The Artisse Intrasaccular Device: A New Intrasaccular Flow Diverter for the Treatment of Cerebral Aneurysms

The Artisse ISD

The original Artisse ISD is a self-expandable, preshaped endovascular implant made from a double layer of DFT wire mesh, made of nitinol with platinum/iridium proximal and distal marker bands available in 2 shapes. With the new Artisse there are 20 sizes ranging from 4.5–8 mm in width in a flared shape. The implants are chosen for treatment based on the aneurysm shape, width, and dome-to-neck ratio (Fig 1 and Table 1). Attached to a pusher wire that allows manipulation through a compatible 0.021 in microcatheter the device is navigated to the target aneurysm. The design allows for full retrieval and redeployment to reposition. The pusher wire is a tapered, ground core wire with platinum radiopaque markers and with a polyimide insulated cobalt chromium detachment element affixed to the distal end of the pusher wire. Detachment of the implant is achieved by using the Artisse detachment device, which delivers up to 2.1 mA of current to the detachment element via the pusher wire. The electrical current energizes the isolated detach element, causing it to dissolve, allowing separation of the implant from the pusher wire.

• Download figure
• Open in new tab
• Download powerpoint

FIG 1.

Photograph of the Artisse ISD. One proximal marker and one marker in the lateral part of the cage are radiopaque.

In Vivo Experiments

The study was performed in compliance with the Good Laboratory Practice Regulations at a federally registered test facility (Certificate Reference Number: INS-200015–0003-009).

The aneurysm model used has been previously described.⁸ Briefly, New Zealand rabbits under intravenously maintained anesthesia were incised medially from the mandibular angle to the manubrium sterni. After exposing the target vessels, a section of the jugular vein was removed. The left common carotid artery was ligated, cut, and guided under the pretracheal muscles to the other side. An end-to-side anastomosis was performed between both common carotid arteries, with the left artery trimmed diagonally to form a Y-shape and maintaining a small opening in the bifurcation. The previously removed vein was trimmed and sewn to the opening at the bifurcation as a blind sac. The created aneurysm was closed with a ligature. To allow for proper healing and avoid interference with the embolization process, a minimum healing period of 3 weeks was implemented.

At embolization, anesthesia was induced by subcutaneous injection of ketamine (75 mg/kg) and xylazine (4 mg/kg). Throughout the embolization, the animals were breathing spontaneously and additional anesthetic was administered via the lateral auricular vein (mixture ratio: 5:1:5; ketamine: 100 mg/mL, xylazine: 20 mg/mL, 0.9% saline: 0.08 mL/kg administered in 10-minute intervals). Acetylsalicylic acid (10 mg/kg) and clopidogrel (1 mg/kg) were administered daily 2 days prior and 30 days postimplantation. We incorporated antiplatelet medication into the protocol as a precautionary measure, because we were unable to anticipate whether dual antiplatelet therapy (DAPT) would be necessary and because DAPT was clinical practice before implantation of an IFD at the time of this study.

Antibiotic (enrofloxacin 7.5 mg/kg) and analgesic (meloxicam 0.3 mg/kg) therapy was given on the day of embolization.

A surgical cut-down of the right femoral artery was performed and a 5F Sheath (Terumo Glidesheath Slender) was inserted under an operation microscope (OPMI MD, Carl Zeiss) under sterile conditions. Heparin (500 U IV) was administered and then a 5F Codman Envoy guiding catheter was placed into the carotid artery. Using a Traxcess 0.014-inch guidewire (MicroVention) and a Rebar-18 microcatheter (Medtronic) was placed into the aneurysm cavity.

Device Sizing and Angiographic Evaluation

Biplane imaging was used for initial diagnostic runs with a 3D rotational angiogram for aneurysm sizing and finding a working projection. Aneurysm dimensions (neck width, aneurysmal height, and width) were determined and adjusted by using a reference sizing device. Due to the difficulty in determining the correct size without any prior experience in an animal model, Sim&Cure software was used to run various simulations and select the Artisse ISD size that provided the best wall apposition and complete coverage of the aneurysm sac. The device was then carefully inserted into the microcatheter and deployed at the aneurysm sac.

After deployment, the microcatheter was removed and immediate postprocedural and delayed angiographic runs were performed. Device placement and flow/stasis within the aneurysm were assessed by using standard angiographic projections. Another angiographic analysis was conducted before euthanization after 90 days. Due to the lack of a sufficient occlusion rating system for IFDs, the occlusion of aneurysms was assessed by using the modified Raymond-Roy classification (mRRC),⁹ which categorizes occlusion as complete (mRRC1), neck remnant (mRRC2), or residual aneurysm with contrast opacification within the coil interstices (mRRC3A) or outside the coil interstices, along the residual aneurysm wall (mRRC3B).¹⁰ Additionally, the O’Kelly-Marotta (OKM) scale was used to assign grades based on the amount of contrast filling (A, B, C, D) and the duration of contrast persistence (stasis grades 1, 2, 3) within the aneurysm lumen.¹¹

Histopathologic Processing, Histomorphometry, and Analysis

After last angiographic control all animals were euthanized with a lethal injection of embutramid-mebezoniumiodid-tetracain solution (1 mL/10 lbs). Aneurysms and a section of the parent artery were excised, fixed on a KliniTray, and immediately fixed in 4% neutral buffered formalin. The segments of the arteries were examined for alterations of the normal structures including the regionals draining lymph nodes. Eventual nature and extent of observed reacting tissue such as hematoma, edema, encapsulation, or other gross findings were recorded. Samples were embedded in methyl methacrylate plastic after dehydration through a series of gradient alcohols and xylene. After polymerization of the methyl methacrylate, subsequent polishing with silicon carbide paper provided a coplanar even surface. The polished surface of the sample was mounted on a microscope glass slide by using optically transparent cyanoacrylate-based glue. Sections were performed at 10 µm thickness with the laser microtome (LLS ROWIAK LaserLabSolutions). The remaining block again was slightly polished and subsequently used for laser microtome sectioning. Final slides were stained with H&E stains.

The tissues were assessed by an experienced pathologist according to a 4-scale grading ranging from minimal to marked for the following parameters: platelet/fibrin thrombus, percentage of endothelialization, neointima formation on the neck surface, aneurysm sac organization, inflammation and neoangiogenesis, parent artery luminal thrombus, wall damage, overall endothelial loss, and overall inflammation (Online Supplemental Data). Additionally, scanning electron microscope imaging was performed on 2 randomly selected animals to confirm neointimal coverage at the neck of the aneurysm.