生物组织光透明机理
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摘要
光学相干断层成像技术(optical coherence tomography, OCT)由于它本身具备的能够无损伤的描述组织内部的皮下组织的微结构而引起了研究人员的极大兴趣。然而,对于许多光学成像技术来说,一个最主要的限制因素就是光线在混沌介质中的穿透深度太小,通常也就只有几个毫米。到目前为止,科研人员已经尝试了多种方法来试图改进光在生物组织中的穿透深度,包括采用不同的提高组织光透明方法。
为了探讨超声波[surgeon-performed (SP)]对生物组织光透明效果的影响及其可能的机理,本论文进一步研究了超声波导入法的增效作用,使用频率为1兆赫兹、能量为0.75瓦、直径为3厘米的超声波探头对豚鼠皮肤预处理15分钟,然后利用光相干断层成像术(optical coherence tomography,OCT)和扫描电子显微镜(Scanning electron microscope,SEM)对成年豚鼠腹部皮肤分别在自然状态下,60%甘油30min处理和60%甘油30min处理联合超声波15min三种不同处理下的光透明效果和豚鼠皮肤表面超微结构进行了比较研究,发现60%甘油处理组在1/e处的光穿透深度提高了8.61%,60%甘油联合超声波组的穿透深度提高了18.61%,另外通过计算斜率得到的结果也证明使用超声波后光透明有明显提高。结果表明,超声波确实大大提高了豚鼠皮肤组织的光透明效果,另外豚鼠皮肤表面的扫描电镜图片显示可能的机理在于超声波使得角质层变得疏松,角质细胞之间间隙变大,细胞易于脱落,降低了表皮角质层的屏障功能,有利于光透明剂的透皮吸收,从而提高了皮肤组织的光透明。
功能性的成像,检测和定量表述活体状态下葡萄糖在上皮和皮下基质层组织中渗透情况以及对组织的光学性质的控制对于许多生物医学的应用来说,包括无损伤或者微损伤的葡萄糖传感器和各种不同级别的诊断和治疗比如说癌症,糖尿病和青光眼,是极其重要的。我们研究了体外情况下猪眼睛巩膜组织中的葡萄糖溶液的渗透情况。由于OCT技术的在纵向深度方向上的高分辨率给我们提供了深度方向上清晰的组织图片,得到了以深度为函数的葡萄糖分子渗透曲线。
我们进一步证实了OCT技术在葡萄糖在猪眼睛巩膜组织中的不同深度的渗透的检测和定量分析。通过计算葡萄糖在巩膜中不同侧向深度处渗透速率和平均渗透速率,我们发现葡萄糖的渗透速率在不同深度的整个组织当中不是均一的,测向渗透速率从侧向渗透初始点的(3.5±0.062)×10~(-6)m/s减小到巩膜内侧面的(1.9887±0.049)×10~(-6)m/s(10%G),(3.5417±0.061)×10~(-6)m/s减小到的(1.2333±0.041)×10~(-6)m/s(20%G),(4.0833±0.075)×10~(-6)m/s减小到1510μm处的(1.1984±0.061)×10~(-6)m/s(40%G)。结果也证实了OCT技术在葡萄糖在巩膜中渗透过程中不同深度处的检测和定量测量应用的可行性。
本文也利用OCT研究了对三种不同浓度葡萄糖在巩膜组织中纵向渗透时的功能成像,非侵入性的测定了三种不同浓度的葡萄糖溶液的渗透系数。结果表明,渗透速率与分析物的浓度成反比关系:即低浓度的葡萄糖比高浓度的葡萄糖有更大的渗透速率。渗透系数从10%浓度葡萄糖的(1.596±0.051)×10~(-5) cm/s降低到40%浓度葡萄糖的(4.247±0.504)×10~(-6) cm/s。药物在生物组织中的渗透时的速率与浓度的成反比的关系在将来可能有着很好的应用前景,很有可能被应用于多种基础学科和临床领域,比如生物组织和细胞的光透明以及临床诊断学。
我们计算得到的实验结果使得我们相信OCT是一个用来研究渗透和分析物(包括药物)在组织中的扩散的很有效的工具。我们未来的研究将集中在巩膜的不同区块(建立在胶原纤维的大小,分布和定向的基础上)的分析物渗透的理论模型的建立方面。另外既然先前已经证明了水合状态在研究渗透速率的实验中起了关键作用,那么我们将来的实验将会在在体状态下进行从而消除水合的因素。
Imaging of biological tissues with optical coherence tomography (OCT) poses a great interest for its capability to noninvasively outline subsurface microstructures within tissues. However, a major limitation for many optical imaging techniques is inadequate depth penetration of light in turbid media, which is bounded to just a few millimeters. There have been several attempts to improve light penetration depth in biological tissues, including application of different tissue optical clearing methods.
Photonic technology in medical imaging, diagnosis and treatment is the current international hot spots of research. The main limiting factor is the light scattering of the biological tissue that restricts light to penetrate the depth of tissue, limiting the scope of application, reducing the optical (microscopic) imaging depth, resolution, contrast ratio and the efficiency of laser treatment.
The effect of ultrasound [surgeon-performed (SP)] on the changes in optical properties and some possible mechanism was investigated. In the paper, Clearing capability of glycerol was much improved with the simultaneous application of ultrasound with a frequency of 1 MHz and a power of 0.75W over a 3 cm probe. Adult cavy’skin of abdomen was chosen to comparatively studied by Optical coherence tomography (OCT) and scanning electronic microscope (SEM) with optical clearing agents in combination with ultrasound. The OCT results found that the 1/e light penetration depth of epidermis and dermis increases by roughly 8.61% from the native to the optically cleared state with 60% G at 30 min,The most significant effect was seen where skin was treated with the combination of 60%G and ultrasound, resulting in a 18.61% increase of optical clearing, meanwhile, the results derived from the OCT signal slope also demonstrate the similar conclusion. The results show that ultrasound enhanced the optical clearing of the cavy skin greatly. The SEM results demonstrated that ultrasound disrupts the highly ordered lipid structure of stratum corneum (SC) and makes the structure of SC loose, which causes the outermost cell of SC easy to exfoliate and decreases the barrier function of skin for the transdermal absorption of optical clearing agents (OCA),which enhances the effect of optical clearing of skin tissue.
Functional imaging, monitoring and quantitative description of glucose diffusion in epithelial and underlying stromal tissues in vivo and controlling of the optical properties of tissues are extremely important for many biomedical applications including the development of noninvasive or minimally invasive glucose sensors as well as for therapy and diagnostics of various diseases, such as cancer, diabetic retinopathy, and glaucoma. The diffusion of glucose was studied in pig sclera tissues in vitro. Because OCT provides depth-resolved imaging of tissues with high in-depth resolution, the glucose diffusion is described as a function of depth.
We demonstrate the capability of the optical coherence tomography (OCT) technique for depth-resolved monitoring and quantifying of glucose diffusion in pig sclera tissues. The depth-resolved and average permeability coefficients of glucose were calculated. We found that the glucose diffusion rate is not uniform and nonlinear throughout the tissue in the lateral depth and is decreased from approximately (3.5±0.062)×10~(-6)m/s at the start point of lateral diffusion to (1.9887±0.049)×10~(-6)m/s close to the inner side of the sclera with the topical application of 10% glycerol(10%G), from (3.5417±0.061)×10~(-6)m/s to (1.2333±0.041)×10~(-6)m/s with the topical application of 20%G, from (4.0833±0.075)×10~(-6)m/s to (1.1984±0.061)×10~(-6)m/s with the topical application of 40%G . Results demonstrated that the OCT technique is capable of depth-resolved monitoring and quantification of glucose diffusion in sclera.
In this study, optical coherence tomography(OCT) was utilized in the functional imaging of glucose axial diffusion through scleral tissues. Permeability coefficients for different concentrations of glucose were quantified nondestructively. Obtained results indicate an inverse proportionality between the permeability coefficnt and the concentration of the analyte in epithelial tissues: in-depth diffusion of solutions with lower glucose concentration was faster than those with a higher concentration. The permeability coefficient decreased from (1.596±0.051)×10~(-5) cm/s of 10% glucose solution to (4.247±0.504)×10~(-6) cm/s of 40% glucose solution. The dependence of the permeability on the concentration of hyperosmotic analytes could potentially be used in various basic sciences and clinical fields, such as optical clearing of tissues and cells as well as in clinical pharmacology.
The presented results encourage us to believe that OCT is an effective tool for studying permeability and analytes (including drug) diffusion in tissues, both in specified regions and at different tissue depths. Our future studies will be focused on development of a theoretical model of analyte diffusion in different scleral compartments (based on the size, distribution, and orientation of collagen fibrils). However, since it has been previously shown that hydration plays a key role in the study of the diffusion rate, our future experiments will be conducted in vivo to eliminate the hydration factor.
为了探讨超声波[surgeon-performed (SP)]对生物组织光透明效果的影响及其可能的机理,本论文进一步研究了超声波导入法的增效作用,使用频率为1兆赫兹、能量为0.75瓦、直径为3厘米的超声波探头对豚鼠皮肤预处理15分钟,然后利用光相干断层成像术(optical coherence tomography,OCT)和扫描电子显微镜(Scanning electron microscope,SEM)对成年豚鼠腹部皮肤分别在自然状态下,60%甘油30min处理和60%甘油30min处理联合超声波15min三种不同处理下的光透明效果和豚鼠皮肤表面超微结构进行了比较研究,发现60%甘油处理组在1/e处的光穿透深度提高了8.61%,60%甘油联合超声波组的穿透深度提高了18.61%,另外通过计算斜率得到的结果也证明使用超声波后光透明有明显提高。结果表明,超声波确实大大提高了豚鼠皮肤组织的光透明效果,另外豚鼠皮肤表面的扫描电镜图片显示可能的机理在于超声波使得角质层变得疏松,角质细胞之间间隙变大,细胞易于脱落,降低了表皮角质层的屏障功能,有利于光透明剂的透皮吸收,从而提高了皮肤组织的光透明。
功能性的成像,检测和定量表述活体状态下葡萄糖在上皮和皮下基质层组织中渗透情况以及对组织的光学性质的控制对于许多生物医学的应用来说,包括无损伤或者微损伤的葡萄糖传感器和各种不同级别的诊断和治疗比如说癌症,糖尿病和青光眼,是极其重要的。我们研究了体外情况下猪眼睛巩膜组织中的葡萄糖溶液的渗透情况。由于OCT技术的在纵向深度方向上的高分辨率给我们提供了深度方向上清晰的组织图片,得到了以深度为函数的葡萄糖分子渗透曲线。
我们进一步证实了OCT技术在葡萄糖在猪眼睛巩膜组织中的不同深度的渗透的检测和定量分析。通过计算葡萄糖在巩膜中不同侧向深度处渗透速率和平均渗透速率,我们发现葡萄糖的渗透速率在不同深度的整个组织当中不是均一的,测向渗透速率从侧向渗透初始点的(3.5±0.062)×10~(-6)m/s减小到巩膜内侧面的(1.9887±0.049)×10~(-6)m/s(10%G),(3.5417±0.061)×10~(-6)m/s减小到的(1.2333±0.041)×10~(-6)m/s(20%G),(4.0833±0.075)×10~(-6)m/s减小到1510μm处的(1.1984±0.061)×10~(-6)m/s(40%G)。结果也证实了OCT技术在葡萄糖在巩膜中渗透过程中不同深度处的检测和定量测量应用的可行性。
本文也利用OCT研究了对三种不同浓度葡萄糖在巩膜组织中纵向渗透时的功能成像,非侵入性的测定了三种不同浓度的葡萄糖溶液的渗透系数。结果表明,渗透速率与分析物的浓度成反比关系:即低浓度的葡萄糖比高浓度的葡萄糖有更大的渗透速率。渗透系数从10%浓度葡萄糖的(1.596±0.051)×10~(-5) cm/s降低到40%浓度葡萄糖的(4.247±0.504)×10~(-6) cm/s。药物在生物组织中的渗透时的速率与浓度的成反比的关系在将来可能有着很好的应用前景,很有可能被应用于多种基础学科和临床领域,比如生物组织和细胞的光透明以及临床诊断学。
我们计算得到的实验结果使得我们相信OCT是一个用来研究渗透和分析物(包括药物)在组织中的扩散的很有效的工具。我们未来的研究将集中在巩膜的不同区块(建立在胶原纤维的大小,分布和定向的基础上)的分析物渗透的理论模型的建立方面。另外既然先前已经证明了水合状态在研究渗透速率的实验中起了关键作用,那么我们将来的实验将会在在体状态下进行从而消除水合的因素。
Imaging of biological tissues with optical coherence tomography (OCT) poses a great interest for its capability to noninvasively outline subsurface microstructures within tissues. However, a major limitation for many optical imaging techniques is inadequate depth penetration of light in turbid media, which is bounded to just a few millimeters. There have been several attempts to improve light penetration depth in biological tissues, including application of different tissue optical clearing methods.
Photonic technology in medical imaging, diagnosis and treatment is the current international hot spots of research. The main limiting factor is the light scattering of the biological tissue that restricts light to penetrate the depth of tissue, limiting the scope of application, reducing the optical (microscopic) imaging depth, resolution, contrast ratio and the efficiency of laser treatment.
The effect of ultrasound [surgeon-performed (SP)] on the changes in optical properties and some possible mechanism was investigated. In the paper, Clearing capability of glycerol was much improved with the simultaneous application of ultrasound with a frequency of 1 MHz and a power of 0.75W over a 3 cm probe. Adult cavy’skin of abdomen was chosen to comparatively studied by Optical coherence tomography (OCT) and scanning electronic microscope (SEM) with optical clearing agents in combination with ultrasound. The OCT results found that the 1/e light penetration depth of epidermis and dermis increases by roughly 8.61% from the native to the optically cleared state with 60% G at 30 min,The most significant effect was seen where skin was treated with the combination of 60%G and ultrasound, resulting in a 18.61% increase of optical clearing, meanwhile, the results derived from the OCT signal slope also demonstrate the similar conclusion. The results show that ultrasound enhanced the optical clearing of the cavy skin greatly. The SEM results demonstrated that ultrasound disrupts the highly ordered lipid structure of stratum corneum (SC) and makes the structure of SC loose, which causes the outermost cell of SC easy to exfoliate and decreases the barrier function of skin for the transdermal absorption of optical clearing agents (OCA),which enhances the effect of optical clearing of skin tissue.
Functional imaging, monitoring and quantitative description of glucose diffusion in epithelial and underlying stromal tissues in vivo and controlling of the optical properties of tissues are extremely important for many biomedical applications including the development of noninvasive or minimally invasive glucose sensors as well as for therapy and diagnostics of various diseases, such as cancer, diabetic retinopathy, and glaucoma. The diffusion of glucose was studied in pig sclera tissues in vitro. Because OCT provides depth-resolved imaging of tissues with high in-depth resolution, the glucose diffusion is described as a function of depth.
We demonstrate the capability of the optical coherence tomography (OCT) technique for depth-resolved monitoring and quantifying of glucose diffusion in pig sclera tissues. The depth-resolved and average permeability coefficients of glucose were calculated. We found that the glucose diffusion rate is not uniform and nonlinear throughout the tissue in the lateral depth and is decreased from approximately (3.5±0.062)×10~(-6)m/s at the start point of lateral diffusion to (1.9887±0.049)×10~(-6)m/s close to the inner side of the sclera with the topical application of 10% glycerol(10%G), from (3.5417±0.061)×10~(-6)m/s to (1.2333±0.041)×10~(-6)m/s with the topical application of 20%G, from (4.0833±0.075)×10~(-6)m/s to (1.1984±0.061)×10~(-6)m/s with the topical application of 40%G . Results demonstrated that the OCT technique is capable of depth-resolved monitoring and quantification of glucose diffusion in sclera.
In this study, optical coherence tomography(OCT) was utilized in the functional imaging of glucose axial diffusion through scleral tissues. Permeability coefficients for different concentrations of glucose were quantified nondestructively. Obtained results indicate an inverse proportionality between the permeability coefficnt and the concentration of the analyte in epithelial tissues: in-depth diffusion of solutions with lower glucose concentration was faster than those with a higher concentration. The permeability coefficient decreased from (1.596±0.051)×10~(-5) cm/s of 10% glucose solution to (4.247±0.504)×10~(-6) cm/s of 40% glucose solution. The dependence of the permeability on the concentration of hyperosmotic analytes could potentially be used in various basic sciences and clinical fields, such as optical clearing of tissues and cells as well as in clinical pharmacology.
The presented results encourage us to believe that OCT is an effective tool for studying permeability and analytes (including drug) diffusion in tissues, both in specified regions and at different tissue depths. Our future studies will be focused on development of a theoretical model of analyte diffusion in different scleral compartments (based on the size, distribution, and orientation of collagen fibrils). However, since it has been previously shown that hydration plays a key role in the study of the diffusion rate, our future experiments will be conducted in vivo to eliminate the hydration factor.
引文
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