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.

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.

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.

The study will include patients (further referred to as 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.

De-identified individual participant data for all primary and secondary outcome measures will be made available.

Data will be available for 5 years after study completion.

Data will be shared electronically by email or by depositing on a secure file share server depending on file type and size. If necessary, non-confidential files will be supplied on a data CD or USB flash drive. When requested, the data will be made available by the PI provided the request does not interfere with publication, compromise intellectual property interests, or precede data analysis. The data acquired and preserved will be governed by Medical University of Silesia policies regarding intellectual property, record retention, and data management.