Experimental study of temperature-sensitive chitosan/β-glycerophosphate embolic material in embolizing the basicranial rete mirabile in swines

Abstract

Abstract. The aim of the present study was to evaluate the feasibility of the non-adhesive temperature-sensitive liquid embolic material, chitosan/β-glycerophosphate (C/GP), in embolizing the basicranial rete mirabile (REM) in a swine model of cerebral arteriovenous malformation (cAVM). A total of 24 domestic swines were used as the experimental animals, among which 12 pigs underwent direct embolization of one side of the REM, while the other 12 pigs underwent embolization of the bilateral REM following anastomosis of the carotid artery and jugular vein. A super-selective microcatheter was introduced into the REM during the embolization procedure, and the C/GP hydrogel was injected until an image of the REM disappeared in the angiography examination. Further angiography examinations were performed after 2 and 6 weeks, and histological examination of the REM was performed after 6 weeks. Of the 24 domestic swines, 23 cases underwent successful thrombosis. Convulsions occurred in one case and that pig died during the embolization procedure. Following embolization, the angiography observations revealed that the embolized REM was no longer able to be developed, and adhesion of the microcatheter tip with the embolic agent did not occur. In addition, no apparent revascularization was observed in the angiography examinations performed at weeks 2 and 6. Therefore, the current preliminary study indicated that use of the non-adhesive temperature-sensitive embolic material was feasible for the embolization of cAVM; thus, C/GP may be used as an ideal embolic material for the treatment of cAVM. IntroductionCerebral arteriovenous malformation (cAVM) is the major cause of intracranial hemorrhage and seizures in young and middle-aged adults, and can seriously threaten their quality of life and life expectancy (1,2). Due to the minimal harm inflicted on patients, endovascular embolization therapy has become an important method for the treatment of cAVM, and the selection of an embolic material is a major determinant towards the treatment efficacy.The ideal cAVM embolic material should have a number of characteristics. Firstly, the material should be liquid, since this enables easy control, good dispersibility and ensures a sufficient injection time. Secondly, the material should exhibit a permanent embolism effect. Finally, the material should be non-toxic. Therefore, a non-adhesive liquid embolic material is ideal. In recent years, this particular material had received considerable attention in the field of endovascular treatment (3).Therefore, the present study investigated chitosan/β-glycerophosphate (C/GP) as the base material. The C/GP solution is liquid at room temperature, but forms a hydrogel at 37.0˚C (body temperature). In addition, the pH of the C/GP solution is compatible with the physiological requests. These two materials have been previously demonstrated to be safe and non-toxic (4); however, the combination of C/GP has not been utilized in previous studies as a non-adhesive temperature-sensitive liquid embolic mat...

Imaging artifacts of Onyx and PHIL on conventional CT, cone-beam CT and MRI in an animal model

“…The rete mirabile (RM) is a fine vascular network, located bilaterally at the cranial base of pigs, consisting of vessels that are similar to human arterioles and has been used as an endovascular embolization model by a number of investigators. 9,11,18–20…”

“…The rete mirabile (RM) is a fine vascular network, located bilaterally at the cranial base of pigs, consisting of vessels that are similar to human arterioles and has been used as an endovascular embolization model by a number of investigators. 9,11,[18][19][20] Embolization of the RM was performed using either Onyx or PHIL. 21 Of the different concentrations that are available for these LEAs, the least viscous concentrations (Onyx 18 and PHIL 25%) were used to achieve effective filling of the RM.…”

Advances in Biomaterials and Technologies for Vascular Embolization

“…[270] The chitosan/β-GP mixture was also used for embolization of cerebral AVM in a porcine model. [268] The chitosan (80.4 kDa) used in the study had a viscosity of 130 mPa s and 94% degree of deacetylation. The optimum ratio between 2% chitosan and 8% β-GP was selected to be 1:1.…”

“…No vessel-wall inflammation or necrosis was observed. [268] The chitosan/β-GP system may also be used as an injectable drug carrier for embolization. [336] It has been shown that the addition of β-GP in chitosan reduces the initial burst release of chlorpheniramine maleate; chitosan alone was associated with a 53% release compared to 15% release in the chitosan/β-GP system within 4 h. [335b] SEM images demonstrated an interconnected pore structure of the chitosan/β-GP system with pore diameters between 5 and 10 µm.…”

Advancements in the development on new liquid embolic agents for use in therapeutic embolisation

“…This material was evaluated in a rabbit renal artery model 72 and in the rete mirabile in swine. 73 Interestingly, these materials have been formulated with indocyanine green and evaluated for potential intraoperative fluorescent imaging and local therapy of hepatocellular carcinoma. 74 Whilst the dye did not affect the gelation rate, the gel transition temperature was above 4 1C making the handling and avoidance of premature gelling of this material very difficult.…”