scholarly journals Thrombogenicity of flow diverters in an ex vivo shunt model: effect of phosphorylcholine surface modification

2016 ◽  
Vol 9 (10) ◽  
pp. 1006-1011 ◽  
Author(s):  
Matthew W Hagen ◽  
Gaurav Girdhar ◽  
John Wainwright ◽  
Monica T Hinds
Keyword(s):  
Surface Modification ◽  
Antiplatelet Therapy ◽  
Ex Vivo ◽  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Preclinical Model ◽  
Platelet Deposition ◽  
Treatment For Cerebral Aneurysms ◽  
Flow Diverters

BackgroundFlow diverters offer a promising treatment for cerebral aneurysms. However, they have associated thromboembolic risks, mandating chronic dual antiplatelet therapy (DAPT). Shield Technology is a phosphorylcholine surface modification of the Pipeline Embolization Device (PED) flow diverter, which has shown significant reductions in material thrombogenicity in vitro.ObjectiveTo compare the thrombogenicity of PED, PED with Shield Technology (PED+Shield), and the Flow-Redirection Endoluminal Device (FRED)—with and without single antiplatelet therapy and DAPT—under physiological flow.MethodsAn established non-human primate ex vivo arteriovenous shunt model of stent thrombosis was used. PED, PED+Shield, and FRED were tested without antiplatelet therapy, with acetylsalicylic acid (ASA) monotherapy, and with DAPT. Radiolabeled platelet deposition was quantified over 1 hour for each device and total fibrin deposition was also quantified.ResultsCumulative statistical analysis showed significantly lower platelet deposition on PED compared with FRED. The same statistical model showed significant decreases in platelet deposition when ASA, clopidogrel, or Shield Technology was used. Direct comparisons of device performances within antiplatelet conditions showed consistent significant decreases in platelet accumulation on PED+Shield relative to FRED. PED+Shield showed significant reductions in platelet deposition compared with unmodified PED without antiplatelet therapy and with DAPT. PED accumulated minimal fibrin with and without Shield Technology.ConclusionsIn this preclinical model, we have shown that the Shield Technology phosphorylcholine modification reduces the platelet-specific thrombogenicity of a flow diverter under physiologically relevant flow with and without DAPT. We have further identified increased fibrin-driven thrombogenicity associated with FRED relative to PED.

scholarly journals Comparison of the In Vitro Hemodynamic Performance of New Flow Diverters for Bypass of Brain Aneurysms

2012 ◽  
Vol 134 (8) ◽  
Author(s):  
Asher L. Trager ◽  
Chander Sadasivan ◽  
Baruch B. Lieber
Keyword(s):  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Parent Artery ◽  
New Device ◽  
Design Changes ◽  
Hemodynamic Performance ◽  
Braiding Angle ◽  
Treatment For Cerebral Aneurysms

One possible treatment for cerebral aneurysms is a porous tubular structure, similar to a stent, called a flow diverter. A flow diverter can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. This excludes the aneurysm from the parent artery and returns the flow of blood to normal. Previous flow diverting devices have been analyzed to determine optimal characteristics, such as braiding angle and wire diameter. From this information, a new optimized device was designed to achieve equivalent hemodynamic performance to the previous best device, but with better longitudinal flexibility to preserve physiological arterial configuration. The new device was tested in vitro in an elastomeric replica of the rabbit elastase induced aneurysm model and is now in the process of being tested in vivo. Particle image velocimetry was utilized to determine the velocity field in the plane of symmetry of the model under pulsatile flow conditions. Device hemodynamic performance indices such as the hydrodynamic circulation were evaluated from the velocity fields. Comparison of these indices with the previous best device and a control shows that the significant design changes of the device did not change its hemodynamic attributes (p > 0.05).

In Vitro Simulation of Flow Diverter Induced Clotting in Aneurysms Using Rennet Activated Milk Flow

2010 ◽  
Author(s):  
Chander Sadasivan ◽  
Jessica M. Schmidtman ◽  
Henry H. Woo ◽  
David J. Fiorella ◽  
Baruch B. Lieber
Keyword(s):  
Blood Cells ◽  
Cerebral Aneurysms ◽  
Coagulation Factors ◽  
Flow Diverter ◽  
Blood Coagulation Factors ◽  
Milk Flow ◽  
In Vitro Simulation ◽  
Flow Stasis ◽  
Flow Diverters

Flow diverters are currently being evaluated in patients with cerebral aneurysms. Blood cells (such as platelets) contact the device mesh as they enter the aneurysm and pro-coagulant factors released by these activated cells accumulate within the aneurysm because of the intra-aneurismal flow stasis created by the device. The efficacy of any flow diverter is thus related to the rate at which blood coagulation factors accumulate within the aneurysm and get converted to thrombus.

Surface Modification of Copolyether-Urethane Catheters with Poly(Ethylene Oxide)

1989 ◽  
Vol 12 (6) ◽  
pp. 390-394 ◽  
Author(s):  
E. Brinkman ◽  
A. Poot ◽  
T. Beugeling ◽  
L. Van Der Does ◽  
A. Bantjes
Keyword(s):  
Surface Modification ◽  
Ethylene Oxide ◽  
Blood Compatibility ◽  
Angle Measurements ◽  
Fold Reduction ◽  
Contact Angle Measurements ◽  
Platelet Deposition ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

Pellethane 2363 80A catheters were modified with poly(ethylene oxide) in order to improve their blood compatibility. Contact angle measurements showed that Pellethane 2363 80A surfaces had increased wettability after this modification. The results of in vitro blood compatibility tests showed that surface modification with poly(ethylene oxide) resulted in a five-fold reduction of platelet deposition. Activation of coagulation was not affected.

Abstract 1122‐000103: FlowDiverter:A Study Safety and Efficacy in a Consecutive Group of 53 Patient and 60 Aneurysm

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Marcelo Bolcato ◽  
ana Carolina Dalmonico ◽  
Leo Ditzel ◽  
Savio Machareti ◽  
Thiago Yoshida ◽  
...  
Keyword(s):  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Consecutive Series ◽  
Safety And Efficacy ◽  
Grading Scale ◽  
Aneurysm Occlusion ◽  
Occlusion Rate ◽  
Flow Diverters

Introduction : Endovascular flow diverters are increasingly used for the treatment of cerebral aneurysms. We assessed the safety and efficacy of the Flow Diverters in a consecutive series of 53 patients and 60 aneurysms. Methods : Inclusion criteria were wide‐neck, blister‐like, or fusiform aneurysms independent of size, treated with the FRED, PIPELINE and SILK between December 2014 and Junho 2021. Assessment criteria were aneurysm occlusion, manifest ischemic stroke, bleeding, or death. The occlusion rate was assessed at 6 months and 1 year with DSA by using the Raymond classification and the O'Kelly‐Marotta grading scale. Results : Fifty three patients (mean age 54.3 years;81.1% female) with 60 aneurysms were treated with 9 Silk, 38 FREDs and 13 Pipeline. Aneurysm size ranged from 2.5 to 30 mm. Deployment of the Flow diverters was successful in 52 aneurysms. Three patient developed mild stroke symptoms that fully receded within days, 4 patients occlusion total carotid because resistant antiagregation and another patient’s development Swelling syndrome. There has been one death. Initial follow‐up at 6 months showed complete occlusion in 90% of the overall study group and 93,33% at 1 year. Conclusions : The flow diverter is a safe device for the treatment of cerebral aneurysms of various types. Our data reveal high occlusion rates at 6 months and 1 year. Long‐term occlusion rates are expected.

A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2935-2945 ◽  
Author(s):  
Julia Kirshner ◽  
Kyle J. Thulien ◽  
Lorri D. Martin ◽  
Carina Debes Marun ◽  
Tony Reiman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Plasma Cells ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Preclinical Model ◽  
Drug Resistant ◽  
Three Dimensional Model ◽  
The Impact

AbstractAlthough the in vitro expansion of the multiple myeloma (MM) clone has been unsuccessful, in a novel three-dimensional (3-D) culture model of reconstructed bone marrow (BM, n = 48) and mobilized blood autografts (n = 14) presented here, the entire MM clone proliferates and undergoes up to 17-fold expansion of malignant cells harboring the clonotypic IgH VDJ and characteristic chromosomal rearrangements. In this system, MM clone expands in a reconstructed microenvironment that is ideally suited for testing specificity of anti-MM therapeutics. In the 3-D model, melphalan and bortezomib had distinct targets, with melphalan targeting the hematopoietic, but not stromal com-partment. Bortezomib targeted only CD138+CD56+ MM plasma cells. The localization of nonproliferating cells to the reconstructed endosteum, in contact with N-cadherin–positive stroma, suggested the presence of MM-cancer stem cells. These drug-resistant CD20+ cells were enriched more than 10-fold by melphalan treatment, exhibited self-renewal, and generated clonotypic B and plasma cell progeny in colony forming unit assays. This is the first molecularly verified demonstration of proliferation in vitro by ex vivo MM cells. The 3-D culture provides a novel biologically relevant preclinical model for evaluating therapeutic vulnerabilities of all compartments of the MM clone, including presumptive drug-resistant MM stem cells.

Preliminary in vitro angiographic comparison of the flow diversion behavior of Evolve and Pipeline devices

2019 ◽  
Vol 12 (6) ◽  
pp. 616-620 ◽  
Author(s):  
Chander Sadasivan ◽  
David Fiorella
Keyword(s):  
High Speed ◽  
Cerebral Aneurysms ◽  
In Vitro Study ◽  
Flow Diversion ◽  
Comparative Efficacy ◽  
Two Parameters ◽  
Almost All ◽  
Flow Diverters ◽  
Better Than

Background and purposeFlow diverters are increasingly used to treat a broad category of cerebral aneurysms. We conducted an in vitro study to angiographically compare the flow diversion effect of Surpass Evolve from Stryker Neurovascular with the Pipeline Shield Embolization Device from Medtronic Neurovascular.MethodsThree copies each of three carotid aneurysm geometries were manufactured from silicone. Evolve and Pipeline flow diverters were deployed in one copy of each geometry; the third copy was used as Control. High-speed angiography was acquired under pulsatile flow in each replica, contrast concentration-time curves within the aneurysms were recorded, and the curves were quantified with six parameters. The parameters were statistically evaluated to compare the flow diversion effect of both devices.ResultsThe Evolve showed greater flow diversion trends in almost all intra-geometry comparisons than the Pipeline. When aggregated over the three geometries, the Evolve was statistically significantly better than the Pipeline in four of the six parameters, and about the same or better (not statistically significant) than the Pipeline in the other two parameters.ConclusionsThe Evolve device demonstrated greater in vitro flow diversion effects than Pipeline. Comparative efficacy of the devices will need to be adjudicated based on clinical outcomes.

scholarly journals Flow Diverters for Intracranial Aneurysms

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yazan J. Alderazi ◽  
Darshan Shastri ◽  
Tareq Kass-Hout ◽  
Charles J. Prestigiacomo ◽  
Chirag D. Gandhi
Keyword(s):  
Antiplatelet Therapy ◽  
Intracranial Aneurysms ◽  
Evidence Base ◽  
Flow Diverter ◽  
Parent Artery ◽  
Comparative Efficacy ◽  
Parent Vessel ◽  
Wide Neck ◽  
Endovascular Devices ◽  
Flow Diverters

Flow diverters (pipeline embolization device, Silk flow diverter, and Surpass flow diverter) have been developed to treat intracranial aneurysms. These endovascular devices are placed within the parent artery rather than the aneurysm sac. They take advantage of altering hemodynamics at the aneurysm/parent vessel interface, resulting in gradual thrombosis of the aneurysm occurring over time. Subsequent inflammatory response, healing, and endothelial growth shrink the aneurysm and reconstruct the parent artery lumen while preserving perforators and side branches in most cases. Flow diverters have already allowed treatment of previously untreatable wide neck and giant aneurysms. There are risks with flow diverters including in-stent thrombosis, perianeurysmal edema, distant and delayed hemorrhages, and perforator occlusions. Comparative efficacy and safety against other therapies are being studied in ongoing trials. Antiplatelet therapy is mandatory with flow diverters, which has highlighted the need for better evidence for monitoring and tailoring antiplatelet therapy. In this paper we review the devices, their uses, associated complications, evidence base, and ongoing studies.

In vitro measurement of the permeability of endovascular coils deployed in cerebral aneurysms

2018 ◽  
Vol 10 (9) ◽  
pp. 896-900 ◽  
Author(s):  
Chander Sadasivan ◽  
Erica Swartwout ◽  
Ari D Kappel ◽  
Henry H Woo ◽  
David J Fiorella ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Packing Density ◽  
Cerebral Aneurysms ◽  
Wire Diameter ◽  
Endovascular Coiling ◽  
Simple Modification ◽  
Flow Through ◽  
Treatment For Cerebral Aneurysms ◽  
Endovascular Coils

Background and purposeAneurysm recurrence is the primary limitation of endovascular coiling treatment for cerebral aneurysms. Coiling is currently quantified by a volumetric porosity measure called packing density (pd). Blood flow through a coil mass depends on the permeability of the coil mass, and not just its pd. The permeability of coil masses has not yet been quantified. Here we measure coil permeability with a traditional falling-head permeameter modified to incorporate idealized aneurysms.MethodsSilicone replicas of idealized aneurysms were manufactured with three different aneurysm diameters (4, 5, and 8 mm). Four different coil types (Codman Trufill Orbit, Covidien Axium, Microvention Microplex 10, and Penumbra 400) were deployed into the aneurysms with a target pd of 35%. Coiled replicas were installed on a falling-head permeameter setup and the time taken for a column of fluid above the aneurysm to drop a certain height was recorded. Permeability of the samples was calculated based on a simple modification of the traditional permeameter equation to incorporate a spherical aneurysm.ResultsThe targeted 35% pd was achieved for all samples (35%±1%, P=0.91). Coil permeabilities were significantly different from each other (P<0.001) at constant pd. Microplex 10 coils had the lowest permeability of all coil types. Data suggest a trend of increasing permeability with thicker coil wire diameter (not statistically significant).ConclusionsA simple in vitro setup was developed to measure the permeabilities of coil masses based on traditional permeametry. Coil permeability should be considered when evaluating the hemodynamic efficacy of coiling instead of just packing density. Coils made of thicker wires may be more permeable, and thus less effective, than coils made from thinner wires. Whether aneurysm recurrence is affected by coil wire diameter or permeability needs to be confirmed with clinical trials.

Use of flow-diverting stents as salvage treatment following failed stent-assisted embolization of intracranial aneurysms

2015 ◽  
Vol 8 (7) ◽  
pp. 692-695 ◽  
Author(s):  
Daniel M Heiferman ◽  
Joshua T Billingsley ◽  
Manish K Kasliwal ◽  
Andrew K Johnson ◽  
Kiffon M Keigher ◽  
...  
Keyword(s):  
Blood Flow ◽  
Intracranial Aneurysms ◽  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Salvage Treatment ◽  
Endovascular Techniques ◽  
Pipeline Embolization Device ◽  
Wall Apposition ◽  
Flow Diverters

Flow-diverting stents, including the Pipeline embolization device (PED) and Silk, have been beneficial in the treatment of aneurysms previously unable to be approached via endovascular techniques. Recurrent aneurysms for which stent-assisted embolization has failed are a therapeutic challenge, given the existing intraluminal construct with continued blood flow into the aneurysm. We report our experience using flow-diverting stents in the repair of 25 aneurysms for which stent-assisted embolization had failed. Nineteen (76%) of these aneurysms at the 12-month follow-up showed improved Raymond class occlusion, with 38% being completely occluded, and all aneurysms demonstrated decreased filling. One patient developed a moderate permanent neurologic deficit. Appropriate stent sizing, proximal and distal construct coverage, and preventing flow diverter deployment between the previously deployed stent struts are important considerations to ensure wall apposition and prevention of endoleak. Flow diverters are shown to be a reasonable option for treating previously stented recurrent cerebral aneurysms.

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