| Vascular targeted photodynamic therapy(V-PDT)is a treatment modality that combines photosensitizer,light and oxygen molecules to selectively treat vascular diseases through photodynamic response.The injury of targeted blood vessels positively correlates to the singlet oxygen generation,which is affected by different dosimetric parameters,including blood flow velocity,photosensitizer concentration and hemoglobin oxygenation concentration.In order to realize the real-time synchronous monitoring of dosimetric parameters in V-PDT,a triple-modality optical imaging system is developed in this thesis,which includes hyperspectral imaging(HSI)module,dual wavelength reflection imaging(DWRI)module and laser speckle contrast imaging(LSCI)module.The dorsal skinfold window chamber(DSWC)of mice is selected as an animal model to study the real-time synchronous monitoring of dosimetric parameters of V-PDT mediated by Hemoporfin,in which DWRI allows for simultaneously monitoring the changes of vascular density and hemoglobin oxygenation concentration with treatment time.While HSI and LSCI are used to monitor the changes of photosensitizer concentration and blood flow velocity with treatment time,respectively.The experimental results show that the triple-modality optical imaging system can realize the synchronous monitoring of V-PDT multi-dosimetric parameters,which provides data support for real-time evaluation of VPDT efficacy and optimization of treatment regimens.Firstly,a triple-modality optical imaging system is developed for real-time simultaneous monitoring of dosimetric parameters,which including vascular density,blood flow velocity,photosensitizer concentration and hemoglobin oxygenation concentration during Hemoporfin-mediated V-PDT.The system integrates HSI,DWRI and LSCI imaging modules into the same stereomicroscope,uses HSI module to monitor the changes of photosensitizer concentration in the process of V-PDT,uses DWRI module to monitor the changes of vascular density and hemoglobin oxygenation concentration during V-PDT,and uses LSCI module to monitor the changes of blood flow velocity in the process of V-PDT.Secondly,the hardware control and image acquisition programs are written based on Lab VIEW to realize the synchronous hardware control among HSI,DWRI and LSCI imaging modules,as well as the acquisition and storage of images in different modes.At the same time,the relevant image processing algorithms are written based on MATLAB to reconstruct the dosimetric parameters such as blood vessel density,blood flow velocity,photosensitizer concentration and hemoglobin oxygenation concentration.Thirdly,the imaging performance of the triple-modality optical imaging system is analyzed by using the resolution board and the checkerboard calibration board,and the effects of the absorption of dual-wavelength radiation and the fluorescence emitted by the excited photosensitizer on the reconstruction of hemoglobin oxygenation concentration are investigated by in vivo experiments,and whether the light dose of dual-wavelength irradiated light reached the threshold of V-PDT therapy caused signal interference to the HSI module.Through the above experiments,it is proved that there is no signal crosstalk among HSI module,DWRI module and LSCI module in the triple-modality optical imaging system,which can realize the real-time synchronous monitoring of dosimetric parameters during V-PDT in vivo.Finally,DSWC model in ICR mouse is chosen as the animal model in vivo,the measurement of Hemoporfin-mediated V-PDT is carried out by using triple-modality optical imaging system.The changes of different dosimetric parameters,including vascular density,blood flow velocity,photosensitizer concentration and hemoglobin oxygenation concentration during V-PDT are monitored,and the relationship between different dosimetric parameters is quantitatively analyzed. |
