Background Endovascular treatment of brain aneurysms with the use of flow diverting stents, coils and intrasaccular flow disrupters, has been challenged by delayed and incomplete occlusion in more than 20% of treated subjects at 12-month follow-up imaging. Other shortcomings include delayed or incomplete aneurysm occlusion in senior population, early spontaneous rupture of large and giant aneurysms as well as continued aneurysm growth despite angiographic occlusion. Low Laser Light Therapy (LLLT, aka Photobiomodulation) is being used successfully for treatment of superficial birthmarks as well as ulcers of mouth mucosa.
Objective We developed a highly flexible optical microfiber technology to deliver LLLT in a preclinical aneurysm animal model and studied early healing response.
Methods Single highly flexible 0.014’ optical microfiber system were developed to deliver low laser light through a standard microcatheter. Optimization of delivery technology was carried out in vitro studies using various human cerebrovascular/aneurysm replica. Subsequently the LLLT system was assessed in a rabbit elastase aneurysm model. Laser wavelength and energy dose calculations based on aneurysm surface calculation, was obtained from previous cell culture and animal studies. Aneurysms were treated with LLLT followed by coils or flow diverters (test group) or with FD or coil only (control group). Pre- and posttreatment angiograms as well as follow-up angiograms at 3- and 10 days were compared. Following angiograms, animals were sacrificed, and aneurysm and parent artery samples were processed for histology studies and immunofluorescence staining.
Results Control samples showed at 3 days still filling of the aneurysm and no significant endothelialization. Albeit partial filling, 3-day sample treated with LLLT, showed amorphous clot filling the aneurysm with early endothelialization of the aneurysm neck and the implant within the parent vessel. At 10 days, FD treated with LLLT showed a complete aneurysm occlusion and neck endothelialization while control aneurysms were still patent with sparse endothelial cells attached to the FD at the aneurysm neck. At 10 days smooth muscle cell actin (SMA, non-specific for myoepithelial cells) and CD 31 (platelet endothelial cell adhesion molecule 1) were found in large numbers in samples treated with LLLT. Although coil compaction at 10 days was seen in both coiled groups, LLLT treated samples showed layering clot/content. Immunostaining revealed high concentration of Fibroblasts and Myofibroblast near the aneurysm wall small number of primarily Lymphocytes and Neutrophils inside the thrombus as compared to the coiled only aneurysms.
Conclusion Preliminary preclinical studies show that LLLT delivered in situ in an animal aneurysm model is feasible. Compared with the control group an early healing response with aneurysm scarring and neck occlusion is observed. Our technology represents a unique combination of implantable devices and LLLT, bringing regenerative medicine into endovascular therapeutic realm.
Disclosures A. Wakhloo: 1; C; Prometheus Therapeutics. 4; C; Prometheus Therapeutics. Y. Uetake: None. S. Greenfield: None. B. Lieber: 4; C; Prometheus Therapeutics.
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