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Biomedical subjects

Jean Raymond

Publications and source records attributed to Jean Raymond.

35 records · Page 2Linked to original sources

Radioactive coil embolization of intracranial aneurysms: minimal inventory to reach target activities in a virtual series of 154 patients.

BACKGROUND AND PURPOSE: Recanalization after selective endovascular treatment of intracranial aneurysms with platinum coils has been widely reported in the literature. Beta radiation emitted from (32)P ion-implanted coils can prevent recanalization in animal models. A complete inventory of radioactive coils may not be realistic; our hypothesis was that it might not be necessary to reach target activities in most aneurysms. A limited supply of three or four types of coils may decrease the inventory difficulties related to the use of an isotope with a half-life of 2 weeks. METHODS: We reviewed 154 aneurysms selectively treated with standard coils. We calculated the volumetric activity obtained if all coils (simulation 1) were radioactive with linear activities of 0.13 (scenario I) or 0.26 microCi/cm (scenario II). Then, we simulated a treatment with standard coils plus a selection of radioactive coils limited to three (simulation 2) or four types of commonly used coils (simulation 3). Resulting activities were calculated and reported to the lesion volume. For each scenario and simulation, the percentage of lesions, in which the target volumetric activity (0.018 microCi/mm3) was reached, was reported. RESULTS: Success in reaching target volumetric activities varied from 55-99% according to different simulations. A supply of four types of coils was sufficient to reach target activities in 86-95% of patients commonly treated in our institution. Target activities were difficult to reach in giant aneurysms. CONCLUSION: It is feasible to reach target activities in most lesions by using a limited coil supply.

Computer Simulation↗

Lingual artery bifurcation aneurysms for training and evaluation of neurovascular devices.

We present a canine lingual artery bifurcation aneurysm and assess its value for training in endovascular techniques and testing new embolic agents. The experimental aneurysm described herein mirrors human bifurcation aneurysms, and with this model, we sought to reproduce endovascular technical difficulties. However, the lesions created in this canine model did not show angiographic or histologic evidence of aneurysmal recurrence. We conclude that this model may be useful for training in endovascular techniques, but because of the lack of sufficient aneurysmal recurrence, it is not suitable for evaluating new embolic agents.

Aneurysm↗

Endovascular treatment of intracranial aneurysms with radioactive coils: initial clinical experience.

BACKGROUND AND PURPOSE: Endovascular treatment of intracranial aneurysms is safe and effective but is associated with angiographic recurrences. Beta radiation prevents recanalization after coil embolization in experimental models. We wanted to assess the feasibility of using radioactive coil embolization to improve long-term results of endovascular treatment. METHODS: Platinum coils were ion-implanted with 0.13 to 0.26 microCi/cm of 32P. Forty-one patients aged 34 to 84 years with 44 aneurysms with a high propensity for recurrences were included. Radioactive coils were introduced into aneurysms to reach a target volumetric activity of 0.018 microCi/mm3. Nonradioactive coils were also used to ensure the same safety and the same angiographic results as the standard procedure. Angiographic results, procedure-related complications, and neurological events during follow-up were recorded. Angiographic follow-up data are available in 36 lesions 6 months after treatment. RESULTS: Forty of 44 aneurysms (91%) could be treated with radioactive coils. Target activities could be reached in 88% of lesions that could actually be coiled (35/40). Total activities ranged from 1.72 to 80.9 microCi, for a mean of 20.13+/-20.80 microCi. Procedure-related complications occurred in 7% of patients. Initial angiographic results were satisfactory (complete occlusions or residual necks) in 75% of lesions. Angiographic recurrences occurred in 11 (31%) of patients followed, within the expected range for standard coils. There was no complication from beta radiation during a mean follow-up period of 10 months. CONCLUSIONS: Radioactive coil embolization is feasible; target volumetric activities can be reached in most aneurysms considered for endovascular treatment.

Adult↗

Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils.

BACKGROUND AND PURPOSE: Our aim in this study was to assess the incidence and determining factors of angiographic recurrences after endovascular treatment of aneurysms. METHODS: A retrospective analysis of all patients with selective endosaccular coil occlusion of intracranial aneurysms prospectively collected from 1992 to 2002 was performed. There were 501 aneurysms in 466 patients (mean+/-SD age, 54.20+/-12.54 years; 74% female). Aneurysms were acutely ruptured (54.1%) or unruptured (45.9%). Mean+/-SD aneurysm size was 9.67+/-5.91 mm with a 4.31+/-1.97-mm neck. The most frequent sites were basilar bifurcation (27.7%) and carotid ophthalmic (18.0%) aneurysms. Recurrences were subjectively divided into minor and major (ideally necessitating re-treatment). The most significant predictors of angiographic recurrence were determined by logistic regression. These results were confirmed by chi2, t tests, or ANOVAs followed, when appropriate, by Tukey's contrasts. RESULTS: Short-term (< or =1 year) follow-up angiograms were available in 353 aneurysms (70.5%) and long-term (>1 year) follow-up angiograms, in 277 (55%), for a total of 383 (76.5%) followed up. Recurrences were found in 33.6% of treated aneurysms that were followed up and that appeared at a mean+/-SD time of 12.31+/-11.33 months after treatment. Major recurrences presented in 20.7% and appeared at a mean of 16.49+/-15.93 months. Three patients (0.8%) bled during a mean clinical follow-up period of 31.32+/-24.96 months. Variables determined to be significant predictors (P<0.05) of a recurrence included aneurysm size > or =10 mm, treatment during the acute phase of rupture, incomplete initial occlusions, and duration of follow-up. CONCLUSIONS: Long-term monitoring of patients treated by endosaccular coiling is mandatory.

Cerebral Angiography↗

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 microCi/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↗

Feasibility of radioactive embolization of intracranial aneurysms using 32P-implanted coils.

BACKGROUND AND PURPOSE: Beta radiation can prevent recanalization after embolization. Our goal was to assess the feasibility of endovascular treatment of intracranial aneurysms using coils of a predetermined activity of 32P per centimeter. METHODS: We studied the total length of coils deployed into 357 intracranial aneurysms. Aneurysmal volumes were estimated using 3 mathematical models. We simulated that coils were implanted with 0.26 microCi/cm of 32P, calculated resulting volumetric activities, and compared them with "effective" levels derived from experimental data and "safe" levels prescribed for the clinical use of 32P in cystic craniopharyngiomas. RESULTS: Effective activities would have been reached in 92% to 98% of lesions had the coils been radioactive at the time of treatment. CONCLUSIONS: Radioactive coil embolization of aneurysms is feasible in most patients.

Adult↗

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 CHEM's unique physical properties.

Aneurysm↗

Ex vivo gene therapy with adenovirus-mediated transforming growth factor beta1 expression for endovascular treatment of aneurysm: results in a canine bilateral aneurysm model.

OBJECTIVE: Endovascular treatment of cerebral aneurysm is safe and effective, but recurrence of disease is frequent compared with results with surgery. The purpose of this study was to determine the effects of recombinant transforming growth factor beta(1) (rTGFbeta(1)) secreted by transplanted autologous vascular smooth muscle cells (VSMC) on results of endovascular treatment. METHODS: VSMC from canine femoral arteries were infected with adenovirus vector encoding rTGFbeta(1)/green fluorescent protein (rTGFbeta(1)/GFP) or GFP only. rTGFbeta(1) production was measured with an enzyme-linked immunosorbent assay, and autocrine and paracrine effects of rTGFbeta(1) on cell functions were quantified with a proliferation assay and collagen synthesis. A bilateral carotid aneurysm model was used to compare angiographic and pathologic results after embolization with sponges seeded (n = 14) or not seeded (n = 34) with VSMC expressing TGFbeta(1) or GFP (n = 7 each). Transgene retention was confirmed with Western blot analysis. RESULTS: In vitro, TGFbeta(1) production varied from 0.9 to 180 ng/mL/d with increasing multiplicity of infection (MOI). Collagen synthesis was doubled at low (<300) MOI and increased by one and a half times at high (>or=300) MOI. rTGFbeta(1) was biologically active, as shown with the mink lung epithelial cell proliferation assay. VSMC grafts showed effective GFP expression up to 3 weeks after transplantation. Angiographic results were improved and neointima thickness was increased with cellular grafts, as compared with controls, but there was no significant difference between aneurysms treated with VSMC encoding rTGFbeta(1)/GFP or GFP vectors. CONCLUSION: Cellular grafts can promote healing of aneurysms, but overexpression of rTGFbeta(1)/GFP did not demonstrate added benefits in this model.

Adenoviridae↗

High-concentration ethylene-vinyl alcohol copolymer and endovascular treatment of experimental aneurysms: feasibility of embolization without protection devices at the neck.

BACKGROUND AND PURPOSE: Coiling of intracranial aneurysms is both safe and effective but may be followed by recurrences. The purpose of this study was to assess the feasibility of endovascular treatment of aneurysms with high-concentration ethylene-vinyl alcohol copolymer (HCEVOH), without the use of protection devices at the neck. METHODS: Wide-necked bifurcation aneurysms with a high propensity for recurrences were constructed in 22 dogs. HCEVOH embolization was performed with a dedicated high-pressure microcatheter in 12 animals. Angiographic results at 3 and 12 weeks and pathologic results at 12 weeks were compared with those of a separate group of 10 animals treated with platinum coils. We used a qualitative scoring system to grade angiographic results, neointima formation, and recanalization at the neck. RESULTS: Intraaneurysmal HCEVOH injections could be performed without carotid emboli and without a protection device in 11 of 12 animals. Fragments detached upon traction of the microcatheters at the end of the procedure on two occasions. Immediate and late angiographic results were not significantly different between the two groups (P =.807), with a tendency for angiographic recurrences at 3 months (angiographic scores were significantly worse in both groups at 12 weeks as compared with T0 [P <.02]). A complete occlusion, including the neck, even at the cost of protrusion of material at the level of the branches, is necessary to decrease risks of recurrences. Neointima formation at the surface of the embolic agent was complete at the neck of aneurysms treated with HCEVOH. The neointimal score was significantly improved with HCEVOH as compared with coil embolization (P =.03). CONCLUSION: HCEVOH embolization of aneurysms without neck protection is feasible. It does not, however, eliminate recurrences in an experimental wide-necked aneurysm model.

Animals↗

In situ beta radiation to prevent recanalization after coil embolization of cerebral aneurysms.

BACKGROUND AND PURPOSE: Endovascular treatment of cerebral aneurysms, a minimally invasive alternative to surgery, is too often followed by recanalization and recurrences. The purpose of this work was to assess if in situ beta radiation can inhibit recanalization after coil embolization. METHODS: Radioactive platinum coils (32P-coils) were produced by ion implantation of 32P. A single-coil arterial occlusion model was used to compare angiographic and pathological results at 1 to 12 weeks after nonradioactive and 32P-coil embolization of maxillary, cervical, and vertebral arteries in 26 dogs. Coils of varying activities were used and results compared to define the minimal activity required to inhibit recanalization. Similar experiments were performed in 16 porcine maxillary and lingual and 8 rabbit axillary arteries. Results of 32P-coil embolization of bifurcation aneurysms were then compared with embolization with nonradioactive coils in 12 dogs at 3 months. RESULTS: Nonradioactive coil embolization of canine arteries led to occlusion at 1 week, followed by recanalization at 2 weeks, which persisted at 3 months in all cases. 32P-coils, ion-implanted with activities above 0.13 microCi/cm, led to persistent occlusion at 3 months in 80% of arteries. 32P-coils ion-implanted with the same activity inhibited recanalization in porcine and rabbit arteries. Bifurcation aneurysms treated with 32P-coils had better angiographic results at 3 months (P=0.006) than aneurysms treated with nonradioactive coils. Arteries occluded were filled with fibrous tissue at 3 months. Aneurysms embolized with 32P-coils showed more complete neointimal coverage of the neck, without recanalization, as compared with aneurysms treated with nonradioactive coils. CONCLUSION: In situ low-dose beta radiation inhibits recanalization after coil embolization and may improve long-term results of endovascular treatment of aneurysms.

Animals↗

Role of the endothelial lining in persistence of residual lesions and growth of recurrences after endovascular treatment of experimental aneurysms.

BACKGROUND AND PURPOSE: We sought to investigate the role of the endothelial lining in aneurysmal persistence and recurrence after endovascular treatment of aneurysms. METHODS: Bilateral venous pouch canine carotid aneurysms were studied by angiography and pathology 1, 2, and 3 weeks after intraoperative collagen sponge embolization, coated or not coated with fibrinogen (n=15). In 12 dogs the endothelial lining of one aneurysm was removed before embolization, and results were compared with a control aneurysm after bilateral sponge embolization. In 4 animals embolization with a sponge covered with endothelium was compared with treatment with a sponge covered with adventitia. In 4 animals an inverted venous pouch aneurysm embolized with an adventitia-covered sponge was compared with a normal aneurysm embolized with an endothelialized sponge. In 3 animals inverted venous pouch aneurysms were embolized with a sponge covered or not covered with endothelium. Control aneurysms (n=3 or 4 each) included untreated normal, inverted, and de-endothelialized venous pouch aneurysms. Angiographic results at 3 weeks were compared by Wilcoxon's test. RESULTS: Endothelialization of the clot that forms on the sponge was complete at 1 week, forming clefts that developed into recurrences. Reversed or de-endothelialized aneurysms spontaneously thrombosed, while normal venous pouch aneurysms remained patent for at least 3 weeks. The addition of fibrinogen, endothelium, or adventitia to the sponges did not prevent recurrences, which occurred routinely after embolization of endothelialized aneurysm. De-endothelialization of the aneurysmal wall improved angiographic results at 3 weeks (P=0.02), while reversing the venous pouch before embolization led to complete healing (P=0.003). CONCLUSIONS: The endothelial lining is essential to the persistence of residual lesions. Early endothelial invasion of the clot leads to recanalization and recurrences after embolization of aneurysms. This observation provides new opportunities to improve results of endovascular treatment of aneurysms.

Aneurysm↗

Cyanoacrylate embolization of experimental aneurysms.

BACKGROUND AND PURPOSE: Cyanoacrylates are effective occlusive agents in neurovascular interventions. To study their potential to improve long-term results of endovascular treatment of aneurysms, we conducted experimental studies in canine aneurysm models. METHODS: Venous pouch carotid aneurysms were constructed in dogs. Results of coil embolization of lateral wall and bifurcation aneurysms were compared. A lateral wall model of embolization with gelatin sponges was used to study the effects of coating sponges with cyanoacrylate on angiographic results and neointima thickness at 3 and 12 weeks. These models were also used to investigate the control of endovascular cyanoacrylate deposition, alone or over a coil placed at the neck of the treated lesions. The results of endovascular cyanoacrylate embolization of bifurcation aneurysms were compared with those of coil embolization at 3 months. RESULTS: Bifurcation aneurysms treated with coils showed more frequent recurrences (P <.01) and thinner neointimas (P <.01) at 3 months than did lateral wall aneurysms. Cyanoacrylate-coated sponges improved angiographic results (P <.05) and led to thicker neointimas at 3 and 12 weeks (P <.05) as compared with uncoated sponges. Endovascular cyanoacrylate deposition with microcatheters led to stray emboli in all cases. Cyanoacrylate delivery was improved by a single coil positioned at the neck of the aneurysm, but parent vessel embolization still occurred in 25% of the animals. Cyanoacrylate embolization of bifurcation aneurysms improved angiographic results at 3 months as compared with coil embolization (P <.01). CONCLUSION: Cyanoacrylate embolization is currently difficult to control. It has the potential to decrease recurrences after endovacular treatment of aneurysms, but a safe method for endovascular delivery has yet to be developed.

Animals↗

Endovascular treatment of experimental wide neck aneurysms: comparison of results using coils or cyanoacrylate with the assistance of an aneurysm neck bridge device.

BACKGROUND AND PURPOSE: Endovascular treatment of wide neck aneurysms often results in incomplete occlusion or aneurysm recurrence. The two goals of the present study were to compare results of coil embolization with or without the assistance of an aneurysm neck bridge device (ANBD) and to explore the use of this instrument to control cyanoacrylate embolization. METHODS: Wide necked bifurcation aneurysms were constructed in 28 dogs. Coil embolization of the aneurysms was performed 2 to 4 weeks later, with (n = 11) or without (n = 10) ANBD assistance. In seven other animals, embolization was performed with cyanoacrylate, injected under the protection of ANBDs. Angiographic results were compared immediately after and at 3 and 12 weeks. Neointima formation at the neck was also compared between groups at 12 weeks. RESULTS: Initial angiographic results and recurrences at 12 weeks were not significantly different in aneurysms coiled with or without ANBDs. Neointimal scores were also similar. The use of one ANBD at the neck was not sufficient to safely deliver cyanoacrylate into aneurysms. Cyanoacrylate embolization led to improved angiographic results (P =.05) and to better neointimal sealing of the neck of the aneurysms at 12 weeks (P =.004). CONCLUSION: ANBDs did not prevent recanalization and recurrences after coil embolization of wide neck aneurysms in this animal study. ANBD-assisted cyanoacrylate embolization was unsafe but could decrease recurrences at 12 weeks.

Animals↗

Alginate for endovascular treatment of aneurysms and local growth factor delivery.

BACKGROUND AND PURPOSE: Coil embolization is safe and effective but may be followed by aneurysm recurrence. Our purpose was to explore the use of alginate as a new embolic agent that could deliver growth factors and improve results of endovascular treatment of aneurysms. METHODS: We first assessed the potential of alginate as a vector for growth factor delivery by using in vitro binding and elution studies. Lateral wall (n = 68) and bifurcation (n = 4) aneurysms were then constructed in six pigs and 36 dogs. We explored iodine-125 transforming growth factor-beta(1) in vivo alginate delivery in 16 canine aneurysms. We next assessed the effects of adding alginate to gelatin sponges on angiographic and pathologic results at 3 weeks (n = 4 each) in an established model used for the study of recanalization and recurrence. We then explored techniques to control endovascular alginate delivery without protection (n = 4), with the protection of a balloon (n = 4), and with the protection of a single coil (n = 12) at the aneurysm neck in 12 porcine aneurysms, four canine lateral wall aneurysms, and four canine bifurcation aneurysms. The stability of cross-linked alginate was studied after intraoperative injections in eight aneurysms. Finally, to determine the value of the material with or without growth factor in promoting aneurysm healing, we compared angiographic results and neointima formation 3 weeks after intraoperative embolization of canine lateral wall aneurysms with alginate blocks with or without platelet-derived growth factor-BB or transforming growth factor-beta(1) (n = 5 each). RESULTS: Growth factors rapidly eluted from alginate in vitro and in vivo. Alginate coating of sponges led to improved angiographic results and thick neointima formation. Intraoperative alginate block embolization did not lead to recurrence, and growth factors delivered with alginate did not show added benefits. Endovascular alginate embolization was complicated by carotid emboli, and the polymer was unstable once injected, causing delayed neurologic deficits. CONCLUSION: Growth factor delivery can be performed with alginate, but formulation changes and improved endovascular control are necessary before contemplating its use in intracranial aneurysms.

Alginates↗

32P-oligodeoxynucleotide-coated coils to prevent arterial recanalization after embolization.

BACKGROUND AND PURPOSE: Endovascular treatment of aneurysms with coils, a less invasive alternative to surgery, is too often associated with recurrences. In a canine model, recanalization after coil embolization can be inhibited by in situ beta radiation. METHODS: Radioactive platinum coils were produced by immersion in a (32)P-oligodeoxynucleotide solution. In vitro and in vivo (32)P-oligodeoxynucleotide elution profiles were assessed after incubation or arterial implantation for 14 days or less. Activities within arteries, thrombi, and coils were measured by scintillation counting. Angiographic and pathologic results no more than 12 weeks after standard platinum and radioactive coil embolization of canine maxillary, cervical, and vertebral arteries were compared among 17 animals. RESULTS: Exposure to (32)P-oligodeoxynucleotide solution at 65 degrees C yielded coils with an average activity of 0.3 microCi/cm. Elution profiles in vitro and in vivo showed that 50% of total activities eluted from coils within 24 hours at first, but coil activities then paralleled the natural decay of (32)P. Radioactivity was present in the thrombi and arterial wall throughout the 14-day observation period. Arteries that were embolized with standard coils recanalized at 2 weeks. Implantation of (32)P-oligodeoxynucleotide-coated coils produced total occlusions in 78.6% of arteries throughout the 12-week observation period. Most arteries that were implanted with radioactive coils were filled with fibrous tissue at 3 months. CONCLUSION: Radioactive coils can be produced by using the binding properties of a (32)P-oligodeoxynucleotide to platinum. Use of these coils in an animal model was effective in preventing recanalization. This method could be performed on site to provide coils tailored to each intervention.

Animals↗