{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:24:52Z","timestamp":1787315092978,"version":"build-2736575974"},"reference-count":24,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"\n OBJECTIVE<\/jats:title>\n Fibrin deposition represents a key step in aneurysm occlusion, promoting endothelization of implants and connective tissue organization as part of the aneurysm-healing mechanism. In this study, the authors introduce a novel in vitro testing platform for flow diverters based on human fibrinogen.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n A flow diverter was deployed in 4 different glass models. The glass models had the same internal parent artery (4 mm) and aneurysm (8 mm) diameters with varying parent artery angulations (paraophthalmic, sidewall, bifurcation, and slightly curved models). The neck size and area were 4 mm and 25 mm\n 2<\/jats:sup>\n , respectively. Human fibrinogen (330 mg\/dl) was circulated within the glass models at varying flow rates (0, 3, 4, and 5 ml\/sec) with or without heparin, calcium chloride, and thrombin for as long as 6 hours or until complete fibrin coverage of the flow diverter\u2019s neck was achieved. Aneurysm neck coverage was defined as macroscopic fibrin deposition occluding the flow diverters\u2019 pores. Flow characteristics after flow diverter deployment were assessed with computational fluid dynamics analysis. The effects of flow rates, heparin, calcium chloride, and thrombin on fibrin deposition rates were tested using 1-way ANOVA and the Tukey test.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n A total of 84 replicates were performed. Human fibrin did not accumulate on the flow diverter stents under static conditions. The fibrin deposition rate on the aneurysm neck was significantly greater with the 5 ml\/sec flow rate as compared to 3 ml\/sec for all models. The paraophthalmic model had the highest inflow velocity of 48.7 cm\/sec. The bifurcation model had the highest maximum shear stress (SS) and maximum normalized shear stress values at the device cells at 843.3 dyne\/cm\n 2<\/jats:sup>\n and 35.1 SS\/SS\n inflow<\/jats:sub>\n , respectively. The fibrin deposition rates of the paraophthalmic and bifurcation models were significantly higher than those of sidewall and slightly curved models for all additive or flow rate comparisons (p = 0.001 for all comparisons). The incorporation of thrombin significantly increased the fibrin deposition rates across all models (p = 0.001 for all models).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n Rates of fibrin deposition varied widely across different configurations and additive conditions in this novel in vitro model system. Fibrin accumulation started at the aneurysm inflow zone where flow velocity and shear stress were the highest. The primary factors influencing fibrin deposition included flow velocities, shear stress, and the addition of thrombin at a physiological concentration. Further research is needed to test the clinical utility of fibrinogen-based models for patient-specific aneurysms.<\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2024.4.jns232567","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T21:23:35Z","timestamp":1720819415000},"page":"154-161","source":"Crossref","is-referenced-by-count":4,"title":["In vitro evaluation of flow diverter performance using a human fibrinogen\u2013based flow model"],"prefix":"10.3171","volume":"142","author":[{"given":"Cem","family":"Bilgin","sequence":"first","affiliation":[{"name":"Departments of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esref Alperen","family":"Bayraktar","sequence":"additional","affiliation":[{"name":"Departments of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Departments of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan R.","family":"Cebral","sequence":"additional","affiliation":[{"name":"Center for Computational Fluid Dynamics, George Mason University, Fairfax, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Kallmes","sequence":"additional","affiliation":[{"name":"Departments of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramanathan","family":"Kadirvel","sequence":"additional","affiliation":[{"name":"Departments of Radiology and"},{"name":"Neurologic Surgery, Mayo Clinic, Rochester, Minnesota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"3","key":"b1","series-title":"Arterioscler Thromb Vasc Biol","first-page":"e13","article-title":"Fibrinogen and fibrin in hemostasis and thrombosis","volume":"37","author":"Kattula S","year":"2017","unstructured":"Kattula S, Byrnes JR, Wolberg AS. Fibrinogen and fibrin in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol. 2017;37(3):e13\u2013e21."},{"key":"b2","series-title":"Subcell Biochem","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/978-3-319-49674-0_13","article-title":"Fibrin formation, structure and properties","volume":"82","author":"Weisel JW","year":"2017","unstructured":"Weisel JW, Litvinov RI. Fibrin formation, structure and properties. Subcell Biochem. 2017;82:405\u2013456."},{"issue":"2","key":"b3","series-title":"Radiology","first-page":"394","article-title":"Cellular mechanisms of aneurysm occlusion after treatment with a flow diverter","volume":"270","author":"Kadirvel R","year":"2014","unstructured":"Kadirvel R, Ding YH, Dai D, Rezek I, Lewis DA, Kallmes DF. Cellular mechanisms of aneurysm occlusion after treatment with a flow diverter. Radiology. 2014;270(2):394\u2013399."},{"issue":"Suppl 1","key":"b4","series-title":"Neurosurgery","first-page":"S13","article-title":"Mechanism of action and biology of flow diverters in the treatment of intracranial aneurysms","volume":"86","author":"Ravindran K","year":"2020","unstructured":"Ravindran K, Casabella AM, Cebral J, Brinjikji W, Kallmes DF, Kadirvel R. Mechanism of action and biology of flow diverters in the treatment of intracranial aneurysms. Neurosurgery. 2020;86(Suppl 1):S13-S19."},{"issue":"3","key":"b5","series-title":"Radiology","first-page":"858","article-title":"Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial","volume":"267","author":"Becske T","year":"2013","unstructured":"Becske T, Kallmes DF, Saatci I. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology. 2013;267(3):858\u2013868."},{"issue":"6","key":"b6","series-title":"Stroke","first-page":"1473","article-title":"SCENT trial","volume":"50","author":"Meyers PM","year":"2019","unstructured":"Meyers PM, Coon AL, Kan PT, Wakhloo AK, Hanel RA. SCENT trial. Stroke. 2019;50(6):1473\u20131479."},{"issue":"9","key":"b7","series-title":"J Neurointerv Surg","first-page":"898","article-title":"Long-term outcomes of flow diversion for unruptured intracranial aneurysms: a systematic review and meta-analysis","volume":"15","author":"Shehata MA","year":"2023","unstructured":"Shehata MA, Ibrahim MK, Ghozy S, Long-term outcomes of flow diversion for unruptured intracranial aneurysms: a systematic review and meta-analysis. J Neurointerv Surg. 2023;15(9):898\u2013902."},{"issue":"4","key":"b8","series-title":"IEEE Trans Med Imaging","first-page":"457","article-title":"Efficient pipeline for image-based patient-specific analysis of cerebral aneurysm hemodynamics: technique and sensitivity","volume":"24","author":"Cebral JR","year":"2005","unstructured":"Cebral JR, Castro MA, Appanaboyina S, Putman CM, Millan D, Frangi AF. Efficient pipeline for image-based patient-specific analysis of cerebral aneurysm hemodynamics: technique and sensitivity. IEEE Trans Med Imaging. 2005;24(4):457\u2013467."},{"issue":"10","key":"b9","series-title":"AJNR Am J Neuroradiol","first-page":"2010","article-title":"Effects of flow-diverting device oversizing on hemodynamics alteration in cerebral aneurysms","volume":"33","author":"Mut F","year":"2012","unstructured":"Mut F, Cebral JR. Effects of flow-diverting device oversizing on hemodynamics alteration in cerebral aneurysms. AJNR Am J Neuroradiol. 2012;33(10):2010\u20132016."},{"issue":"45-46","key":"b10","series-title":"Comput Methods Appl Mech Eng","first-page":"3567","article-title":"Simulation of intracranial aneurysm stenting: techniques and challenges","volume":"198","author":"Appanaboyina S","year":"2009","unstructured":"Appanaboyina S, Mut F, L\u00f6hner R, Putman C, Cebral J. Simulation of intracranial aneurysm stenting: techniques and challenges. Comput Methods Appl Mech Eng. 2009;198(45-46):3567\u20133582."},{"issue":"1","key":"b11","series-title":"Int J Numer Methods Biomed Eng","first-page":"73","article-title":"Fast numerical solutions of patient-specific blood flows in 3D arterial systems","volume":"26","author":"Mut F","year":"2010","unstructured":"Mut F, Aubry R, L\u00f6hner R, Cebral JR. Fast numerical solutions of patient-specific blood flows in 3D arterial systems. Int J Numer Methods Biomed Eng. 2010;26(1):73\u201385."},{"issue":"2","key":"b12","series-title":"J Neurosurg","first-page":"284","article-title":"Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils","volume":"91","author":"Bavinzski G","year":"1999","unstructured":"Bavinzski G, Talazoglu V, Killer M, Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils. J Neurosurg. 1999;91(2):284\u2013293."},{"issue":"4","key":"b13","series-title":"AJNR Am J Neuroradiol","first-page":"579","article-title":"Histological findings in ruptured aneurysms treated with GDCs: six examples at varying times after treatment","volume":"24","author":"Groden C","year":"2003","unstructured":"Groden C, Hagel C, Delling G, Zeumer H. Histological findings in ruptured aneurysms treated with GDCs: six examples at varying times after treatment. AJNR Am J Neuroradiol. 2003;24(4):579\u2013584."},{"issue":"5","key":"b14","series-title":"Neurosurgery","first-page":"1203","article-title":"Acute human histopathology of an intracranial aneurysm treated using Guglielmi detachable coils: case report and review of the literature","volume":"43","author":"Stiver SI","year":"1998","unstructured":"Stiver SI, Porter PJ, Willinsky RA, Wallace MC. Acute human histopathology of an intracranial aneurysm treated using Guglielmi detachable coils: case report and review of the literature. Neurosurgery. 1998;43(5):1203\u20131208."},{"issue":"7","key":"b15","series-title":"AJNR Am J Neuroradiol","first-page":"1216","article-title":"Mechanisms of healing in coiled intracranial aneurysms: a review of the literature","volume":"36","author":"Brinjikji W","year":"2015","unstructured":"Brinjikji W, Kallmes DF, Kadirvel R. Mechanisms of healing in coiled intracranial aneurysms: a review of the literature. AJNR Am J Neuroradiol. 2015;36(7):1216\u20131222."},{"issue":"11","key":"b16","series-title":"Biomacromolecules","first-page":"4642","article-title":"Influence of divalent metal ions on the precipitation of the plasma protein fibrinogen","volume":"22","author":"Stamboroski S","year":"2021","unstructured":"Stamboroski S, Boateng K, Lierath J, Influence of divalent metal ions on the precipitation of the plasma protein fibrinogen. Biomacromolecules. 2021;22(11):4642\u20134658."},{"issue":"7","key":"b17","series-title":"Biochimie","first-page":"449","article-title":"Metal-ion catalyzed oxidation affects fibrinogen activity on platelet aggregation and adhesion","volume":"79","author":"Belisario MA","year":"1997","unstructured":"Belisario MA, Di Domenico C, Pelagalli A, Della Morte R, Staiano N. Metal-ion catalyzed oxidation affects fibrinogen activity on platelet aggregation and adhesion. Biochimie. 1997;79(7):449\u2013455."},{"issue":"2","key":"b18","series-title":"Interv Neuroradiol","first-page":"150","article-title":"In vitro angiographic comparison of the flow-diversion performance of five neurovascular stents","volume":"24","author":"Dholakia RJ","year":"2018","unstructured":"Dholakia RJ, Kappel AD, Pagano A, In vitro angiographic comparison of the flow-diversion performance of five neurovascular stents. Interv Neuroradiol. 2018;24(2):150\u2013161."},{"issue":"1","key":"b19","series-title":"J Neurosurg","first-page":"150","article-title":"Benchtop proof of concept and comparison of iron- and magnesium-based bioresorbable flow diverters","volume":"139","author":"Oliver AA","year":"2022","unstructured":"Oliver AA, Bilgin C, Vercnocke AJ. Benchtop proof of concept and comparison of iron- and magnesium-based bioresorbable flow diverters. J Neurosurg. 2022;139(1):150\u2013156."},{"issue":"6","key":"b20","series-title":"J Neurointerv Surg","first-page":"616","article-title":"Preliminary in vitro angiographic comparison of the flow diversion behavior of Evolve and Pipeline devices","volume":"12","author":"Sadasivan C","year":"2020","unstructured":"Sadasivan C, Fiorella D. Preliminary in vitro angiographic comparison of the flow diversion behavior of Evolve and Pipeline devices. J Neurointerv Surg. 2020;12(6):616\u2013620."},{"issue":"7","key":"b21","series-title":"Blood","first-page":"1509","article-title":"Fibrinogen induces endothelial cell adhesion and spreading via the release of endogenous matrix proteins and the recruitment of more than one integrin receptor","volume":"75","author":"Dejana E","year":"1990","unstructured":"Dejana E, Lampugnani MG, Giorgi M, Gaboli M, Marchisio PC. Fibrinogen induces endothelial cell adhesion and spreading via the release of endogenous matrix proteins and the recruitment of more than one integrin receptor. Blood. 1990;75(7):1509\u20131517."},{"issue":"3","key":"b22","series-title":"AJNR Am J Neuroradiol","first-page":"490","article-title":"In vitro evaluation of intra-aneurysmal, flow-diverter-induced thrombus formation: a feasibility study","volume":"37","author":"Gester K","year":"2016","unstructured":"Gester K, L\u00fcchtefeld I, B\u00fcsen M, In vitro evaluation of intra-aneurysmal, flow-diverter-induced thrombus formation: a feasibility study. AJNR Am J Neuroradiol. 2016;37(3):490\u2013496."},{"issue":"8","key":"b23","series-title":"J Neurointerv Surg","first-page":"746","article-title":"Cellular responses to flow diverters in a tissue-engineered aneurysm model","volume":"13","author":"Liu W","year":"2021","unstructured":"Liu W, Dai D, Ding YH. Cellular responses to flow diverters in a tissue-engineered aneurysm model. J Neurointerv Surg. 2021;13(8):746\u2013751."},{"key":"b24","series-title":"J Neurosurg","article-title":"How the elastase-induced rabbit aneurysm heals following flow diverter treatment: a histopathological study","author":"Dai D","unstructured":"Dai D, Bilgin C, Ding Y, How the elastase-induced rabbit aneurysm heals following flow diverter treatment: a histopathological study. J Neurosurg. 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