基于显微光谱的组织切片细胞纳米结构研究

细胞纳米结构的探测对癌症的早期诊断以及筛查具有非常重要的意义。空域低相干相位显微镜可以探测细胞的纳米结构获取系统参数,但是显微镜的系统参数和细胞纳米结构参数之间存在着复杂的非线性相关关系,需要研究方法加以定量分析。因此,基于一维高斯场模型加一维多层介质模型模拟空域低相干相位显微镜的背散射光谱,实验结果表明模型预测结果与实际测量结果基本一致。对已知纳米结构的组织切片光谱建模, 通过统计方法分析了系统参数与细胞纳米结构参数的相关关系,验证了系统参数确实能反映细胞纳米结构参数的变化,并量化了系统参数的反映水平。研究成果为基于空域低相干相位显微镜的癌症早期诊断提供了新的理论基础和方法依据。     

Live cell refractometry using microfluidic devices

Using Hilbert phase microscopy for extracting quantitative phase images, we measured the average refractive index associated with live cells in culture. To decouple the contributions to the phase signal from the cell refractive index and thickness, we confined the cells in microchannels. The results are confirmed by comparison with measurements of spherical cells in suspension.     

Brain tissue classification based on DTI using an improved Fuzzy C-means algorithm with spatial constraints

We present an effective method for brain tissue classification based on diffusion tensor imaging (DTI) data. The method accounts for two main DTI segmentation obstacles: random noise and magnetic field inhomogeneities. In the proposed method, DTI parametric maps were used to resolve intensity inhomogeneities of brain tissue segmentation because they could provide complementary information for tissues and define accurate tissue maps. An improved fuzzy c-means with spatial constraints proposal was used to enhance the noise and artifact robustness of DTI segmentation. Fuzzy c-means clustering with spatial constraints (FCM_S) could effectively segment images corrupted by noise, outliers, and other imaging artifacts. Its effectiveness contributes not only to the introduction of fuzziness for belongingness of each pixel but also to the exploitation of spatial contextual information. We proposed an improved FCM_S applied on DTI parametric maps, which explores the mean and covariance of the feature spatial information for automated segmentation of DTI. The experiments on synthetic images and real-world datasets showed that our proposed algorithms, especially with new spatial constraints, were more effective.     

Cell refractive index tomography by digital holographic microscopy

For what we believe to be the first time, digital holographic microscopy is applied to perform optical diffraction tomography of a pollen grain. Transmission phase images with nanometric axial accuracy are numerically reconstructed from holograms acquired for different orientations of the rotating sample; then the three-dimensional refractive index spatial distribution is computed by inverse radon transform. A precision of 0.01 for the refractive index estimation and a spatial resolution in the micrometer range are demonstrated.     

Field-based angle-resolved light-scattering study of single live cells

We perform field-based angle-resolved light-scattering measurements from single live cells. We use a laser interferometer to acquire phase and amplitude images of cells at the image plane. The angular scattering spectrum is calculated from the Fourier transform of the field transmitted through the cells. A concurrent 3D refractive index distribution of the same cells is measured using tomographic phase microscopy. By measuring transient increases in light scattering by single cells during exposure to acetic acid, we correlate the scattering properties of single cells with their refractive index distributions and show that results are in good agreement with a model based on the Born approximation.     

Imaging iron stores in the brain using magnetic resonance imaging

For the last century, there has been great physiological interest in brain iron and its role in brain function and disease. It is well known that iron accumulates in the brain for people with Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down syndrome, AIDS and in the eye for people with macular degeneration. Measuring the amount of nonheme iron in the body may well lead to not only a better understanding of the disease progression but an ability to predict outcome. As there are many forms of iron in the brain, separating them and quantifying each type have been a major challenge. In this review, we present our understanding of attempts to measure brain iron and the potential of doing so with magnetic resonance imaging. Specifically, we examine the response of the magnetic resonance visible iron in tissue that produces signal changes in both magnitude and phase images. These images seem to correlate with brain iron content, perhaps ferritin specifically, but still have not been successfully exploited to accurately and precisely quantify brain iron. For future quantitative studies of iron content we propose four methods: correlating R2' and phase to iron content; applying a special filter to the phase to obtain a susceptibility map; using complex analysis to extract the product of susceptibility and volume content of the susceptibility source; and using early and late echo information to separately predict susceptibility and volume content.     

Time-resolved off-axis digital holography for characterization of ultrafast phenomena in water

We present the application of time-resolved off-axis digital holography for the investigation of refractive index/transmission properties of laser-induced plasma filaments in water. Time evolution of both amplitude- and phase-contrast images of the self-focused beam in water was characterized with temporal resolution better than 50 fs. To the best of our knowledge, this is the first attempt to characterize the propagation of femtosecond laser pulse in nonlinear media using off-axis digital holography.     

Investigation of noise properties in grating-based x-ray phase tomography with reverse projection method

The relationship between noise variance and spatial resolution in grating-based x-ray phase computed tomography(PCT) imaging is investigated with reverse projection extraction method, and the noise variances of the reconstructed absorption coefficient and refractive index decrement are compared. For the differential phase contrast method, the noise variance in the differential projection images follows the same inverse-square law with spatial resolution as in conventional absorption-based x-ray imaging projections. However, both theoretical analysis and simulations demonstrate that in PCT the noise variance of the reconstructed refractive index decrement scales with spatial resolution follows an inverse linear relationship at fixed slice thickness, while the noise variance of the reconstructed absorption coefficient conforms with the inverse cubic law. The results indicate that, for the same noise variance level, PCT imaging may enable higher spatial resolution than conventional absorption computed tomography(ACT), while ACT benefits more from degraded spatial resolution. This could be a useful guidance in imaging the inner structure of the sample in higher spatial resolution.     

Spectral-domain optical coherence phase microscopy for quantitative phase-contrast imaging

We describe a novel microscopy technique for quantitative phase-contrast imaging of a transparent specimen. The technique is based on depth-resolved phase information provided by common path spectral-domain optical coherence tomography and can measure minute phase variations caused by changes in refractive index and thickness inside the specimen. We demonstrate subnanometer level path-length sensitivity and present images obtained on reflection from a known phase object and human epithelial cheek cells.     

Power-dependent shaping of vortex solitons in optical lattices with spatially modulated nonlinear refractive index

We address vortex solitons supported by optical lattices featuring modulation of both the linear and nonlinear refractive indices. We find that when the modulation is out of phase the competition between both effects results in remarkable shape transformations of the solitons that profoundly affect their properties and stability. Nonlinear refractive index modulation is found to impose restrictions on the maximal power of off-site solitons, which are shown to be stable only below a maximum nonlinearity modulation depth.     

Needle-based refractive index measurement using low-coherence interferometry

We present a novel needle-based device for the measurement of refractive index and scattering using low-coherence interferometry. Coupled to the sample arm of an optical coherence tomography system, the device detects the scattering response of, and optical path length through, a sample residing in a fixed-width channel. We report use of the device to make near-infrared measurements of tissues and materials with known optical properties. The device could be used to exploit the refractive index variations of tissue for medical and biological diagnostics accessible by needle insertion.     

The effect of physiological noise in phase functional magnetic resonance imaging: from blood oxygen level-dependent effects to direct detection of neuronal currents

Recently, the possibility to use both magnitude and phase image sets for the statistical evaluation of fMRI has been proposed, with the prospective of increasing both statistical power and the spatial specificity. In the present work, several issues that affect the spatial and temporal stability in fMRI phase time series in the presence of physiologic noise processes are reviewed, discussed and illustrated by experiments performed at 3 T. The observed phase value is a fingerprint of the underlying voxel averaged magnetic field variations. Those related to physiological processes can be considered static or dynamic in relation to the temporal scale of a 2D acquisition and will play out on different spatial scales as well: globally across the entire images slice, and locally depending on the constituents and their relative fractions inside the MRI voxel. The 'static' respiration-induced effects lead to magneto-mechanic scan-to-scan variations in the global magnetic field but may also contribute to local BOLD fluctuations due to respiration-related variations in arterial carbon dioxide. Likewise, the 'dynamic' cardiac-related effects will lead to global susceptibility effects caused by pulsatile motion of the brain as well as local blood pressure-related changes in BOLD and changes in blood flow velocity. Finally, subject motion may lead to variations in both local and global tissue susceptibility that will be especially pronounced close to air cavities. Since dissimilar manifestations of physiological processes can be expected in phase and in magnitude images, a direct relationship between phase and magnitude scan-to-scan fluctuations cannot be assumed a priori. Therefore three different models were defined for the phase stability, each dependent on the relation between phase and magnitude variations and the best will depend on the underlying noise processes. By experiments on healthy volunteers at rest, we showed that phase stability depends on the type of post-processing and can be improved by reducing the low-frequency respiration-induced mechano-magnetic effects. Although the manifestations of physiological noise were in general more pronounced in phase than in magnitude images, due to phase wraps and global Bo effects, we suggest that a phase stability similar to that found in magnitude could theoretically be achieved by adequate correction methods. Moreover, as suggested by our experimental data regarding BOLD-related phase effects, phase stability could even supersede magnitude stability in voxels covering dense microvascular networks with BOLD-related fluctuations as the dominant noise contributor. In the interest of the quality of both BOLD-based and nc-MRI methods, future studies are required to find alternative methods that can improve phase stability, designed to match the temporal and spatial scale of the underlying neuronal activity.     

Tissue self-affinity and polarized light scattering in the born approximation: a new model for precancer detection

Light scattered from biological tissues can exhibit an inverse power law spectral component. We develop a model based on the Born approximation and von Karman (self-affine) spatial correlation of submicron tissue refractive index to account for this. The model is applied to light scattering spectra obtained from excised esophagi of normal and carcinogen-treated rats. Power law exponents used to fit dysplastic tissue site spectra are significantly smaller than those from normal sites, indicating that changes in tissue self-affinity can serve as a potential biomarker for precancer.     

Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity

We have developed a novel phase-resolved optical coherence tomography (OCT) and optical Doppler tomography (ODT) system that uses phase information derived from a Hilbert transformation to image blood flow in human skin with fast scanning speed and high velocity sensitivity. Using the phase change between sequential scans to construct flow-velocity imaging, this technique decouples spatial resolution and velocity sensitivity in flow images and increases imaging speed by more than 2 orders of magnitude without compromising spatial resolution or velocity sensitivity. The minimum flow velocity that can be detected with an axial-line scanning speed of 400 Hz and an average phase change over eight sequential scans is as low as 10 microm/s, while a spatial resolution of 10 microm is maintained. Using this technique, we present what are to our knowledge the first phase-resolved OCT/ODT images of blood flow in human skin.     

Symmetric multilayer slab waveguide structure with a negative index material: TM case

The present paper deals with the theoretical modeling of symmetrical multilayer planar waveguide structure. One of the layers is considered as a negative refractive index material. We take the appropriate field distributions for p-polarization and impose the boundary conditions to derive the mode equation and other necessary formulae for the proposed structure. The effect of the negative-index layer on the modal refractive index, power flow, and penetration depth of the waveguide is studied. Also, we compare our computed results with those obtained for a similar conventional four-layer structure. It is observed that the presence of the negative-index material reduces the power flowing in the guiding layer and enhances the power flowing in the surroundings.     

部分相干涡旋光束在大气湍流中的远场传输特性

运用广义惠更斯-菲涅耳原理,详细研究了部分相干涡旋光束在湍流介质中的远场传输规律.研究表明,部分相干涡旋光束的光谱相干度及光强分布与光束的拓扑电荷数、空间相对相干长度及湍流介质的折射率结构常数等因素有关.在湍流介质中,光谱相干度存在相位奇点,并且随着空间相对相干长度的增大,相干涡旋逐渐演化为强度涡旋,而湍流介质的强弱对部分相干涡旋光束的影响则相反,随着湍流介质的折射率常数的增大,强度涡旋逐渐演化为相干涡旋.     

Dispersion modified slot optical waveguides

Advent of slot waveguide structures had opened a new era where light can be confined in low index slot guarded by high index slabs. Already in use SOI slot waveguides (contrast ratio is 2.42) have two distinct properties over the conventional waveguides, i.e. high E-field amplitude, optical power, optical intensity in low index materials, and strong E-field confinement localized to nanometer-size low index regions. We hereby propose a low refractive index contrast ratio slot waveguide structure (ratio is 1.18) comprising of commercially available glass material. Novelty lies in showing high E-field amplitude, optical power, optical intensity, and strong E-field confinement in low index slot regions despite of lowest ever reported contrast ratio. A systematic numerical study on the higher order dispersion characteristics of the widely studied SOI-based slot structure and of our proposed low refractive index contrast slot structure is carried out. It has been demonstrated that low refractive index contrast ratio slot optical waveguide GVD properties are quite different than SOI slot optical waveguide. The less normal dispersion existing in this kind of waveguide could have an impact on their applications in various nonlinear or linear applications.     

Frequency resolved analysis of thermally induced refractive index changes in fiber amplifiers

Temperature induced refractive index changes are an important aspect in today's fiber amplifiers with high average power. For many processes, their time dependence is critical. Here, we analyze the impact of radial heat diffusion on the optical phase. We modulated the pump power in a 10?W amplifier and measured the frequency response of the optical phase. We compared the result with the calculated frequency response of the temperature in the fiber core, which shows the same characteristics. Additionally, we analyzed the influence of fiber parameters on the temperature dynamics.     

Direct observation of self-focusing with subdiffraction limited resolution using near-field scanning optical microscope

The self-focusing effect in As2S3 glass has been studied using a near-field scanning optical microscope. Optical images of fine features in the self-focused beam were directly measured at the self-focus with approximately 100 nm spatial resolution. Because of the unusually large nonlinear refractive index at 690 nm, filaments with minimum size of 0.3 &mgr;m were observed in a 1.6 mW beam propagating through the 1.7 &mgr;m thin film. A qualitative analysis of our experimental results is presented. We show that nonparaxiality is responsible for arresting self-focusing, as predicted by recent theories.     

低频振荡电位的能量和相位稳定性与偶极子电流活动相关性的仿真

能量和相位是分析脑节律的重要物理量, 虽有许多研究, 但其与脑组织电特性和脑节律源的关系尚不完全清楚, 弄清这一问题有助于脑电测量及脑功能和疾病的分析. 为此, 借鉴脑电正问题研究方法, 大脑可看作均匀球, 脑组织电特性用导体各向同性和各向异性电导率来表示, 脑节律源用准静态偶极子电流来模拟, 其活动表达为较低频率的正弦振荡, 在改变该活动的振幅和相位时程时, 用球表面剖分网格的振荡电位仿真脑节律, 提取节律的能量和相位, 计算源和节律的窄带相位稳定性. 结果表明: 仿真节律的能量随电导率增大而减小, 受网格位置、电导率各向异性、偶极子电流幅值和偏心位置影响较大; 但仿真节律的相位稳定性只与自身的相位时程有关. 说明能量与相位稳定性电学意义无交集, 同时用来分析脑节律可提供更多神经信息; 能量的电学意义更复杂, 取决于包括测量条件在内的多种因素; 相位稳定性的优势在于它仅与脑节律相位时程直接相关, 可预测的是脑的非线性导致的相位时程越离散, 则相位稳定性越差.