James Ryan Mason, DO, MPH 1, Guyla Gal, MD 2, Goetz Benndorf, MD, PhD 2 1 Swedish Medical Center, Seattle, Washington 2 University of Southern Denmark, Odense

Disclosures: JRM:None GB:None Gal:Consultant - Balt Extrusion Consultant - Penumbra

Purpose: Onyx ® is a well established non-adhesive liquid embolic agent for the endovascular treatment (EVT) of brain arteriovenous malformations (AVMs). Comprised of Ethylene-Vinyl Alcohol copolymer (EVOH), tantalum powder for radiopacity in Dimethyl sulfoxide (DMSO) solvent, it offers some advantages over traditional adhesive liquids such as NBCA (acrylic glue) and has improved feasibility and safety of EVT of cerebral arteriovenous (AV) shunting lesions. Nevertheless, complications may occur, potentially attributable in part to its inferior radiographic visibility when compared to standard iodine-based vascular contrast medium.

Purpose: We hypothesize that some of these complications may be the result of loss of visual control during therapeutic Onyx ® injections under fluoroscopy with subsequent “silent migration” or invisible reflux into small terminal arteries or via “dangerous anastomoses” causing inadvertent occlusion of normal territories. The purpose of this study was to evaluate the radiographic visualization of Onyx ® in comparison to iodine-based contrast medium using a newly developed calibrated vascular model and state-of-the-art angiographic equipment. Thalamoperforators (Rr. diencephalici inf.post.) may arise from the P1 segment, basilar artery or superior cerebellar artery an can measure between 0.1 and 1.0 mm. They give off mammillary branches measuring between 0.12 and 0.37mm ( micron) after Lang and Brunner, Drawing modified after J. Lang (Lanz & Wachsmuth, Springer 1985)

Purpose: Many essential perforating cerebral vessels are known to have diameters as small as 120 microns and average in outer diameters ranging from 330 to 520 microns. Given these known vessel sizes, we devised a model to test visualization of onyx between 100 and 500 microns. Clival branches - “dangerous anastomoses” from ECA to ICA Thalamoperforators

This stepwise reduced diameter model was then connected to a microcatheter which allow for injections very similar to clinical scenarios Microcatheter Microcatheter 500μ 350μ 250μ 175μ 100μ Methods: A vascular model was built using tubing of stepwise reduced calibrated inside diameters: 500 microns, 380 microns, 250 microns, 175 microns and 100 microns.

Methods: The Model had identical outside diameters. 500μ 380μ 250μ 175μ100μ Microcatheter

Methods: Philips Allura system under the following settings: Cerebral 2 f/sec Unsubtracted DSA “Blank” Roadmap in “Embo”- Mode 3 (high dose) FD size = 6 inch SID = 90 Table Height = +5 Microcatheter 500μ 380μ 250μ 175μ100μ Injections performed with the following: Contrast - Standard vascular Iodine contrast medium (non-diluted Omnipaque ® 300) Onyx – Onyx ® -18, Ethylene-Vinyl Alcohol copolymer (EVOH), tantalum powder for radiopacity in Dimethyl sulfoxide (DMSO) solvent Microcatheter Model

Results: Model injected with contrast, unsubtracted DSA Contrast in tubing

Results: Model injected with contrast, unsubtracted DSA Model

Results: Model injected with contrast, unsubtracted DSA Microcatheter

Results: Model injected with contrast, unsubtracted DSA Contrast entering Contrast leaving Microcatheter

Results: Model injected with contrast, unsubtracted DSA Contrast in gaps between tubing

Results: Model injected with contrast, unsubtracted DSA 500μ 380μ250μ175μ100μ Contrast in tubing 500μ 380μ250μ175μ100μ The Model had identical outside diameters.

Results: Model injected with contrast, unsubtracted DSA 500μ 350μ 250μ 175μ 100μ Stepwise reduced inside diameters 500μ 380μ250μ175μ100μ Microcatheter Microcatheter

Results: Model injected with contrast, Roadmap 500μ 350μ 250μ 175μ 100μ 500μ 380μ250μ175μ100μ Stepwise reduced inside diameters Microcatheter Microcatheter

Results: Model injected with contrast, Roadmap Microcatheter Microcatheter Contrast in gaps between tubing

Results: Onyx ® vs. Contrast, unsubtracted DSA Onyx Contrast Microcatheter Microcatheter Microcatheter Microcatheter

Results: Onyx ® vs. Contrast, unsubtracted DSA Onyx Contrast entering Contrast leaving Onyx entering Oynx exiting Contrast

Results: Onyx ® vs. Contrast, unsubtracted DSA Onyx seen in gaps between tubing Contrast seen in gaps between tubing Onyx Contrast

Results: Onyx ® vs. Contrast, unsubtracted DSA 500μ 380μ250μ175μ100μ Stepwise reduced inside diameters 350μ 250μ 175μ 100μ 500μ Onyx Contrast 500μ 380μ250μ 175μ100μ Microcatheter Microcatheter

Results: Onyx ® vs. Contrast, unsubtracted DSA 500μ 380μ250μ175μ Beginning loss of visualization of contrast around 175 micron. 350μ 250μ 175μ 100μ 500μ Onyx Contrast 500μ 380μ250μ Beginning loss of visualization of Onyx around 250 microns. Microcatheter Microcatheter

Results: Onyx ® vs. Contrast, Roadmap Onyx 500μ 380μ250μ175μ100μ Contrast 350μ 250μ 175μ 100μ 500μ 500μ 380μ250μ 175μ100μ Microcatheter Microcatheter

Results: Onyx ® vs. Contrast, Roadmap Onyx seen entering gaps Contrast seen entering gaps Contrast 350μ 250μ 175μ 100μ 500μ Onyx Microcatheter Microcatheter

Results: Onyx ® vs. Contrast, Roadmap Beginning loss of visualization of contrast around 250 microns. Contrast 500μ 380μ 500μ 380μ250μ 350μ 250μ 175μ 100μ 500μ Onyx Beginning loss of visualization of Onyx ® around 380 microns. Microcatheter Microcatheter

Conclusions 1: 1.A newly designed calibrated vascular model allowed evaluation and comparison of radiographic visualization of contrast medium and a liquid embolic agent under standardized and reproducible experimental conditions. 2.Visualization of both contrast and Onyx ® -18 is under “blank” Road Map is inferior compared to unsubtracted DSA. 3.Loss of visual control during therapeutic injections of liquid embolic agents, such as Onyx ® -18 may occur earlier than previously known, and thus may be associated with the risk of “silent migration” into small perforating arteries, “dangerous anastomoses” or reflux channels with potentially serious clinical consequences.

Conclusions 2: 1.This is to our knowledge the first visualization test for a liquid embolic using a vascular model with a stepwise calibrated decreasing diameter to simulate flux conditions comparable to human vasculature. 2.This model could also be used to help test and calibrate fluoroscopy and angiographic machines, compare visualization between different manufacturers, as well as test visualization of various contrast and liquid embolic agents.

References: 1. Loffroy R, Guiu B, Cercueil J, Krause D. Endovascular therapeutic embolisation: An overview of occluding agents and their effects on embolised tissues. Current vascular pharmacology. 2009;7(2): Lang J. Clinical anatomy of the head: Neurocranium, orbit, craniocervical regions. Springer-Verlag; Brunner FX: Über die Arterien des Hirnstammes. Vorkommen, Zahl, Durchmesser und Variationen. Thesis 1978, University Würzburg.