High-resolution Optical Imaging System Research Articles

Extended depth of field of an imaging system with an annular aperture.

A common drawback of high-resolution optical imaging systems is a short depth of field. In this work, we address this problem by considering a 4f-type imaging system with a ring-shaped aperture in the front focal plane of the second lens. The aperture makes the image consist of nearly non-diverging Bessel-like beams and considerably extends the depth of field. We consider both spatially coherent and incoherent systems and show that only incoherent light is able to form sharp and non-distorted images with extraordinarily long depth of field.

Template-free synthesis of perovskite (PEA)2PbI4 nanowires by ion-intercalation processing for single-nanowire photodetectors

Being different from the bulk semiconductors, one-dimensional (1D) semiconductor nanowires (NWs) have showed advantages such as high-density data storage, large-scale optoelectronic integration, and high-resolution optical imaging systems. Here, a template-free synthesis of perovskite (PEA)2PbI4 NWs by ion-intercalation processing and their applications for single-nanowire based photodetectors Ag/(PEA)2PbI4/Ag fabricated through interdigital electrodes, are presented. The dark current from the as-fabricated photodetectors Ag/(PEA)2PbI4/Ag is very low (∼ 4.792 ×10−11 A) due to the large electrode spacing, and a high responsivity of 2.098 A/W with a specific detectivity of 1.752 × 1012 Jones under 4.99 μW/cm2 520 nm illumination, and a high responsivity of 1.998 A/W with a specific detectivity of 1.669 × 1012 Jones under 5.01 μW/cm2 365 nm illumination, were obtained at − 5 V. Therefore, such a feasible synthesis method provides a promising way for low-cost, template-free, easy transferring for solution-synthesized perovskite NWs with high yield and repeatability, as well as for enhanced-performance individual NW optoelectronics.

A Convolutional Neural Network to Classify Phytoplankton Images Along the West Antarctic Peninsula

AbstractHigh-resolution optical imaging systems are quickly becoming universal tools to characterize and quantify microbial diversity in marine ecosystems. Automated classification systems such as convolutional neural networks (CNNs) are often developed to identify species within the immense number of images (e.g., millions per month) collected. The goal of our study was to develop a CNN to classify phytoplankton images collected with an Imaging FlowCytobot for the Palmer Antarctica Long-Term Ecological Research project. A relatively small CNN (~2 million parameters) was developed and trained using a subset of manually identified images, resulting in an overall test accuracy, recall, and f1-score of 93.8, 93.7, and 93.7%, respectively, on a balanced dataset. However, the f1-score dropped to 46.5% when tested on a dataset of 10,269 new images drawn from the natural environment without balancing classes. This decrease is likely due to highly imbalanced class distributions dominated by smaller, less differentiable cells, high intraclass variance, and interclass morphological similarities of cells in naturally occurring phytoplankton assemblages. As a case study to illustrate the value of the model, it was used to predict taxonomic classifications (ranging from genus to class) of phytoplankton at Palmer Station, Antarctica, from late austral spring to early autumn in 2017‐2018 and 2018‐2019. The CNN was generally able to identify important seasonal dynamics such as the shift from large centric diatoms to small pennate diatoms in both years, which is thought to be driven by increases in glacial meltwater from January to March. This shift in particle size distribution has significant implications for the ecology and biogeochemistry of these waters. Moving forward, we hope to further increase the accuracy of our model to better characterize coastal phytoplankton communities threatened by rapidly changing environmental conditions.

A Convolutional Neural Network to Classify Phytoplankton Images Along the West Antarctic Peninsula

Abstract High-resolution optical imaging systems are quickly becoming universal tools to characterize and quantify microbial diversity in marine ecosystems. Automated classification systems such as convolutional neural networks (CNNs) are often developed to identify species within the immense number of images (e.g., millions per month) collected. The goal of our study was to develop a CNN to classify phytoplankton images collected with an Imaging FlowCytobot for the Palmer Antarctica Long-Term Ecological Research project. A relatively small CNN (~2 million parameters) was developed and trained using a subset of manually identified images, resulting in an overall test accuracy, recall, and f1-score of 93.8, 93.7, and 93.7%, respectively, on a balanced dataset. However, the f1-score dropped to 46.5% when tested on a dataset of 10,269 new images drawn from the natural environment without balancing classes. This decrease is likely due to highly imbalanced class distributions dominated by smaller, less differentiable cells, high intraclass variance, and interclass morphological similarities of cells in naturally occurring phytoplankton assemblages. As a case study to illustrate the value of the model, it was used to predict taxonomic classifications (ranging from genus to class) of phytoplankton at Palmer Station, Antarctica, from late austral spring to early autumn in 2017‐2018 and 2018‐2019. The CNN was generally able to identify important seasonal dynamics such as the shift from large centric diatoms to small pennate diatoms in both years, which is thought to be driven by increases in glacial meltwater from January to March. This shift in particle size distribution has significant implications for the ecology and biogeochemistry of these waters. Moving forward, we hope to further increase the accuracy of our model to better characterize coastal phytoplankton communities threatened by rapidly changing environmental conditions.

Generation of 2D Airy beams with switchable metasurfaces.

Airy beams exhibit intriguing characteristics, such as diffraction-free propagation, self-acceleration, and self-healing, which have aroused great research interest. However, the spatial light modulator that generates Airy beams has problems such as narrow operational bandwidth, high cost, poor phase discretization, and single realization function. In the visible region (λ∼532 nm), we proposed a switchable all-dielectric metasurface for generating transmissive and reflective two-dimensional (2D) Airy beams. The metasurface was mainly composed of titanium dioxide nanopillars and vanadium dioxide substrate. Based on the Pancharatnam-Berry phase principle, a high-efficient Airy beam can be generated by controlling the phase transition of vanadium dioxide and changing the polarization state of the incident light. The optimized optical intensity conversion efficiencies of the transmissive and reflective metasurfaces were as high as 97% and 70%, respectively. In the field of biomedical and applied physics, our designed switchable metasurface is expected to offer the possibility of creating compact optical and photonic platforms for efficient generation and dynamic modulation of optical beams and open up a novel path for the application of high-resolution optical imaging systems.

The detection of cervical neoplasia via optical ımaging: a pilot clinical study.

The present study aims to develop a new high-resolution imaging system for the early diagnosis of cervical neoplasia based on increased vessel density of the cervical tissue. An optical device was developed to obtain high contrast and resolution images of vascular structures of the cervix in the present study. The device utilizes a telecentric lens to capture cervix images under light illumination with a wavelength of 550nm emitted from LEDs. Images were obtained using the telecentric lens with or without acetic acid application to the cervix. Image processing algorithms were used to contrast and extract the skeleton of the vascular structures on the cervix. In the evaluation of the vascular density, the cervical images were divided into 12 o'clock positions, and the fractal dimension of the vascularity was calculated for each dial area between the o'clock positions. The region with the largest fractal dimension was accepted as the region with the highest probability of lesion. The range of vessel sizes was split into small classes of "bins" for each dial area with the highest fractal dimension. To validate the system's success in differentiating between normal and HSIL lesions, forty five patients who underwent colposcopy and biopsy were included in a pilot study. The system correctly classified four HSIL cases out of five and failed to detect one HSIL case, achieving an accuracy rate of 97.8% with an 80% sensitivity and 100% specificity. The developed high-resolution optical imaging system may potentially be used in detecting cervical neoplasia just before the biopsy and reduce the number of false-positive cases.

Integrative microendoscopic system combined with conventional microscope for live animal tissue imaging.

Intravital optical imaging technology is essential for minimally invasive optical diagnosis and treatment in small animal disease models. High-resolution imaging requires high-resolution optical probes, and high-resolution optical imaging systems based on highly precise and advanced technologies and therefore, associated with high-system costs. Besides, in order to acquire small animal live images, special types of animal imaging setups are indispensable. In this paper, a microendoscopic system is designed as an add-on to existing conventional imaging microscopes, reducing the price of complete confocal endomicroscopic systems. The proposed attachable system can be configured for confocal microscopes from common manufacturers and this enables users to acquire live animal cellular images from a conventional system. It features a 4f optical plane relay system, a rotary stage for side-view endoscopic probes, and an endoscopic probe mount which swings between the horizontal and the vertical. The system could be widely useful for biological studies of animal physiology and disease models.

Development of a Single-Board Computer High-Resolution Microendoscope (PiHRME) to Detect Cervical Cancer in Low-Resource Settings

Abstract 35 Almost 90% of cervical cancer deaths occur in developing countries, with the highest incidence rates occurring in Central and South America and sub-Saharan Africa.1 While early detection and treatment of cervical precancerous lesions effectively prevent the development of invasive cervical cancer, limited resources and infrastructure make it difficult to implement standard cervical cancer screening methods in low-resource areas. In many low-resource areas, health workers use visual inspection of the cervix following the application of acetic acid (VIA) to identify precancerous lesions. While VIA reduces cervical cancer mortality, it is associated with a low specificity. A number of recent studies have shown that high-resolution optical imaging can identify precancerous lesions in vivo with higher specificity than VIA; however, the cost of these imaging systems is a barrier to wider scale implementation. We therefore have developed a low-cost, high-resolution microendoscope controlled by a single-board computer (PiHRME) to detect cervical precancerous lesions at the point-of-care. The PiHRME allows healthcare providers to image the cervix in vivo and view cervical epithelial cells in real time with sub-cellular resolution. Here we demonstrate that a low cost ($35) single-board computer, the Raspberry Pi, can be used to reduce the cost and improve the mobility of a high-resolution optical imaging system without compromising its spatial resolution. Thus, HRME screening of cervical cancer can be made more accessible in low-resource areas. The PiHRME is currently being evaluated in a pilot study in El Salvador to assess its effectiveness at the point-of-care. 1American Cancer Society. Global Cancer Facts & Figures 3rd Edition. Atlanta: American Cancer Society; 2015. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Sonia Parra No relationship to disclose Pelham Keahey No relationship to disclose Kathleen Schmeler Research Funding: Cepheid Patents, Royalties, Other Intellectual Property: UpToDate Mauricio Maza No relationship to disclose Philip Castle Honoraria: Roche, Cepheid Consulting or Advisory Role: Cepheid, GE Healthcare, Guided Therapeutics, ClearPath, Merck, Genticel, Teva, Inovio Pharmaceuticals, Hologic Rebecca R. Richards-Kortum Honoraria: Jannsen Global Services Research Funding: Merck Patents, Royalties, Other Intellectual Property: Patents

Computed Optical Interferometric Imaging: Methods, Achievements, and Challenges.

Three-dimensional high-resolution optical imaging systems are generally restricted by the trade-off between resolution and depth-of-field as well as imperfections in the imaging system or sample. Computed optical interferometric imaging is able to overcome these longstanding limitations using methods such as interferometric synthetic aperture microscopy (ISAM) and computational adaptive optics (CAO) which manipulate the complex interferometric data. These techniques correct for limited depth-of-field and optical aberrations without the need for additional hardware. This paper aims to outline these computational methods, making them readily available to the research community. Achievements of the techniques will be highlighted, along with past and present challenges in implementing the techniques. Challenges such as phase instability and determination of the appropriate aberration correction have been largely overcome so that imaging of living tissues using ISAM and CAO is now possible. Computed imaging in optics is becoming a mature technology poised to make a significant impact in medicine and biology.

Design and simulation of high resolution optical imaging system based on near-field using solid immersion lens with NA = 2.2

In this work, by changing annular aperture zones transmittance, we could get a spot size smaller than any reported one by utilizing annular aperture. Where, by dividing the annular aperture to more than three zones and utilizing of Sony corporation Produced SIL that has NA higher than 2, we could improve imaging resolution for radial polarization (RP); also we could decrease the FWHM from around to near . Here, the FWHM variation, according to the refractive index changing, has decreased to zero for RP. After that, circular polarization (CP) has been introduced to get a spot size less than . This image resolution improving can be applied to enhance optical data storage, microscopes and lithographic and other high accurate optical systems.

Infinium Assay for Large-scale SNP Genotyping Applications

Genotyping variants in the human genome has proven to be an efficient method to identify genetic associations with phenotypes. The distribution of variants within families or populations can facilitate identification of the genetic factors of disease. Illumina's panel of genotyping BeadChips allows investigators to genotype thousands or millions of single nucleotide polymorphisms (SNPs) or to analyze other genomic variants, such as copy number, across a large number of DNA samples. These SNPs can be spread throughout the genome or targeted in specific regions in order to maximize potential discovery. The Infinium assay has been optimized to yield high-quality, accurate results quickly. With proper setup, a single technician can process from a few hundred to over a thousand DNA samples per week, depending on the type of array. This assay guides users through every step, starting with genomic DNA and ending with the scanning of the array. Using propriety reagents, samples are amplified, fragmented, precipitated, resuspended, hybridized to the chip, extended by a single base, stained, and scanned on either an iScan or Hi Scan high-resolution optical imaging system. One overnight step is required to amplify the DNA. The DNA is denatured and isothermally amplified by whole-genome amplification; therefore, no PCR is required. Samples are hybridized to the arrays during a second overnight step. By the third day, the samples are ready to be scanned and analyzed. Amplified DNA may be stockpiled in large quantities, allowing bead arrays to be processed every day of the week, thereby maximizing throughput.

Infinium Assay for Large-scale SNP Genotyping Applications

Genotyping variants in the human genome has proven to be an efficient method to identify genetic associations with phenotypes. The distribution of variants within families or populations can facilitate identification of the genetic factors of disease. Illumina's panel of genotyping BeadChips allows investigators to genotype thousands or millions of single nucleotide polymorphisms (SNPs) or to analyze other genomic variants, such as copy number, across a large number of DNA samples. These SNPs can be spread throughout the genome or targeted in specific regions in order to maximize potential discovery. The Infinium assay has been optimized to yield high-quality, accurate results quickly. With proper setup, a single technician can process from a few hundred to over a thousand DNA samples per week, depending on the type of array. This assay guides users through every step, starting with genomic DNA and ending with the scanning of the array. Using propriety reagents, samples are amplified, fragmented, precipitated, resuspended, hybridized to the chip, extended by a single base, stained, and scanned on either an iScan or Hi Scan high-resolution optical imaging system. One overnight step is required to amplify the DNA. The DNA is denatured and isothermally amplified by whole-genome amplification; therefore, no PCR is required. Samples are hybridized to the arrays during a second overnight step. By the third day, the samples are ready to be scanned and analyzed. Amplified DNA may be stockpiled in large quantities, allowing bead arrays to be processed every day of the week, thereby maximizing throughput.

Nanoscale Live Cell Optical Imaging of the Dynamics of Intracellular Microvesicles in Neural Cells

Recent advances in biotechnology and imaging technology have provided great opportunities to investigate cellular dynamics. Conventional imaging methods such as transmission electron microscopy, scanning electron microscopy, and atomic force microscopy are powerful techniques for cellular imaging, even at the nanoscale level. However, these techniques have limitations applications in live cell imaging because of the experimental preparation required, namely cell fixation, and the innately small field of view. In this study, we developed a nanoscale optical imaging (NOI) system that combines a conventional optical microscope with a high resolution dark-field condenser (Cytoviva, Inc.) and halogen illuminator. The NOI system's maximum resolution for live cell imaging is around 100 nm. We utilized NOI to investigate the dynamics of intracellular microvesicles of neural cells without immunocytological analysis. In particular, we studied direct, active random, and moderate random dynamic motions of intracellular microvesicles and visualized lysosomal vesicle changes after treatment of cells with a lysosomal inhibitor (NH4Cl). Our results indicate that the NOI system is a feasible, high-resolution optical imaging system for live small organelles that does not require complicated optics or immunocytological staining processes.

High-Resolution Microendoscopy for the Detection of Cervical Neoplasia in Low-Resource Settings

Cervical cancer is the second leading cause of cancer death among women in developing countries. Developing countries often lack infrastructure, cytotechnologists, and pathologists necessary to implement current screening tools. Due to their low cost and ease of interpretation at the point-of-care, optical imaging technologies may serve as an appropriate solution for cervical cancer screening in low resource settings. We have developed a high-resolution optical imaging system, the High Resolution Microendoscope (HRME), which can be used to interrogate clinically suspicious areas with subcellular spatial resolution, revealing changes in nuclear to cytoplasmic area ratio. In this pilot study carried out at the women's clinic of Princess Marina Hospital in Botswana, 52 unique sites were imaged in 26 patients, and the results were compared to histopathology as a reference standard. Quantitative high resolution imaging achieved a sensitivity and specificity of 86% and 87%, respectively, in differentiating neoplastic (≥CIN 2) tissue from non-neoplastic tissue. These results suggest the potential promise of HRME to assist in the detection of cervical neoplasia in low-resource settings.

Targeting of α ν β 3 -Integrins Expressed on Tumor Tissue and Neovasculature Using Fluorescent Small Molecules and Nanoparticles

Receptor-specific small molecules and nanoparticles are widely used in molecular imaging of tumors. Although some studies have described the relative strengths and weaknesses of the two approaches, reports of a direct comparison and analysis of the two strategies are lacking. Herein, we compared the tumor-targeting characteristics of a small near-infrared fluorescent compound (cypate-peptide conjugate) and relatively large perfluorocarbon-based nanoparticles (250 nm diameter) for imaging alpha(nu)beta(3)-integrin receptor expression in tumors. Near-infrared fluorescent small molecules and nanoparticles were administered to living mice bearing subcutaneous or intradermal syngeneic tumors and imaged with whole-body and high-resolution optical imaging systems. The nanoparticles, designed for vascular constraint, remained within the tumor vasculature while the small integrin-avid ligands diffused into the tissue to target integrin expression on tumor and endothelial cells. Targeted small-molecule and nanoparticle contrast agents preferentially accumulated in tumor tissue with tumor-to-muscle ratios of 8 and 7, respectively, compared with 3 for nontargeted nanoparticles. Fluorescent small molecular probes demonstrate greater overall early tumor contrast and rapid visualization of tumors, but the vascular-constrained nanoparticles are more selective for detecting cancer-induced angiogenesis. A combination of both imaging agents provides a strategy to image and quantify integrin expression in tumor tissue and tumor-induced neovascular systems.

Spatiotemporal patterns of neural activity in response to electroacupuncture stimulation in the rodent primary somatosensory cortex

Objectives: Optical imaging technique enables the recording of cortical activities in multiple sites of the primary somatosensory cortex in real time. The present study was aimed to visualize neural activity in response to the acupuncture stimulation in the rodent primary somatosensory cortex by a high-resolution optical imaging system using voltage-sensitive dyes.Methods: Optical imaging was exploited to examine the temporal–spatial characteristic of rat primary somatosensory cortex during electroacupuncture stimulation (6 mA intensity and 2 ms duration) at two pairs of acupuncture points (ST36-SP6 or GB34-BL57).Results: In terms of magnitude and duration of the optical response, there was no difference between ST36-SP6 and GB34-BL57 stimulations. Maximally activated sites by electroacupuncture stimulation to the different acupuncture points were spatially differentiated in rat primary somatosensory cortex.Discussion: The results indicate that neuronal responses to electroacupuncture stimulation can be visualized in rat primary somatosensory cortex using an optical imaging system. The topographical mapping of acupuncture points in primary somatosensory cortex will make a significant contribution to the understanding of neural mechanisms of the acupuncture treatment and Meridian phenomena.

A quantum gas microscope for detecting single atoms in a Hubbard-regime optical lattice

Recent years have seen tremendous progress in creating complex atomic many-body quantum systems. One approach is to use macroscopic, effectively thermodynamic ensembles of ultracold atoms to create quantum gases and strongly correlated states of matter, and to analyse the bulk properties of the ensemble. For example, bosonic and fermionic atoms in a Hubbard-regime optical lattice can be used for quantum simulations of solid-state models. The opposite approach is to build up microscopic quantum systems atom-by-atom, with complete control over all degrees of freedom. The atoms or ions act as qubits and allow the realization of quantum gates, with the goal of creating highly controllable quantum information systems. Until now, the macroscopic and microscopic strategies have been fairly disconnected. Here we present a quantum gas 'microscope' that bridges the two approaches, realizing a system in which atoms of a macroscopic ensemble are detected individually and a complete set of degrees of freedom for each of them is determined through preparation and measurement. By implementing a high-resolution optical imaging system, single atoms are detected with near-unity fidelity on individual sites of a Hubbard-regime optical lattice. The lattice itself is generated by projecting a holographic mask through the imaging system. It has an arbitrary geometry, chosen to support both strong tunnel coupling between lattice sites and strong on-site confinement. Our approach can be used to directly detect strongly correlated states of matter; in the context of condensed matter simulation, this corresponds to the detection of individual electrons in the simulated crystal. Also, the quantum gas microscope may enable addressing and read-out of large-scale quantum information systems based on ultracold atoms.

Delayed signal propagation via CA2 in rat hippocampal slices revealed by optical recording.

Signal propagation from mossy fibers to CA1 neurons was investigated in rat hippocampal slices by a combination of electrical and optical recordings. The slices were prepared by oblique sectioning of the middle part of the hippocampus to preserve fiber connections. The mossy fibers were stimulated to induce population spikes (PSs) and excitatory postsynaptic potentials in the middle part of the CA1 region. Latencies of maximal PSs in CA1 varied widely among slices; they ranged from 7 to 13.5 ms, with two maxima at 9 and 11.5 ms. The fastest PSs probably are evoked by the Schaffer collaterals that connect the CA3 and CA1 regions in the well-known trisynaptic circuit. However, the slower PSs suggest the existence of additional delayed inputs. To determine the source of the delayed input, slices were stained with a voltage-sensitive dye, RH482, and the optical signals relevant to membrane potential changes were detected by a high-resolution optical imaging system. Optical recording of responses to mossy fiber stimulation indicated two distinct types of signal propagation from CA3 to CA1. In preparations evincing the fast type of propagation, signals spread to CA1 within 7.2 ms after the mossy fiber stimulation. During such propagation, activity flowed directly from CA3 to the stratum radiatum of CA1. Other preparations illustrated slow signal propagation, in which optical signals were generated in CA2 before spreading to CA1. During such slow signal transmission, activity persisted in CA2 and its surrounding area for 3 ms before propagating to the strata radiatum and oriens in CA1. In such cases, CA1 activity was detected within 10.8 ms of mossy fiber stimulation. In some slices, a mixture of the fast and slow propagation patterns was observed, indicating that these two transmission modes can coexist. Our data reveal that CA2 neurons can transmit delayed excitatory signals to CA1 neurons. We therefore conclude that consideration of electrical signal propagation through the hippocampus should include flow through the CA2 region in addition to the traditional dentate gyrus-CA3-CA1 trisynaptic circuit.

High-Resolution Optical Measurements of Surface Roughness for Beta-Layered Deuterium-Tritium Solid Inside a Re-Entrant Copper Cylinder

A high-resolution optical imaging system and custom-designed image analysis software are used to make surface roughness measurements for deuterium-tritium (D-T) solid layers, equilibrated inside a ...