Surgical intervention is still the gold standard in the treatment of ruptured cerebral aneurysms. However, as previously discussed, surgery may not always be an option due to the location of the aneurysm, the size of the aneurysm, or the medical condition of the patient. In this case endovascular methods such as Guglielmi detachable coil (GDC) or balloon embolization are often used. However, these techniques do not always achieve complete occlusion of the embolism and have been known to allow continued intercranial bleeding from the aneurysm. The fundamental premise of the use of embolic liquids in the treatment of ruptured cerebral aneurysms is to develop liquid materials which may be delivered endovascularly to the aneurysm and polymerize or precipitate in situ on contact with blood in order to directly fill the aneurysm. Theoretically the polymerization or precipitation process would conform to the geometry of the aneurysm and completely fill the aneurysm, leading to complete occlusion and cessation of cerebral bleeding.
One set of embolic liquids which have been considered are monomers which polymerize in situ on contact with blood. However, the use of such materials could lead to a number of toxic effects such as the release of initiator, the release of residual monomer, the development of heat in the case of an exothermic polymerization, or the consumption of heat in the case of an endothermic polymerization.
An alternative set of embolic liquids which have been considered are preformed polymers which are dissolved in biocompatible solvents and precipitate in situ on contact with blood. This approach was first developed by Mandai et al. (1) and Kinugasa et al. (2) in 1992 with cellulose acetate polymer mixed with bismuth trioxide dissolved in dimethyl sulfoxide (DMSO). It was found that upon contact with blood, the dimethyl sulfoxide dissolved away from the contact site and allowed the cellulose acetate polymer to precipitate. When the solution was slowly injected into the blood the polymer ballooned, filled the aneurysm, and solidified in the shape of the aneurysm in approximately five minutes. Canine testing showed complete occlusion of the aneurysms with preservation of the parent blood vessel in all cases. In addition, polymer migration from the aneurysm was not observed. Clinical testing demonstrated similar positive results including complete occlusion of even irregularly shaped aneurysms. However, since these studies were conducted it has been found that DMSO may be toxic in intravascular applications.
This paper investigates various organic solvents which may be used as alternatives to DMSO. A change in the organic solvent may effect the embolic properties of the cellulose acetate polymer; thus this paper also investigates various preformed polymers which may be used as alternatives to cellulose acetate. The solubility parameters, precipitation behavior, and viscosities of several polymer - solvent combinations were tested in order to optimize the embolic properties of the solutions.
1. Mandai S, Kinugasa K, Ohmoto T. Direct thrombosis of aneurysms with cellulose acetate polymer. Part I: results of thrombosis in experimental aneurysms. J Neurosurg 1992; 77: 497-500.
2. Kinugasa K, Mandai S, Terai Y, Kamata I, Sugiu K, Ohmoto T, Nishimoto A. Direct thrombosis of aneurysms with cellulose acetate polymer. Part II: preliminary clinical experience. J Neurosurg 1992: 77: 501-7.
3. Mottu F, Gailloud P, Massuelle D, Rufenacht DA, Doelker E. In vitro assessment of new embolic liquids prepared from preformed polymers and water miscible solvents for aneurysm treatment. Biomaterials 21 (2000); 8; 803-811.