Effect of Motexafin lutetium-mediated ultrasound-guided red laser photodynamic therapy on endothelial dysfunction using a new automatic ultrasound image processing software

Abstract

Abstract Background As is well recognized, the majority of atherosclerosis start with an inflammatory process, resulting in endothelial dysfunction. Purpose In this study, we developed an experimental photosensitizer Motexafin lutetium (Lu-Tex)-mediated photodynamic therapy system, and investigated its effectiveness on endothelial dysfunction improvement in an animal model of balloon dilation injury, using a new automatic ultrasound image processing software. Methods Briefly, Golden Syrian hamsters' femoral artery underwent balloon dilatation injury. After four weeks, femoral arteries of the treatment group at the lesion region, treated using Motexafin lutetium - mediated fiber optic catheter-based red low level laser (742 nm, 150 J/cm2) photodynamic therapy. In order to evaluate endothelial-dependent relaxation, acetylcholine-mediated dilation (AMD) was measured during the infusion of acetylcholine at a rate of 0.5 μg/kg/min and endothelial independent relaxation was evaluated by measuring nitroglycerin mediated dilation (NMD) during the infusion of nitroglycerin at a rate of 5μg/kg/min. For off-line analysis, a computerized analysis method for evaluating instantaneous changes in the wall of the hamster femoral artery was used. For automatic measurement of the mean wall thickness and the lumen diameter from longitudinal B-mode ultrasound images, two algorithms, i.e., maximum gradient and dynamic programming were composed and implemented. Reference points and cost function were based on dynamic programming and maximum gradient, respectively. Results Results from computerized B-mode ultrasound image processing software showed significant differences in AMD between the treated and the non-treated hamsters (p<0.05), whereas there were no significant differences in NMD between the treatment and normal groups (p>0.05). Conclusion Cytotoxic and anti-inflammatory effect of Motexafin lutetium, induced by red laser photodynamic therapy accompanied by photobiomodulation effect of red laser, can cause to reduce the immune cells in intimal layer and improve the endothelial dysfunction via increasing the endothelial nitric oxide synthase function. Furthermore, it is concluded that the new automatic method enables accurate and repeated evaluation of the endothelial dysfunction using photodynamic therapy in this model. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab