本文選題：組織光透明技術(shù) + 光透明劑��； 參考：《華中科技大學(xué)》2012年博士論文

【摘要】：組織光透明技術(shù)是通過(guò)向生物組織中引入高滲透、高折射、生物相容的化學(xué)試劑,以此來(lái)暫時(shí)降低光在組織中的散射、提高光在組織中的穿透深度。這為光學(xué)分子成像在活體的應(yīng)用、及光子醫(yī)學(xué)診療技術(shù)在臨床中的應(yīng)用帶來(lái)了新契機(jī)。其中,針對(duì)皮膚光透明的研究更成為熱點(diǎn),但有關(guān)皮膚光透明的機(jī)制并不清楚,涉及定量研究很少,在體皮膚光透明機(jī)制的研究更是未見(jiàn)報(bào)道,這直接影響了皮膚光透明技術(shù)的發(fā)展與應(yīng)用。 本文的工作正是圍繞皮膚光透明的物理機(jī)制與生理機(jī)制,從組織模型、離體皮膚以及在體皮膚等不同層次展開(kāi),主要的研究?jī)?nèi)容如下： 1)將組織模型用于研究皮膚光透明的物理機(jī)制：結(jié)合電鏡所得到脂肪乳溶液中散射微粒的粒徑分布,根據(jù)米氏散射理論建立組織模型散射性質(zhì)的預(yù)測(cè)方法。將脂肪乳溶液分別與六種光透明劑混合,均能獲得不同程度的光透明效果。其中,PEG200、PEG400作用會(huì)使脂肪乳溶液微粒出現(xiàn)聚集、變得不再均勻；其余四種光透明劑加入后能保持組織模型的均勻性,理論預(yù)測(cè)與實(shí)驗(yàn)測(cè)量證實(shí)高折射率光透明劑加入會(huì)降低混合液的散射、使其變得更透明。因此,皮膚光透明的物理機(jī)制可歸結(jié)于背景折射率的提高或者散射微粒尺度的變化。 2)建立基于偏最小二乘法的脫水模型,使其能根據(jù)近紅外反射譜定量提取皮膚含水量,為皮膚光透明的脫水機(jī)制研究提供新方法。研究了六種光透明劑分別作用于離體皮膚后所致含水量的動(dòng)態(tài)變化,并與積分球測(cè)量結(jié)合IAD算法所得皮膚約化散射系數(shù)進(jìn)行比較。發(fā)現(xiàn)光透明劑作用均能使皮膚含水量和約化散射系數(shù)降低,兩者相關(guān)性極高；但甘油與山梨醇等多元醇所引起的皮膚約化散射系數(shù)變化明顯于高于含水量的變化。這說(shuō)明脫水在離體皮膚光透明作用中起主導(dǎo)作用,但并非皮膚光透明的唯一機(jī)制。 3) HE染色、電子顯微鏡成像及二次諧波成像,觀測(cè)皮膚微結(jié)構(gòu)、超微結(jié)構(gòu)及膠原變化。發(fā)現(xiàn)皮膚結(jié)構(gòu)并沒(méi)有明顯改變,但真皮層變��；膠原纖維直徑變細(xì)、排列更加緊密；真皮層膠原纖維未出現(xiàn)離體實(shí)驗(yàn)中的解離。這說(shuō)明在體皮膚光透明機(jī)制與離體存在差異,離體的研究并不完全適合于在體情形。 4)建立基于反射譜提取皮膚生理與光學(xué)特性的分析方法：利用蒙特卡羅模擬建立反射譜與光學(xué)參數(shù)查找表格,并結(jié)合皮膚組分與結(jié)構(gòu)特點(diǎn)優(yōu)化查找表格；建立皮膚的光學(xué)近似模型,采用最小二乘法擬合從皮膚漫反射光譜中獲得皮膚生理與光學(xué)特性參數(shù),包括皮膚黑色素體積分?jǐn)?shù)M、血液體積分?jǐn)?shù)B、血氧飽和度S、500nn波長(zhǎng)約化散射系數(shù)和瑞利散射比例F等。并通過(guò)人體實(shí)驗(yàn)評(píng)價(jià)了基于反射光譜測(cè)量提取皮膚生理參數(shù)與光學(xué)特性參數(shù)的準(zhǔn)確性與有效性。這為定量研究在體皮膚光透明機(jī)制提供重要監(jiān)測(cè)手段。 5)動(dòng)態(tài)監(jiān)測(cè)在體皮膚光透明過(guò)程,建立皮膚光透明過(guò)程中生理與光學(xué)特性的關(guān)聯(lián),揭示在體皮膚光透明機(jī)制：利用反射光譜測(cè)量對(duì)在體皮膚光透明過(guò)程進(jìn)行動(dòng)態(tài)監(jiān)測(cè),定量獲取皮膚約化散射系數(shù)、血液濃度和血氧飽和度在光透明過(guò)程中的變化；并利用OCT成像觀測(cè)光透明作用下大鼠皮膚光學(xué)成像深度的改善。結(jié)果表明,在體大鼠皮膚局部涂抹PEG400與噻酮混合液、并結(jié)合物理按摩,能使得皮膚表面反射光譜及約化散射系數(shù)顯著下降,皮膚血液體積分?jǐn)?shù)顯著上升,皮膚血氧飽和度基本不變；約化散射系數(shù)的降低使得大鼠皮膚淺層OCT反射信號(hào)減弱、深層反射信號(hào)增強(qiáng),OCT成像深度增加。 以上從組織模型、離體皮膚與在體皮膚等多層次開(kāi)展研究,有助于揭示皮膚光透明的物理機(jī)制與生理機(jī)制：光透明劑的高折射可提高細(xì)胞間液的折射率、使皮膚各成分的折射率匹配；其高滲透性可導(dǎo)致皮膚脫水、散射微粒尺度改變；部分試劑可能與皮膚發(fā)生某種可逆反應(yīng)、而改變散射微粒的尺寸。這為發(fā)展高效、安全的皮膚光透明方法提供重要理論基礎(chǔ)。
[Abstract]:In this paper , the application of the optical molecular imaging in the living body and the application of the photon medical diagnosis and treatment technology in clinic have brought a new opportunity for the application of optical molecular imaging in the living body and the application of the photon medicine diagnosis and treatment technology in clinic .

The work of this paper is based on the physical mechanism and physiological mechanism of light transparency of skin , from the different levels of tissue model , ex vivo skin and body skin , the main research contents are as follows :

1 ) The tissue model is used to study the physical mechanism of skin light transparency : the particle size distribution of the scattering particles in the fat emulsion solution is obtained by combining the electron microscope , and the prediction method of the scattering property of the tissue model is established according to the Mi ' s scattering theory , and different degrees of light transparency can be obtained by mixing the fat emulsion solution with the six kinds of optical transparency agents , wherein the PEG200 and PEG400 function to cause the particles of the fat emulsion solution to accumulate and become more uniform ;
Therefore , the physical mechanism of skin light transparency can be attributed to the improvement of the background refractive index or the change of scattering particle size .

2 ) A dehydration model based on partial least square method is established to quantitatively extract the moisture content of skin according to the near infrared reflectance spectrum , which provides a new method for the research on the dehydration mechanism of skin light transparency .
However , the change of skin - induced scattering coefficient caused by polyhydric alcohol such as glycerol and sorbitol is obviously higher than that of water content , which indicates that dehydration plays a leading role in the light - transparent action of the isolated skin , but is not the only mechanism for the transparency of skin light .

3 ) HE staining , electron microscope imaging and second harmonic imaging were used to observe the microstructure , ultrastructure and collagen change of skin .
the diameter of the collagen fibers is thinner and the arrangement is more compact ;
The dissociation of collagen fibers in the dermis of dermis was not observed . This suggests that there is a difference between the mechanism of optical transparency and the ex vivo , and the ex vivo study is not completely suitable for the case .

4 ) establishing an analysis method for extracting skin physiology and optical characteristics based on a reflection spectrum , establishing a reflection spectrum and an optical parameter lookup table by using Monte Carlo simulation , and optimizing a lookup table in combination with the characteristics of the skin component and the structure ;
An optical approximation model of skin was established . The parameters of skin physiology and optical properties were obtained from the diffuse reflectance spectra of skin by using least square method . The accuracy and validity of the parameters of skin physiology and optical properties were evaluated by human body experiments .

5 ) dynamically monitoring the optical transparency process of the body , establishing the relation between the physiological and optical characteristics in the transparent process of the skin , and disclosing the optical transparency mechanism of the body : performing dynamic monitoring on the transparent process of the skin of the body by utilizing the reflection spectrum measurement , and quantitatively acquiring the change of the skin reduction scattering coefficient , the blood concentration and the blood oxygen saturation in the light transparent process ;
The results showed that the surface reflection spectrum and the scattering coefficient of skin were significantly decreased , the volume fraction of skin blood increased significantly , and the oxygen saturation of the skin remained unchanged .
The reduction of the reduced scattering coefficient resulted in a decrease in the OCT reflex signal in the superficial OCT of the rat skin , enhanced deep reflection signal , and an increase in OCT imaging depth .

It is helpful to reveal the physical mechanism and physiological mechanism of light transparency of skin , which can improve the refractive index of intercellular fluid and match the refractive index of each component of skin .
Its high permeability can cause skin dehydration , scattering particle scale change ;
Some of the reagents may react with the skin to change the size of the scattering particles . This provides an important theoretical basis for developing an efficient and safe method of skin phototransparency .

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.51

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 熊麗曾;新型促滲劑噻酮[J];精細(xì)與專用化學(xué)品;2004年21期

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本文編號(hào)：1765327