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Biomedical subjects

Philippe Leblanc

Publications and source records attributed to Philippe Leblanc.

7 recordsLinked to original sources

Safety and effectiveness of radioactive coil embolization of aneurysms: effects of radiation on recanalization, clot organization, neointima formation, and surrounding nerves in experimental models.

BACKGROUND AND PURPOSE: Recanalization after coil embolization can be prevented by radiation emitted from 32P coils. We wanted to determine the upper limits of 32P activities that could be implanted onto coils with respect to the potential injury to nearby nerves, delay in organization of the clot, and effects on neointima formation and recanalization. METHODS: We studied the effects of various 32P activities on recanalization and organization of thrombus after coil occlusion of canine arteries and on neointima formation at the neck of canine carotid bifurcation aneurysms. We also tested potential injury to nerves in the vicinity of radioactive or nonradioactive coils in 3 models: the brachial plexus (near proximal vertebral arteries) and the lingual nerve in a lingual artery bifurcation aneurysm model, both models being treated by radioactive or standard coil occlusion. Finally, we wrapped lingual nerves with nonradioactive or high-activity coils and studied their effects on lingual nerves and tongues. Results were assessed with a pathological scoring system and compared with Mann-Whitney and Kruskal-Wallis tests. RESULTS: No deleterious effect of radiation on nerves could be detected. Neointima formation was not hampered, scores of aneurysms treated with 32P-coils being significantly better when compared with treatments with standard coils (P=0.002). Arteries treated with high-activity coils (>3.39 microCi) showed absent recanalization but delayed organization of the clot at 3 months compared with low-activity or nonradioactive coils (P<0.05). CONCLUSIONS: beta-Radiation can prevent recanalization after coil occlusion. We could not demonstrate any deleterious effects of radioactivity on nervous structure or on neointima formation. Delayed organization of thrombus provides a rational basis to establish an upper limit for 32P activities to be implanted onto coils.

Animals↗

Production of radioactive particles for endovascular therapeutic interventions.

Recanalization is a common phenomenon that decreases the efficacy of embolization procedures. It can be inhibited by beta-radiation. Two novel ways of producing radioactive particles are described, by neutron beam irradiation of gold-containing microspheres, or by using the 32P binding capacity of zirconium-containing microspheres. Particles were tested in vivo, to assess their ability to deliver radioactivity locally, using canine renal artery, porcine rete mirabile, and rabbit ear embolization models. Both radioactive microspheres (198Au and 32P) showed no detectable activity outside the target territory. 32P microspheres demonstrated typical radiation changes in a porcine rete mirabile arteriovenous malformation model.

Animals↗

Active pixel sensor array as a detector for electron microscopy.

A new high-resolution recording device for transmission electron microscopy (TEM) is urgently needed. Neither film nor CCD cameras are systems that allow for efficient 3-D high-resolution particle reconstruction. We tested an active pixel sensor (APS) array as a replacement device at 200, 300, and 400 keV using a JEOL JEM-2000 FX II and a JEM-4000 EX electron microscope. For this experiment, we used an APS prototype with an area of 64 x 64 pixels of 20 microm x 20 microm pixel pitch. Single-electron events were measured by using very low beam intensity. The histogram of the incident electron energy deposited in the sensor shows a Landau distribution at low energies, as well as unexpected events at higher absorbed energies. After careful study, we concluded that backscattering in the silicon substrate and re-entering the sensitive epitaxial layer a second time with much lower speed caused the unexpected events. Exhaustive simulation experiments confirmed the existence of these back-scattered electrons. For the APS to be usable, the back-scattered electron events must be eliminated, perhaps by thinning the substrate to less than 30 microm. By using experimental data taken with an APS chip with a standard silicon substrate (300 microm) and adjusting the results to take into account the effect of a thinned silicon substrate (30 microm), we found an estimate of the signal-to-noise ratio for a back-thinned detector in the energy range of 200-400 keV was about 10:1 and an estimate for the spatial resolution was about 10 microm.

Cryoelectron Microscopy↗

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↗

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↗

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↗