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

【摘要】：組織光透明技術是通過向生物組織中引入高滲透、高折射、生物相容的化學試劑,以此來暫時降低光在組織中的散射、提高光在組織中的穿透深度。這為光學分子成像在活體的應用、及光子醫(yī)學診療技術在臨床中的應用帶來了新契機。其中,針對皮膚光透明的研究更成為熱點,但有關皮膚光透明的機制并不清楚,涉及定量研究很少,在體皮膚光透明機制的研究更是未見報道,這直接影響了皮膚光透明技術的發(fā)展與應用。 本文的工作正是圍繞皮膚光透明的物理機制與生理機制,從組織模型、離體皮膚以及在體皮膚等不同層次展開,主要的研究內容如下： 1)將組織模型用于研究皮膚光透明的物理機制：結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的預測方法。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,理論預測與實驗測量證實高折射率光透明劑加入會降低混合液的散射、使其變得更透明。因此,皮膚光透明的物理機制可歸結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態(tài)變化,并與積分球測量結合IAD算法所得皮膚約化散射系數(shù)進行比較。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。這說明脫水在離體皮膚光透明作用中起主導作用,但并非皮膚光透明的唯一機制。 3) HE染色、電子顯微鏡成像及二次諧波成像,觀測皮膚微結構、超微結構及膠原變化。發(fā)現(xiàn)皮膚結構并沒有明顯改變,但真皮層變��；膠原纖維直徑變細、排列更加緊密；真皮層膠原纖維未出現(xiàn)離體實驗中的解離。這說明在體皮膚光透明機制與離體存在差異,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特性的分析方法：利用蒙特卡羅模擬建立反射譜與光學參數(shù)查找表格,并結合皮膚組分與結構特點優(yōu)化查找表格；建立皮膚的光學近似模型,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特性參數(shù),包括皮膚黑色素體積分數(shù)M、血液體積分數(shù)B、血氧飽和度S、500nn波長約化散射系數(shù)和瑞利散射比例F等。并通過人體實驗評價了基于反射光譜測量提取皮膚生理參數(shù)與光學特性參數(shù)的準確性與有效性。這為定量研究在體皮膚光透明機制提供重要監(jiān)測手段。 5)動態(tài)監(jiān)測在體皮膚光透明過程,建立皮膚光透明過程中生理與光學特性的關聯(lián),揭示在體皮膚光透明機制：利用反射光譜測量對在體皮膚光透明過程進行動態(tài)監(jiān)測,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程中的變化；并利用OCT成像觀測光透明作用下大鼠皮膚光學成像深度的改善。結果表明,在體大鼠皮膚局部涂抹PEG400與噻酮混合液、并結合物理按摩,能使得皮膚表面反射光譜及約化散射系數(shù)顯著下降,皮膚血液體積分數(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反射信號減弱、深層反射信號增強,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展研究,有助于揭示皮膚光透明的物理機制與生理機制：光透明劑的高折射可提高細胞間液的折射率、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、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。
[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 .

【學位授予單位】：華中科技大學
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R318.51

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相關期刊論文 前1條

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本文編號：1765327