Risk Factors of Middle Cerebral Artery Aneurysm.

Middle Cerebral Artery Aneurysm Clinical Trial

— MCAA  

Official title:

A Case-control Study of Independent Predictors of Middle Cerebral Artery Aneurysm.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03493035
• Other study ID #: SilesianMUNch1
• Status: Completed
• Start date: June 16, 2015
• Est. completion date: June 15, 2017

Study information

• Verified date: February 2019
• Source: Medical University of Silesia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

According to the current view, cerebral aneurysms are acquired degenerative lesions resulting from hemodynamic stress. This single-center case-control study will be carried out at the Department of Neurosurgery, Regional Hospital in Sosnowiec, Medical University of Silesia in Katowice, Poland between June 2015 and June 2017. The aim of the study is to determine morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal middle cerebral artery (MCA) bifurcations and to analyze their relationship with aneurysm formation. A minimum of 75 cases and 75 age- and sex-matched controls will be required for the study. Characteristics of the MCA bifurcations will be determined with computed tomography angiography (CTA) and transcranial color-coded sonography (TCCS). The following variables will be evaluated as potential risk factors for MCA aneurysm formation: radii and cross-sectional area of the main MCA trunk and its branches, tortuosity of MCA trunk, asymmetry ratio, area ratio, the angle between the post-bifurcation branches, the angles between the MCA trunk and the larger and smaller branch, volume flow rate, mean flow velocity and pulsatility index of the MCA. All morphometric and hemodynamic parameters will be assessed as potential risk factors for MCA aneurysm formation.

Description:

Current evidence suggests that a principal factor involved in formation, enlargement and rupture of cerebral aneurysms are hemodynamic forces acting at arterial bifurcation. The objective of this case-control study is to determine morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal MCA bifurcations and to analyze their relationship with aneurysm formation. This single-center case-control study will be carried out at the Department of Neurosurgery, Regional Hospital in Sosnowiec, Medical University of Silesia in Katowice, Poland between June 2015 and June 2017. The study will include patients (cases) with unruptured MCA aneurysm diagnosed on three-dimensional computed tomography angiography (3D CTA). The controls will be patients with no evidence of intracranial pathologies on 3D CTA, referred to establish the etiology of minor symptoms, such as headache or vertigo. A minimum of 75 cases and 75 age- and sex-matched controls will be required for the study.

CTA scans data in DICOM format will be transferred to Mimics Innovation Suite (MIS) platform (Materialise, Leuven, Belgium). Image segmentation and creation of three-dimensional (3D) models will be carried out with Mimics v.17.0 MIS software (Materialise, Leuven, Belgium). The segmentation process will include main trunks of the MCA and the post-bifurcation branches. Trifurcations of the main MCA trunk will be excluded from the morphometric analysis. MCA bifurcations from the aneurysm patients will be divided into two groups: the An group with aneurysmal MCA bifurcations and the non-An group with contralateral non-aneurysmal MCA bifurcations. Also, MCA bifurcations from the controls will be divided into two groups: R-MCA group with bifurcations of the right MCA and the L-MCA group with bifurcations of the left MCA. Morphometric analysis will include the following parameters: radii and cross-sectional area of the main MCA trunk and its branches (for the larger and smaller branch, respectively), tortuosity of MCA trunk, asymmetry ratio, area ratio, the angle between the post-bifurcation branches, the angles between the MCA trunk and the larger and smaller branch. All TCCS examinations will be performed using a Vivid 3 Pro (GE Healthcare, Chicago, Illinois, USA) equipped with a multi-frequency transcranial probe (1.5-3.6 MHz). Angle-corrected mean blood flow velocity, peak systolic velocity and end-diastolic velocity will be measured for both MCAs. Pulsatility index and volume flow rate in each vessel will be calculated as well. The protocol of the study was approved by the Institutional Review Board, and written informed consent will be sought from all the study participants. All morphometric and hemodynamic parameters will be assessed as potential risk factors for MCA aneurysm formation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: June 15, 2017
• Est. primary completion date: June 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Definition and recruitment of cases The study will include patients (further referred to as cases) with unruptured MCA aneurysm diagnosed on three-dimensional computed tomography angiography (3D CTA).

Case inclusion criteria

• all patients with unruptured MCA aged between 18-75 years Case exclusion criteria

• refusal to participate in the study

• inability to give informed consent

• presence of multiple cerebral aneurysms

• presence of pathologies, other than MCA aneurysm, in the central nervous system that could have a potential effect on cerebral blood flow (e.g. ischemic stroke, intracerebral or subarachnoid hemorrhage)

• severe systemic disorders (e.g. neoplastic disease)

• severe heart failure or multi-organ failure

• hemodynamically significant internal carotid artery stenosis

• pregnancy

• family history of cerebral aneurysms.

Definition and recruitment of controls The controls will be patients with no evidence of intracranial pathologies on 3D CTA, referred to establish the etiology of minor symptoms, such as headache or vertigo.

Inclusion criteria for the controls

• all patients aged between 18-75 years with no evidence of intracranial pathologies on 3D CTA Exclusion criteria for the controls

• refusal to participate in the study

• inability to give informed consent

• presence of pathologies in the central nervous system that could have a potential effect on cerebral blood flow (e.g. ischemic stroke, intracerebral or subarachnoid hemorrhage)

• severe systemic disorders (e.g. neoplastic disease)

• severe heart failure or multi-organ failure

• hemodynamically significant internal carotid artery stenosis

• pregnancy

• family history of cerebral aneurysms.

Related Conditions & MeSH terms

• Aneurysm
• Intracranial Aneurysm
• Middle Cerebral Artery Aneurysm

Intervention

Diagnostic Test:
• Computed tomography angiography (3D CTA)
CTA scans data in DICOM format was used to morphometric analysis of aneurysmal and non-aneurysmal MCA bifurcations.
• Transcranial color-coded sonography (TCCS)
TCCS was used to assess of hemodynamic parameters of aneurysmal and non-aneurysmal MCA bifurcations.

Locations

Country	Name	City	State
Poland	Wojciech Kaspera	Sosnowiec	Smorzykk@gmail.com

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Silesia

Country where clinical trial is conducted

Poland, 

References & Publications (8)

Baharoglu MI, Lauric A, Safain MG, Hippelheuser J, Wu C, Malek AM. Widening and high inclination of the middle cerebral artery bifurcation are associated with presence of aneurysms. Stroke. 2014 Sep;45(9):2649-55. doi: 10.1161/STROKEAHA.114.005393. Epub 2 — View Citation

Bor AS, Velthuis BK, Majoie CB, Rinkel GJ. Configuration of intracranial arteries and development of aneurysms: a follow-up study. Neurology. 2008 Feb 26;70(9):700-5. doi: 10.1212/01.wnl.0000302176.03551.35. — View Citation

Can A, Ho AL, Dammers R, Dirven CM, Du R. Morphological parameters associated with middle cerebral artery aneurysms. Neurosurgery. 2015 Jun;76(6):721-6; discussion 726-7. doi: 10.1227/NEU.0000000000000713. — View Citation

Ingebrigtsen T, Morgan MK, Faulder K, Ingebrigtsen L, Sparr T, Schirmer H. Bifurcation geometry and the presence of cerebral artery aneurysms. J Neurosurg. 2004 Jul;101(1):108-13. — View Citation

Kaspera W, Ladzinski P, Larysz P, Hebda A, Ptaszkiewicz K, Kopera M, Larysz D. Morphological, hemodynamic, and clinical independent risk factors for anterior communicating artery aneurysms. Stroke. 2014 Oct;45(10):2906-11. doi: 10.1161/STROKEAHA.114.00605 — View Citation

Rossitti S. Shear stress in cerebral arteries carrying saccular aneurysms. A preliminary study. Acta Radiol. 1998 Nov;39(6):711-7. — View Citation

Sasaki T, Kakizawa Y, Yoshino M, Fujii Y, Yoroi I, Ichikawa Y, Horiuchi T, Hongo K. Numerical Analysis of Bifurcation Angles and Branch Patterns in Intracranial Aneurysm Formation. Neurosurgery. 2018 Aug 21. doi: 10.1093/neuros/nyy387. [Epub ahead of prin — View Citation

Tütüncü F, Schimansky S, Baharoglu MI, Gao B, Calnan D, Hippelheuser J, Safain MG, Lauric A, Malek AM. Widening of the basilar bifurcation angle: association with presence of intracranial aneurysm, age, and female sex. J Neurosurg. 2014 Dec;121(6):1401-10 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Computed tomography angiography (CTA) analysis of the cross-sectional area of the MCA bifurcations.	CTA scans in DICOM format will be used to create three-dimensional (3D) models of MCA bifurcation using Mimics Innovation Suite platform (Materialise, Leuven, Belgium). The points including the largest curvature of MCA main trunk and two post-bifurcations branches will be automatically calculated according to the centreline fitted with a computer-aided design (CAD) tool. In these points the cross-sectional area (mm2) of the MCA trunk and its two post-bifurcation branches will be calculated automatically.	from 16 June 2015 to 15 June 2017
Primary	Computed tomography angiography (CTA) analysis of the best fit diameter of the MCA bifurcations.	CTA scans in DICOM format will be used to create three-dimensional (3D) models of MCA bifurcation using Mimics Innovation Suite platform (Materialise, Leuven, Belgium). The points including the largest curvature of MCA main trunk and two post-bifurcations branches will be automatically calculated according to the centreline fitted with a computer-aided design (CAD) tool. In these points the best fit diameter (mm) of the MCA trunk and its two post-bifurcation branches will be calculated automatically.	from 16 June 2015 to 15 June 2017
Primary	Computed tomography angiography (CTA) analysis of the angles between the MCA bifurcations components.	CTA scans in DICOM format will be used to create three-dimensional (3D) models of MCA bifurcation using Mimics Innovation Suite platform (Materialise, Leuven, Belgium). The points of the largest curvature of MCA main trunk and two post-bifurcations branches will be calculated according to the centreline fitted automatically with a computer-aided design (CAD) tool. The centrelines and the largest curvature points will be exported to 3-matic v.9.0 MIS software. Three points of the largest curvatures (the main MCA trunk and two post-bifurcations branches) together with the point of the intersection of both centrelines passing through the main trunk MCA and both branches will determine the arms and the apex of the three angles. The following angle values will be calculated automatically: the angle between the post-bifurcation branches (a angle) and the angles between the MCA trunk and the larger and the smaller branches (ß and ? angle).	from 16 June 2015 to 15 June 2017
Primary	Pulsatility Index (PI) as calculated from transcranial color-coded sonography (TCCS) blood flow velocities (cm/s)	The assessment of blood flow velocities in both MCAs will be performed by transcranial color-coded sonography (TCCS) using a Vivid 3 Pro (GE Healthcare, Chicago, Illinois, USA) equipped with a multi-frequency transcranial probe (1.5-3.6 MHz). For both MCAs the following will be automatically measured: mean blood flow velocity (V) [cm/s]; peak systolic velocity (Vps) [cm/s]; end-diastolic velocity (Ved) [cm/s] The velocity measurements will be used to calculate in each vessel the pulsatility index (PI), calculated using the following formula: PI=(Vps-Ved)/V	from 16 June 2015 to 15 June 2017
Primary	Volume Flow Rate (VFR) as calculated from transcranial color-coded sonography (TCCS) blood flow velocities (cm/s)	The assessment of blood flow velocities in both MCAs will be performed by transcranial color-coded sonography (TCCS) using a Vivid 3 Pro (GE Healthcare, Chicago, Illinois, USA) equipped with a multi-frequency transcranial probe (1.5-3.6 MHz). For both MCAs the following will be automatically measured: mean blood flow velocity (V) [cm/s]; peak systolic velocity (Vps) [cm/s]; end-diastolic velocity (Ved) [cm/s] The velocity measurements will be used to calculate in each vessel the volume flow rate (VFR) using the following formula: VFR=V*p, where p - a cross-sectional area of the main MCA trunk, calculated from the morphometric analysis	from 16 June 2015 to 15 June 2017