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- 摘要
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- 实验方案
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In Vivo 3D Imaging of Retinal Neovascularization Using Multimodal Photoacoustic Microscopy and Optical Coherence Tomography Imaging
摘要: The pathological process of neovascularization of the retina plays a critical role in causing vision loss in several diseases, including diabetes, retinal vein occlusion, and sickle cell disease. Retinal neovascularization can lead to vitreous hemorrhage and retinal detachment, yet the pathological process of neovascularization is a complex phenomenon under active investigation. Understanding and monitoring retinal neovascularization is critically important in clinical ophthalmology. This study describes a novel multimodal ocular imaging system which combines photoacoustic microscopy (PAM) and a spectral domain optical coherence tomography (SD-OCT) to improve the visualization of retinal neovascularization (RNV), their depth, and the surrounding anatomy in living rabbits. RNV was induced in New Zealand rabbits by intravitreal injection of vascular endothelial growth factor (VEGF). The retinal vasculature before and after injection at various times was monitored and evaluated using multimodal imaging including color fundus photography, fluorescein angiography (FA), OCT, and PAM. In vivo experiments demonstrate that PAM imaging distinctly characterized the location as well as the morphology of individual RNV with high contrast at a safe laser energy of 80 nJ. SD-OCT was used to identify a cross-sectional structure of RNV. In addition, dynamic changes in the retinal morphology and retinal neovascularization were observed at day 4, 5, 6, 7, 9, 11, 14, 28, and day 35 after VEGF injection. PAM demonstrated high-resolution optical absorption of hemoglobin and vascular imaging of the retina and choroid with increased depth of penetration. With the current multimodal imaging system, RNV can be easily visualized in both 2D and 3D angiography. This multimodal ocular imaging system provides improved characterization of the microvasculature in a safe manner in larger rabbit eyes.
关键词: PAM,VEGF,multimodal imaging,optical coherence tomography,photoacoustic microscopy,retinal neovascularization,vascular endothelial growth factor,OCT
更新于2025-09-23 15:22:29
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[IEEE 2018 7th Electronic System-Integration Technology Conference (ESTC) - Dresden, Germany (2018.9.18-2018.9.21)] 2018 7th Electronic System-Integration Technology Conference (ESTC) - Phase Determination in SLID Bonding
摘要: Solid-liquid interdiffusion (SLID) bonding is a technique based on intermetallic compounds (IMCs), enabling a thermal stability at temperatures far surpassing the bonding temperature. The technique has been developed as a die attach and interconnection technology for high-temperature applications, but is also excellent for fine-pitch bonding, and for obtaining bonds with thin layers of well-defined metallurgy. Determining the phases of IMC in a SLID bond is crucial in order to understand and predict the properties of the bond. The re-melting temperature of the bond is defined by the IMCs present, and thus directly defines the high-temperature range the SLID bond can survive. Furthermore, the phases present in a SLID bond determines whether the bond is at thermal equilibrium, or if reactions to form new IMCs are expected over the lifetime of the SLID bond (at the actual application temperature). Also, material properties such as electrical conductivity and elastic modulus will depend on which phase is present in a SLID bond. The two most common SLID systems are treated in this paper: Cu–Sn has a relatively simple phase diagram, with two IMCs. The possible phases in a Cu–Sn SLID bond are easily identified by Energy-Dispersive X-ray Spectroscopy (EDX) in the Scanning Electron Microscope (SEM), and they are easily differentiated in optical microscopy as well as in SEM microscopy. Routine investigations of spatial distribution of the various phases can thus be performed by microscopy. Au–Sn has a more complex phase diagram. Au and Au–Sn IMCs are easily distinguished in optical microscopy, but not so easily in SEM. The different IMCs are not discernable neither by microscopy nor by EDX. By using Electron Backscatter Diffraction (EBSD) in combination with electron microscopy and EDX, we demonstrate phase identification and the spatial distribution of phases in a complex Au–Sn SLID bond.
关键词: EBSD,TLP bonding,SLID bonding,EDX,microscopy
更新于2025-09-23 15:22:29
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Dual-Modal In Vivo Fluorescence/Photoacoustic Microscopy Imaging of Inflammation Induced by GFP-Expressing Bacteria
摘要: In this study, dual-modal fluorescence and photoacoustic microscopy was performed for noninvasive and functional in vivo imaging of inflammation induced by green fluorescent protein (GFP) transfected bacteria in mice ear. Our imaging results demonstrated that the multimodal imaging technique is able to monitor the tissue immunovascular responses to infections with molecular specificity. Our study also indicated that the combination of photoacoustic and fluorescence microscopy imaging can simultaneously track the biochemical changes including the bacterial distribution and morphological change of blood vessels in the biological tissues with high resolution and enhanced sensitivity. Consequently, the developed method paves a new avenue for improving the understanding of the pathology mechanism of inflammation.
关键词: GFP-expressing bacteria,fluorescence imaging,biosensor,photoacoustic microscopy,inflammation/infection
更新于2025-09-23 15:22:29
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Numerical analysis of single-point spectroscopy curves used in photo-carrier dynamics measurements by Kelvin probe force microscopy under frequency-modulated excitation
摘要: In recent years, the investigation of the complex interplay between the nanostructure and photo-transport mechanisms has become of crucial importance for the development of many emerging photovoltaic technologies. In this context, Kelvin probe force microscopy under frequency-modulated excitation has emerged as a useful technique for probing photo-carrier dynamics and gaining access to carrier lifetime at the nanoscale in a wide range of photovoltaic materials. However, some aspects about the data interpretation of techniques based on this approach are still the subject of debate, for example, the plausible presence of capacitance artifacts. Special attention shall also be given to the mathematical model used in the data-fitting process as it constitutes a determining aspect in the calculation of time constants. Here, we propose and demonstrate an automatic numerical simulation routine that enables to predict the behavior of spectroscopy curves of the average surface photovoltage as a function of a frequency-modulated excitation source in photovoltaic materials, enabling to compare simulations and experimental results. We describe the general aspects of this simulation routine and we compare it against experimental results previously obtained using single-point Kelvin probe force microscopy under frequency-modulated excitation over a silicon nanocrystal solar cell, as well as against results obtained by intensity-modulated scanning Kelvin probe microscopy over a polymer/fullerene bulk heterojunction device. Moreover, we show how this simulation routine can complement experimental results as additional information about the photo-carrier dynamics of the sample can be gained via the numerical analysis.
关键词: Kelvin probe force microscopy,nanostructured photovoltaics,numerical simulations,photo-carrier dynamics,carrier dynamics,carrier recombination,carrier lifetime
更新于2025-09-23 15:22:29
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RGB color coded images in scanning electron microscopy of biological surfaces
摘要: We present here a methodological approach for the creation of color images in scanning electron microscopy by processing grayscale images taken simultaneously from at least three different detectors in a scanning electron microscope. The final color images are then produced by merging together those grayscale images in RGB color space. We show the images from non-conductive standard sample together with those obtained from real microbiological samples. The first one represents a microbial biofilm naturally grown on fiber glass filter. The other shows individual Bacillus subtilis cells from batch culture. All the image handling was done in open source image processing software ImageJ or GNU Image Manipulation Program (Gimp) or, alternatively, in proprietary AnalySis 3.2 Pro software processing suite.
关键词: high resolution,color images,scanning electron microscopy,biological surfaces
更新于2025-09-23 15:22:29
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Detection of Circulating Tumor Cells in Fluorescence Microscopy Images Based on ANN Classifier
摘要: Circulating tumor cells (CTCs) is a clinical biomarker for cancer metastasis. CTCs are cells circulating in the body of patients by being separated from primary cancer and entering into blood vessel. CTCs spread every positions in the body, and this is one of the cause of cancer metastasis. To analyze them, pathologists get information about metastasis without invasive test. CTCs test is conducted by analyzing the blood sample from patient. The fluorescence microscope generates a large number of images per each sample, and images contain a lot of cells. There are only a few CTCs in images and cells often have blurry boundaries. So CTCs identification is not an easy work for pathologists. In this paper, we develop an automatic CTCs identification method in fluorescence microscopy images. This proposed method has three section. In the first approach, we conduct the cell segmentation in images by using filtering methods. Next, we compute feature values from each CTC candidate region. Finally, we identify CTCs using artificial neural network algorithm. We apply the proposed method to 5895 microscopy images (7 samplesas), and evaluate the effectiveness of our proposed method by using leave-one-out cross validation. We achieve the result of performance tests, a true positive rate is 92.57% and false positive rate is 9.156%.
关键词: Fluorescence microscopy image,Artificial neural network,Feature analysis,Computer aided diagnosis,Circulating tumor cells
更新于2025-09-23 15:22:29
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Carbon Dots Dispersed on Graphene/SiO <sub/>2</sub> /Si: A Morphological Study
摘要: Low-dimensional carbon materials occupy a relevant role in the field of nanotechnology. Herein, the authors report a study conducted by atomic force microscopy and Raman spectroscopy on the deposition of carbon dots onto graphene surfaces. The study aims at understanding if and how the morphology and the microstructure of chemical vapor deposited graphene on Si/SiO2 may change due to the interaction with the carbon dots. Potential alteration in the graphene’s electrical properties might be detrimental for optoelectronic applications. The deposition of carbon dots dispersed in water and ethanol solvents are explored to investigate the effect of solvents with different fluidic properties. The obtained results indicate that the carbon dots do not alter the quality of graphene.
关键词: Raman spectroscopy,carbon dots,atomic force microscopy,chemical vapor deposited graphene
更新于2025-09-23 15:22:29
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In vivo confocal microscopy morphometric analysis of corneal subbasal nerve plexus in dry eye disease using newly developed fully automated system
摘要: Purpose To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software BACCMetrics,^ and to further investigate its diagnostic performance in discriminating DED patients. Methods IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann–Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls. Results Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/ mm2; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm2; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm2; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm2; always p < 0.024). CNFW value had the highest diagnostic power in discriminating DED patients (AUC = 0.828). When the diagnosis of DED was made based on either CNFW or CNBD, the sensitivity was 97.4% and the specificity 46.7%. Conclusions The software ACCMetrics was able to rapidly detect SNP alterations occurring in the setting of DED and showed good diagnostic performance in discriminating DED patients.
关键词: Dry eye,Sub-basal nerve plexus,Automated analysis,ACCMetrics,In vivo confocal microscopy
更新于2025-09-23 15:22:29
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Depinning Field of Vortex Domain Wall in Wide Magnetic Wires with Asymmetric Notches Using Magneto-Optical Kerr Effect Microscopy
摘要: We examined the pinning and depinning fields of the vortex domain wall (VDW) in wide permalloy wires to better understand VDW dynamic behavior. Our sample device has differently designed notches at the center of a 2-μm-wide wire. The notch depth ratio ranged from 0.2 to 0.8, and the asymmetric angles of the notches are 45°, 60°, and 75°. The depinning field was found to have two distribution ranges, similar to how the depinning field depends on VDW chirality in submicron size width wire. Our results also showed that the VDW depinning behavior of a wide wire is the same as that of a narrow wire. The asymmetric notch angle affected the depinning field, which was similar to the results of simulation with 400-nm wire. This suggests that the wide wire depinning field is similar to that of narrow wire.
关键词: vortex domain wall,Magneto-optical Kerr effect microscopy,depinning field
更新于2025-09-23 15:22:29
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In vivo measurement of blood clot mechanics from computational fluid dynamics based on intravital microscopy images
摘要: Ischemia which leads to heart attacks and strokes is one of the major causes of death in the world. Whether an occlusion occurs or not depends on the ability of a growing thrombus to resist flow forces exerted on its structure. This manuscript provides the first known in vivo measurement of how much stress a clot can withstand, before yielding to the surrounding blood flow. Namely, Lattice-Boltzmann Method flow simulations are performed based on 3D clot geometries, which are estimated from intravital microscopy images of laser-induced injuries in cremaster microvasculature of live mice. In addition to reporting the blood clot yield stresses, we also show that the thrombus 'core' does not experience significant deformation, while its 'shell' does. This indicates that the shell is more prone to embolization. Therefore, drugs should be designed to target the shell selectively, while leaving the core intact to minimize excessive bleeding. Finally, we laid down a foundation for a nondimensionalization procedure which unraveled a relationship between clot mechanics and biology. Hence, the proposed framework could ultimately lead to a unified theory of thrombogenesis, capable of explaining all clotting events. Thus, the findings presented herein will be beneficial to the understanding and treatment of heart attacks, strokes and hemophilia.
关键词: Yielding,Blood,Simulation,Microscopy,Thrombus,Lattice Boltzmann Method
更新于2025-09-23 15:22:29