE),
using high-resolution vessel wall MRI, is linked to aneurysm instability (i.e.,
ruptured, symptomatic, or growing over time). Indeed, recent cross-sectional
studies that included both ruptured intracranial aneurysms and UIAs suggested
that, on 3.0-T vessel wall MRI, circumferential AWE more frequently manifests
in unstable (i.e., ruptured, symptomatic, or having a morphologic structure
that changes over time) rather than in stable (i.e., incidental or
non-evolving) intracranial aneurysms. Although the prevalence of
circumferential AWE was over 80% in unstable intracranial aneurysms, reflecting
a high sensitivity to determine unstable status, 30% of stable UIAs also
presented this pattern, reflecting the low specificity of this finding. Having
an individually based imaging for UIA instability would allow physicians to
characterize aneurysms as appropriate for conservative management or requiring
invasive treatment to prevent rupture.

With the U-CAN project using a combination of innovative aspects in terms of
approach, interdisciplinary collaboration and technologies, we aim to improve
the prediction of aneurysm growth by identifying advanced but routinely
accessible imaging parameters as well as clinical and anatomical risk factors
for aneurysm growth. This project establishes new directions for optimal and
personalized management of UIAs to decrease the impact of futile follow-up and
the risk of unrecognized, evolving UIA. Overall, we could also expect to
improve the impact of follow-up on the patient*s quality of life.

Our primary aim is to evaluate in clinical practice the predictive value of
unruptured intracranial aneurysm wall enhancement for aneurysm growth. It will
allow to set up a secure, efficient and personalized follow-up.

A prospective observational international multicenter study

The proposed study adds administration of gadolinium to the MRA-protocol for
additional aneurysm wall imaging. The use of gadolinium is safe and painless
and is often used in clinical practice. In rare cases the use of gadolinium can
cause an allergic reaction. In this case, the radiology staff will handle
according to the protocol of allergic reactions. Furthermore, included patients
have to complete a questionnaire about possible risk factors (ethnic origin,
use of cigarettes/alcohol, medical history, medication use). The extent of
burden and risks for participants of this study are estimated to be negligible.