Real Time Monitoring Of Dose Parameters In Vascular Targeted Photodynamic Therapy

Vascular targeted photodynamic therapy(V-PDT),working as a therapeutic method with high effectiveness for port wine stains and malignant tumors,realizes cellular damage through singlet oxygen(¹O₂)-induced necrosis or apoptosis.The production of¹O₂stems from interactive activities among photosensitizers,light and oxygen during V-PDT,with its yield significantly affected by photosensitizer dosage,incident laser power,and blood oxygen saturation.Therefore,it indicates critical importance of real-time monitoring on relative parameter dosage during V-PDT since ¹O₂generation exerts a direct impact on the final efficacy.Optical imaging technology is widely used in clinical diagnosis and treatment for its advantages of non-destructive,rapid,accurate and non-invasive detection.In this thesis,a narrow-band optical imaging system was employed to quantitatively study the vascular damage affected by the photodynamic dosage.The results showed that,in Hemoporfin-mediated photodynamic therapy,distinct diameter contraction rates were observed for different veins.In order to achieve the highest vascular area contraction rate,optimizations on the incident laser power as well as the applied drug quantity is of nonnegligible necessity.Meanwhile,to overcome limitations during single imaging technology,a hyperspectral-speckle imaging system was designed and developed for real-time monitoring on multiple parameters including photosensitizer concentration,blood flow velocity,blood oxygen saturation and vascular diameter contraction rate.It was proved that the system can be applied in multiple-parameter monitoring.The excellent performance of hyperspectral-speckle imaging system during Hemoporfin-PDT proved itself a promising candidate to provide theoretical basis for both revealing the mechanism of V-PDT and prompting the development of personalized therapeutics.Main focuses of this thesis are presented as follows:(1)Quantitative investigation on photodynamic dosage-dependent vascular damage was carried out utilizing the narrow-band optical imaging system.By establishing the dorsal skin-fold window chamber(DSWC)model of ICR mice,vascular damage affected by Hemoporfin concentration and laser power density was quantitatively evaluated followed by quantitative study on the relation between photodynamic dosage and vascular response.(2)Development of an optical imaging system capable of multiple-parameter monitoring during Hemoporfin-PDT was carried out through combination of hyperspectral imaging(HSI)technology and laser speckle imaging(LSI)technology.Specifically,HSI monitors vascular diameter contraction rate,blood oxygen saturation and photosensitizer concentration while LSI takes charge of blood flow.Furthermore,hardware control,image acquisition and data storage are realized through self-programming by Lab View.Hyperspectral images and laser speckle images of the DSWC model in Hemoporfin-PDT were provided by the hyperspectral-speckle imaging system followed by image registration,image segmentation and data analysis through self-programming by Matlab hence extracting key parameters including photosensitizer concentration,blood flow velocity,blood oxygen saturation and vascular diameter contraction rate.In the end,the intrinsic relation between different parameters was analyzed to verify the validity of hyperspectral-speckle imaging system and evaluate the actual value in clinical application therefore offering basis for personalized therapeutic scheme formulation.