Multi-mode Optical Imaging System And Its Application For Vascular Targeted Photodynamic Therapy

Vascular targeted photodynamic therapy(V-PDT)has shown good selectivity and efficacy in treating vascular-related diseases including age-related macular degeneration(AMD),port-wine stains(PWS),prostate cancer(PCa)and so on.To further understand the mechanism of V-PDT and accurately assess and predict its efficacy,we monitored parallel spatio-temporal characteristics of hematoporphyrin methyl ether(HMME)/ vascular microcirculation using developed multi-mode optical imaging system(including narrow band imaging(NBI),fluorescence imaging(FI)and laser speckle imaging(LSI))in the in vivo experiment of ICR mouse dorsal skinfold window chamber(DSWC)model.The biodistribution of HMME was mapped by HMME fluorescence which was excited at 532 nm and emitted at 610-630 nm.The changes in vascular morphology induced by PDT were measured by NBI at 540-560 nm.The integration of FI and NBI is achieved using a timesharing camera with a filter wheel.Blood flow dynamics was visualized by LSI through a separate camera.Finally,the V-PDT effect was assessed with analyzing multiple V-PDT dose parameters including HMME concentration,vascular size,and blood flow velocity.Our results suggest that multi-mode optical imaging system for quantifying photosensitizer concentrations and vascular damage will be a useful tool for the understanding of V-PDT effect.The main research work is as follows:(1)With the goal of multi-parameter monitoring,the system design has been carried out from the aspects of light source,optical path and hardware and software control.By combining FI,NBI,LSI to build a multi-mode optical imaging system and evaluate system performance,such as the spatial resolution of the system and the image registration work done for the two-way optical path of the stereo microscope and the CCD target surface size.Thereby parallel monitoring of photosensitizer fluorescence,vascular morphology and blood flow changes during V-PDT was completed.At the same time,for the fluorescence imaging technology,only the temporal and spatial distribution of the photosensitizer fluorescence and the relative change in concentration can be obtained,a method for detecting the concentration of photosensitizer was proposed and the effectiveness of the method was verified by model experiments to realize the quantification of photosensitizer concentration and its spatiotemporal distribution detection.(2)The multi-mode optical imaging system was used to monitor the process of the in vivo experiment of ICR mouse DSWC model and obtain the photosensitizer fluorescence images,narrow-band images and speckle images in the process.Then,the images acquired by the system are processed by Matlab program to realize image matching,blood vessel segmentation,region of interest extraction,data analysis,etc.,and quantitatively obtain information such as photosensitizer concentration,blood vessel size and blood flow velocity.In addition,the feasibility of the system in parallel monitoring of V-PDT dose parameters was further verified by analyzing the relationship between different signals.