| This Ph.D project involved making a major contribution to the development and evaluation of a prototype medical optical biopsy system for the diagnosis and localization of early nasopharyngeal carcinoma.Nasopharyngeal Carcinoma, commonly abbreviated to NPC, has already been noted by many authors to be a malignant disease particular to southern Chinese, with a yearly incidence of between 20 and 25/105, while is a rare disease in the western country. In recent year, optical imaging have become the basis for a high level of research activity toward the development of novel, noninvasive technologies for tissue diagnostics, which frequently called "Optical Biopsy". In contrast to histopathological examinations, optical biopsy is non-invasive and it do not require sampling by a thin-needle biopsy and the material amount is not limited, radiation is delivered and received by fibers and signals are measured in a real time, the same areas can be also analyzed repeatedly. The dissertation deals with the development and evaluation of optical biopsy for tissue characterization especially to detect malignant and pre-malignant lesions for nasopharynx, which is important to improve the probability of successful therapy.In Chapter One, the significance of diagnosis and localization for early NPC was discussed for the successful treatment of NPC. Optical biopsy has been firstly employed for the early detection of NPC based on the analysis and summary of modality of current clinical diagnosis for NPC, which mainly including standard method of nasal endoscope, and CT and MRI, as well as serological tests to detect elevated IgA levels against the EBV antigen. Next, the developmental current status and perspectives, as well as the principle and merits of optical biopsy have been reviewed in the world spectrum. Though a large variety of techniques have been proposed based on optical biopsy for tissue characterization, however, this dissertation is restricted to the laser induced exogenous fluorescence imaging technique for the diagnosis of early NPC.in/ ?Dissertation submitted for Ph.D at Zhejiang University (Department of Optical Engineering)______In Chapter Two, one of the most important things in optical biopsy is the choice of photosensitizer, which can be used to increase the contrast in the fluorescence imaging between normal tissue and malignant and premalignant lesions. The spectral properties of second-generation new photosensitizer ZnPcS2P2, PsD-007, HMME, and as well as traditional photosensitizer HpD by comparison have been studied, respectively. Experimental results show that the maximum absorption peaks for PsD-007, HMME and HpD in the physiological saline with 10 percent serum appear at 405nm in the soret region, while 670nm for ZnPcS2P2- The Excitation-Emission Matrix of HMME is presented and discussed in detail. When excited by the light at the wavelength of 488nm and 514.5nm, the fluorescence emission peaks for PsD-007, HMME and HpD appear at 625nm and 685nm, respectively. The fluorescent excited efficiency of the same photosensitizer with the same concentration excited by the light at the wavelength of 488nm is twice higher than that of 514.5nm, and the fluorescence intensity 625nm is third higher than that of 514.5nm. Furthermore, The fluorescent excited efficiency of HMME is the highest, and the PsD-007 is lowest. Therefore, it can be concluded from the above results that HMME and ZnPcS2P2 is the optimal photosensitizer for photodynamic diagnosis and photodynamic therapy, respectively. Secondly, the time-resolved fluorescence spectroscopy and the lifetime of HMME were investigated intensively, which can be contributed to the lifetime imaging for the optical biopsy of NPC in the near future. Finally, the photobleaching property of HMME, particularly its photobleaching time was studied for the possible and maximum examination time for clinical application.In Chapter Three, the methods and techniques for measurement of tissue optical properties were briefly outlined. A short introduction to K...
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