光透明技術(shù)在生物光學(xué)成像深度拓展及對(duì)比增強(qiáng)中的應(yīng)用研究
發(fā)布時(shí)間：2018-09-14 10:43
【摘要】：生物光學(xué)成像技術(shù)具有無(wú)創(chuàng)、高分辨,高對(duì)比度及快速等特點(diǎn),可實(shí)現(xiàn)微米或亞微米量級(jí)高分辨的生物組織的微結(jié)構(gòu)及功能成像,在疾病檢測(cè)及臨床應(yīng)用研究中呈現(xiàn)出廣闊的應(yīng)用前景。然而,由于大多數(shù)生物組織所具有的渾濁、高散射特性,嚴(yán)重限制了光在組織中的穿透深度,使得多種光學(xué)成像技術(shù)無(wú)法實(shí)現(xiàn)對(duì)組織更深層的結(jié)構(gòu)進(jìn)行成像。因此,本文的研究目的是以譜域光學(xué)相干層析成像(Spectral-domain OCT,SD-OCT)及光聲顯微成像技術(shù)(Photoacoustic microscopy,PAM)為例,利用組織光透明技術(shù)(Tissue optical clearing,TOC),研究提高生物光學(xué)成像探測(cè)深度的方法,提升光學(xué)成像技術(shù)探測(cè)組織深層的形態(tài)結(jié)構(gòu)與功能特征的能力,以提供更加豐富有價(jià)值的組織圖像及參數(shù)信息用于對(duì)醫(yī)學(xué)疾病的診斷與治療。針對(duì)以上研究目的,本研究利用TOC技術(shù)及超聲波與光學(xué)透明劑(Optical clearing agents,OCAs)相結(jié)合的方法,提升了兩種光學(xué)成像方法的成像深度,實(shí)現(xiàn)更深層的高對(duì)比度的組織結(jié)構(gòu)成像,并定性定量分析了由OCAs所引起的組織光學(xué)特性參數(shù)的變化,討論了OCAs劑量對(duì)成像效果及光穿透深度的影響。本論文的主要研究?jī)?nèi)容和結(jié)果如下:首先,針對(duì)OCT在生物組織成像中,由于受到組織高散射的影響而導(dǎo)致成像深度淺、圖像對(duì)比度低等問(wèn)題,基于TOC技術(shù),選取OCAs葡萄糖作用于人的離體的正常與結(jié)腸癌組織,成功實(shí)現(xiàn)OCT對(duì)葡萄糖在兩種組織中的整個(gè)擴(kuò)散過(guò)程實(shí)時(shí)動(dòng)態(tài)監(jiān)控。并深入分析了oct信號(hào)強(qiáng)度、葡萄糖滲透系數(shù)(permeabilitycoefficients,pc)、葡萄糖在兩種組織內(nèi)所引起光衰減系數(shù)(attenuationcoefficients,ac)等參數(shù)變化規(guī)律及測(cè)量結(jié)果。研究結(jié)果表明葡萄糖對(duì)提高oct在對(duì)正常和癌變的結(jié)腸組織成像中圖像的對(duì)比度、成像深度有效性和實(shí)用性。同時(shí),通過(guò)定性定量評(píng)價(jià)與分析,發(fā)現(xiàn)葡萄糖在癌變結(jié)腸組織中pc是正常結(jié)腸組織的1.65倍,光的ac最大值及最小值分別是正常結(jié)腸組織的2.44和1.18倍。進(jìn)而提出通過(guò)計(jì)算與比較由ocas在不同組織中引起的組織特性參數(shù)的差異,可用來(lái)提高oct對(duì)正常和病變組織的識(shí)別能力,這對(duì)拓寬oct的應(yīng)用具有重要的應(yīng)用價(jià)值。其次,為了進(jìn)一步提高ocas在組織中的滲透速率及光透明效果(opticalclearingeffects,oce),進(jìn)而促使光在組織中的穿透更深,在上一研究基礎(chǔ)上,提出采用超聲波協(xié)同葡萄糖策略,加快葡萄糖在正常和癌變結(jié)腸組織中的滲透,并實(shí)現(xiàn)oct對(duì)葡萄糖在組織中整個(gè)滲透過(guò)程的實(shí)時(shí)動(dòng)態(tài)監(jiān)測(cè)。深入研究了由超聲波導(dǎo)入所引起的葡萄糖pc、oce、oct信號(hào)強(qiáng)度及1/e光穿透深度等參數(shù)變化及計(jì)算結(jié)果。研究結(jié)果表明經(jīng)超聲協(xié)同,葡萄糖在兩種組織中的pc分別被提高了約1.87和2.14倍,oct信號(hào)強(qiáng)度被提高了約12.5%和10.8%,1/e光穿透深度被提高了約1.28和1.27倍。并證明超聲協(xié)同葡萄糖策略可作為一種促進(jìn)ocas擴(kuò)散,進(jìn)一步增強(qiáng)光在組織中穿透深度的有效方法,為進(jìn)一步拓展oct成像能力提供新的思路與和理論依據(jù)。最后,為了深入了解ocas濃度及作用時(shí)間對(duì)oce、pam信號(hào)幅值、圖像對(duì)比度及光的穿透深度等特征的影響,利用覆蓋于皮膚組織下的仿體誘發(fā)光聲信號(hào),實(shí)現(xiàn)了pam對(duì)經(jīng)不同濃度甘油處理后的皮膚組織下仿體圖像的變化進(jìn)行了實(shí)時(shí)動(dòng)態(tài)監(jiān)控。定性定量評(píng)價(jià)與分析了濃度對(duì)OCE、成像質(zhì)量及光聲信號(hào)幅值等特征之間的影響與的變化規(guī)律。研究結(jié)果不僅表明甘油對(duì)增強(qiáng)PAM成像深度及信號(hào)強(qiáng)度有效性,還證明甘油濃度與增強(qiáng)OCE、提高PAM成像能力之間存在緊密的相關(guān)性,其中60%甘油OCE最好、40%次之、20%最差,但相對(duì)于后兩組,60%甘油組取得最佳組織OCE所需的時(shí)間卻最長(zhǎng),并發(fā)現(xiàn)組織OCE并非隨甘油作用時(shí)間的延長(zhǎng)而呈現(xiàn)線性增加的趨勢(shì)。此研究結(jié)果對(duì)更有效的利用OCAs增加組織OCE,進(jìn)而提高光學(xué)成像技術(shù)的成像能力具有重要的指導(dǎo)意義。本論文重點(diǎn)對(duì)TOC技術(shù)在OCT與PAM成像深度拓展及圖像對(duì)比增強(qiáng)中的應(yīng)用進(jìn)行了深入的研究。并定性評(píng)價(jià)了TOC技術(shù)對(duì)提升此兩種技術(shù)成像能力的有效性,定量分析了由OCAs引起的生物組織光學(xué)特性參數(shù)的變化規(guī)律,及OCAs濃度對(duì)增強(qiáng)組織OCE與成像深度及圖像對(duì)比度之間的相關(guān)性。本論文的研究成果為T(mén)OC技術(shù)提升光學(xué)成像技術(shù)在生命科學(xué)與工程科學(xué)領(lǐng)域中的成像能力和應(yīng)用范圍,及完善TOC技術(shù)理論評(píng)價(jià)體系,提供重要的理論依據(jù)及實(shí)驗(yàn)參考。
[Abstract]:Bio-optical imaging technology is noninvasive, high-resolution, high-contrast and fast. It can realize high-resolution micro-or sub-micron-scale imaging of the microstructure and function of biological tissues. It has a broad application prospect in disease detection and clinical application. However, due to the turbidity and high scattering characteristics of most biological tissues. Therefore, the purpose of this paper is to take spectral-domain optical coherence tomography (SD-OCT) and photoacoustic microscopy (PAM) as examples, and to utilize groups. Tissue optical clearing (TOC) is a new technique to improve the detection depth of bio-optical imaging, and to enhance the ability of optical imaging to detect the morphological structure and functional characteristics of deep tissue in order to provide more valuable tissue images and parameter information for the diagnosis and treatment of medical diseases. Aim: In this study, TOC technology and the combination of ultrasonic and optical clearing agents (OCAs) were used to enhance the imaging depth of the two optical imaging methods, to achieve deeper high contrast tissue imaging, and qualitative and quantitative analysis of the changes of tissue optical properties caused by OCAs was discussed. The main contents and results of this paper are as follows: Firstly, for the problems of low contrast and shallow imaging depth caused by high tissue scattering, OCAs glucose was selected to act on human normal in vitro based on TOC technology. With colon cancer tissues, OCT can monitor the whole glucose diffusion process in both tissues in real time and dynamically. The changes of OCT signal intensity, permeability coefficients (pc) and attenuation coefficients (ac) induced by glucose in the two tissues were analyzed and measured. Results. The results showed that glucose could improve the contrast, depth efficiency and practicability of OCT in normal and cancerous colon tissue imaging. Meanwhile, through qualitative and quantitative evaluation and analysis, it was found that the PC of glucose in cancerous colon tissue was 1.65 times that of normal colon tissue, and the maximum and minimum AC of light were positive respectively. 2.44 and 1.18 times of normal colon tissue. It is suggested that the ability of OCT to recognize normal and pathological tissues can be improved by calculating and comparing the differences of tissue characteristic parameters caused by OCAs in different tissues, which is of great value in broadening the application of Oct. Secondly, the osmotic rate of OCAs in tissues can be further increased. Based on the previous study, the ultrasound-assisted glucose strategy was proposed to accelerate the permeation of glucose into normal and cancerous colon tissues and to realize the real-time and dynamic monitoring of glucose permeation in tissues by Oct. The changes of glucose pc, oce, OCT signal intensity and 1/e light penetration depth caused by ultrasound were studied. The results showed that the PC of glucose in the two tissues was increased about 1.87 and 2.14 times, the OCT signal intensity was increased about 12.5% and 10.8%, and the 1/e light penetration depth was increased by ultrasound. It is proved that the ultrasound-glucose coordination strategy can be used as an effective method to promote the diffusion of OCAs and further enhance the depth of light penetration in tissues. It provides a new idea and theoretical basis for further expanding the imaging ability of Oct. Finally, in order to further understand the amplitude of oce, PAM signal and image contrast of OCAs concentration and action time. The PAM was used to monitor the changes of the bionic images of skin tissue after glycerol treatment with different concentrations. The effects of concentration on OCE, imaging quality and photoacoustic signal amplitude were evaluated and analyzed qualitatively and quantitatively. The results not only show that glycerol is effective in enhancing the imaging depth and signal intensity of PAM, but also prove that there is a close correlation between glycerol concentration and enhancing OCE and improving the imaging ability of PAM. It is found that OCE does not increase linearly with the prolongation of glycerol exposure time. The results of this study have important guiding significance for more effective use of OCAs to increase tissue OCE and improve the imaging ability of optical imaging technology. The application of TOC technology in image contrast enhancement is studied in depth, and the effectiveness of TOC technology in enhancing the imaging ability of these two technologies is evaluated qualitatively. The variation law of optical characteristic parameters of biological tissues caused by OCAs is analyzed quantitatively, and the correlation between OCE concentration and imaging depth and image contrast is discussed. The research results of this paper provide important theoretical basis and experimental reference for TOC technology to enhance the imaging ability and application scope of optical imaging technology in the field of life science and engineering science, and to improve the TOC technology theoretical evaluation system.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R318.51
[Abstract]:Bio-optical imaging technology is noninvasive, high-resolution, high-contrast and fast. It can realize high-resolution micro-or sub-micron-scale imaging of the microstructure and function of biological tissues. It has a broad application prospect in disease detection and clinical application. However, due to the turbidity and high scattering characteristics of most biological tissues. Therefore, the purpose of this paper is to take spectral-domain optical coherence tomography (SD-OCT) and photoacoustic microscopy (PAM) as examples, and to utilize groups. Tissue optical clearing (TOC) is a new technique to improve the detection depth of bio-optical imaging, and to enhance the ability of optical imaging to detect the morphological structure and functional characteristics of deep tissue in order to provide more valuable tissue images and parameter information for the diagnosis and treatment of medical diseases. Aim: In this study, TOC technology and the combination of ultrasonic and optical clearing agents (OCAs) were used to enhance the imaging depth of the two optical imaging methods, to achieve deeper high contrast tissue imaging, and qualitative and quantitative analysis of the changes of tissue optical properties caused by OCAs was discussed. The main contents and results of this paper are as follows: Firstly, for the problems of low contrast and shallow imaging depth caused by high tissue scattering, OCAs glucose was selected to act on human normal in vitro based on TOC technology. With colon cancer tissues, OCT can monitor the whole glucose diffusion process in both tissues in real time and dynamically. The changes of OCT signal intensity, permeability coefficients (pc) and attenuation coefficients (ac) induced by glucose in the two tissues were analyzed and measured. Results. The results showed that glucose could improve the contrast, depth efficiency and practicability of OCT in normal and cancerous colon tissue imaging. Meanwhile, through qualitative and quantitative evaluation and analysis, it was found that the PC of glucose in cancerous colon tissue was 1.65 times that of normal colon tissue, and the maximum and minimum AC of light were positive respectively. 2.44 and 1.18 times of normal colon tissue. It is suggested that the ability of OCT to recognize normal and pathological tissues can be improved by calculating and comparing the differences of tissue characteristic parameters caused by OCAs in different tissues, which is of great value in broadening the application of Oct. Secondly, the osmotic rate of OCAs in tissues can be further increased. Based on the previous study, the ultrasound-assisted glucose strategy was proposed to accelerate the permeation of glucose into normal and cancerous colon tissues and to realize the real-time and dynamic monitoring of glucose permeation in tissues by Oct. The changes of glucose pc, oce, OCT signal intensity and 1/e light penetration depth caused by ultrasound were studied. The results showed that the PC of glucose in the two tissues was increased about 1.87 and 2.14 times, the OCT signal intensity was increased about 12.5% and 10.8%, and the 1/e light penetration depth was increased by ultrasound. It is proved that the ultrasound-glucose coordination strategy can be used as an effective method to promote the diffusion of OCAs and further enhance the depth of light penetration in tissues. It provides a new idea and theoretical basis for further expanding the imaging ability of Oct. Finally, in order to further understand the amplitude of oce, PAM signal and image contrast of OCAs concentration and action time. The PAM was used to monitor the changes of the bionic images of skin tissue after glycerol treatment with different concentrations. The effects of concentration on OCE, imaging quality and photoacoustic signal amplitude were evaluated and analyzed qualitatively and quantitatively. The results not only show that glycerol is effective in enhancing the imaging depth and signal intensity of PAM, but also prove that there is a close correlation between glycerol concentration and enhancing OCE and improving the imaging ability of PAM. It is found that OCE does not increase linearly with the prolongation of glycerol exposure time. The results of this study have important guiding significance for more effective use of OCAs to increase tissue OCE and improve the imaging ability of optical imaging technology. The application of TOC technology in image contrast enhancement is studied in depth, and the effectiveness of TOC technology in enhancing the imaging ability of these two technologies is evaluated qualitatively. The variation law of optical characteristic parameters of biological tissues caused by OCAs is analyzed quantitatively, and the correlation between OCE concentration and imaging depth and image contrast is discussed. The research results of this paper provide important theoretical basis and experimental reference for TOC technology to enhance the imaging ability and application scope of optical imaging technology in the field of life science and engineering science, and to improve the TOC technology theoretical evaluation system.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R318.51
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