利用近红外光激发的光声血管造影成像

利用近红外光结合对应波长的光吸收增强对照剂来实现在体小鼠脑皮层血管的光声成像.近红外光在生物组织上有较深的穿透能力;而作为光吸收增强剂的外源染料吲哚菁绿注射到血液系统后则增加了血管对光的选择性吸收,从而增强了血管光声信号的强度.实验在不破坏脑头皮和头盖骨的前提下,通过静脉注射吲哚菁绿,获得小鼠脑皮层血管的光声造影成像.光声重建的血管网络与小鼠脑部解剖照片相当符合.实验结果证明近红外光结合光吸收增强剂的光声血管造影技术对于开展光声脑功能成像,光声分子成像提供了潜在的可行性. 关键词： 光声成像 光吸收增强剂 血管造影 光声信号     

光学CT图象重建的数值模拟研究─Kosenbrock坐标轮换法

时间分辨光学 ＣＴ技术因其对生物组织体的无损性，在生物成象领域引起了广泛的兴趣和研究，已提出许多方案，意在克服由于生物组织体中的多光散射效应所造成的成象障碍．本文简述了基于扩散方程近似的光学ＣＴ正向问题有限元解法，提出采用直接搜索优化算法一Ｒｏｓｅｎｂｒｏｃｋ坐标轮换法求解时间分辨光学 ＣＴ中的图象重建问题，给出了基于积分光强和光子平均飞行时间及其加权组合的二维图象重建问题的数值模拟结果，证实了该方法的可行性．     

光学CT图象重建的数值模拟研究─Kosenbrock坐标轮换法

时间分辨光学CT技术因其对生物组织体的无损性,在生物成象领域引起了广泛的兴趣和研究,已提出许多方案,意在克服由于生物组织体中的多光散射效应所造成的成象障碍.本文简述了基于扩散方程近似的光学CT正向问题有限元解法,提出采用直接搜索优化算法-Rosenbrock坐标轮换法求解时间分辨光学CT中的图象重建问题,给出了基于积分光强和光子平均飞行时间及其加权组合的二维图象重建问题的数值模拟结果,证实了该方法的可行性.     

生物组织单光程光谱技术的理论研究

高灵敏度光谱检测技术在临床诊疗和组织光学参数测量中具有极其重要的意义。文章提出了一种差分调制激光光谱技术,将经过生物组织后的散射光与参考光的光程差转换为光谱信号的频率特征,通过相敏检测技术将不同频率的信号进行分离,从而实现生物组织散射光的光程分离。文章分析了差分调制激光光谱的机理及信号的谱特征,并基于文献中的生物组织散射光的光程分布,从理论上讨论了差拍信号的谱特征,即光源调制速率一定时,光谱信号中的主频成分位置只与散射光和参考光的光程差有关;生物组织对光信号的衰减系数会影响光谱信号中频率成分的能量强度分布。分析结果表明,差分调制激光光谱能对生物组织的光谱信号进行光程分离,从而实现生物组织的单光程光谱检测。     

Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography

Polarization-sensitive optical coherence tomography (PS-OCT) was used to characterize completely the polarization state of light backscattered from turbid media. Using a low-coherence light source, one can determine the Stokes parameters of backscattered light as a function of optical path in turbid media. To demonstrate the application of this technique we determined the birefringence and the optical axis in fibrous tissue (rodent muscle) and in vivo rodent skin. PS-OCT has potentially useful applications in biomedical optics by imaging simultaneously the structural properties of turbid biological materials and their effects on the polarization state of backscattered light. This method may also find applications in material science for investigation of polarization properties (e.g., birefringence) in opaque media such as ceramics and crystals.     

离散坐标法在计算生物组织内光场空间角分布中的应用

从辐射传输理论出发,研究了准直光照下层状生物组织内漫射光场的角分布.在辐射传输方程的基础上,采用离散坐标法得到了描述层状生物组织内漫射光传输问题的微分方程组形式,并用特征值-特征矢量方法对其进行了求解,给出了通解形式.结合边界条件对两类典型生物组织内漫射光场角分布进行了数值计算-各向同性组织和前向散射组织,给出了组织内不同深度处漫射光场空间角分布曲线.通过对计算结果比较分析,得到了生物组织内漫射光场空间角分布随深度的变化规律,及边界效应和光学参量对组织内漫射光场空间角分布的影响.     

Estimate of the Contribution of Localized Light Absorption by Blood Vessels to the Optical Properties of Biological tissue

A simple analytical procedure of considering localized light absorption by blood vessels and its effect on the absorption characteristics of multicomponent biological tissue is proposed. The final results are presented in the form of a single integral of elementary functions. A comparison of the estimates obtained with data in the literature shows their good agreement. The limiting cases of random and ordered arrangement of vessels are considered. It was shown that, in the blue spectral range, the absorption coefficient of biological tissues can reach saturation when it ceases to be dependent on the optical characteristics of blood and is determined only by the diameter of vessels and their volume concentration. The depth of light penetration into tissue and the reflection coefficient of tissue are estimated for both a localized and a homogeneously distributed absorber. Possible biomedical applications of the results obtained are illustrated.     

Time-reversed ultrasonically encoded optical focusing into scattering media

Light focusing plays a central role in biomedical imaging, manipulation, and therapy. In scattering media, direct light focusing becomes infeasible beyond one transport mean free path. All previous methods1-3 to overcome this diffusion limit lack a practical internal "guide star."4 Here we proposed and experimentally validated a novel concept, called Time-Reversed Ultrasonically Encoded (TRUE) optical focusing, to deliver light into any dynamically defined location inside a scattering medium. First, diffused coherent light is encoded by a focused ultrasonic wave to provide a virtual internal "guide star"; then, only the encoded light is time-reversed and transmitted back to the ultrasonic focus. The TRUE optical focus-defined by the ultrasonic wave-is unaffected by multiple scattering of light. Such focusing is especially desirable in biological tissue where ultrasonic scattering is ~1000 times weaker than optical scattering. Various fields including biomedical and colloidal optics can benefit from TRUE optical focusing.     

视细胞浓度分布对散射光偏振性的影响

人眼视网膜是一种具有高散射特性的生物组织。基于米氏散射理论研究光在视网膜组织中的传输过程对生物组织散射成像具有重要意义。根据解剖学上视网膜结构与细胞分布的特点,引入分子动力学领域的静态结构因子修正辐射传递理论,并采用离散坐标法求解视细胞对散射光偏振性的影响。结果表明散射光偏振性取决于视细胞尺寸与浓度分布等因素。在不同的极角和光程位置,散射光束的偏振性呈现波动性变化,视锥细胞核比视杆细胞核具有更强的散射特性,散射光束的偏振特性变化随散射角的增大而增大。     

Recent advances in wavefront shaping techniques for biomedical applications

Due to the highly inhomogeneous distributions of refractive indexes, light propagation in complex media such as biological tissue experiences multiple light scattering events. The suppression and control of multiple light scattering events are investigated because they offer the possibility of optical focusing and imaging through biological tissues, and they may open new avenues for diagnosis and treatment of several human diseases. In order to provide insight into how new optical techniques can address the issues of multiple light scattering in biomedical applications, the recent progress in optical wavefront-shaping techniques is summarized.     

High-resolution ultrasound-modulated optical tomography in biological tissues

We present a novel implementation of high-resolution ultrasound-modulated optical tomography that, based on optical contrast, can image several millimeters deep into soft biological tissues. A long-cavity confocal Fabry-Perot interferometer, which provides a large etendue and a short response time, was used to detect the ultrasound-modulated coherent light that traversed the scattering biological tissue. Using 15-MHz ultrasound, we imaged with high-contrast light-absorbing structures placed >3 mm below the surface of chicken breast tissue. The resolution along the axial and the lateral directions with respect to the ultrasound propagation direction was better than 70 and 120 microm, respectively. The resolution can be scaled down further by use of higher ultrasound frequencies. This technology is complementary to other imaging technologies, such as confocal microscopy and optical-coherence tomography, and has the potential for broad biomedical applications.     

生物组织光学特性参数的无创检测理论与技术

无创定量确定生物组织的光学特性在医学诊断和治疗领域中有着很重要的意义和广泛的应用前景。作为生物组织光学特性参数无创检测技术的理论基础 ,首先简要介绍了描述散射介质中光传播及分布的漫散射理论及蒙特卡罗模拟算法 ;然后分别介绍了用漫散射理论和蒙特卡罗模拟算法无创定量确定生物组织光学特性参数的具体方法 ;最后总结了到目前为止无创定量确定生物组织光学特性参数的研究成果 ,并对今后的工作作了展望     

Light transport in laser irradiated turbid media, application in medicine and image processing

Much effort is being made in the study of light propagation in human tissue due to the development and wide use of lasers for surgical and therapeutic applications. When a picosecond light pulse is incident on biological tissue, part of the light is reflected back owing to specular surface reflection and the rest of the light penetrates the tissue and encounters multiple scattering and absorption processes. An analysis has been presented for modeling of light distribution in human tissue. The influence of the refractive index, scattering phase function and scattering albedo on light distribution in laser irradiated tissue has been demonstrated.     

生物组织多光谱偏振特性研究

生物组织内部结构复杂且具有较强的散射特性,而光作为生物组织检测的重要信息载体,其自身特性包括颜色、幅值、偏振等都对信息获取有较大的影响.结合偏振成像,对生物组织多光谱偏振特性展开了研究,依据不同微粒尺寸的分布建立了均匀单层生物组织模型,结合瑞利和米氏散射理论模拟了基于单个微粒的两种散射事件.瑞利散射具有较好的前向后向散...     

圆柱坐标系下生物组织中激光传输的七流模拟

提出了圆柱坐标系下生物组织中激光传输的七流模型,根据此模型进行的计算结果与直角坐标系下七流模型的计算结果比较,二者吻合较好.在此基础上,研究了组织光学性质对激光在组织内传输过程的影响,结果表明:散射效应使入射激光分布到更大的组织范围内,并使激光的穿透率降低,但其影响是有限的,即当散射系数增大到一定程度后,组织内的激光能量分布就不再有明显的变化.相对而言,吸收系数对组织内激光能量分布的影响比散射系数要大,各向异性系数增大使组织内的散射趋于前向散射,激光能量分布也更深入组织内部.     

Monte Carlo Simulations of Reflected Spectra Derived from Tissue Phantom with Double-Peak Particle Size Distribution

We made a tissue phantom with double-peak particle size distribution, which has polystyrene particles of cell nuclear size and mitochondrial size, and measured the spectrum from the tissue phantom using a single optical fiber. In this paper we investigate the characterization method for the tissue phantom with double-peak particle size distribution by comparing the measured spectra with the calculated ones using the Monte Carlo (MC) method. It is first shown that the Mie phase function characterizes better than the Henyey-Greenstein (H-G) phase function in MC calculation. Next, we compare the measurement spectra with those obtained by modeling as single-peak, conventional modeling for particle size distribution, and for double-peak particle size distribution. The single-peak modeling is found to cause considerable error for the tissue phantom with double-peak particle size distribution, which seems to simulate a biological tissue. We suggest that if one simulates the particle size distribution of a biological tissue by conventional modeling, the accuracy of estimation will be lower.     

光交联技术的生物应用研究进展

光交联反应作为一种快速、简单和时空可控的交联工具广泛地应用于化学、生物、医学和材料等不同研究领域。本文详细介绍了常用的小分子光交联基团的结构、分类及反应机理,重点综述了光交联技术在生物医学领域的应用研究,并对其应用前景进行了展望。目前大多光交联基团仅对紫外和可见光具有敏感性,紫外和可见光穿透力弱、组织吸收强和散射等问题严重限制了该技术在生物体内的应用研究。因此,进一步研究光交联技术在生物体系的应用和开发长波长光(如近红外或远红外光)介导的新交联技术对于药物研发和疾病诊疗具有重要的科学意义。     

Spatial Localization of Biosensor Fluorescence Signals in Human Skin under the Effect of Eequalization of the Refractive Index of the Surrounding Medium

A priority line of biomedical applications of optics is the development of noninvasive diagnostic methods based on the scanning of fluorescence radiation of biosensors embedded in biological tissue. Their main advantage is a high sensitivity and selectivity with respect to given parameters of tissues and their variations. In this study, we present a method for and results of modeling of excitation and propagation of fluorescence radiation in a multilayer randomly inhomogeneous highly scattering and absorbing medium imitating human skin. The model takes into account the spatially inhomogeneous distribution of skin fluorophores and their photophysical characteristics. Both the spatial distribution of fluorescence of skin tissues and the possibility of localization of a detected fluorescence signal are studied. The spatial distribution of fluorescence centers (fluorophores) in the medium is assumed to closely follow the spatial distribution of collagen fibers of the skin. The equalization of the refractive indices at the air-skin interface is shown to lead to a higher degree of localization of the fluorescence signal detected from a biosensor located in a near-surface skin layer.     

A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors

The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy.     

Theoretical and experimental study of the intensity distribution in biological tissues

Based on the diffusion approximate theory （DA）, a theoretical model about the distribution of the intensity of a narrow collimation beam illuminating on a semi-lnfinite biological tissue is developed. In order to verify the correctness of the model, a novel method of measuring the distributions of the intensity of light in Intralipid-10% suspension at 650 nm is presented and ts of the distributions of the distance-dependent intensity of scattering light in different directions are made. The investigations show that the results from our diffusion model are in good agreement with the experimental results beyond and in the areas around the light source, and the distance-dependent intensity in the incident direction attenuates approximately in the exponential form. Furthermore, our theoretic results indicate the anisotropic characteristics of the intensity in different directions of scattering light inside the biological tissue.