scholarly journals Label-free imaging of collagen fibers in tissue slices using phase imaging with computational specificity

2021 ◽  
Author(s):  
Masayoshi Sakakura ◽  
Gabriel Popescu ◽  
Andre Kajdacsy-Balla ◽  
Virgilia Macias
Keyword(s):  
Second Harmonic ◽  
Imaging Modality ◽  
High Specificity ◽  
Ground Truth ◽  
Collagen Fibers ◽  
Nonlinear Susceptibility ◽  
Phase Imaging ◽  
Label Free ◽  
Tissue Slices ◽  
Disease Stratification

Evaluating the tissue collagen content in addition to the epithelial morphology has been proven to offer complementary information in histopathology, especially in disease stratification and patient survivability prediction. One imaging modality widely used for this purpose is second harmonic generation microscopy (SHGM), which reports on the nonlinear susceptibility associated with the collagen fibers. Another method is polarization light microscopy (PLM) combined with picrosirius-red (PSR) tissue staining. However, SHGM requires expensive equipment and provides limited throughput, while PLM and PSR staining are not part of the routine pathology workflow. Here, we advance phase imaging with computational specificity (PICS) to computationally infer the collagen distribution of unlabeled tissue, with high specificity. PICS utilizes deep learning to translate quantitative phase images (QPI) into corresponding PSR images with high accuracy and speed. Our results indicate that the distributions of collagen fiber orientation, length, and straightness reported by PICS closely match the ones from ground truth.

Label-free second-harmonic phase imaging of biological specimen by digital holographic microscopy

2010 ◽  
Vol 35 (24) ◽  
pp. 4102 ◽  
Author(s):  
Etienne Shaffer ◽  
Corinne Moratal ◽  
Pierre Magistretti ◽  
Pierre Marquet ◽  
Christian Depeursinge
Keyword(s):  
Second Harmonic ◽  
Digital Holographic Microscopy ◽  
Phase Imaging ◽  
Label Free ◽  
Biological Specimen ◽  
Harmonic Phase ◽  
Holographic Microscopy ◽  
Harmonic Phase Imaging

scholarly journals Label-free SARS-CoV-2 detection and classification using phase imaging with computational specificity

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Neha Goswami ◽  
Yuchen R. He ◽  
Yu-Heng Deng ◽  
Chamteut Oh ◽  
Nahil Sobh ◽  
...  
Keyword(s):  
Neural Network ◽  
Influenza A ◽  
Digital Pathology ◽  
Ground Truth ◽  
Optical Path Length ◽  
Phase Imaging ◽  
Processing Unit ◽  
Label Free ◽  
Interferometric Method ◽  
Viral Particles

AbstractEfforts to mitigate the COVID-19 crisis revealed that fast, accurate, and scalable testing is crucial for curbing the current impact and that of future pandemics. We propose an optical method for directly imaging unlabeled viral particles and using deep learning for detection and classification. An ultrasensitive interferometric method was used to image four virus types with nanoscale optical path-length sensitivity. Pairing these data with fluorescence images for ground truth, we trained semantic segmentation models based on U-Net, a particular type of convolutional neural network. The trained network was applied to classify the viruses from the interferometric images only, containing simultaneously SARS-CoV-2, H1N1 (influenza-A virus), HAdV (adenovirus), and ZIKV (Zika virus). Remarkably, due to the nanoscale sensitivity in the input data, the neural network was able to identify SARS-CoV-2 vs. the other viruses with 96% accuracy. The inference time for each image is 60 ms, on a common graphic-processing unit. This approach of directly imaging unlabeled viral particles may provide an extremely fast test, of less than a minute per patient. As the imaging instrument operates on regular glass slides, we envision this method as potentially testing on patient breath condensates. The necessary high throughput can be achieved by translating concepts from digital pathology, where a microscope can scan hundreds of slides automatically.

scholarly journals Digital Histology by Phase Imaging Specific Biomarkers for Human Tumoral Tissues Discrimination

2021 ◽  
Vol 11 (13) ◽  
pp. 6142
Author(s):  
José Luis Ganoza-Quintana ◽  
Félix Fanjul-Vélez ◽  
José Luis Arce-Diego
Keyword(s):  
Fractal Dimension ◽  
Phase Contrast ◽  
Tissue Type ◽  
P Value ◽  
Phase Imaging ◽  
The Novel ◽  
Label Free ◽  
External Scale ◽  
Tissue Slices ◽  
Fresh Tissue

Histology is the diagnosis gold standard. Conventional biopsy presents artifacts, delays, or human bias. Digital histology includes automation and improved diagnosis. It digitalizes microscopic images of histological samples and analyzes similar parameters. The present approach proposes the novel use of phase contrast in clinical digital histology to improve diagnosis. The use of label-free fresh tissue slices prevents processing artifacts and reduces processing time. Phase contrast parameters are implemented and calculated: the external scale, the fractal dimension, the anisotropy factor, the scattering coefficient, and the refractive index variance. Images of healthy and tumoral samples of liver, colon, and kidney are employed. A total of 252 images with 10×, 20×, and 40× magnifications are measured. Discrimination significance between healthy and tumoral tissues is assessed statistically with ANOVA (p-value < 0.005). The analysis is made for each tissue type and for different magnifications. It shows a dependence on tissue type and image magnification. The p-value of the most significant parameters is below 10−5. Liver and colon tissues present a great overlap in significant phase contrast parameters. The 10× fractal dimension is significant for all tissue types under analysis. These results are promising for the use of phase contrast in digital histology clinical praxis.

Second Harmonic Generation Imaging (SHG) in the Non-Linear Optical Microscopy of Living Cells

1998 ◽  
Vol 4 (S2) ◽  
pp. 414-415
Author(s):  
P.J. Campagnola ◽  
L.M. Loew
Keyword(s):  
Second Harmonic Generation ◽  
Optical Microscopy ◽  
Harmonic Generation ◽  
Focal Plane ◽  
Laser Scanning ◽  
Second Harmonic ◽  
High Specificity ◽  
Nonlinear Susceptibility ◽  
Interfacial Region ◽  
Contrast Mechanism

In recent years there has been considerable interest in two and three-photon excited fluorescence in laser scanning optical microscopy. Because absorption is confined tot he focal plane of the objective, these techniques provide intrinsic optical sectioning without the use of a confocal aperture. In addition, photobleaching and phototoxicity are greatly reduced above and below the focal plane. We have adapted a two-photon microscope to utilize surface second harmonic generation (SHG) as a new contrast mechanism for nonlinear optical biological imaging.Surface SHG was first described by Shen [1] and arises from the second order nonlinear susceptibility, χ(2). Signal will only arise from a non-centrosymmetric environment such as an interfacial region. Thus this technique has the potential to probe cellular membranes at high specificity. Further, since SHG results from an induced polarization and not absorption, photobleaching considerations are greatly reduced over fluorescence based methods.

scholarly journals Epi-illumination gradient light interference microscopy for imaging opaque structures

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Mikhail E. Kandel ◽  
Chenfei Hu ◽  
Ghazal Naseri Kouzehgarani ◽  
Eunjung Min ◽  
Kathryn Michele Sullivan ◽  
...  
Keyword(s):  
Multiple Scattering ◽  
Imaging Modality ◽  
Single Cells ◽  
Scattering Problem ◽  
Biological Tissues ◽  
Interference Microscopy ◽  
Model Organisms ◽  
Phase Imaging ◽  
Label Free ◽  
Light Interference

Abstract Multiple scattering and absorption limit the depth at which biological tissues can be imaged with light. In thick unlabeled specimens, multiple scattering randomizes the phase of the field and absorption attenuates light that travels long optical paths. These obstacles limit the performance of transmission imaging. To mitigate these challenges, we developed an epi-illumination gradient light interference microscope (epi-GLIM) as a label-free phase imaging modality applicable to bulk or opaque samples. Epi-GLIM enables studying turbid structures that are hundreds of microns thick and otherwise opaque to transmitted light. We demonstrate this approach with a variety of man-made and biological samples that are incompatible with imaging in a transmission geometry: semiconductors wafers, specimens on opaque and birefringent substrates, cells in microplates, and bulk tissues. We demonstrate that the epi-GLIM data can be used to solve the inverse scattering problem and reconstruct the tomography of single cells and model organisms.

scholarly journals Phase imaging with computational specificity (PICS) for measuring dry mass changes in sub-cellular compartments

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mikhail E. Kandel ◽  
Yuchen R. He ◽  
Young Jae Lee ◽  
Taylor Hsuan-Yu Chen ◽  
Kathryn Michele Sullivan ◽  
...  
Keyword(s):  
Cell Biology ◽  
Imaging System ◽  
High Specificity ◽  
Dry Mass ◽  
Live Cells ◽  
Phase Imaging ◽  
Label Free ◽  
Quantitative Phase Imaging ◽  
Cell Nuclei ◽  
Quantitative Phase

AbstractDue to its specificity, fluorescence microscopy has become a quintessential imaging tool in cell biology. However, photobleaching, phototoxicity, and related artifacts continue to limit fluorescence microscopy’s utility. Recently, it has been shown that artificial intelligence (AI) can transform one form of contrast into another. We present phase imaging with computational specificity (PICS), a combination of quantitative phase imaging and AI, which provides information about unlabeled live cells with high specificity. Our imaging system allows for automatic training, while inference is built into the acquisition software and runs in real-time. Applying the computed fluorescence maps back to the quantitative phase imaging (QPI) data, we measured the growth of both nuclei and cytoplasm independently, over many days, without loss of viability. Using a QPI method that suppresses multiple scattering, we measured the dry mass content of individual cell nuclei within spheroids. In its current implementation, PICS offers a versatile quantitative technique for continuous simultaneous monitoring of individual cellular components in biological applications where long-term label-free imaging is desirable.

scholarly journals Radiochemistry, Production Processes, Labeling Methods, and ImmunoPET Imaging Pharmaceuticals of Iodine-124

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 414
Author(s):  
Krishan Kumar ◽  
Arijit Ghosh
Keyword(s):  
Physical Properties ◽  
Imaging Modality ◽  
Target Selection ◽  
Positron Emission Tomography Imaging ◽  
High Sensitivity ◽  
High Specificity ◽  
Production Processes ◽  
Positron Emission ◽  
Significant Research ◽  
Clinical Environments

Target-specific biomolecules, monoclonal antibodies (mAb), proteins, and protein fragments are known to have high specificity and affinity for receptors associated with tumors and other pathological conditions. However, the large biomolecules have relatively intermediate to long circulation half-lives (>day) and tumor localization times. Combining superior target specificity of mAbs and high sensitivity and resolution of the PET (Positron Emission Tomography) imaging technique has created a paradigm-shifting imaging modality, ImmunoPET. In addition to metallic PET radionuclides, 124I is an attractive radionuclide for radiolabeling of mAbs as potential immunoPET imaging pharmaceuticals due to its physical properties (decay characteristics and half-life), easy and routine production by cyclotrons, and well-established methodologies for radioiodination. The objective of this report is to provide a comprehensive review of the physical properties of iodine and iodine radionuclides, production processes of 124I, various 124I-labeling methodologies for large biomolecules, mAbs, and the development of 124I-labeled immunoPET imaging pharmaceuticals for various cancer targets in preclinical and clinical environments. A summary of several production processes, including 123Te(d,n)124I, 124Te(d,2n)124I, 121Sb(α,n)124I, 123Sb(α,3n)124I, 123Sb(3He,2n)124I, natSb(α, xn)124I, natSb(3He,n)124I reactions, a detailed overview of the 124Te(p,n)124I reaction (including target selection, preparation, processing, and recovery of 124I), and a fully automated process that can be scaled up for GMP (Good Manufacturing Practices) production of large quantities of 124I is provided. Direct, using inorganic and organic oxidizing agents and enzyme catalysis, and indirect, using prosthetic groups, 124I-labeling techniques have been discussed. Significant research has been conducted, in more than the last two decades, in the development of 124I-labeled immunoPET imaging pharmaceuticals for target-specific cancer detection. Details of preclinical and clinical evaluations of the potential 124I-labeled immunoPET imaging pharmaceuticals are described here.

scholarly journals Identification of Skin Lesions by Using Single-Step Multiframe Detector

2021 ◽  
Vol 10 (1) ◽  
pp. 144
Author(s):  
Yu-Ping Hsiao ◽  
Chih-Wei Chiu ◽  
Chih-Wei Lu ◽  
Hong Thai Nguyen ◽  
Yu Sheng Tseng ◽  
...  
Keyword(s):  
Ground Truth ◽  
Skin Lesions ◽  
Single Step ◽  
Single Shot ◽  
Accuracy Rate ◽  
Tissue Slices ◽  
Image Detection ◽  
Sensitivity Rate ◽  
Diagnosis Accuracy ◽  
Artificial Intelligence Algorithm

An artificial intelligence algorithm to detect mycosis fungoides (MF), psoriasis (PSO), and atopic dermatitis (AD) is demonstrated. Results showed that 10 s was consumed by the single shot multibox detector (SSD) model to analyze 292 test images, among which 273 images were correctly detected. Verification of ground truth samples of this research come from pathological tissue slices and OCT analysis. The SSD diagnosis accuracy rate was 93%. The sensitivity values of the SSD model in diagnosing the skin lesions according to the symptoms of PSO, AD, MF, and normal were 96%, 80%, 94%, and 95%, and the corresponding precision were 96%, 86%, 98%, and 90%. The highest sensitivity rate was found in MF probably because of the spread of cancer cells in the skin and relatively large lesions of MF. Many differences were found in the accuracy between AD and the other diseases. The collected AD images were all in the elbow or arm and other joints, the area with AD was small, and the features were not obvious. Hence, the proposed SSD could be used to identify the four diseases by using skin image detection, but the diagnosis of AD was relatively poor.

scholarly journals Advanced Label-Free Laser Scanning Microscopy and Its Biological Imaging Application

2021 ◽  
Vol 11 (3) ◽  
pp. 1002
Author(s):  
Xue Wang ◽  
Xinchao Lu ◽  
Chengjun Huang
Keyword(s):  
Laser Scanning ◽  
Second Harmonic ◽  
Biological Tissues ◽  
Biological Imaging ◽  
Laser Scanning Microscopy ◽  
Scanning Microscopy ◽  
Localized Surface Plasmon ◽  
Label Free ◽  
Coherent Raman ◽  
Surface Plasmon Microscopy

By eliminating the photodamage and photobleaching induced by high intensity laser and fluorescent molecular, the label-free laser scanning microscopy shows powerful capability for imaging and dynamic tracing to biological tissues and cells. In this review, three types of label-free laser scanning microscopies: laser scanning coherent Raman scattering microscopy, second harmonic generation microscopy and scanning localized surface plasmon microscopy are discussed with their fundamentals, features and recent progress. The applications of label-free biological imaging of these laser scanning microscopies are also introduced. Finally, the performance of the microscopies is compared and the limitation and perspectives are summarized.

Enhancement of second harmonic generation using a novel asymmetric metal–graphene–insulator–metal plasmonic waveguide

2018 ◽  
Vol 27 (01) ◽  
pp. 1850003 ◽  
Author(s):  
Mohamadreza Soltani
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Nonlinear Optical ◽  
Second Harmonic ◽  
Field Enhancement ◽  
The Other ◽  
Nonlinear Susceptibility ◽  
Optical Process ◽  
Large Enhancement ◽  
Nonlinear Optical Process

Here, we propose a novel plasmonic structure, called asymmetric plasmonic nanocavity grating (APNCG), which is shown to dramatically enhance nonlinear optical process of second harmonic generation (SHG). The proposed structure consists of two different metals on both sides of lithium niobate and a thin layer of graphene. By using two different metals the nonlinear susceptibility of the waveguide would be increased noticeably causing to increase SHG. On the other hand, it consists of two identical gratings on one side. By two identical gratings, the pump beam is coupled to two opposing SPP waves, which interfere with each other and result in SPP standing wave in the region between the two gratings. The distance between two gratings will be optimized to reach the highest SHG. It will be shown that by optimizing the geometry of proposed structure and using different metals, field enhancement in APNCG waveguides can result in large enhancement of SHG.

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