| BackgroundThe history of intracranial aneurysm is very long. IN the fourteenth century BC the Egyptians treated intracranial aneurysms by magico-religious therapies, but the nature and site of occurrence of these lesions are not mentioned. Intracranial aneurysm is a very common disease in adult, Autopsy studies have shown that the overall frequency in the general population ranges from 0.2 to 9.9 percent (mean frequency, approximately 5 percent). But most of them are very little and 50-80% of them did not rupture for the life. Kids seldom suffer from this disease, most of the patients are ranging from 40 to 60, and the ratio between men and women is 2:3. In the age distribution of the patients, a low incidence was found in the 30's, a sharp increase took place in the 40's; the peak was reached in the 50's, but stayed high in the 60's. Most intracranial aneurysms locate at the circle of Willis, the internal carotid artery was most frequently involved, followed by the anterior communicating, middle cerebral arteries and vertebrobasilar. Just followed Cerebral thrombosis and Hypertensive intracerebral hemorrhage, intracranial aneurysm is the third factor inducing stroke and 34% of the subarachnoid hemorrhage and 5-15% of the stroke were caused by intracranial aneurysms. Little and unruptured intracranial aneurysms are difficult to find. The symptoms include there aspects they are hemorrhage, Ischemia and compression. CTA (computed tomography ang iography) and MRA (magnetic resonance angiography) were used more and more as to diagnosis this disease, but DSA (Digital subtraction angiography) is still the golden standard. There are there choices to treat intracranial aneurysms medical treatment, clipping and embolizing. In 2002 ISAT (International Subarachnoid Aneurysm Trial) reported that 190 of 801 (23.7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30.6%) allocated neurosurgical treatment (p=0.0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6%(95% CI 8.9-34.2) and 6.9%(2.5-11.3), respectively. They believed that in patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. In 2010 ISAT reported 2143 patients with ruptured intracranial aneurysms were enrolled between 1994 and 2002 at 43 neurosurgical centres and randomly assigned to clipping or coiling,24 rebleeds had occurred more than 1 year after treatment. Of these,13 were from the treated aneurysm (ten in the coiling group and three in the clipping group; log rank p=0·06 by intention-to-treat analysis). There were 8447 person-years of follow-up in the coiling group and 8177 person-years of follow-up in the clipping group. Four rebleeds occurred from a pre-existing aneurysm and six from new aneurysms. At 5 years,11% (112 of 1046) of the patients in the endovascular group and 14%(144 of 1041) of the patients in the neurosurgical group had died (log-rank p=0·03). The risk of death at 5 years was significantly lower in the coiling group than in the clipping group (relative risk 0.77,95% CI 0.61-0.98; p=0·03), but the proportion of survivors at 5 years who were independent did not differ between the two groups:endovascular 83%(626 of 755) and neurosurgical 82%(584 of 713). They believed there was an increased risk of recurrent bleeding from a coiled aneurysm compared with a clipped aneurysm, but the risks were small. The risk of death at 5 years was significantly lower in the coiled group than it was in the clipped group. The standardised mortality rate for patients treated for ruptured aneurysms was increased compared with the general population.Now embolization was accepted by doctors and patients more and more but at the same time, wide-necked aneurysms are still very difficult to satisfactory treatment. To overcome this difficulties, different kinds of new technology and new embolic agent emerged such as remodeling technique, embolization with the aid of stent, coated coils and liquid embolic agent. They have optimize the outcome of embolization, but it is also not perfect. By now, GDCs (Guglielmi detachable coils) are the best choice on clinical, but even the aneurysm was completely embolized by GDCs, they can only occupy about 20%-30% of the space in aneurysm which could be main factor of recurrence. Because of the good scalability of liquid embolic agent, they can occupy most of the space in aneurysm, so it was believed that liquid embolic agent could be the best choice. NBCA (N-butyl-2 cyanoacrylate) and EVOH (Ethylene vinyl alcohol copolymer) are the leader of liquid embolic agent; They were approved by the FDA for the intravascular treatment of cerebral arteriovenous malformation in 2000 and 2005 respectively. NBCA works instantly, completely occludes vessels, and is permanent. But gluing of the catheter within the vascular pedicle during slow injection period will cause fatal mistake. EVOH is nonadhesive but the solvent dimethyl sulfoxide have the potential risk of excessive inflammatory reaction or vessel damage. Recently, alginate and some thermosensitive polymer have attracted us, in the liquid form they are nontoxic water-based liquid that can flow in the blood, causing no adverse effects, but in the gel form they can quickly occupy the aneurysm. They do not need organic solvents and the viscosity is suitable can not cause "adhesion" effect. Chitosan/β-Glycerophosphate have all the qualities above and they are liquid below 37℃, gelling above 37℃. Based on the thermosensitive quality, we make the feasibility assessment of C/GP as a new liquid embolic agent.PurposeWe sought to assess the feasibility of thermosensitive Chitosan/β-Glycerophosphate for embolotherapy in vitro and in vivo.MethodsFirstly, we get 5 samples of C/GP by mixing Chitosan/β-Glycerophosphate at the ratio of 7:1. We record how many minutes they cost between the form transition in the water bath of 37℃.Secondly, we get 4ml of embolic agent by mixing Chitosan/B-Glycerophosphate/tantalum powder at the ratio of 7:1:3. The renal arteries in nine rabbits were embolized with C/GP. Animals were studied angiographically and sacrificed at 1 week (n=3),4 weeks (n=3). and 8 weeks (n=3) after embolotherapy. Histology was obtained at the same time.Thirdly, we construct nine aneurysms using an elastase-reduced model in rabbits. Three weeks after the procedure, the aneurysms were embolized using C/GP in combination with an inflated balloon. One month after the embolotherapy, animals were studied angiographically and histological.ResultsFirstly, the five samples cost 120.11s,119.93s,119.85s,120.08s,120.04s separately to fulfill the transition and the average is 120s.Secondly, The renal artery was successfully embolized with 1-1.5ml of C/GP solution which was injected between 1.8 and 2 minutes, no catheter adhesion was observed in all cases. It was easily handled between the procedures of injection and syringing catheter after injection, no occlusion of the catheter with this material was founded. The angiogram before embolization obviously showed the renal artery and its peripheral branches, the angiogram immediately obtained after embolization showed whole occlusion of the target renal artery in all cases. With the support of tantalum powder, this material was clearly shown in the angiographic images, the renal artery and most of its peripheral branches were embolized with the same gel. During 8 weeks period, there is no recanalization observed and found in the follow-up angiograms.The injection of C/GP into the renal artery aroused the blood clot. The gel combined with thrombus caused the completely occlusion of the renal artery. The endothelium damage and the inflammatory reaction was mild in the renal artery. Then the occlusion led to the infarction of the kidney at the same time we didn't notice any inflammatory reaction in the infarction kidney. Finally, from the observation, it showed that the color of the embolization kidney was pale and the size of it was shrank considerably compared with the control kidney. The normal glomerular were completely replaced by fibrous tissue.Thirdly, nine elastase-reduced aneurysms in rabbits were successfully constructed. All animals tolerated the induction well. Aneurysm size was measured using a workstation, and the mean height was 3.39 mm, the mean width was 9.55mm, and the mean diameter of the neck of the aneurysm was 2.63 mm.The aneurysms were successfully embolized with C/GP solution which was injected by microcatheter in combination with an inflated balloon between 1.8 and 2 minutes, no catheter adhesion was observed in all cases. It was easily handled between the procedures of injection and syringing catheter after injection, no occlusion of the catheter with this material was founded. The angiogram before embolization obviously showed the aneurysms, the angiogram immediately obtained after embolization showed whole occlusion of the aneurysms in all cases. With the support of tantalum powder, this material was clearly shown in the angiographic images and the process of embolization is clearly visible. During four weeks period, there is no recanalization observed and found in the follow-up angiograms.The injection of C/GP into the renal artery aroused the blood clot then caused granulation tissue formed in the surrounding area, leading to complete occlusion of the aneurysm. Histological evaluation showed that the walls of the aneurysms were thinner than those of the aneurysm-bearing vessels. The elastic lamina had been dissolved as intended. No inflammation or foreign body reaction was observed in the adjacent tissue of the aneurysm. All aneurysms were completely occluded, and there were no signs of recanalization. We found a thin layer of endothelium over the entire neck of all aneurysms which lead to the healing of the aneurysms.ConclusionsThermosensitive C/GP have the potential to be a good liquid embolic agent.
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