Research On Theory And Method In Detecting Colorectal Cancer With Laser-Induced Fluorescence

The detection and localization of tumors at their early stage is extremely crucial for radical treatment of cancer, through which the life of the patients may be markedly prolonged. Laser spectroscopy is a promising technique in detecting and localizing human tumor tissues. Compared to routine diagnosing methods used in clinic, this technique is fast, noninvasive, quantitative and can be used in vivo. In this dissertation, the main principles, mechanisms and methods for detecting cancerous colorectal tissues with laser-induced-fluorescence are studied in detail. The research in this thesis is mainly funded by the National Key Research Project of the Ninth-Five-Year-Project titled "Research on autofluorescence diagnosing system for early colorectal cancer detection at endoscopy ". The main contents of this dissertation include:1. The transportation of laser in human tissues is studied at first. The limitation of diffusion approximation-a useful tool in tissue optical diagnosing is analyzed using electromagnetic theory and transportation theory. A novel analytical model with three parameters is proposed for accurate fitting of the local diffuse reflectance profile. Based on this model, a new iteration procedure is devised to inversely calculate the optical parameters of tissues, with the data from Monte Carlo simulations.2. The relation between the pathology of tissue and its endogenous fluorophores and fluorescence spectra is also studied. The correlation of pathology of colorectal tissues to its fluorescent molecules and microscopic structures is explored. It's proven that the main cause of decreased fluorescence in carcinoma may be ascribed to the destruction of tissue architecture and variation of biochemical composition.3. The excitation, emission and propagation of tissue fluorescence are described with an analytical model. By employing Monte Carlo method and a multi-layer model, the autofluorescence emission- of colorectal tissue is simulated for the first time. It'sdemonstrated that more than 95 percent of fluorescence is emitted from mucosa and submucosa with ultraviolet excitation, and the increased thickness of mucosa of tumor is an important factor for decreased fluorescence.4. The interplay of absorption and scattering can substantially distort the measured fluorescence. In order to extract the intrinsic fluorescence from measured fluorescence, a novel algorithm is given by measuring spectrum of diffuse reflectance. When measured under the same geometry, intrinsic fluorescence can be recovered from measured fluorescence together with diffuse reflectance. More accurate information may be providedwith the recovered intrinsic fluorescence.5. In view of the difficulty in acquiring the autofluorescence of colorectal tissue, an easy-to-use fluorescence measurement system is developed with high sensitivity and high signal-to-noise ratio. In vivo and in vitro measurements made with this system clearly show the main changes of fluorescence spectra between normal and cancerous tissues are position of peak, width of peak and trend of profile. Through statistic analyzing of three type of ratio value at selected fluorescence intensities, it's tested that ratio method for discriminant diagnosis may be not reliable and sensitive enough.6. Aimed to resolve the imperfections of the current diagnose method using fluorescence spectra, a multivariate statistical algorithm based on principal component analysis (PCA) and Bayes discrimination has been developed. Validation on this algorithm has shown its high sensitivity, high specificity and high robustness.