皮肤光透明的物理机制与生理机制研究

发布时间：2018-04-17 21:21

本文选题：组织光透明技术 + 光透明剂　；参考：《华中科技大学》2012年博士论文

【摘要】：组织光透明技术是通过向生物组织中引入高渗透、高折射、生物相容的化学试剂,以此来暂时降低光在组织中的散射、提高光在组织中的穿透深度。这为光学分子成像在活体的应用、及光子医学诊疗技术在临床中的应用带来了新契机。其中,针对皮肤光透明的研究更成为热点,但有关皮肤光透明的机制并不清楚,涉及定量研究很少,在体皮肤光透明机制的研究更是未见报道,这直接影响了皮肤光透明技术的发展与应用。本文的工作正是围绕皮肤光透明的物理机制与生理机制,从组织模型、离体皮肤以及在体皮肤等不同层次展开,主要的研究内容如下： 1)将组织模型用于研究皮肤光透明的物理机制：结合电镜所得到脂肪乳溶液中散射微粒的粒径分布,根据米氏散射理论建立组织模型散射性质的预测方法。将脂肪乳溶液分别与六种光透明剂混合,均能获得不同程度的光透明效果。其中,PEG200、PEG400作用会使脂肪乳溶液微粒出现聚集、变得不再均匀；其余四种光透明剂加入后能保持组织模型的均匀性,理论预测与实验测量证实高折射率光透明剂加入会降低混合液的散射、使其变得更透明。因此,皮肤光透明的物理机制可归结于背景折射率的提高或者散射微粒尺度的变化。 2)建立基于偏最小二乘法的脱水模型,使其能根据近红外反射谱定量提取皮肤含水量,为皮肤光透明的脱水机制研究提供新方法。研究了六种光透明剂分别作用于离体皮肤后所致含水量的动态变化,并与积分球测量结合IAD算法所得皮肤约化散射系数进行比较。发现光透明剂作用均能使皮肤含水量和约化散射系数降低,两者相关性极高；但甘油与山梨醇等多元醇所引起的皮肤约化散射系数变化明显于高于含水量的变化。这说明脱水在离体皮肤光透明作用中起主导作用,但并非皮肤光透明的唯一机制。 3) HE染色、电子显微镜成像及二次谐波成像,观测皮肤微结构、超微结构及胶原变化。发现皮肤结构并没有明显改变,但真皮层变薄；胶原纤维直径变细、排列更加紧密；真皮层胶原纤维未出现离体实验中的解离。这说明在体皮肤光透明机制与离体存在差异,离体的研究并不完全适合于在体情形。 4)建立基于反射谱提取皮肤生理与光学特性的分析方法：利用蒙特卡罗模拟建立反射谱与光学参数查找表格,并结合皮肤组分与结构特点优化查找表格；建立皮肤的光学近似模型,采用最小二乘法拟合从皮肤漫反射光谱中获得皮肤生理与光学特性参数,包括皮肤黑色素体积分数M、血液体积分数B、血氧饱和度S、500nn波长约化散射系数和瑞利散射比例F等。并通过人体实验评价了基于反射光谱测量提取皮肤生理参数与光学特性参数的准确性与有效性。这为定量研究在体皮肤光透明机制提供重要监测手段。 5)动态监测在体皮肤光透明过程,建立皮肤光透明过程中生理与光学特性的关联,揭示在体皮肤光透明机制：利用反射光谱测量对在体皮肤光透明过程进行动态监测,定量获取皮肤约化散射系数、血液浓度和血氧饱和度在光透明过程中的变化；并利用OCT成像观测光透明作用下大鼠皮肤光学成像深度的改善。结果表明,在体大鼠皮肤局部涂抹PEG400与噻酮混合液、并结合物理按摩,能使得皮肤表面反射光谱及约化散射系数显著下降,皮肤血液体积分数显著上升,皮肤血氧饱和度基本不变；约化散射系数的降低使得大鼠皮肤浅层OCT反射信号减弱、深层反射信号增强,OCT成像深度增加。以上从组织模型、离体皮肤与在体皮肤等多层次开展研究,有助于揭示皮肤光透明的物理机制与生理机制：光透明剂的高折射可提高细胞间液的折射率、使皮肤各成分的折射率匹配；其高渗透性可导致皮肤脱水、散射微粒尺度改变；部分试剂可能与皮肤发生某种可逆反应、而改变散射微粒的尺寸。这为发展高效、安全的皮肤光透明方法提供重要理论基础。
[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 .

【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R318.51

【参考文献】