Computational single fundus image restoration techniques: a review.

Fundus cameras are widely used by ophthalmologists for monitoring and diagnosing retinal pathologies. Unfortunately, no optical system is perfect, and the visibility of retinal images can be greatly degraded due to the presence of problematic illumination, intraocular scattering, or blurriness caused by sudden movements. To improve image quality, different retinal image restoration/enhancement techniques have been developed, which play an important role in improving the performance of various clinical and computer-assisted applications. This paper gives a comprehensive review of these restoration/enhancement techniques, discusses their underlying mathematical models, and shows how they may be effectively applied in real-life practice to increase the visual quality of retinal images for potential clinical applications including diagnosis and retinal structure recognition. All three main topics of retinal image restoration/enhancement techniques, i.e., illumination correction, dehazing, and deblurring, are addressed. Finally, some considerations about challenges and the future scope of retinal image restoration/enhancement techniques will be discussed.

A case of alveolar soft tissue sarcoma detected by ultrasound examination.

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Plug-and-play DPC-based quantitative phase microscope.

Point-of-care testing (POCT) plays an increasingly important role in biomedical research and health care. Quantitative phase microscopes (QPMs) with good contrast, no invasion, no labeling, high speed and automation could be effectively applied for POCT. However, most QPMs are fixed on the optical platform with bulky size, lack of timeliness, which remained challenging in POCT solutions. In this paper, we proposed a plug-and-play QPM with multimode imaging based on the quantitative differential phase contrast (qDPC) method. The system employs a programmable LED array as the light source and uses the GPU to accelerate the calculation, which can realize multi-contrast imaging with six modes. Accurate phase measurement and real-time phase imaging are implemented by the proposed qDPC algorithms for quantitative phase targets and biomedical samples. A 3D electric control platform is designed for mechanical control of field of view and focusing without manual operations. The experimental results verify the robustness and high performance of the setup. Even a rookie could finish the POCT scheme for biomedical applications at the scene using the QPM with a compact size of 140 × 165 × 250 mm3.

MUTE: A multilevel-stimulated denoising strategy for single cataractous retinal image dehazing.

In this research, we studied the duality between cataractous retinal image dehazing and image denoising and proposed that the dehazing task for cataractous retinal images can be achieved with the combination of image denoising and sigmoid function. To do so, we introduce the double-pass fundus reflection model in the YPbPr color space and developed a multilevel stimulated denoising strategy termed MUTE. The transmission matrix of the cataract layer is expressed as the superposition of denoised raw images of different levels weighted by pixel-wise sigmoid functions. We further designed an intensity-based cost function that can guide the updating of the model parameters. They are updated by gradient descent with adaptive momentum estimation, which gives us the final refined transmission matrix of the cataract layer. We tested our methods on cataract retinal images from both public and proprietary databases, and we compared the performance of our method with other state-of-the-art enhancement methods. Both visual assessments and objective assessments show the superiority of the proposed method. We further demonstrated three potential applications including blood vessel segmentation, retinal image registrations, and diagnosing with enhanced images that may largely benefit from our proposed methods.

Antimicrobial peptides in Dendrobium officinale: Genomic parameters, peptide structures, and gene expression patterns.

A weak codon usage bias was found in Dendrobium catenatum (D. officiale) antimicrobial peptides (AMPs), after the analysis of relative synonymous codon usage, GC contents, and the effective number of codons. The codon usage preference was mainly influenced by natural selection pressure. The self-optimized prediction method and SWISS-MODEL were applied for peptide structural and domain analyses, and some typical antimicrobial domains were found in D. officinale AMP amino sequences, such as knot1 domain, gibberellins-stimulated domain, cupin_1 domain, defensin_like domain, and SLR1-BP (S locus-related glycoprotein 1 binding pollen coat protein) domain. To investigate the AMPs gene expression pattern, abiotic stresses, such as salt stress, drought stress, salicylic acid (SA), and methyl jasmonate (JA), were applied and the gene expression levels were detected by the real-time fluorescent quantitative polymerase chain reaction. Results showed that, even though the basic AMPs gene expressions were low, some AMPs can still be induced by salt dress, while the drought dress did not show the same impact. The SA and JA signaling pathways might be involved in most of the AMPs expressions. The natural selection of the D. officinale AMPs and thus forming diverse types of AMPs enhanced the plant's innate immunity and disease resistance capability, which would lead to a better understanding of the molecular mechanism for D. officinale adapting to the environment. The finding that salt stress, SA, and JA signaling pathways can induce AMP expression lays a foundation for the further development and functional verification of D. officinale AMPs.

Retinex-qDPC: Automatic background-rectified quantitative differential phase contrast imaging.

BACKGROUND AND OBJECTIVE: The quality of quantitative differential phase contrast reconstruction (qDPC) can be severely degenerated by the mismatch of the background of two oblique illuminated images, yielding problematic phase recovery results. These background mismatches may result from illumination patterns, inhomogeneous media distribution, or other defocusing layers. In previous reports, the background is manually calibrated which is time-consuming, and unstable, since new calibrations are needed if any modification to the optical system was made. It is also impossible to calibrate the background from the defocusing layers, or for high dynamic observation as the background changes over time. The background mismatch reduces the experimental robustness of qDPC and largely limits its applications. To tackle the mismatch of background and increases the experimental robustness, we propose the Retinex-qDPC. METHODS: In Retinex-qDPC, we replace the data fidelity term of the previous cost function for qDPC inverse problem, by the images' edge features yielding L2-Retinex-qDPC and L1-Retinex-qDPC for high background-robustness qDPC reconstruction. The split Bregman method is used to solve the L1-Retinex DPC. We compare both Retinex-qDPC models against state-of-the-art DPC reconstruction algorithms including total-variation regularized qDPC, and isotropic-qDPC using both simulated and experimental data. RESULTS: Retinex qDPC can significantly improve the phase recovery quality by suppressing the impact of mismatch background. Within, the L1-Retinex-qDPC is better than L2-Retinex and other state-of-the-art qDPC algorithms. CONCLUSIONS: The Retinex-qDPC increases the experimental robustness against background illumination without any modification of the optical system, which will benefit all qDPC applications.

Luminosity rectified blind Richardson-Lucy deconvolution for single retinal image restoration.

BACKGROUND AND OBJECTIVE: Due to imperfect imaging conditions, retinal images can be degraded by uneven/insufficient illumination, blurriness caused by optical aberrations and unintentional motions. Degraded images reduce the effectiveness of diagnosis by an ophthalmologist. To restore the image quality, in this research we propose the luminosity rectified Richardson-Lucy (LRRL) blind deconvolution framework for single retinal image restoration. METHODS: We established an image formation model based on the double-pass fundus reflection feature and developed a differentiable non-convex cost function that jointly achieves illumination correction and blind deconvolution. To solve this non-convex optimization problem, we derived the closed-form expression of the gradients and used gradient descent with Nesterov-accelerated adaptive momentum estimation to accelerate the optimization, which is more efficient than the traditional half quadratic splitting method. RESULTS: The LRRL was tested on 1719 images from three public databases. Four image quality matrixes including image definition, image sharpness, image entropy, and image multiscale contrast were used for objective assessments. The LRRL was compared against the state-of-the-art retinal image blind deconvolution methods. CONCLUSIONS: Our LRRL corrects the problematic illumination and improves the clarity of the retinal image simultaneously, showing its superiority in terms of restoration quality and implementation efficiency. The MATLAB code is available on Github.

An apparatus for qualitative assessment of the shading ratio of oblique illumination and real-time high-contrast imaging.

Oblique illumination imaging can significantly improve the contrast of transparent thin samples. However, in traditional oblique illumination methods, either the condenser is offset or a block is added to the condenser, which makes it complicated and challenged to build a stable oblique illumination imaging. Herein, we present a method to measure the optimal shading ratio of oblique illumination in an inverted microscope, and develop an apparatus for stable high-speed high-contrast imaging with uniform brightness. At optimal shading ratio, the oblique illumination imaging has better imaging quality than differential interference contrast, which characteristic is independent on sample. In oblique illumination with low magnification objective, the images have uneven brightness. According to target brightness, we have developed a brightness unevenness correction algorithm to form uniform background brightness for oblique illumination. Integrating the algorithm with imaging acquisition, corrected oblique illumination microscopy is appropriate to observe living cells with high contrast.

Targets and Potential Mechanism of Scutellaria baicalensis in Treatment of Primary Hepatocellular Carcinoma Based on Bioinformatics Analysis.

OBJECTIVE: To analyze the target and potential mechanism of Scutellaria baicalensis (SB) in the treatment of HCC based on bioinformatics, so as to provide suggestions for the diagnosis, treatment, and drug development of hepatocellular carcinoma (HCC). METHODS: The regulated gene targets of SB were screened by gene expression pattern clustering and differential analysis of gene expression data of HepG2 cells treated with SB at 0 h, 1 h, 3 h, 6 h, 12 h, and 24 h. The module genes related to HCC were identified by the weighted gene coexpression network analysis (WGCNA). KEGG and GO enrichment were used to analyze the molecular function and structure of the module, and GSEA was used to evaluate the different functional pathways between normal people and patients with HCC. Then, the module gene was used for univariate Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to build a prognostic model. The protein-protein interaction network (PPI) was used to analyze the core genes regulated by SB (CGRSB) of the module, and the survival curve revealed the CGRSB impact on patient survival. The CIBERSORT algorithm combined with correlation analysis to explore the relationship between CGRSB and immune infiltration. Finally, the single-cell sequencing technique was used to analyze the distribution of CGRSB at the cellular level. RESULTS: SB could regulate 903 genes, of which 234 were related to the occurrence of HCC. The prognosis model constructed by these genes has a good effect in evaluating the survival of patients. KEGG and GO enrichment analysis showed that the regulation of SB on HCC mainly focused on some cell proliferation, apoptosis, and immune-related functions. GSEA enrichment analysis showed that these functions are related to the occurrence of HCC. A total of 24 CGRSB were obtained after screening, of which 13 were significantly related to survival, and most of them were unfavorable factors for patient survival. The correlation analysis of gene expression showed that most of CGRSB was significantly correlated with T cells, macrophages, and other functions. The results of single-cell analysis showed that the distribution of CGRSB in macrophages was the most. CONCLUSION: SB has high credibility in the treatment of HCC, such as CDK2, AURKB, RRM2, CENPE, ESR1, and PRIM2. These targets can be used as potential biomarkers for clinical diagnosis. The research also shows that the p53 signal pathway, MAPK signal pathway, apoptosis pathway, T cell receptor pathway, and macrophage-mediated tumor immunity play the most important role in the mechanism of SB in treating HCC.

Topology design of digital metamaterials for ultra-compact integrated photonic devices based on mode manipulation.

Precise manipulation of mode order in silicon waveguides plays a fundamental role in the on-chip all-optical interconnections and is still a tough task in design when the functional region is confined to a subwavelength footprint. In this paper, digital metamaterials consisting of silicon and air pixels are topologically designed by an efficient method combining 2D finite element method for optical simulations, density method for material description and method of moving asymptotes for optimization. Only around 150 iterations are required for searching satisfactory solutions. Six high-quality and efficient conversions between four TE-polarized modes are achieved in a functional region with footprint 0.645λ 2 (center wavelength λ = 1550 nm). Based on asymmetric mode conversion, a reciprocal optical diode with high contrast ratio is further obtained with the optimization starting from TE0-to-TE1 mode converter. Moreover, we successfully design a 1 × 2 demultiplexer with footprint 1.0λ 2 and demonstrate a simple mode division multiplexing system with satisfactory performances. Finally, by changing the refractive index to an equivalent value, quasi-3D designs are obtained and the functionalities are validated in 3D simulations for both free-standing and SOI configurations.

Trapping and Manipulation of Single Cells in Crowded Environments.

Optical tweezers provide a powerful tool to trap and manipulate living cells, which is expected to help people gain physiological insights at single-cell level. However, trapping and manipulating single cells under crowded environments, such as blood vessels and lymph nodes, is still a challenging task. To overcome this issue, an annular beam formed by the far-field Bessel beam is introduced to serve as an optical shield to isolate the target cells from being disturbed. With this scheme, we successfully trapped and manipulated single blood cells in a crowded environment. Furthermore, we demonstrated manipulation of two lymphocytes ejected from a lymph node independently with dual-trap optical tweezers, which paves the way for exploring cell interactions under living conditions. Such technique might be helpful in the study of how natural killer cells response to virus-infected cells or cancer cells.

Calculation of optical forces for arbitrary light beams using the Fourier ray method.

The ray-optics (RO) model is a reasonable method to calculate optical force in geometrical optics regime. However, the RO model fails to calculate the optical force produced by diffractive optical field and other arbitrary structured light beams. We propose the Fourier ray (FR) method to calculate the optical force for arbitrary incident beams. Combining the Fourier optics and the geometrical optics, the FRs are defined as rays that inlay on the plane waves weighted by the Fourier angular spectrum of the incident beam. According to traditional RO model and FR method, we can analyze optical forces on a microsphere immersed in various beams. To validate the FR method, forces of the fundamental Gaussian beam and Airy beam are respectively calculated and compared with traditional method. In addition, optical forces in three arbitrary structured light beams are demonstrated as well. Our simulations show that the FR method is able to evaluate the optical forces generated by diffractive optical field and complex structured light beams, and give a solid prediction of their trapping performances. In RO regime, the Fourier ray method is a universal method to predict the interaction between bead and complex optical field.

Nonparaxial structured vectorial abruptly autofocusing beam: erratum.

In this erratum, the function z(θ) in equation (7) of Opt. Lett.44, 2843 (2019)OPLEDP0146-959210.1364/OL.44.002843 has been corrected.

Skew line ray model of nonparaxial Gaussian beam.

Many ray-optics models have been proposed to describe the propagation of paraxial Gaussian beam. However, those paraxial ray-optics models are inapplicable to the beams that violate the paraxial condition. In this paper, we present a skew line ray (SLR) based model to represent the propagation properties of nonparaxial Gaussian beam under the oblate spheroidal coordinates. The free-space evolution of complex wavefront of the light beam including amplitude and phase is derived via this model. Our analysis demonstrates that the SLR model is available for both nonparaxial and paraxial conditions, and can be used to precisely describe the propagation of complex wavefront. Furthermore, this model changes the transverse density of rays while propagating. The behavior influences the transverse intensity distribution and makes the optical rays become concentrated towards the center. We believe that this ray-optics model can be further developed to describe other kind of structured beams such as Laguerre-Gauss and Bessel-Gauss beams.

[Effects of Xue-Bi-Jing combined with forsythia suspension on the liver gene expression levels of rats with sepsis model].

OBJECTIVE: To study the effects of "XUE BI JING plus LIANQIAO" injection on gene expression levels of rats with sepsis model. METHODS: One hundred and twenty rats were randomly divided into sham operation group, sepsis model group, Te-neng group and "XUE BI JING plus forsythia suspension" group. The sepsis model of rats was prepared by "CLP" method. Tai neng group was treated by peritoneal injection Imipenem/ Cilastatin (0.18 g/kg); "XUE BI JING plus LIANQIAO" group was treated by peritoneal injection Imipenem/ Cilastatin (0.18 g/kg) plus "xue-bi-jing" (10 ml/kg) and "liang ge san" (18 g/200 g) by intragastric administration 2 times a day; the sham operation group and model group were treated by peritoneal injection of normal saline (10 ml/kg). The survival rates at 48h and 72h were observed for all groups. The gene expression levels of livers in all groups were detected by BiostarR-40s chip. The NCBI database was used to inquest Gene function and class. RESULTS: The survival rates at 48h and 72h in "XUE BI JING+ forsythia suspension" group were 83.3% and 76.7% which were significantly higher than those (30.0% and 16.7%) in sepsis model group and those (60.0% and 33.3%) in Te-neng group (P < 0.01). Model group/control group have 305 differential expression genes with 159 up-regulation genes and 146 down-regulation genes. Tai-neng group/model group have 386 differential expression genes with 206 up-regulation genes and 180 down-regulation genes. "XUE BI JING plus forsythia suspension" group/model group have 342 differential expression genes with 102 up-regulation genes and 240 downregulation genes. The genes with up-regulation in model group/ control group and with down-regulation in"XUE BI JING plus forsythia suspension" group/model group were 24. The genes with down-regulation in the model group/ sham operation group and with up-regulation in "XUE BI JING plus forsythia suspension"group/model group were 16. CONCLUSION: "XUE BI JING plus forsythia suspension" can reduce the mortality of rats with sepsis, which could be due to the expression of relative regulation genes.