Mueller矩阵在生物医学检测方面应用的实验研究

Mueller矩阵是公认的能很好地表述介质偏振特性的一种方法,由于散射光偏振在生物组织无创伤诊断技术等诸多领域中的重要应用价值,对组织散射特性的Mueller矩阵的研究成为国际上组织光学的热点之一。研究设计了一种新的测量Mueller矩阵的实验装置:斜入射正接收装置,并推导出一组后续数据处理的算法。由此所获得的Mueller矩阵空间分布图的清晰度不亚于其它所报道的,并且测量方法具有结构简单、方便、准确等优点。实验结果表明:入射角影响Mueller矩阵空间分布图;随着介质浓度的增大,随机介质后向散射Mueller矩阵各元素的空间分布图样减小;同时列举了真实生物组织样品(肌肉组织)的后向散射Mueller矩阵的实测结果,由此证明各向异性生物组织的后向散射Mueller矩阵各元素的空间分布图样与纤维的走向有关。     

偏振光成像技术用于肿瘤病变检测的研究进展

偏振光成像是一种非标记、无损伤检测技术,它与现有非偏振光学方法硬件兼容,但能提供更丰富的样品结构和光学信息,并且对亚波长微观结构变化十分敏感.最近,偏振光成像方法在生物医学,特别是肿瘤癌症检测领域显示出很好的应用前景.本文介绍了常用的偏振光散射成像方法,包括偏振差、偏振度、旋转线偏振成像、偏振显微、穆勒矩阵成像等,并展示这些偏振方法在生物医学领域,特别是癌症检测方面的最新研究进展.目前偏振差、偏振度等成像方法已被初步用于皮肤癌的诊断,而穆勒矩阵包含更为丰富的组织微观结构信息,因而具有更好的诊断应用前景.通过对穆勒矩阵进行分解、变换等处理,可获得具有明确物理意义的成像参数,并发展为针对不同应用的特异性方法.目前,随着新型光源、偏振器件和探测器的出现,特别是数据计算处理能力的急剧提升,偏振成像在数据解释和测量方法方面的研究快速发展,已经在生物医学领域显示出很好的应用前景.     

生物组织光学特性的测量方法及医学应用

对生物组织光学特性参数的测量方法及其在医学上的应用进行了全面论述,分析了测量误差的来源,结果表明测量结果的客观性取决于模型假设（如散射的各向同性或异性、边界的匹配与否等）、测量技术、实验装置、定标方法和介质非均匀性等。测量方法可用于诊断生物组织的生理病理状态和测量组织结构     

光通过散射介质聚焦的空间位相逐个单元调节方法

本研究在分析现有散射介质聚焦方法的基础上,提出一种利用单元裂解进行波前位相调制,将经过强散射介质的散射光聚焦的快速收敛方法.文中详细地描述了这一新方法的原理,并同现有逐个单元调节方法进行运行对比.单元裂解方法的物理本质,即为实现空间光调制器的调制各单元光波之间同位相干涉.本方法具有更高的信噪比,并且聚焦收敛的速度快.这一新方法为进一步开展生物成像的光学理论研究提供了新思路.     

内陆湖泊主要藻种散射特性

通过室内培养4种主要淡水藻种--铜绿微囊藻(Microcystis aeruginosa)、普通小球藻(Chlorella vulgaris)、梅尼小环藻(Cyclotella meneghiniana)以及卵形隐藻(Cryptomonas ovata), 测定其散射和后向散射特征参数、用单位叶绿素a浓度的散射值和后向散射值来表征4种藻的散射和后向散射能力。结果表明, 铜绿微囊藻散射和后向散射能力最强, 其次为梅尼小环藻, 普通小球藻的能力最弱。通过计算后向散射概率, 显示铜绿微囊藻和梅尼小环藻的后向散射概率值较高, 普通小球藻和卵形隐藻的后向散射概率值较低。后向散射特性影响因子分析显示, 影响后向散射值的主要因素有叶绿素a浓度及藻蓝蛋白色素比例。当叶绿素a浓度不断增加时, 其后向散射值不断增大; 当藻类所含叶绿素a比重不断上升时, 其后向散射值也不断增大。而细胞粒径与后向散射值之间未表现出很好的相关性。因此, 通过单位叶绿素a散射和后向散射概率特征可以辨别出藻细胞形态较为接近的铜绿微囊藻和普通小球藻。     

基于旋转偏振角的线偏振扫描成像方法研究

提出一种基于旋转偏振角的新的偏振光成像方法:改变入射线偏振光偏振角和检偏角,采集样品图像系列,总结出背向散射光2个正交偏振分量的光强差关于入射线偏振光偏振角和检偏角的函数关系式.通过对模拟散射介质,猪肉脂肪,猪肉骨骼肌和牛肉骨骼肌等样品进行实验,论证了偏振差函数式中各个参数与样品光学特性之间的联系,并从中提取出2个相互独立的参数,分别表征样品的纤维方向角和光学各向异性度,从而实现对样品浅表层光学特性进行定量测量.和普通光强图像相比,用这些独立的光学信息生成不同基色的图像,能更直观明了地区分组织结构差异,具有潜在的临床医学应用价值,如成为一种皮肤疾病、皮肤损伤的检测方法.     

组织模型偏振散射光谱特性研究

结合偏振门技术和米氏散射理论,建立了组织模型的偏振散射差分光谱理论模型.计算分析了粒子群的平均尺寸、相对折射率变化时后向偏振散射差分光谱的特征.结果表明,利用偏振门技术测量的差分光谱主要是来自表层粒子的光信号,偏振散射差分光谱对粒子平均尺寸及相对折射率的变化比较敏感,随着粒子平均尺寸的增加,光谱振荡频率将增加,而随着相对折射率的减小,光谱的振幅减小,且差分光强值减小.该方法对于早期癌症检测具有潜在应用意义.     

利用皮秒激光对高散射介质中的物体成像的研究

本文分析了激光脉冲在高散射介质中的传输特性,研究一种利用皮秒激光二次谐波互相关方法对高散射介质中的物体成像的技术,得到５００μｍ的空间分辨率,该技术有望在医学诊断中得到应用     

基于压缩感知和散斑相关法的散射介质成像方法研究

散射介质成像是生物医学成像领域的一个重要研究方向,对生物医学临床的诊断有着重大的意义。结合散斑相关法和压缩感知技术,提出了一种散射介质成像方法。该方法与传统散射介质成像方法相比,将减少图像采集、图像重建所记录的数据量,提高图像处理的效率,并且降低了系统的搭建成本。试验结果表明,结合TVAL3信号重构算法和双谱分析法的散射图像重建算法,随着采样率的增大,峰值信噪比平稳上升,为散射介质成像方法在生物医学成像领域的运用提供了一种有效方案。     

Wigner-Ville分布法估计生物组织散射元平均间距

生物组织散射元平均间距是描述生物组织微观结构和超声散射特性的重要参数。文中构造了生物组织散射元一维超声散射模型,提出用Ｗｉｇｎｅｒ－Ｖｉｌｅ分布函数方法估计生物组织散射元平均间距,仿真结果表明这一方法具有良好的空间分辨率,能检测出生物组织散射元平均间距细微的非均匀性变化,且有良好的抗噪声性等一系列优良特性     

Distinguishing structural features between Crohn's disease and gastrointestinal luminal tuberculosis using Mueller matrix derived parameters

Recently, the incidence of inflammatory bowel diseases, especially the Crohn's disease (CD) and gastrointestinal luminal tuberculosis (ITB), has grown rapidly worldwide. Currently there is no general gold standard to distinguish between CD and ITB tissues, which both have tuberculosis and surrounding fibrous structures. Mueller matrix imaging technique is suitable for describing the location, density and distribution behavior of such fibrous structures. In this study, we apply the Mueller matrix microscopic imaging to the CD and ITB tissue samples. The 2D Mueller matrix images of the CD and ITB tissue slices are measured using the Mueller matrix microscope developed in our previous study, then the Mueller matrix polar decomposition and Mueller matrix transformation parameters are calculated. To evaluate the distribution features of the fibrous structures surrounding the tuberculosis areas more quantitatively and precisely, we analyze the retardance related Mueller matrix derived parameters, which show clear different distribution behaviors between the CD and ITB tissues, using the Tamura image processing method. It is demonstrated that the Mueller matrix derived parameters can reveal the structural features of tuberculosis areas and be used as quantitative indicators to distinguish between CD and ITB tissues, which may be useful for the clinical diagnosis.      

Mueller matrix decomposition for polarized light assessment of biological tissues

The Mueller matrix represents the transfer function of an optical system in its interactions with polarized light and its elements relate to specific biologically or clinically relevant properties. However, when many optical polarization effects occur simultaneously, the resulting matrix elements represent several “lumped” effects, thus hindering their unique interpretation. Currently, no methods exist to extract these individual properties in turbid media. Here, we present a novel application of a Mueller matrix decomposition methodology that achieves this objective. The methodology is validated theoretically via a novel polarized‐light propagation model, and experimentally in tissue simulating phantoms. The potential of the approach is explored for two specific biomedical applications: monitoring of changes in myocardial tissues following regenerative stem cell therapy, through birefringence‐induced retardation of the light's linear and circular polarizations, and non‐invasive blood glucose measurements through chirality‐induced rotation of the light's linear polarization. Results demonstrate potential for both applications. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Detection and identification of optical activity using polarimetry – applications to biophotonics,biomedicine and biochemistry

Polarized light that is reflected or transmitted through chiral specimens can be used to detect and identify biological and chemical materials including human tissue. The determination of the silent footprints of the chiral properties of the biological materials on scattered polarized light is the basis for these investigations. It is of primary importance to identify which combinations of the elements of the Mueller matrix for reflected or for transmitted light can be used to determine the optical activity of the biochemical materials. The optical activity of chiral materials is characterized by optical rotation and circular dichroism. The explicit analytical dependence of these specific elements of the Mueller matrix, upon the angles of incidence and scatter, upon the wavelength and upon the type of chirality has the potential to provide experimentalists with guidance in determining the optimum use of optical polarimetric scatterometers. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Investigation on the potential of Mueller matrix imaging for digital staining

Digital staining based on Mueller matrix measurements and their derivatives was investigated. Mueller matrix imaging was performed at the microscopic level on gastric tissue sections. Full Mueller matrices (4 × 4) were reconstructed using recorded images, followed by the extraction of polarization parameters. The most effective parameters and their combinations were extracted from Mueller matrix elements, principal component scores and polarization parameters respectively to classify samples into three categories – i.e. cancer, dysplasia and intestinal metaplasia/normal glands for various regions of interest sizes. It was observed that two‐step classification yielded higher classification accuracy than the traditional one‐step classification and that pixel classification based on Mueller matrix elements yielded higher accuracy than that based on polarization parameters and derived principal components. Moreover, Mueller matrix images with a lower spatial resolution generated higher classification accuracy but those with a higher spatial resolution revealed more morphological details.ns.

The original stained image (top) and the digital staining image (bottom).     

Refractive index measurement using single fiber reflectance spectroscopy

A method using single fiber reflectance spectroscopy to measure the refractive indices of transparent and turbid media over a broad wavelength range is presented and tested. For transparent liquid samples, the accuracy is within 0.2%, and the accuracy increases with increasing wavelength. For liquid turbid media, the accuracy is within 0.3% and increases with decreasing wavelength. For solid turbid samples, such as human skin, the accuracy critically depends on the optical contact between the fiber and sample surface. It is demonstrated that this technique has the potential to measure refractive indices of biological tissue in vivo.      

Optimizing the classification of biological tissues using machine learning models based on polarized data

Polarimetric data is nowadays used to build recognition models for the characterization of organic tissues or the early detection of some diseases. Different Mueller matrix-derived polarimetric observables, which allow a physical interpretation of a specific characteristic of samples, are proposed in literature to feed the required recognition algorithms. However, they are obtained through mathematical transformations of the Mueller matrix and this process may loss relevant sample information in search of physical interpretation. In this work, we present a thorough comparative between 12 classification models based on different polarimetric datasets to find the ideal polarimetric framework to construct tissues classification models. The study is conducted on the experimental Mueller matrices images measured on different tissues: muscle, tendon, myotendinous junction and bone; from a collection of 165 ex-vivo chicken thighs. Three polarimetric datasets are analyzed: (A) a selection of most representative metrics presented in literature; (B) Mueller matrix elements; and (C) the combination of (A) and (B) sets. Results highlight the importance of using raw Mueller matrix elements for the design of classification models.     

SIMPLIFIED CAPACITANCE MONITORING FOR THE DETERMINATION OF CAMPYLOBACTER SPP. GROWTH RATES

Capacitance monitoring is commonly used as an efficient means to generate growth curves of bacterial pathogens. However, the use of capacitance monitoring with Campylobacter spp. was previously determined to be difficult due to the complexity of the required media. We investigated capacitance monitoring using a simplified medium for the efficient and reproducible construction of growth curves for Campylobacter spp . It was determined that Campylobacter spp. should initially be propagated on Mueller Hinton plates in a microaerobic atmosphere (5% O₂, 10% CO₂, 85% N₂) at 37C for 24 h, followed by transfer to Mueller Hinton biphasic cultures for 6 h at 37C in a microaerobic atmosphere. Serial dilutions of the Campylobacter spp. cultures should be used for inoculation of Bactometer wells that contain 1 mL Mueller Hinton broth supplemented with 0.1 M sodium pyruvate for the completion of Campylobacter spp. growth curves with the Bactometer.

PRACTICAL APPLICATIONS

Growth rates can vary greatly among Campylobacter isolates; therefore, the rapid and reproducible methods described will prove useful in studies where the generation of growth curves is critical for subsequent experimental analyses.