Igor Salazkin

Cold hibernated elastic memory foams for endovascular interventions

Cold hibernated elastic memory (CHEM) polyurethane-based foam is a new shape memory polymeric self-deployable structure. Standard cytotoxicity and mutagenicity tests were conducted on CHEM in vitro, to ensure biocompatibility before studying potential medical applications. In vivo, lateral wall aneurysms were constructed on both carotid arteries of eight dogs. Aneurysms were occluded per-operatively with CHEM blocks. In two dogs, CHEM embolization was compared with gelatin sponge fragment embolization. Internal maxillary arteries (Imax) were also occluded with CHEM using a 6F transcatheter technique. Angiography and pathology were used to study the evolution of aneurysms and Imax at 3 and 12 weeks. Imax embolized with CHEM foam remained occluded at 3 weeks. Most aneurysms embolized with CHEM showed a small residual crescent of opacification at initial angiography, but angiographic scores were significantly better at 3 weeks. Thick neointima formation over the CHEM at the neck of aneurysms was demonstrated at pathology. The foamy nature of CHEM favours the ingrowth of cells involved in neointima formation. New devices for endovascular interventions could be designed using CHEMs unique physical properties.

The Varying Porosity of Braided Self-Expanding Stents and Flow Diverters: An Experimental Study

BACKGROUND AND PURPOSE: Braided self-expandable stents and flow diverters of uniform construction may develop zones of heterogeneous porosity in vivo. Unwanted stenoses may also occur at the extremities of the device. We studied these phenomena in dedicated benchtop experiments. MATERIALS AND METHODS: Five braided devices of decreasing porosity were studied. To simulate discrepancies in diameters between the landing zones of the parent vessel and the aneurysm neck area, device extremities were inserted into silicone tubes of various diameters (2–3 mm), leaving the midportion free to react to experimental manipulations, which included axial approximation of the tubes (0–7 mm), and curvature (0–135°), with or without axial compression (0–2 mm). The length of the landing zone was sequentially decreased to study terminal device stenosis. RESULTS: All devices adopted a conformation characterized by 3 different zones: bilateral landing zones, a middle compaction zone, and 2 transition zones. It is possible, during deployment, to compact stents and FDs to decrease porosity, but a limiting factor was the transition zone, which remained relatively unchanged and of higher porosity than the expansion zone. Length of the transition zone increased when devices were constrained in smaller tubes. Heterogeneities in porosity with compaction and curvatures were predictable and followed simple geometric rules. Extremity stenoses occurred increasingly with decreasing length of the landing zone. CONCLUSIONS: Braided self-expandable devices show predictable changes in porosity according to device size, vessel diameter, and curvature. Adequate landing zones are required to prevent terminal device stenosis.

Role of the Endothelial Lining in Recurrences After Coil Embolization: Prevention of Recanalization by Endothelial Denudation

Background and Purpose— Endovascular treatment can improve the outcome of patients treated for ruptured intracranial aneurysms as compared with surgical clipping, but angiographic recurrences are frequent. Endothelial denudation before coil embolization may prevent recanalization and improve results of endovascular treatment. Methods— We compared angiographic and pathological results 3 months after coil occlusion of paired canine arteries (n=16), with or without previous denudation of the endothelial lining using an endovascular device. The technique was then used to denude the neck of carotid venous pouch bifurcation aneurysms before coil embolization in 8 dogs, and the angiographic evolution at 12 weeks was compared with 7 control aneurysms treated by coiling only. Qualitative scoring systems were used to compare angiographic results with time and neointimal coverage at the neck of aneurysm after necropsy. The evolution of angiographic scores was analyzed using Wilcoxon signed rank tests whereas angiographic and neointimal scores of the 2 groups were compared using the Mann–Whitney test. Results— All arteries embolized with platinum coils recanalized, whereas most arteries (12/16 or 75%) denuded before coil embolization remained occluded at 3 and 12 weeks (P < 0.001). Aneurysms treated with coils without previous denudation tended to recur, with angiographic scores significantly worse at 12 weeks as compared with T0 (P = 0.015). Median angiographic and neointimal scores were significantly better at 12 weeks with endothelial denudation (P = 0.011 and 0.026, respectively). Conclusion— Endothelial denudation can prevent recanalization after coil embolization.

Flow Diverters Can Occlude Aneurysms and Preserve Arterial Branches: A New Experimental Model

BACKGROUND AND PURPOSE: FDs are new intracranial stents designed to occlude aneurysms while preserving flow to jailed arterial branches. We tested this fundamental principle in a new aneurysm model. MATERIALS AND METHODS: Canine lateral wall aneurysms, featuring a branch located immediately opposite the aneurysm, were created in 16 animals to study the effects on aneurysm or branch occlusion using single HP stents (n = 4), 2 overlapping HP stents (n = 4), or an FD (n = 8). Two other animals, in which an efferent arterial branch was anastomosed to the aneurysm fundus, were also treated with FDs. Angiographic results after deployment, at 2 weeks, and at 3 months were scored using an ordinal scale. The metal porosity of the FSS and the amount of FSS neointima formation was determined by postmortem photography. RESULTS: FDs led to better angiographic occlusion scores compared with HP stents (P = .026). FDs were significantly more likely to occlude the aneurysm than the branch (P = .01). When the branch was switched to originate from the aneurysm fundus, the FDs became ineffective (0/2). Neointimal closure of the aneurysm ostium was significantly better with FDs than with single or double HP stents (P = .039). Angiographic occlusion correlated with metallic porosity and neointimal tissue coverage (Spearman ρ = −0.81; P = .001). CONCLUSIONS: In this study, flow diverters occluded lateral wall aneurysms more readily than branches. Metal device porosity strongly influenced the occlusion rate.

Flow diverters failing to occlude experimental bifurcation or curved sidewall aneurysms: an in vivo study in canines

OBJECT Flow diverters (FDs) are increasingly used to treat complex intracranial aneurysms, but preclinical studies that could guide clinical applications are lacking. The authors designed a modular aneurysm model in canines to address this problem. METHODS Three variants of one modular aneurysm model were constructed in 21 animals. Sidewall (n=5), curved sidewall (n=5), and end-wall bifurcation (n=7) aneurysms were treated with prototype 36-wire FDs. Four more end-wall bifurcation aneurysms were treated with prototype 48-wire lower-porosity FDs. Angiographic results postimplantation and at 3 months were scored with an ordinal scale. Animals were euthanized at 3 (n=17) or 6 (n=3) months, and the FD covering the aneurysm ostium was photographed to analyze metallic porosity and amount of neointima formation. RESULTS Straight sidewall aneurysms were better occluded than curved sidewall and end-wall bifurcation aneurysms at the 3-month angiography follow-up (p=0.010). Flow diverters failed to occlude curved sidewall aneurysms (n=0/5) and all but one (n=1/7) end-wall bifurcation aneurysm. Angiographic results were no better (n=0/4) using a 48-wire FD (p=0.788). Branches jailed by the FD (n=16) remained patent in all cases. Metallic porosity was decreased (p=0.014) and neointimal closure of the aneurysm ostium was more complete (p=0.040) in sidewall aneurysms than in curved or bifurcation variants of the model. CONCLUSIONS Flow diverters may succeed in treating straight sidewall aneurysms, but the same device repeatedly fails to occlude curved sidewall and end-wall bifurcation aneurysms. In vivo studies can be designed to test basic principles that, once validated, may serve to guide clinical use of new devices.

Mechanisms of Occlusion and Recanalization in Canine Carotid Bifurcation Aneurysms Embolized with Platinum Coils: An Alternative Concept

BACKGROUND AND PURPOSE: Endovascular treatment of aneurysms may result in complete or incomplete occlusions or may be followed by recurrences. The goal of the present study was to better define pathologic features associated with so-called healing or recurrences after coiling and to propose an alternative concept to the currently accepted view. MATERIALS AND METHODS: Experimental canine venous pouch aneurysms were created by using a T-type (group A, N = 29) or a Y-type constructed bifurcation (group B, N = 37) between the carotid arteries. Coil embolization was performed 2 weeks later; and angiography, immediately after and at 12 weeks. Angiographic results, neointima formation at the neck, endothelialization, and organization of thrombus were compared between groups by using qualitative scores and immunohistochemistry. RESULTS: Angiographic results at 3 months were significantly better in group A than in group B (P = .001). Macroscopic neointimal scores were also better (P = .012). Only 10/32 aneurysms with satisfactory results at angiography were completely sealed by neointima formation. Animals with residual or recurrent aneurysms had significantly worse neointimal scores than those with completely occluded ones (P = .0003). On histologic sections, the neointima was constantly present in “healed” and in recurrent aneurysms. This neointima was a multicellular layer of α-actin+ cells in a collagenous matrix, covered with a single layer of nitric oxide synthetase (NOS+) endothelial cells, whether it completely occluded the neck of the aneurysm or dived into the recurring or residual space between the aneurysm wall and the coil mass embedded in organizing thrombus. CONCLUSION: Complete angiographic occlusions at 3 months can be associated with incomplete neointimal closure of the neck at pathology. Thrombus organization, endothelialization, and neointima formation can occur concurrently with recurrences.

Endovascular Aortic Aneurysm Repair with Stent-Grafts: Experimental Models Can Reproduce Endoleaks

PURPOSE To develop canine aneurysm models that can reproduce type II endoleaks after endovascular aneurysm repair (EVAR) with stent-grafts. MATERIALS AND METHODS A fusiform infrarenal abdominal aortic aneurysm model (AAA) was surgically created with a jugular vein patch, while preserving collateral vessels (n = 3). To allow comparative studies within the same animal, a bilateral iliac aneurysm model was also constructed with venous patches and surgical re-implantation of the sacroiliac trunk (n = 3). Stent-grafts were implanted by femoral approach at least 2 months later in both aortic and iliac models. Follow-up imaging was performed by Doppler ultrasound (US) and angiography until animals were killed 3 months after EVAR. RESULTS Angiography revealed immediate type II leaks in all cases. Leaks were still present at autopsy 3 months after EVAR in all cases, and were revealed at pre-death angiography in all but one case. At autopsy, leaks were characterized by the presence of large endothelialized channels that formed within the thrombus between the stent-graft and the aneurysmal wall. CONCLUSION As shown in this pilot study, persistent type II leaks after EVAR can be reproduced in aortic and iliac animal models. The iliac model can be created bilaterally in the same animal, thus allowing for comparative evaluation of different therapies. These models could be used to better understand the mechanisms of endoleak, and to assess future developments aimed to improve the outcomes after EVAR.

Beta Radiation and Inhibition of Recanalization After Coil Embolization of Canine Arteries and Experimental Aneurysms How Should Radiation Be Delivered

Background and Purpose— Beta radiation prevents recanalization after coil embolization. We sought to determine the effects of varying coil caliber, length, activity of 32P per centimeter of coil or per volume, and spatial distribution of coils on recanalization. Methods— We studied the angiographic evolution of 81 canine maxillary, cervical, and vertebral arteries implanted with a variety of nonradioactive (n=29 arteries) or radioactive (n=52) devices. We compared 1- or 2-caliber 0.015 or 0.010 coils ion-implanted or not with 3 different activity levels (0.05 to 0.08, 0.06 to 0.12, 0.18 to 0.32 &mgr;Ci/cm) of 32P and totaling 4, 8, and 16 cm in length for the same arterial volume. We also compared inhibition of recanalization by beta radiation delivered by stents, after coil occlusion proximal to or within the stent, with that delivered by coils placed within nonradioactive stents. We finally studied the angiographic evolution of canine lateral wall carotid aneurysms treated with 1 or 2 stents of various activity levels positioned inside the parent artery across the neck. Animals were killed at 4 and 12 weeks for macroscopic photography and pathological examination. Results— All arteries (29 of 29) occluded with nonradioactive devices were recanalized, while 49 of 52 arteries (94%) implanted with 32P devices were occluded at 4 weeks. All aneurysms treated with stents, radioactive or not, demonstrated residual filling of the sac or of channels leading to the aneurysms at follow-up angiography at 4 weeks. Conclusions— The recanalization process found in the canine arterial occlusion model is minimally affected by coil caliber, number, and length or packing density. Beta radiation reliably inhibits this process, but thrombosis is an essential condition for the efficacy of a radioactive coil strategy.

Aneurysm Rupture after Endovascular Flow Diversion: the Possible Role of Persistent Flows through the Transition Zone Associated with Device Deformation

Haemorrhagic complications can occur following aneurysm treatment with flow diverters (FD), but the underlying mechanism remains unknown. We describe a case where deformation of the device may have contributed to the complication. A patient with a giant, previously unruptured cavernous aneurysm that extended intracranially to cause oedema of the internal capsule was treated with flow diversion. Treatment was followed by multiple episodes of peri-aneurysmal haemorrhages within eight days. A deformation of the device which occurred where it curved to cross the aneurysm neck created residual flows which, in the presence of a stent stenosis immediately beyond the neck, may have contributed to the observed ruptures. Following multiple haemorrhages the patient subsequently died. Autopsy demonstrated early red thrombus partially bridging the struts of the flow diverter, and intra-aneurysmal thrombus of various ages. Microscopic pathology showed an aneurysm wall consisting of collagen infiltrated with neutrophils, but the wall was absent near the cerebral peduncle, adjacent to the brain haemorrhage. Radiographs of the extracted specimen confirmed deformation of the FD construct, located at the transition zone of the stent, leading to increased pore size and porosity. The site of the deformation correlated with the angiographic presence of a continued blood inflow jet into the aneurysm. Stent deformation at the transition zone may promote persistent blood entry into the aneurysm, and in turn potentially contribute to haemorrhagic complications.

Testing Flow Diverters in Giant Fusiform Aneurysms: A New Experimental Model Can Show Leaks Responsible for Failures

BACKGROUND AND PURPOSE: FDs are the latest, most promising tool to treat giant and complex aneurysms. Currently available experimental aneurysm models do not reproduce the potential clinical difficulties of treating these lesions with FDs. MATERIALS AND METHODS: Six large or giant canine fusiform aneurysms were created on the distal carotid arteries of 4 animals. Four of the aneurysms had multiple arterial branches originating from the aneurysm; 2 other aneurysms had all branches clipped at the time of aneurysm construction. Aneurysms were treated with multiple telescoping prototype flow-diverting stents (total of 15 FDs). Angiography was carried out before and immediately after implantation, at 2 weeks, and immediately before sacrifice at 12 weeks. Macroscopic photography of specimens was performed, followed by biopsies of selected regions of the tissue formed on the surface of FDs. RESULTS: Technical or device-related difficulties occurred in 2 of 6 aneurysm treatments. Fusiform aneurysms with branches intact remained widely patent (mean angiographic score, 3), whereas aneurysms with clipped branches had only small residua (mean angiographic score, 1) at 12 weeks. The presence of very small defects in neointima formation on the surface of FDs, or leaks, was sufficient for residual filling of the aneurysms, which served as reservoirs to feed branches. CONCLUSIONS: Experimental canine fusiform carotid aneurysms may reproduce many of the difficulties associated with the treatment of giant aneurysms and could be appropriate for preclinical testing of FD stents.