Abstract 044: Endovascular photobiomodulation accelerates the complete healing of intracranial aneurysms treated with flow diverters
Authors: Wakhloo A. , Lylyk P. N. , Lylyk I. , Uetake Y. , Greenfield S. , McSweeney T. , Lylyk P. , Lieber B. B. 
Published: January 2025

Introduction
Endovascular treatment of intracranial aneurysms (IA) with use of flow diverters (FD), coils and endosaccular implants has been challenged by incomplete occlusion in up to 50% of the patients, delayed aneurysm recanalization. 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. Photobiomodulation is being used successfully for the treatment of superficial birthmarks.

Material and Methods
A highly flexible optical microfiber system was developed to deliver laser light through a standard microcatheter. Optimization of delivery technology was carried out in vitro in cerebrovascular/aneurysm replica. Subsequently, the PBM system was assessed using a rabbit elastase aneurysm model. Laser wavelength and energy dose calculations based on aneurysm size were obtained from previous cell culture and animal studies. A total of 85 rabbit elastase aneurysms were treated with PBM followed by coils or flow diverters (test group) or with FD or coil only (control group). Pre‐ and post‐treatment and follow‐up angiograms were compared at 3, 7, and 10 days. Following angiograms, animals were sacrificed and aneurysm and parent artery samples were processed for histology. The PBM system was then used in 11 patients with 12 7‐20 mm wide‐necked large aneurysms. Patients were treated with an FD and endosaccular PBM in 9 aneurysms, while in 3 aneurysms the laser was activated within the parent artery. Depending on IA size, treatment time varied from several to 20 minutes.

Results
Control samples in experimental studies showed no significant endothelialization at 3 days and still filling the aneurysm. Albeit partial filling, a 3‐day sample treated with PBM showed an amorphous clot filling the aneurysm with early endothelialization of the aneurysm neck and the implant within the parent vessel. At 7‐10 days, FD treated with PBM showed a complete aneurysm occlusion in most of the samples and neck endothelialization, while control aneurysms were still patent with sparse endothelial cells attached to the FD at the aneurysm neck. At 7‐10 days, smooth muscle cell actin and CD 31 positive cells were found in large numbers in samples treated with PBM. Although coil compaction at 10 days was seen in both coiled groups, PBM‐treated samples revealed a high concentration of Fibroblasts and myofibroblasts near the aneurysm wall and a small number of primarily Lymphocytes and Neutrophils inside the thrombus compared to coiled‐only aneurysms. In patients treated with FD and LT, at 7‐30 days follow‐up, a nearly complete occlusion of the aneurysms with neck remnant was found in 6 out of 12 aneurysms. No implant stenosis or intimal hyperplasia was observed. None of the patients experienced any adverse events.

Conclusion
Our preliminary preclinical study shows that PBM delivered in situ is feasible and applicable in patients treated with FD. PBM may lead to an early and more complete aneurysm occlusion without any added treatment risk. Our technology represents a unique introduction of regenerative medicine into the endovascular therapeutic realm. Adjustment of energy applied and a larger long‐term cohort study are needed.