Study to Evaluate Cerebral AneurysmFlow Results in Occlusion

AneurysmFlow R1.0 is an approved (CE labeled, cleared in US, Canada and Argentina), software
tool intended to provide relevant information on the blood flow in a cerebral aneurysm and
its parent artery based on angiography. It provides color coded and vector field
representation of a digital subtraction angiography (DSA). It can quantify blood flow rates
in the artery based on DSA and 3-D Rotational Angiogram (3DRA) data. It can visualize blood
flow patterns in an aneurysm based on DSA data. Specifically, it calculates the Mean Aneurysm
Flow Amplitude (MAFA) ratio to measure the volumetric flow rate quotient before and after
Flow Diverter Stent (FDS) implantation in the region of interest. It is manufactured by
Philips Medical Systems bv., a Philips Healthcare company.

120 subjects with unruptured, >5mm saccular aneurysm(s) located in the anterior intracranial
circulation and suitable for an endovascular treatment with a Flow Diverter Stent will be
enrolled in the study. The enrollment period is expected to last for 1 year.

Physician investigators participating in this study are expected to follow their normal
clinical practice in enrolling, treating and following patients with intracranial aneurysms
that are amenable to treatment with flow diverter stents. No additional procedures are
required of patients in order to participate in this observational study.

Pre-Screening

Patients presenting with intracranial saccular aneurysm(s) will be evaluated by the neuro
interventional team, in accordance with institutional practice, to establish an appropriate
treatment plan based on the patient's medical condition and available diagnostic screening
procedures prior to recruitment in the study. More than one aneurysm in a single patient may
be treated, but only one target aneurysm treated with an FDS device will be considered as
part of this study. If treatment of the aneurysm with the FDS is deemed appropriate, the
institution's guidelines regarding their ethics committee and informed consent process will
be followed.

Screening

After obtaining the consent form(s) approved by the local research ethics board (REB), the
principal investigator will screen the potential investigation subjects for the CARO study.
The principal investigator or his delegates on the study team will enter data in a
pre-designed digital Case Report Form (e-CRF). This will include patient demographics,
relevant past medical and surgical history, and specific target aneurysm data along with
pre-procedural/screening imaging details.

Only patients who meet all inclusion and none of the exclusion criteria will qualify for this
study. The measurement and size of each aneurysm will be verified by the principal
investigator. If the size of the aneurysm is acceptable, then it will be included in the
study. It is recommended that this measurement should be done within 180 days before the
procedure.

Index Procedure and Discharge

The investigator will proceed with standard of care procedures on the day of Index Procedure
(i.e. FDS insertion) for the target aneurysm(s). Then, endovascular treatment procedure
details should be provided for each eligible patient. Blood flow velocity will be calculated
using the dedicated software AneurysmFlow (Philips Healthcare, Best, The Netherlands), which
will be installed on standard of care imaging equipment. For this purpose, digital
subtraction angiograms will be acquired during the procedure; just before and right after
placement of the FDS. Calculation of blood flow velocity will be performed automatically on
the AneurysmFlow software. There are no additional devices or medications required for the
study. The AneurysmFlow software uses standard-of-care 2D DSA and 3D-RA image sequences to
determine this flow information. All raw image sequences will be stored for future reference.

This study will not make any recommendation on patient management or on treatment strategy.
Also, this software will not disrupt standard-of-care workflow for the interventionalist.

Follow-Ups (6 and 12 months)

All registry patients treated with FDS are expected to follow their routine post treatment
clinical visits, which will include a standard-of-care head imaging (e.g. Computed Tomography
Angiography (CTA), Magnetic Resonance Angiography (MRA) and/or DSA) test to classify aneurysm
occlusion (i.e. Raymond-Roy Occlusion Classification I) at 6 months (±49 days) and 12 months
(±49 days). During the 6 and 12 month follow up visits, patient medical charts will be
accessed to collect adverse events (if applicable) and document any post-treatment
neurological deterioration (neurological assessment, modified Rankin Scale). De-identified
data (i.e. clinical notes, imaging reports etc.) will be entered in the relevant e-CRF
sections. All (serious) adverse events (i.e. re-operations, ruptures and deaths) whether or
not related to the investigational device will be collected and reported conform local rules
and regulations.

The total duration of the study is expected to take approximately 2.5 years. Patient
enrollment will take place between September 2018 and September 2019. Each subject will be in
the study for 1 year (follow-up).

Inclusion Criteria:

- Subject with unruptured, ≥5mm saccular aneurysm(s) located in the anterior
intracranial circulation and suitable for an endovascular treatment with a Flow
Diverter Stent

- Subject is 18 years of age or older, or of legal age to give informed consent per
state or national law.

- Subject is available for clinical follow-ups.

Exclusion Criteria:

- Non-saccular brain aneurysm(s) (i.e. dissecting, fusiform, atherosclerotic, mycotic,
bifurcational). Prior aneurysm treatment with either endovascular (stenting, coiling)
or surgical (clipping) techniques.

- Endovascular treatment assisted with coils or intracranial stents

- Significant or severe allergy to intra-arterial contrast medium uncontrolled by
pre-procedure medications.

- Severe kidney disease (Glomerular Filtration Rate < 60).

- Subjects not willing (or able) to attend post FDS insertion standard-of-care follow up
clinic visits requiring DSA, head MRI or CTA imaging.

- Subject participates in a potentially confounding drug or device trial during the
course of the study.

- Subject meets an exclusion criteria according to national law (e.g. age, pregnant
woman, breast feeding woman).