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Assessment of the risk of rupture of intracranial aneurysms by ultrasound

English title Assessment of the risk of rupture of intracranial aneurysms by ultrasound
Applicant Perren Fabienne
Number 159654
Funding scheme Interdisciplinary projects
Research institution Unité de Neurosonologie Service de Neurologie HUG
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2016 - 31.12.2019
Approved amount 439'000.00
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All Disciplines (4)

Discipline
Neurophysiology and Brain Research
Biomedical Engineering
Neurology, Psychiatry
Fluid Dynamics

Keywords (7)

intracranial aneurysm; arterial wall; elasticity and stiffness; histology; biomechanical properties; cerebral hemorrhage; ultrasound

Lay Summary (French)

Lead
Evaluation par ultrasons du risque de rupture d’anévrismes intracrâniensErfassung des Risikos einer Ruptur intrakranieller Aneurysmen mittels Doppler-UltraschallAssessment of the risk of rupture of intracranial aneurysms by ultrasound Les anévrismes intracrâniens, dilatations pathologiques de vaisseaux cérébraux, sont fréquents. Ils peuvent être toute une vie asymptomatiques, mais s’ils se rupturent les conséquences sont souvent catastrophiques. Comme on ne peut toujours pas visualiser La paroi des vaisseaux n’étant toujours pas visualisable in vivo, il manque encore à l’heure actuelle des paramètres pour évaluer ce risque de rupture. Ce projet propose de tenter d’améliorer l’estimation de ce risque.
Lay summary

Contenu et but du projet de recherché
Les facteurs prédictifs du risque de développement et rupture d’anévrismes intracrâniens restent peu fiables et sont basés sur des études démographiques statistiques de larges populations de patients. Ces études ISUAI et plus récemment PHASES montrent comme facteur de risque de développement, mais aussi de rupture d’anévrismes, entre autres l’âge, l’hypertension, la taille et localisation, et la survenue d’hémorragies antérieures sur d’autres anévrismes. Des maladies héréditaires avec défaut d’élasticité de tissus ayant un taux de rupture d’anévrismes très élevé, nous postulons que la présence d’une artériopathie généralisée avec déficit relatif d’élasticité des vaisseaux étant une des causes de développement et de rupture de ces anévrismes. Nous allons donc comparer in vivo : des patients porteurs d’anévrismes intracrâniens non-rompus stables pendant une période de 6 mois, avec ceux ayant subi une rupture d’anévrisme intracrânien ainsi qu’avec des sujets sains. Pour ceci, l’élasticité des vaisseaux (techniquement accessibles) avoisinant les anévrismes sera mesurée par des investigations ultrasonographiques dans le but de pouvoir mieux prédire la rupture d’anévrismes.

Contexte scientifique et social du projet de recherche
Projet interdisciplinaire clinique et de recherche fondamentale entre l’unité neurosonologie du service de neurologie des HUG et le laboratoire d’hémodynamique cardiovasculaire de l’EPFL avec un volet d’expériences non-invasives d’ultrasons chez des patients et sujets sains, et un volet d’analyses de tissu de parois d’anévrismes par histologie et microscopie confocale. La rupture d’anévrismes étant une cause de mortalité et d’invalidité non-négligeable, le but de ce projet est de mieux pouvoir estimer le risque de rupture et ainsi mieux guider des interventions.

Mots clés
Anévrismes intracrâniens ; élasticité de la paroi artérielle ; imagerie ultrasonographique ; évaluation du risque de rupture.

 

Direct link to Lay Summary Last update: 20.04.2015

Responsible applicant and co-applicants

Employees

Collaboration

Group / person Country
Types of collaboration
University of Heidelberg, University Clinic Mannheim, Dept. Neurology Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Toronto Western Hospital, University Health Network, Dept. of Neuroradiology Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Laboratoire d'ondes acoustiques, Institut Langevin, Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
EAN Individual talk European Academy of Neurology 02.07.2019 Oslo, Norway Perren Fabienne;
ESNCH 2016 Talk given at a conference Superfast Ultrasound Imaging 19.05.2019 Berlin, Germany Perren Fabienne;
ESNCH 2019 Talk given at a conference In Vivo Adaptative Focusing for Clinical enhanced Transcranial Ultrafast Ultrasound Imaging 05.04.2019 Linz, Austria Perren Fabienne;
Swiss Stroke Society Talk given at a conference UFD ULTRASOUND ASSESSMENT OF THE RISK OF RUPTURE OF INTRACRANIAL ANEURYSMS 15.01.2019 Zurich, Switzerland Perren Fabienne; Puke Liene;
WCN 2017 Talk given at a conference TCCD ULTRASOUND IN GUIDING VASOSPASM TREATMENT AFTER aSAH 16.09.2017 Kyoto, Japan Perren Fabienne;


Abstract

1. SUMMARY OF THE RESEARCH PLAN Background Intracranial aneurysms account for 2-4% of the general population in western countries and are principally observed in subjects’ aged 50 and above (Rinkel GJ et al. 1998). They result from a pathological dilatation of the arterial wall that can rupture and lead to hemorrhage. Indeed spontaneous rupture of cerebral aneurysms constitutes the most common cause of subarachnoidal hemorrhage (SAH) (Oldenkott & Stolz 1969, Niizuma et al. 1979, Reynolds & Shaw 1981). A common complication of SAH is vasospasm which is often responsible for delayed ischemic neurological deficits (DINDs) in affected patients (Fleisher et al 1977, Weir et al. 1978, Kistler et al. 1983, Sloan 1994). The rupture of aneurysm occurs in 10/100'000 subjects per year but the prevalence is 2000-­-4000/100'000. The ISUIA study showed that if the risk of aneurysm development increases with age, the risk of rupture tends to decrease (Wiebers et al. 2003). Most cerebral aneurysms go unnoticed until they are discovered by chance or until they burst provoking death or permanent damage to the patient. However, it is currently still impossible to image the wall itself in vivo and to perform proper analysis of stress field within the aneurysmal wall. This limits substantially the assessment of the potential risk of rupture, which remains subjective and mainly based on the location, geometry, patient’s age, health, family medical history, and size of the aneurysm. Moreover, the decision of whether to treat incidental intracranial aneurysms is complicated by limitations in current knowledge of their natural history. Very recently, the development of PHASES (Population, Hypertension, Age, Size aneurysm, Earlier subarachnoid hemorrhage from another aneurysm, Site of aneurysm) score based on a systematic review and pooled analysis of individual patient data from 8382 patients in 6 prospective cohort studies with subarachnoid hemorrhage as outcome may be an aid for prediction of the risk of rupture of incidental intracranial aneurysms. It showed that the mean observed 1-year risk of aneurysm rupture was 1.4% and the 5-year risk was 3.4%. Predictors were age, hypertension, history of subarachnoid hemorrhage, aneurysm size and location and geographical region (Greving JP et al. 2014). Because an underlying arteriopathy might contribute to the development and rupture of intracranial aneurysms, a rapid non-­invasive and inexpensive tool for the in vivo assessment of the biomechanical properties of the arterial wall and the changes associated with the risk of rupture would be needed. Working Hypothesis Structural changes in the arterial walls of patients diagnosed with intracranial aneurysms result in mechanical modification of the elasticity detectable by ultrasound imaging. Ultrasound methods, like B­-mode, M-mode and high­-resolution echo-­tracking, combined to arterial blood pressure and applanation tonometry are able to non-­invasively determine internal diameter, compliance, distensibility, elastic modulus and stiffness of the arterial wall. Furthermore, the very recent one-dimensional transient elastography and supersonic shear imaging technique may be a promising application to the arterial wall elasticity assessment (Couade M et al. 2010, 2011). These noninvasive ultrasound imaging techniques therefore allow assessing the arterial wall elastic properties of arteries located in the vicinity of the intracranial aneurysms. Specific Aims The aim is to assess biomechanical properties of the arterial wall in the vicinity of intracranial aneurysms and specifically: •To compare in vivo biomechanical properties (e.g. elasticity, compliance) of the arterial wall in patients carrying unruptured/ruptured cerebral aneurysms with healthy matched controls. •To analyze elastin and collagen content of the arterial wall of specimens of arteries situated in the vicinity of ruptured aneurysms using histological and confocal microscopic properties. •To test whether ruptured versus unruptured aneurysms differentiate with respect to parameters of extracranial arteries compared to normal matched subjects and compare for gender differences (male vs female).•Try to establish a risk-­score after diagnosis of intracranial aneurysms for the unruptured asymptomatic intracranial aneurysms. •To follow the arterial wall biomechanical properties in the same patients and assess eventual modifications over time and to establish whether changes in wall parameters of extracranial parent arteries over time have a predictive value for rupture of aneurysms. Experimental Design and Methods Patients diagnosed previously (CTA/MRA, DSA) with either ruptured, or unruptured for 6 months stable, intracranial aneurysms (obtained from the databases of Prof. K. Schaller, Geneva and Prof. D. Rüfenacht, Zurich) and their healthy (MRI/MRA, clinical data) matched controls (age, gender, body mass index and blood pressure) will be recruited. Noninvasive high-­-resolution echo-­-tracking system, blood pressure and applanation tonometry measurements will be used to determine internal diameter, compliance, distensibility, elastic modulus and stiffness of ipsi-­ and contralateral common, external and internal carotid, vertebral and temporal arteries in both populations (patients and controls). Additionally, a new ultrasound technique to determine arterial elasticity based on ultrafast ultrasound elastography will also be performed in patients and controls. Medical history, physical examination and ECG will be gained from all the subjects. Patients and controls suffering or with past history of cardiovascular or additional cerebrovascular disease will be excluded. All the subjects will be examined under basal conditions in a supine position. Subgroup off-­line analysis (gender, number and location of aneurysms) will also be performed. To assess eventual changes over time this procedure will be repeated at 24 months. Additionally, biomechanical properties (elastic modulus) and histology (quantification of elastin and collagen) of postoperative specimens of the arterial wall of arteries carrying ruptured intracranial aneurysms will be studied. Expected Value of the Proposed Project To fulfill the need for a low­-cost, non­-invasive, tool that summarizes clinical and neuroradiological information and evaluates the risk of rupture (rupture-­risk score) of intracranial aneurysms, enhance our pathophysiologic understanding and possibly to identify and improve the outcome of those who would most benefit from treatment. In conclusion, if “aneurysms at risk” could be reliably identified the therapeutic decisions for either medical or surgical / endovascular treatment could be made more rationally.
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