Bio-medical Optical Imaging Depth And Contrast Enhancement Based On Tissues Optical Clearing Technology

The ability of optical imaging techniques to realize fast, noninvasive,morphological and functional imaging of biological tissue with a resolution of micrometer to sub-micrometer scale and high contrast renders it broad prospect to be a powerful tool in clinical diagnosis. However, most biological tissues are turbid and highly scattering media. This property seriously prevents optical imaging technology from achieving high-resolution and high-contrast imaging of tissues beyond a certain depth. Regarding the above mentioned limitations, this thesis applies tissue optical clearing(TOC)technology and ultrasound methods in two novel optical imaging methods,spectral-domain optical coherence tomography(SD-OCT) and photoacoustic microscopy(PAM) to study the TOC technology to effectively increase the light penetration depth and enhance the imaging contrast of optical imaging methods in deeper tissues, while still accurately represent the morphological and functional information of various biological tissues. The change of tissue optical properties caused by optical clearing agents(OCAs) is qualitatively and quantitatively analyzed, and the enhancing effect of imaging depth and contrast is studied. The main research work can be summarized as follows:Firstly, for the problem of limited imaging depth and image contrast of OCT caused by the high scattering in tissues, glucose(G) is chosen as OCAs for normal and malignant colon tissues, and dynamic OCT imaging of G permeation in these tissues are obtained. The effect of the tissue optical clearing caused by G permeation is investigated quantitatively by the relationship among the change of OCT signal intensity, optical attenuationcoefficients(AC)、1/e light penetration depth and permeability coefficients(PC) of OCAs between normal and malignant colon tissues. The results suggest that the PC and AC in cancerous tissue are significantly higher than those in the normal colon tissue. G permeability, maximum and minimum AC in cancerous tissue is 1.65 times, 2.44 times and 1.18 times of that in normal tissue, respectively. The results demonstrate the imaging depth and contrast enhancing effect of glucose for OCT. Meanwhile, the research suggest that using OCT, quantitative measurements of OCAs PC and optical AC after applying G can potentially differentiate cancerous tissue from normal tissue,thus OCAs permeability monitoring may provide a method for colon cancer discrimination.Secondly, to further increase OCAs permeation and optical clearing effects(OCE) in biological tissues, a method combining ultrasound(Sonophoretic delivery, SP) and G synergy is employed to improve light penetration in normal and malignant colon tissues in vitro. Dynamic OCT imaging of G permeation in these tissues is obtained. To evaluate the effect of ultrasound mediation, the percentages of OCT signal enhancement(PSE)、OCE and 1/e light penetration depth are calculated for G alone and G/SP treatments. Results show that the mean PC of G/SP in normal and malignant colon tissues are increased by 1.87 and 2.14 times than G alone treatment,respectively. The PSE in normal colon tissues are 12.5 % higher with G/SP than G alone treatment. In the cancerous colon tissues the PSE improvement with G/SP is 10.8 % higher than with G alone treatment. The maximum of 1/e light penetration depth in normal and malignant colon tissues are improved by1.28 and 1.27 times of G alone, respectively. The obtained PC shows a significant enhancement with ultrasound mediated. The results indicate that ultrasound can effectively enhance the tissue OCE and G permeation rate as well as increase the light penetration depth into biological tissues.Thirdly, to further study the dynamics of OCE induced by hyperosmotic agents of different concentrations, a quantitative investigation of the effect of glycerol concentration on the imaging contrast and light penetration depth isstudied. PAM is used as the optical imaging method. Dynamic PAM imaging of a biological-tissue-mimicking phantom after applying 20 %, 40 % and60 % glycerol is obtained. The obtained photoacoustic signal amplitude changes are evaluated as a function of the concentration of glycerol. The results reveal that the PA signal amplitudes are enhanced with the increasing glycerol concentration, and higher concentration of glycerol produces better light penetration and OCE. However, higher concentration OCAs demonstrates slower permeation rate. Taking both OCE and permeation rate into consideration, it is recommended 40 % glycerol would be the most suitable choice as the OCAs. This study demonstrates that application of glycerol as OCAs reduces the tissue scattering and is beneficial to PAM imaging and optical diagnosis in clinical dermatology. In order to achieve optimal optical imaging depth and contrast enhancement, the concentration of applied OCAs should be carefully designed and the best onset time of different concentrations of applied OCAs should be taken into consideration.In conclusion, this thesis focuses on applying TOC technology to enhance the imaging depth and contrast of OCT and PAM technology. The imaging depth and contrast of OCT and PAM on biological tissues are successfully improved through TOC technology. The change of optical properties of biological tissues through TOC technology is analyzed qualitatively and quantitatively. Thus, this thesis supplies an effective,convenient, fast and cheap method for expanding the application of biological optical imaging technology provides an experimental study theoretical basis for TOC technology to be applied on optical imaging methods as a means to improve light penetration depth and imaging contrast.