In vivo multimodal nonlinear optical imaging of mucosal tissue

NASA Astrophysics Data System (ADS)

Sun, Ju; Shilagard, Tuya; Bell, Brent; Motamedi, Massoud; Vargas, Gracie

2004-05-01

We present a multimodal nonlinear imaging approach to elucidate microstructures and spectroscopic features of oral mucosa and submucosa in vivo. The hamster buccal pouch was imaged using 3-D high resolution multiphoton and second harmonic generation microscopy. The multimodal imaging approach enables colocalization and differentiation of prominent known spectroscopic and structural features such as keratin, epithelial cells, and submucosal collagen at various depths in tissue. Visualization of cellular morphology and epithelial thickness are in excellent agreement with histological observations. These results suggest that multimodal nonlinear optical microscopy can be an effective tool for studying the physiology and pathology of mucosal tissue.

Observation of Multimode Quantum Correlations in Fiber Optical Solitons

NASA Astrophysics Data System (ADS)

Spälter, S.; Korolkova, N.; König, F.; Sizmann, A.; Leuchs, G.

1998-07-01

Quantum correlations of photon numbers in different spectral components of ultrashort optical solitons have been observed experimentally. These correlations are crucial for the understanding and characterization of the internal quantum structure of soliton pulses and contribute significantly to soliton squeezing by spectral filtering. The accessible information on the nonclassical state of the correlated spectral components is discussed with the example of two modes. The method may be generalized to obtain a complete quantum description of a multimode field.

Nearest clusters based partial least squares discriminant analysis for the classification of spectral data.

PubMed

Song, Weiran; Wang, Hui; Maguire, Paul; Nibouche, Omar

2018-06-07

Partial Least Squares Discriminant Analysis (PLS-DA) is one of the most effective multivariate analysis methods for spectral data analysis, which extracts latent variables and uses them to predict responses. In particular, it is an effective method for handling high-dimensional and collinear spectral data. However, PLS-DA does not explicitly address data multimodality, i.e., within-class multimodal distribution of data. In this paper, we present a novel method termed nearest clusters based PLS-DA (NCPLS-DA) for addressing the multimodality and nonlinearity issues explicitly and improving the performance of PLS-DA on spectral data classification. The new method applies hierarchical clustering to divide samples into clusters and calculates the corresponding centre of every cluster. For a given query point, only clusters whose centres are nearest to such a query point are used for PLS-DA. Such a method can provide a simple and effective tool for separating multimodal and nonlinear classes into clusters which are locally linear and unimodal. Experimental results on 17 datasets, including 12 UCI and 5 spectral datasets, show that NCPLS-DA can outperform 4 baseline methods, namely, PLS-DA, kernel PLS-DA, local PLS-DA and k-NN, achieving the highest classification accuracy most of the time. Copyright © 2018 Elsevier B.V. All rights reserved.

Spectrally resolved far-fields of terahertz quantum cascade lasers.

PubMed

Brandstetter, Martin; Schönhuber, Sebastian; Krall, Michael; Kainz, Martin A; Detz, Hermann; Zederbauer, Tobias; Andrews, Aaron M; Strasser, Gottfried; Unterrainer, Karl

2016-10-31

We demonstrate a convenient and fast method to measure the spectrally resolved far-fields of multimode terahertz quantum cascade lasers by combining a microbolometer focal plane array with an FTIR spectrometer. Far-fields of fundamental TM0 and higher lateral order TM1 modes of multimode Fabry-Pérot type lasers have been distinguished, which very well fit to the results obtained by a 3D finite-element simulation. Furthermore, multimode random laser cavities have been investigated, analyzing the contribution of each single laser mode to the total far-field. The presented method is thus an important tool to gain in-depth knowledge of the emission properties of multimode laser cavities at terahertz frequencies, which become increasingly important for future sensing applications.

Silicon Nitride Grating Coupler with Flexible Bandwidth Incorporating a Serially Concatenated Multimode Interference Filter

NASA Astrophysics Data System (ADS)

Kim, Woo-Ju; Lee, Hak-Soon; Lee, Sang-Shin

2012-04-01

A compact silicon nitride grating coupler with flexible bandwidth was demonstrated taking advantage of a basic grating integrated with a serially connected multistage multimode interference (MMI) filter. The spectral response could be tailored by varying the order of the MMI filter, without affecting the basic grating structure. The dependence of the spectral response of the proposed device on the order of the MMI stage was thoroughly investigated. As regards the fabricated grating coupler with a four-stage MMI filter, the observed spectral bandwidth was efficiently altered from 53 to 21 nm in the ˜1550 nm spectral band.

Integrated photoacoustic microscopy, optical coherence tomography, and fluorescence microscopy for multimodal chorioretinal imaging

NASA Astrophysics Data System (ADS)

Tian, Chao; Zhang, Wei; Nguyen, Van Phuc; Huang, Ziyi; Wang, Xueding; Paulus, Yannis M.

2018-02-01

Current clinical available retinal imaging techniques have limitations, including limited depth of penetration or requirement for the invasive injection of exogenous contrast agents. Here, we developed a novel multimodal imaging system for high-speed, high-resolution retinal imaging of larger animals, such as rabbits. The system integrates three state-of-the-art imaging modalities, including photoacoustic microscopy (PAM), optical coherence tomography (OCT), and fluorescence microscopy (FM). In vivo experimental results of rabbit eyes show that the PAM is able to visualize laser-induced retinal burns and distinguish individual eye blood vessels using a laser exposure dose of 80 nJ, which is well below the American National Standards Institute (ANSI) safety limit 160 nJ. The OCT can discern different retinal layers and visualize laser burns and choroidal detachments. The novel multi-modal imaging platform holds great promise in ophthalmic imaging.

A multimodal spectral approach to characterize rhythm in natural speech.

PubMed

Alexandrou, Anna Maria; Saarinen, Timo; Kujala, Jan; Salmelin, Riitta

2016-01-01

Human utterances demonstrate temporal patterning, also referred to as rhythm. While simple oromotor behaviors (e.g., chewing) feature a salient periodical structure, conversational speech displays a time-varying quasi-rhythmic pattern. Quantification of periodicity in speech is challenging. Unimodal spectral approaches have highlighted rhythmic aspects of speech. However, speech is a complex multimodal phenomenon that arises from the interplay of articulatory, respiratory, and vocal systems. The present study addressed the question of whether a multimodal spectral approach, in the form of coherence analysis between electromyographic (EMG) and acoustic signals, would allow one to characterize rhythm in natural speech more efficiently than a unimodal analysis. The main experimental task consisted of speech production at three speaking rates; a simple oromotor task served as control. The EMG-acoustic coherence emerged as a sensitive means of tracking speech rhythm, whereas spectral analysis of either EMG or acoustic amplitude envelope alone was less informative. Coherence metrics seem to distinguish and highlight rhythmic structure in natural speech.

Multimodal quantitative phase and fluorescence imaging of cell apoptosis

NASA Astrophysics Data System (ADS)

Fu, Xinye; Zuo, Chao; Yan, Hao

2017-06-01

Fluorescence microscopy, utilizing fluorescence labeling, has the capability to observe intercellular changes which transmitted and reflected light microscopy techniques cannot resolve. However, the parts without fluorescence labeling are not imaged. Hence, the processes simultaneously happen in these parts cannot be revealed. Meanwhile, fluorescence imaging is 2D imaging where information in the depth is missing. Therefore the information in labeling parts is also not complete. On the other hand, quantitative phase imaging is capable to image cells in 3D in real time through phase calculation. However, its resolution is limited by the optical diffraction and cannot observe intercellular changes below 200 nanometers. In this work, fluorescence imaging and quantitative phase imaging are combined to build a multimodal imaging system. Such system has the capability to simultaneously observe the detailed intercellular phenomenon and 3D cell morphology. In this study the proposed multimodal imaging system is used to observe the cell behavior in the cell apoptosis. The aim is to highlight the limitations of fluorescence microscopy and to point out the advantages of multimodal quantitative phase and fluorescence imaging. The proposed multimodal quantitative phase imaging could be further applied in cell related biomedical research, such as tumor.

Multimodal Nonlinear Optical Microscopy

PubMed Central

Yue, Shuhua; Slipchenko, Mikhail N.; Cheng, Ji-Xin

2013-01-01

Because each nonlinear optical (NLO) imaging modality is sensitive to specific molecules or structures, multimodal NLO imaging capitalizes the potential of NLO microscopy for studies of complex biological tissues. The coupling of multiphoton fluorescence, second harmonic generation, and coherent anti-Stokes Raman scattering (CARS) has allowed investigation of a broad range of biological questions concerning lipid metabolism, cancer development, cardiovascular disease, and skin biology. Moreover, recent research shows the great potential of using CARS microscope as a platform to develop more advanced NLO modalities such as electronic-resonance-enhanced four-wave mixing, stimulated Raman scattering, and pump-probe microscopy. This article reviews the various approaches developed for realization of multimodal NLO imaging as well as developments of new NLO modalities on a CARS microscope. Applications to various aspects of biological and biomedical research are discussed. PMID:24353747

Stent-induced coronary artery stenosis characterized by multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Wang, Han-Wei; Simianu, Vlad; Locker, Mattew J.; Cheng, Ji-Xin; Sturek, Michael

2011-02-01

We demonstrate for the first time the applicability of multimodal nonlinear optical (NLO) microscopy to the interrogation of stented coronary arteries under different diet and stent deployment conditions. Bare metal stents and Taxus drug-eluting stents (DES) were placed in coronary arteries of Ossabaw pigs of control and atherogenic diet groups. Multimodal NLO imaging was performed to inspect changes in arterial structures and compositions after stenting. Sum frequency generation, one of the multimodalities, was used for the quantitative analysis of collagen content in the peristent and in-stent artery segments of both pig groups. Atherogenic diet increased lipid and collagen in peristent segments. In-stent segments showed decreased collagen expression in neointima compared to media. Deployment of DES in atheromatous arteries inhibited collagen expression in the arterial media.

Advances in combined endoscopic fluorescence confocal microscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Risi, Matthew D.

Confocal microendoscopy provides real-time high resolution cellular level images via a minimally invasive procedure. Results from an ongoing clinical study to detect ovarian cancer with a novel confocal fluorescent microendoscope are presented. As an imaging modality, confocal fluorescence microendoscopy typically requires exogenous fluorophores, has a relatively limited penetration depth (100 μm), and often employs specialized aperture configurations to achieve real-time imaging in vivo. Two primary research directions designed to overcome these limitations and improve diagnostic capability are presented. Ideal confocal imaging performance is obtained with a scanning point illumination and confocal aperture, but this approach is often unsuitable for real-time, in vivo biomedical imaging. By scanning a slit aperture in one direction, image acquisition speeds are greatly increased, but at the cost of a reduction in image quality. The design, implementation, and experimental verification of a custom multi-point-scanning modification to a slit-scanning multi-spectral confocal microendoscope is presented. This new design improves the axial resolution while maintaining real-time imaging rates. In addition, the multi-point aperture geometry greatly reduces the effects of tissue scatter on imaging performance. Optical coherence tomography (OCT) has seen wide acceptance and FDA approval as a technique for ophthalmic retinal imaging, and has been adapted for endoscopic use. As a minimally invasive imaging technique, it provides morphological characteristics of tissues at a cellular level without requiring the use of exogenous fluorophores. OCT is capable of imaging deeper into biological tissue (˜1-2 mm) than confocal fluorescence microscopy. A theoretical analysis of the use of a fiber-bundle in spectral-domain OCT systems is presented. The fiber-bundle enables a flexible endoscopic design and provides fast, parallelized acquisition of the optical coherence tomography data. However, the multi-mode characteristic of the fibers in the fiber-bundle affects the depth sensitivity of the imaging system. A description of light interference in a multi-mode fiber is presented along with numerical simulations and experimental studies to illustrate the theoretical analysis.

Multimodal full-field optical coherence tomography on biological tissue: toward all optical digital pathology

NASA Astrophysics Data System (ADS)

Harms, F.; Dalimier, E.; Vermeulen, P.; Fragola, A.; Boccara, A. C.

2012-03-01

Optical Coherence Tomography (OCT) is an efficient technique for in-depth optical biopsy of biological tissues, relying on interferometric selection of ballistic photons. Full-Field Optical Coherence Tomography (FF-OCT) is an alternative approach to Fourier-domain OCT (spectral or swept-source), allowing parallel acquisition of en-face optical sections. Using medium numerical aperture objective, it is possible to reach an isotropic resolution of about 1x1x1 ìm. After stitching a grid of acquired images, FF-OCT gives access to the architecture of the tissue, for both macroscopic and microscopic structures, in a non-invasive process, which makes the technique particularly suitable for applications in pathology. Here we report a multimodal approach to FF-OCT, combining two Full-Field techniques for collecting a backscattered endogeneous OCT image and a fluorescence exogeneous image in parallel. Considering pathological diagnosis of cancer, visualization of cell nuclei is of paramount importance. OCT images, even for the highest resolution, usually fail to identify individual nuclei due to the nature of the optical contrast used. We have built a multimodal optical microscope based on the combination of FF-OCT and Structured Illumination Microscopy (SIM). We used x30 immersion objectives, with a numerical aperture of 1.05, allowing for sub-micron transverse resolution. Fluorescent staining of nuclei was obtained using specific fluorescent dyes such as acridine orange. We present multimodal images of healthy and pathological skin tissue at various scales. This instrumental development paves the way for improvements of standard pathology procedures, as a faster, non sacrificial, operator independent digital optical method compared to frozen sections.

A simple integrated ratiometric wavelength monitor based on multimode interference structure

NASA Astrophysics Data System (ADS)

Hatta, Agus Muhamad; Farrell, Gerald; Wang, Qian

2008-09-01

Wavelength measurement or monitoring can be implemented using a ratiometric power measurement technique. A ratiometric wavelength monitor normally consists of a Y-branch splitter with two arms: an edge filter arm with a well defined spectral response and a reference arm or alternatively, two edge filters arms with opposite slope spectral responses. In this paper, a simple configuration for an integrated ratiometric wavelength monitor based on a single multimode interference structure is proposed. By optimizing the length of the MMI and the two output port positions, opposite spectral responses for the two output ports can be achieved. The designed structure demonstrates a spectral response suitable for wavelength measurement with potentially a 10 pm resolution over a 100 nm wavelength range.

Local field enhancement and thermoplasmonics in multimodal aluminum structures

NASA Astrophysics Data System (ADS)

Wiecha, Peter R.; Mennemanteuil, Marie-Maxime; Khlopin, Dmitry; Martin, Jérôme; Arbouet, Arnaud; Gérard, Davy; Bouhelier, Alexandre; Plain, Jérôme; Cuche, Aurélien

2017-07-01

Aluminum nanostructures have recently been at the focus of numerous studies due to their properties including oxidation stability and surface plasmon resonances covering the ultraviolet and visible spectral windows. In this article, we reveal a facet of this metal relevant for both plasmonic purposes and photothermal conversion. The field distribution of high-order plasmonic resonances existing in two-dimensional Al structures is studied by nonlinear photoluminescence microscopy in a spectral region where electronic interband transitions occur. The polarization sensitivity of the field intensity maps shows that the electric field concentration can be addressed and controlled on demand. We use a numerical tool based on the Green dyadic method to analyze our results and to simulate the absorbed energy that is locally converted into heat. The polarization-dependent temperature increase of the Al structures is experimentally quantitatively measured, and is in an excellent agreement with theoretical predictions. Our work highlights Al as a promising candidate for designing thermal nanosources integrated in coplanar geometries for thermally assisted nanomanipulation or biophysical applications.

Simultaneous Teleportation of the Spectral and Polarization States of a Photon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humble, Travis S; Bennink, Ryan S; Grice, Warren P

2008-01-01

We describe how spectrally multimode, polarization-entangled photons simultaneously teleport quantum information encoded into the spectral and polarization degrees of freedom of a single photon using sum frequency generation to implement a Bell-state measurement.

FIBER AND INTEGRATED OPTICS: Analysis of the characteristics of a radio signal at the output of a multimode interference-type fiber channel

NASA Astrophysics Data System (ADS)

Bratchikov, A. N.; Glukhov, I. P.

1992-02-01

An analysis is made of a theoretical model of an interference fiber channel for transmission of microwave signals. It is assumed that the channel consists of a multimode fiber waveguide with a step or graded refractive-index profile. A typical statistic of a longitudinal distribution of inhomogeneities is also assumed. Calculations are reported of the interference losses, the spectral profile of the output radio signal, the signal/noise ratio in the channel, and of the dependences of these parameters on: the type, diameter, and the length of the multimode fiber waveguide; the spectral width of the radiation source; the frequency offset between the interfering optical signals.

Image recovery from defocused 2D fluorescent images in multimodal digital holographic microscopy.

PubMed

Quan, Xiangyu; Matoba, Osamu; Awatsuji, Yasuhiro

2017-05-01

A technique of three-dimensional (3D) intensity retrieval from defocused, two-dimensional (2D) fluorescent images in the multimodal digital holographic microscopy (DHM) is proposed. In the multimodal DHM, 3D phase and 2D fluorescence distributions are obtained simultaneously by an integrated system of an off-axis DHM and a conventional epifluorescence microscopy, respectively. This gives us more information of the target; however, defocused fluorescent images are observed due to the short depth of field. In this Letter, we propose a method to recover the defocused images based on the phase compensation and backpropagation from the defocused plane to the focused plane using the distance information that is obtained from a 3D phase distribution. By applying Zernike polynomial phase correction, we brought back the fluorescence intensity to the focused imaging planes. The experimental demonstration using fluorescent beads is presented, and the expected applications are suggested.

Theoretical analysis of the performance of code division multiple access communications over multimode optical fiber channels. Part 1: Transmission and detection

NASA Astrophysics Data System (ADS)

Walker, Ernest L.

1994-05-01

This paper presents results of a theoretical investigation to evaluate the performance of code division multiple access communications over multimode optical fiber channels in an asynchronous, multiuser communication network environment. The system is evaluated using Gold sequences for spectral spreading of the baseband signal from each user employing direct-sequence biphase shift keying and intensity modulation techniques. The transmission channel model employed is a lossless linear system approximation of the field transfer function for the alpha -profile multimode optical fiber. Due to channel model complexity, a correlation receiver model employing a suboptimal receive filter was used in calculating the peak output signal at the ith receiver. In Part 1, the performance measures for the system, i.e., signal-to-noise ratio and bit error probability for the ith receiver, are derived as functions of channel characteristics, spectral spreading, number of active users, and the bit energy to noise (white) spectral density ratio. In Part 2, the overall system performance is evaluated.

Co-registered Topographical, Band Excitation Nanomechanical, and Mass Spectral Imaging Using a Combined Atomic Force Microscopy/Mass Spectrometry Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ovchinnikova, Olga S.; Tai, Tamin; Bocharova, Vera

The advancement of a hybrid atomic force microscopy/mass spectrometry imaging platform demonstrating for the first time co-registered topographical, band excitation nanomechanical, and mass spectral imaging of a surface using a single instrument is reported. The mass spectrometry-based chemical imaging component of the system utilized nanothermal analysis probes for pyrolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. We discuss the basic instrumental setup and operation and the multimodal imaging capability and utility are demonstrated using a phase separated polystyrene/poly(2-vinylpyridine) polymer blend thin film. The topography and band excitation images showedmore » that the valley and plateau regions of the thin film surface were comprised primarily of one of the two polymers in the blend with the mass spectral chemical image used to definitively identify the polymers at the different locations. Data point pixel size for the topography (390 nm x 390 nm), band excitation (781 nm x 781 nm), mass spectrometry (690 nm x 500 nm) images was comparable and submicrometer in all three cases, but the data voxel size for each of the three images was dramatically different. The topography image was uniquely a surface measurement, whereas the band excitation image included information from an estimated 10 nm deep into the sample and the mass spectral image from 110-140 nm in depth. Moreover, because of this dramatic sampling depth variance, some differences in the band excitation and mass spectrometry chemical images were observed and were interpreted to indicate the presence of a buried interface in the sample. The spatial resolution of the mass spectral image was estimated to be between 1.5 m 2.6 m, based on the ability to distinguish surface features in that image that were also observed in the other images.« less

Co-registered Topographical, Band Excitation Nanomechanical, and Mass Spectral Imaging Using a Combined Atomic Force Microscopy/Mass Spectrometry Platform

DOE PAGES

Ovchinnikova, Olga S.; Tai, Tamin; Bocharova, Vera; ...

2015-03-18

The advancement of a hybrid atomic force microscopy/mass spectrometry imaging platform demonstrating for the first time co-registered topographical, band excitation nanomechanical, and mass spectral imaging of a surface using a single instrument is reported. The mass spectrometry-based chemical imaging component of the system utilized nanothermal analysis probes for pyrolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. We discuss the basic instrumental setup and operation and the multimodal imaging capability and utility are demonstrated using a phase separated polystyrene/poly(2-vinylpyridine) polymer blend thin film. The topography and band excitation images showedmore » that the valley and plateau regions of the thin film surface were comprised primarily of one of the two polymers in the blend with the mass spectral chemical image used to definitively identify the polymers at the different locations. Data point pixel size for the topography (390 nm x 390 nm), band excitation (781 nm x 781 nm), mass spectrometry (690 nm x 500 nm) images was comparable and submicrometer in all three cases, but the data voxel size for each of the three images was dramatically different. The topography image was uniquely a surface measurement, whereas the band excitation image included information from an estimated 10 nm deep into the sample and the mass spectral image from 110-140 nm in depth. Moreover, because of this dramatic sampling depth variance, some differences in the band excitation and mass spectrometry chemical images were observed and were interpreted to indicate the presence of a buried interface in the sample. The spatial resolution of the mass spectral image was estimated to be between 1.5 m 2.6 m, based on the ability to distinguish surface features in that image that were also observed in the other images.« less

Photon pair generation with tailored frequency correlations in graded-index multimode fibers.

PubMed

Pourbeyram, Hamed; Mafi, Arash

2018-05-01

We study theoretically the generation of photon pairs with controlled spectral correlations via the four-wave mixing process in graded-index multimode optical fibers (GIMFs). We show that the quantum correlations of the generated photons in GIMFs can be preserved over a wide spectral range for a tunable pump source. Therefore, GIMFs can be utilized as quantum-state-preserving tunable sources of photons. In particular, we have shown that it is possible to generate factorable two-photon states, which allow for heralding of pure-state single photons without the need for narrowband spectral post filtering. We also elaborate on the possibility of simultaneously generating correlated and uncorrelated photon pairs in the same optical fiber.

Multimodal device for assessment of skin malformations

NASA Astrophysics Data System (ADS)

Bekina, A.; Garancis, V.; Rubins, U.; Spigulis, J.; Valeine, L.; Berzina, A.

2013-11-01

A variety of multi-spectral imaging devices is commercially available and used for skin diagnostics and monitoring; however, an alternative cost-efficient device can provide an advanced spectral analysis of skin. A compact multimodal device for diagnosis of pigmented skin lesions was developed and tested. A polarized LED light source illuminates the skin surface at four different wavelengths - blue (450 nm), green (545 nm), red (660 nm) and infrared (940 nm). Spectra of reflected light from the 25 mm wide skin spot are imaged by a CMOS sensor. Four spectral images are obtained for mapping of the main skin chromophores. The specific chromophore distribution differences between different skin malformations were analyzed and information of subcutaneous structures was consecutively extracted.

Evaluation of the role of CD207 on Langerhans cells in a murine model of atopic dermatitis by in situ imaging using Cr:forsterite laser-based multimodality nonlinear microscopy

NASA Astrophysics Data System (ADS)

Lee, Jyh-Hong; Tsai, Ming-Rung; Sun, Chi-Kuang; Chiang, Bor-Luen

2012-11-01

Atopic dermatitis (AD) is an allergic inflammatory disease of skin. It remains unclear that CD207 of Langerhans cells (LCs) plays a central role in the development of allergic sensitization. There is little data on LCs within the microenviroment in vivo. We used a murine model of epicutaneous (EC) ovalbumin (OVA) sensitization inducing an inflammatory skin resembling AD to explore the role of CD207 in the pathogenesis of AD. Cr:forsterite laser-based multimodality nonlinear microscopy was applied for in situ imaging. Peritoneal injections of Alexa Fluor 647-rat anti-mouse CD207 into mice were performed to specifically trace the LCs. Peritoneal injections of OVA-Alexa Fluor 647 conjugate into mice were performed to specifically trace the OVA. We found that combining Alexa Fluor fluorescent probes with multimodality nonlinear microscopy permitted the unequivocal in situ imaging of CD207-expressing LCs. The relevant time-course, expressional, and functional studies reveal that CD207 of LCs plays an essential role during the induction of EC sensitization. We establish and validate that Cr:forsterite laser-based multimodality nonlinear microscopy is applicable for the specific detection of labeled mAb-bound LCs and labeled antigen. We suggest that CD207-expressing LCs initiate the allergic response through the CD207 mediated epicutaneous sensitization associated with the development of AD.

Rapid Screening of Cancer Margins in Tissue with Multimodal Confocal Microscopy

PubMed Central

Gareau, Daniel S.; Jeon, Hana; Nehal, Kishwer S.; Rajadhyaksha, Milind

2012-01-01

Background Complete and accurate excision of cancer is guided by the examination of histopathology. However, preparation of histopathology is labor intensive and slow, leading to insufficient sampling of tissue and incomplete and/or inaccurate excision of margins. We demonstrate the potential utility of multimodal confocal mosaicing microscopy for rapid screening of cancer margins, directly in fresh surgical excisions, without the need for conventional embedding, sectioning or processing. Materials/Methods A multimodal confocal mosaicing microscope was developed to image basal cell carcinoma margins in surgical skin excisions, with resolution that shows nuclear detail. Multimodal contrast is with fluorescence for imaging nuclei and reflectance for cellular cytoplasm and dermal collagen. Thirtyfive excisions of basal cell carcinomas from Mohs surgery were imaged, and the mosaics analyzed by comparison to the corresponding frozen pathology. Results Confocal mosaics are produced in about 9 minutes, displaying tissue in fields-of-view of 12 mm with 2X magnification. A digital staining algorithm transforms black and white contrast to purple and pink, which simulates the appearance of standard histopathology. Mosaicing enables rapid digital screening, which mimics the examination of histopathology. Conclusions Multimodal confocal mosaicing microscopy offers a technology platform to potentially enable real-time pathology at the bedside. The imaging may serve as an adjunct to conventional histopathology, to expedite screening of margins and guide surgery toward more complete and accurate excision of cancer. PMID:22721570

Global optimization of multimode interference structure for ratiometric wavelength measurement

NASA Astrophysics Data System (ADS)

Wang, Qian; Farrell, Gerald; Hatta, Agus Muhamad

2007-07-01

The multimode interference structure is conventionally used as a splitter/combiner. In this paper, it is optimised as an edge filter for ratiometric wavelength measurement, which can be used in demodulation of fiber Bragg grating sensing. The global optimization algorithm-adaptive simulated annealing is introduced in the design of multimode interference structure including the length and width of the multimode waveguide section, and positions of the input and output waveguides. The designed structure shows a suitable spectral response for wavelength measurement and a good fabrication tolerance.

Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls

NASA Astrophysics Data System (ADS)

Zanello, Marc; Poulon, Fanny; Pallud, Johan; Varlet, Pascale; Hamzeh, H.; Abi Lahoud, Georges; Andreiuolo, Felipe; Ibrahim, Ali; Pages, Mélanie; Chretien, Fabrice; di Rocco, Federico; Dezamis, Edouard; Nataf, François; Turak, Baris; Devaux, Bertrand; Abi Haidar, Darine

2017-02-01

Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

Fiber Bragg grating inscription in optical multicore fibers

NASA Astrophysics Data System (ADS)

Becker, Martin; Elsmann, Tino; Lorenz, Adrian; Spittel, Ron; Kobelke, Jens; Schuster, Kay; Rothhardt, Manfred; Latka, Ines; Dochow, Sebastian; Bartelt, Hartmut

2015-09-01

Fiber Bragg gratings as key components in telecommunication, fiber lasers, and sensing systems usually rely on the Bragg condition for single mode fibers. In special applications, such as in biophotonics and astrophysics, high light coupling efficiency is of great importance and therefore, multimode fibers are often preferred. The wavelength filtering effect of Bragg gratings in multimode fibers, however is spectrally blurred over a wide modal spectrum of the fiber. With a well-designed all solid multicore microstructured fiber a good light guiding efficiency in combination with narrow spectral filtering effect by Bragg gratings becomes possible.

Device, Algorithm and Integrated Modeling Research for Performance-Drive Multi-Modal Optical Sensors

DTIC Science & Technology

2012-12-17

to!feature!aided!tracking! using !spectral! information .! ! !iii! •! A!novel!technique!for!spectral!waveband!selection!was!developed!and! used !as! part! of ... of !spectral! information ! using !the!tunable!single;pixel!spectrometer!concept.! •! A! database! was! developed! of ! spectral! reflectance! measurements...exploring! the! utility! of ! spectral! and! polarimetric! information !to!help!with!the!vehicle!tracking!application.!Through!the! use ! of ! both

Integrated femtosecond stimulated Raman scattering and two-photon fluorescence imaging of subcellular lipid and vesicular structures

NASA Astrophysics Data System (ADS)

Li, Xuesong; Lam, Wen Jiun; Cao, Zhe; Hao, Yan; Sun, Qiqi; He, Sicong; Mak, Ho Yi; Qu, Jianan Y.

2015-11-01

The primary goal of this study is to demonstrate that stimulated Raman scattering (SRS) as a new imaging modality can be integrated into a femtosecond (fs) nonlinear optical (NLO) microscope system. The fs sources of high pulse peak power are routinely used in multimodal nonlinear microscopy to enable efficient excitation of multiple NLO signals. However, with fs excitations, the SRS imaging of subcellular lipid and vesicular structures encounters significant interference from proteins due to poor spectral resolution and a lack of chemical specificity, respectively. We developed a unique NLO microscope of fs excitation that enables rapid acquisition of SRS and multiple two-photon excited fluorescence (TPEF) signals. In the in vivo imaging of transgenic C. elegans animals, we discovered that by cross-filtering false positive lipid signals based on the TPEF signals from tryptophan-bearing endogenous proteins and lysosome-related organelles, the imaging system produced highly accurate assignment of SRS signals to lipid. Furthermore, we demonstrated that the multimodal NLO microscope system could sequentially image lipid structure/content and organelles, such as mitochondria, lysosomes, and the endoplasmic reticulum, which are intricately linked to lipid metabolism.

Time- and spectrally resolved characteristics of flavin fluorescence in U87MG cancer cells in culture

NASA Astrophysics Data System (ADS)

Horilova, Julia; Cunderlikova, Beata; Marcek Chorvatova, Alzbeta

2015-05-01

Early detection of cancer is crucial for the successful diagnostics of its presence and its subsequent treatment. To improve cancer detection, we tested the progressive multimodal optical imaging of U87MG cells in culture. A combination of steady-state spectroscopic methods with the time-resolved approach provides a new insight into the native metabolism when focused on endogenous tissue fluorescence. In this contribution, we evaluated the metabolic state of living U87MG cancer cells in culture by means of endogenous flavin fluorescence. Confocal microscopy and time-resolved fluorescence imaging were employed to gather spectrally and time-resolved images of the flavin fluorescence. We observed that flavin fluorescence in U87MG cells was predominantly localized outside the cell nucleus in mitochondria, while exhibiting a spectral maximum under 500 nm and fluorescence lifetimes under 1.4 ns, suggesting the presence of bound flavins. In some cells, flavin fluorescence was also detected inside the cell nuclei in the nucleoli, exhibiting longer fluorescence lifetimes and a red-shifted spectral maximum, pointing to the presence of free flavin. Extra-nuclear flavin fluorescence was diminished by 2-deoxyglucose, but failed to increase with 2,4-dinitrophenol, the uncoupler of oxidative phosphorylation, indicating that the cells use glycolysis, rather than oxidative phosphorylation for functioning. These gathered data are the first step toward monitoring the metabolic state of U87MG cancer cells.

Multimodal label-free ex vivo imaging using a dual-wavelength microscope with axial chromatic aberration compensation.

PubMed

Filippi, Andrea; Dal Sasso, Eleonora; Iop, Laura; Armani, Andrea; Gintoli, Michele; Sandri, Marco; Gerosa, Gino; Romanato, Filippo; Borile, Giulia

2018-03-01

Label-free microscopy is a very powerful technique that can be applied to study samples with no need for exogenous fluorescent probes, keeping the main benefits of multiphoton microscopy, such as longer penetration depths and intrinsic optical sectioning while enabling serial multitechniques examinations on the same specimen. Among the many label-free microscopy methods, harmonic generation (HG) is one of the most intriguing methods due to its generally low photo-toxicity and relative ease of implementation. Today, HG and common two-photon microscopy (TPM) are well-established techniques, and are routinely used in several research fields. However, they require a significant amount of fine-tuning to be fully exploited, making them quite difficult to perform in parallel. Here, we present our designed multimodal microscope, capable of performing simultaneously TPM and HG without any kind of compromise thanks to two, separate, individually optimized laser sources with axial chromatic aberration compensation. We also apply our setup to the examination of a plethora of ex vivo samples to prove its capabilities and the significant advantages of a multimodal approach. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Multimode resistive switching in nanoscale hafnium oxide stack as studied by atomic force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Y., E-mail: houyi@pku.edu.cn, E-mail: lfliu@pku.edu.cn; IMEC, Kapeldreef 75, B-3001 Heverlee; Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D, B-3001 Heverlee

2016-07-11

The nanoscale resistive switching in hafnium oxide stack is investigated by the conductive atomic force microscopy (C-AFM). The initial oxide stack is insulating and electrical stress from the C-AFM tip induces nanometric conductive filaments. Multimode resistive switching can be observed in consecutive operation cycles at one spot. The different modes are interpreted in the framework of a low defect quantum point contact theory. The model implies that the optimization of the conductive filament active region is crucial for the future application of nanoscale resistive switching devices.

"Photonic lantern" spectral filters in multi-core Fiber.

PubMed

Birks, T A; Mangan, B J; Díez, A; Cruz, J L; Murphy, D F

2012-06-18

Fiber Bragg gratings are written across all 120 single-mode cores of a multi-core optical Fiber. The Fiber is interfaced to multimode ports by tapering it within a depressed-index glass jacket. The result is a compact multimode "photonic lantern" filter with astrophotonic applications. The tapered structure is also an effective mode scrambler.

Mobile, Multi-modal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia

DTIC Science & Technology

2015-10-01

eyes and image choroidal vessels/capillaries using CARS intravital microscopy Subtask 3: Measure oxy-hemoglobin levels in PBI test and control eyes...AWARD NUMBER: W81XWH-14-1-0537 TITLE: Mobile, Multi-modal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia...4. TITLE AND SUBTITLE Mobile, Multimodal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia 5a. CONTRACT NUMBER W81XWH

Analysis of a single ring resonator with 2×2 90-degree multimode waveguide turning couplers

NASA Astrophysics Data System (ADS)

Chiu, C. L.; Liao, Yen-Hsun

2016-02-01

A novel design of a single ring resonator with two low-loss 2×2 90-degree multimode waveguide turning mirror couplers based on a InP structure. The coupling factor of the 2×2 90-degree multimode waveguide turning mirror coupler is inversed for K=0.85 to K=0.15 when one folding is achieved. The 2×2 90-degree turning mirror coupler for K=0.15 is (3/4)Lπ in length. Its length is reduced 3 times than the conventional straight 2×2 multimode waveguide interference coupler (9/4)Lπ in length for K=0.15. The cavity length of the curve waveguide (90-degree arc length) in this ring resonator with two 2×2 90-degree multimode waveguide turning couplers is decreased 1/2 times than with two 2×2 MMI couplers (180-degree arc length). The free spectral range (FSR) is increased 2 times. The output spectral response gets a FSR of 82 GHz for the device and a contrast of 4 dB and FWHM of 0.24 nm for the drop port. The results of numerical analysis calculated by the transfer functions in a single ring resonator are agreement with the experimental results.

Single and low order mode interrogation of a multimode sapphire fiber Bragg grating sensor with tapered fibers

NASA Astrophysics Data System (ADS)

Grobnic, Dan; Mihailov, Stephen J.; Ding, H.; Bilodeau, F.; Smelser, Christopher W.

2005-05-01

Multimode sapphire fiber Bragg gratings (SFBG) made with an IR femtosecond laser and a phase mask were probed using tapered single mode fibers of different taper diameters producing single and low order mode reflection/transmission responses. A configuration made of an input single mode tapered fiber and multimode silica fiber used for output coupling was also tested and has delivered a filtered multimode transmission spectrum. The tapered coupling improved the spectral resolution of the SFBG as compared to its multimode responses previously reported. Such improvements facilitate the utilization of the SFBG as a high temperature sensor. Wavelength shifts of the single mode response were monitored as a function of temperature up to 1500 °C and were consistent with the measurement obtained from the multimode response published previously.

CARS module for multimodal microscopy

NASA Astrophysics Data System (ADS)

Zadoyan, Ruben; Baldacchini, Tommaso; Carter, John; Kuo, Chun-Hung; Ocepek, David

2011-03-01

We describe a stand alone CARS module allowing upgrade of a two-photon microscope with CARS modality. The Stokes beam is generated in a commercially available photonic crystal fiber (PCF) using fraction of the power of femtosecond excitation laser. The output of the fiber is optimized for broadband CARS at Stokes shifts in 2900cm-1 region. The spectral resolution in CARS signal is 50 cm-1. It is achieved by introducing a bandpass filter in the pump beam. The timing between the pump and Stokes pulses is preset inside the module and can be varied. We demonstrate utility of the device on examples of second harmonic, two-photon fluorescence and CARS images of several biological and non-biological samples. We also present results of studies where we used CARS modality to monitor in real time the process of fabrication of microstructures by two-photon polymerization.

Simultaneous fluorescence and quantitative phase microscopy with single-pixel detectors

NASA Astrophysics Data System (ADS)

Liu, Yang; Suo, Jinli; Zhang, Yuanlong; Dai, Qionghai

2018-02-01

Multimodal microscopy offers high flexibilities for biomedical observation and diagnosis. Conventional multimodal approaches either use multiple cameras or a single camera spatially multiplexing different modes. The former needs expertise demanding alignment and the latter suffers from limited spatial resolution. Here, we report an alignment-free full-resolution simultaneous fluorescence and quantitative phase imaging approach using single-pixel detectors. By combining reference-free interferometry with single-pixel detection, we encode the phase and fluorescence of the sample in two detection arms at the same time. Then we employ structured illumination and the correlated measurements between the sample and the illuminations for reconstruction. The recovered fluorescence and phase images are inherently aligned thanks to single-pixel detection. To validate the proposed method, we built a proof-of-concept setup for first imaging the phase of etched glass with the depth of a few hundred nanometers and then imaging the fluorescence and phase of the quantum dot drop. This method holds great potential for multispectral fluorescence microscopy with additional single-pixel detectors or a spectrometer. Besides, this cost-efficient multimodal system might find broad applications in biomedical science and neuroscience.

CHARACTERIZING PHOTORECEPTOR CHANGES IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY USING ADAPTIVE OPTICS.

PubMed

Roberts, Philipp K; Nesper, Peter L; Onishi, Alex C; Skondra, Dimitra; Jampol, Lee M; Fawzi, Amani A

2018-01-01

To characterize lesions of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) by multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO). We included patients with APMPPE at different stages of evolution of the placoid lesions. Color fundus photography, spectral domain optical coherence tomography, infrared reflectance, fundus autofluorescence, and AOSLO images were obtained and registered to correlate microstructural changes. Eight eyes of four patients (two women) were included and analyzed by multimodal imaging. Photoreceptor reflectivity within APMPPE lesions was more heterogeneous than in adjacent healthy areas. Hyperpigmentation on color fundus photography appeared hyperreflective on infrared reflectance and on AOSLO. Irregularity of the interdigitation zone and the photoreceptor inner and outer segment junctions (IS/OS) on spectral domain optical coherence tomography was associated with photoreceptor hyporeflectivity on AOSLO. Interruption of the interdigitation zone or IS/OS was associated with loss of photoreceptor reflectivity on AOSLO. Irregularities in the reflectivity of the photoreceptor mosaic are visible on AOSLO even in inactive APMPPE lesions, where the photoreceptor bands on spectral domain optical coherence tomography have recovered. Adaptive optics scanning laser ophthalmoscopy combined with multimodal imaging has the potential to enhance our understanding of photoreceptor involvement in APMPPE.

In vivo evaluation of adipose- and muscle-derived stem cells as a treatment for nonhealing diabetic wounds using multimodal microscopy

NASA Astrophysics Data System (ADS)

Li, Joanne; Pincu, Yair; Marjanovic, Marina; Bower, Andrew J.; Chaney, Eric J.; Jensen, Tor; Boppart, Marni D.; Boppart, Stephen A.

2016-08-01

Impaired skin wound healing is a significant comorbid condition of diabetes, which often results in nonhealing diabetic ulcers due to poor peripheral microcirculation, among other factors. The effectiveness of the regeneration of adipose-derived stem cells (ADSCs) and muscle-derived stem cells (MDSCs) was assessed using an integrated multimodal microscopy system equipped with two-photon fluorescence and second-harmonic generation imaging. These imaging modalities, integrated in a single platform for spatial and temporal coregistration, allowed us to monitor in vivo changes in the collagen network and cell dynamics in a skin wound. Fluorescently labeled ADSCs and MDSCs were applied topically to the wound bed of wild-type and diabetic (db/db) mice following punch biopsy. Longitudinal imaging demonstrated that ADSCs and MDSCs provided remarkable capacity for improved diabetic wound healing, and integrated microscopy revealed a more organized collagen remodeling in the wound bed of treated mice. The results from this study verify the regenerative capacity of stem cells toward healing and, with multimodal microscopy, provide insight regarding their impact on the skin microenvironment. The optical method outlined in this study, which has the potential for in vivo human use, may optimize the care and treatment of diabetic nonhealing wounds.

Nanodiamond Landmarks for Subcellular Multimodal Optical and Electron Imaging

PubMed Central

Zurbuchen, Mark A.; Lake, Michael P.; Kohan, Sirus A.; Leung, Belinda; Bouchard, Louis-S.

2013-01-01

There is a growing need for biolabels that can be used in both optical and electron microscopies, are non-cytotoxic, and do not photobleach. Such biolabels could enable targeted nanoscale imaging of sub-cellular structures, and help to establish correlations between conjugation-delivered biomolecules and function. Here we demonstrate a sub-cellular multi-modal imaging methodology that enables localization of inert particulate probes, consisting of nanodiamonds having fluorescent nitrogen-vacancy centers. These are functionalized to target specific structures, and are observable by both optical and electron microscopies. Nanodiamonds targeted to the nuclear pore complex are rapidly localized in electron-microscopy diffraction mode to enable “zooming-in” to regions of interest for detailed structural investigations. Optical microscopies reveal nanodiamonds for in-vitro tracking or uptake-confirmation. The approach is general, works down to the single nanodiamond level, and can leverage the unique capabilities of nanodiamonds, such as biocompatibility, sensitive magnetometry, and gene and drug delivery. PMID:24036840

Multimodal optoacoustic and multiphoton fluorescence microscopy

NASA Astrophysics Data System (ADS)

Sela, Gali; Razansky, Daniel; Shoham, Shy

2013-03-01

Multiphoton microscopy is a powerful imaging modality that enables structural and functional imaging with cellular and sub-cellular resolution, deep within biological tissues. Yet, its main contrast mechanism relies on extrinsically administered fluorescent indicators. Here we developed a system for simultaneous multimodal optoacoustic and multiphoton fluorescence 3D imaging, which attains both absorption and fluorescence-based contrast by integrating an ultrasonic transducer into a two-photon laser scanning microscope. The system is readily shown to enable acquisition of multimodal microscopic images of fluorescently labeled targets and cell cultures as well as intrinsic absorption-based images of pigmented biological tissue. During initial experiments, it was further observed that that detected optoacoustically-induced response contains low frequency signal variations, presumably due to cavitation-mediated signal generation by the high repetition rate (80MHz) near IR femtosecond laser. The multimodal system may provide complementary structural and functional information to the fluorescently labeled tissue, by superimposing optoacoustic images of intrinsic tissue chromophores, such as melanin deposits, pigmentation, and hemoglobin or other extrinsic particle or dye-based markers highly absorptive in the NIR spectrum.

Design and demonstration of multimodal optical scanning microscopy for confocal and two-photon imaging

NASA Astrophysics Data System (ADS)

Chun, Wanhee; Do, Dukho; Gweon, Dae-Gab

2013-01-01

We developed a multimodal microscopy based on an optical scanning system in order to obtain diverse optical information of the same area of a sample. Multimodal imaging researches have mostly depended on a commercial microscope platform, easy to use but restrictive to extend imaging modalities. In this work, the beam scanning optics, especially including a relay lens, was customized to transfer broadband (400-1000 nm) lights to a sample without any optical error or loss. The customized scanning optics guarantees the best performances of imaging techniques utilizing the lights within the design wavelength. Confocal reflection, confocal fluorescence, and two-photon excitation fluorescence images were obtained, through respective implemented imaging channels, to demonstrate imaging feasibility for near-UV, visible, near-IR continuous light, and pulsed light in the scanning optics. The imaging performances for spatial resolution and image contrast were verified experimentally; the results were satisfactory in comparison with theoretical results. The advantages of customization, containing low cost, outstanding combining ability and diverse applications, will contribute to vitalize multimodal imaging researches.

Optimization of an integrated wavelength monitor device

NASA Astrophysics Data System (ADS)

Wang, Pengfei; Brambilla, Gilberto; Semenova, Yuliya; Wu, Qiang; Farrell, Gerald

2011-05-01

In this paper an edge filter based on multimode interference in an integrated waveguide is optimized for a wavelength monitoring application. This can also be used as a demodulation element in a fibre Bragg grating sensing system. A global optimization algorithm is presented for the optimum design of the multimode interference device, including a range of parameters of the multimode waveguide, such as length, width and position of the input and output waveguides. The designed structure demonstrates the desired spectral response for wavelength measurements. Fabrication tolerance is also analysed numerically for this structure.

Simultaneous multimodal ophthalmic imaging using swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

PubMed Central

Malone, Joseph D.; El-Haddad, Mohamed T.; Bozic, Ivan; Tye, Logan A.; Majeau, Lucas; Godbout, Nicolas; Rollins, Andrew M.; Boudoux, Caroline; Joos, Karen M.; Patel, Shriji N.; Tao, Yuankai K.

2016-01-01

Scanning laser ophthalmoscopy (SLO) benefits diagnostic imaging and therapeutic guidance by allowing for high-speed en face imaging of retinal structures. When combined with optical coherence tomography (OCT), SLO enables real-time aiming and retinal tracking and provides complementary information for post-acquisition volumetric co-registration, bulk motion compensation, and averaging. However, multimodality SLO-OCT systems generally require dedicated light sources, scanners, relay optics, detectors, and additional digitization and synchronization electronics, which increase system complexity. Here, we present a multimodal ophthalmic imaging system using swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (SS-SESLO-OCT) for in vivo human retinal imaging. SESLO reduces the complexity of en face imaging systems by multiplexing spatial positions as a function of wavelength. SESLO image quality benefited from single-mode illumination and multimode collection through a prototype double-clad fiber coupler, which optimized scattered light throughput and reduce speckle contrast while maintaining lateral resolution. Using a shared 1060 nm swept-source, shared scanner and imaging optics, and a shared dual-channel high-speed digitizer, we acquired inherently co-registered en face retinal images and OCT cross-sections simultaneously at 200 frames-per-second. PMID:28101411

Multimodal nonlinear imaging of arabidopsis thaliana root cell

NASA Astrophysics Data System (ADS)

Jang, Bumjoon; Lee, Sung-Ho; Woo, Sooah; Park, Jong-Hyun; Lee, Myeong Min; Park, Seung-Han

2017-07-01

Nonlinear optical microscopy has enabled the possibility to explore inside the living organisms. It utilizes ultrashort laser pulse with long wavelength (greater than 800nm). Ultrashort pulse produces high peak power to induce nonlinear optical phenomenon such as two-photon excitation fluorescence (TPEF) and harmonic generations in the medium while maintaining relatively low average energy pre area. In plant developmental biology, confocal microscopy is widely used in plant cell imaging after the development of biological fluorescence labels in mid-1990s. However, fluorescence labeling itself affects the sample and the sample deviates from intact condition especially when labelling the entire cell. In this work, we report the dynamic images of Arabidopsis thaliana root cells. This demonstrates the multimodal nonlinear optical microscopy is an effective tool for long-term plant cell imaging.

Spectral mapping tools from the earth sciences applied to spectral microscopy data.

PubMed

Harris, A Thomas

2006-08-01

Spectral imaging, originating from the field of earth remote sensing, is a powerful tool that is being increasingly used in a wide variety of applications for material identification. Several workers have used techniques like linear spectral unmixing (LSU) to discriminate materials in images derived from spectral microscopy. However, many spectral analysis algorithms rely on assumptions that are often violated in microscopy applications. This study explores algorithms originally developed as improvements on early earth imaging techniques that can be easily translated for use with spectral microscopy. To best demonstrate the application of earth remote sensing spectral analysis tools to spectral microscopy data, earth imaging software was used to analyze data acquired with a Leica confocal microscope with mechanical spectral scanning. For this study, spectral training signatures (often referred to as endmembers) were selected with the ENVI (ITT Visual Information Solutions, Boulder, CO) "spectral hourglass" processing flow, a series of tools that use the spectrally over-determined nature of hyperspectral data to find the most spectrally pure (or spectrally unique) pixels within the data set. This set of endmember signatures was then used in the full range of mapping algorithms available in ENVI to determine locations, and in some cases subpixel abundances of endmembers. Mapping and abundance images showed a broad agreement between the spectral analysis algorithms, supported through visual assessment of output classification images and through statistical analysis of the distribution of pixels within each endmember class. The powerful spectral analysis algorithms available in COTS software, the result of decades of research in earth imaging, are easily translated to new sources of spectral data. Although the scale between earth imagery and spectral microscopy is radically different, the problem is the same: mapping material locations and abundances based on unique spectral signatures. (c) 2006 International Society for Analytical Cytology.

Precise Spatially Selective Photothermolysis Using Modulated Femtosecond Lasers and Real-time Multimodal Microscopy Monitoring.

PubMed

Huang, Yimei; Lui, Harvey; Zhao, Jianhua; Wu, Zhenguo; Zeng, Haishan

2017-01-01

The successful application of lasers in the treatment of skin diseases and cosmetic surgery is largely based on the principle of conventional selective photothermolysis which relies strongly on the difference in the absorption between the therapeutic target and its surroundings. However, when the differentiation in absorption is not sufficient, collateral damage would occur due to indiscriminate and nonspecific tissue heating. To deal with such cases, we introduce a novel spatially selective photothermolysis method based on multiphoton absorption in which the radiant energy of a tightly focused near-infrared femtosecond laser beam can be directed spatially by aiming the laser focal point to the target of interest. We construct a multimodal optical microscope to perform and monitor the spatially selective photothermolysis. We demonstrate that precise alteration of the targeted tissue is achieved while leaving surrounding tissue intact by choosing appropriate femtosecond laser exposure with multimodal optical microscopy monitoring in real time.

Precise Spatially Selective Photothermolysis Using Modulated Femtosecond Lasers and Real-time Multimodal Microscopy Monitoring

PubMed Central

Huang, Yimei; Lui, Harvey; Zhao, Jianhua; Wu, Zhenguo; Zeng, Haishan

2017-01-01

The successful application of lasers in the treatment of skin diseases and cosmetic surgery is largely based on the principle of conventional selective photothermolysis which relies strongly on the difference in the absorption between the therapeutic target and its surroundings. However, when the differentiation in absorption is not sufficient, collateral damage would occur due to indiscriminate and nonspecific tissue heating. To deal with such cases, we introduce a novel spatially selective photothermolysis method based on multiphoton absorption in which the radiant energy of a tightly focused near-infrared femtosecond laser beam can be directed spatially by aiming the laser focal point to the target of interest. We construct a multimodal optical microscope to perform and monitor the spatially selective photothermolysis. We demonstrate that precise alteration of the targeted tissue is achieved while leaving surrounding tissue intact by choosing appropriate femtosecond laser exposure with multimodal optical microscopy monitoring in real time. PMID:28255346

Multimodal microscopy and the stepwise multi-photon activation fluorescence of melanin

NASA Astrophysics Data System (ADS)

Lai, Zhenhua

The author's work is divided into three aspects: multimodal microscopy, stepwise multi-photon activation fluorescence (SMPAF) of melanin, and customized-profile lenses (CPL) for on-axis laser scanners, which will be introduced respectively. A multimodal microscope provides the ability to image samples with multiple modalities on the same stage, which incorporates the benefits of all modalities. The multimodal microscopes developed in this dissertation are the Keck 3D fusion multimodal microscope 2.0 (3DFM 2.0), upgraded from the old 3DFM with improved performance and flexibility, and the multimodal microscope for targeting small particles (the "Target" system). The control systems developed for both microscopes are low-cost and easy-to-build, with all components off-the-shelf. The control system have not only significantly decreased the complexity and size of the microscope, but also increased the pixel resolution and flexibility. The SMPAF of melanin, activated by a continuous-wave (CW) mode near-infrared (NIR) laser, has potential applications for a low-cost and reliable method of detecting melanin. The photophysics of melanin SMPAF has been studied by theoretical analysis of the excitation process and investigation of the spectra, activation threshold, and photon number absorption of melanin SMPAF. SMPAF images of melanin in mouse hair and skin, mouse melanoma, and human black and white hairs are compared with images taken by conventional multi-photon fluorescence microscopy (MPFM) and confocal reflectance microscopy (CRM). SMPAF images significantly increase specificity and demonstrate the potential to increase sensitivity for melanin detection compared to MPFM images and CRM images. Employing melanin SMPAF imaging to detect melanin inside human skin in vivo has been demonstrated, which proves the effectiveness of melanin detection using SMPAF for medical purposes. Selective melanin ablation with micrometer resolution has been presented using the Target system. Compared to the traditional selective photothermolysis, this method demonstrates higher precision, higher specificity and deeper penetration. Therefore, the SMPAF guided selective ablation of melanin is a promising tool of removing melanin for both medical and cosmetic purposes. Three CPLs have been designed for low-cost linear-motion scanners, low-cost fast spinning scanners and high-precision fast spinning scanners. Each design has been tailored to the industrial manufacturing ability and market demands.

Multimodal biophotonic workstation for live cell analysis.

PubMed

Esseling, Michael; Kemper, Björn; Antkowiak, Maciej; Stevenson, David J; Chaudet, Lionel; Neil, Mark A A; French, Paul W; von Bally, Gert; Dholakia, Kishan; Denz, Cornelia

2012-01-01

A reliable description and quantification of the complex physiology and reactions of living cells requires a multimodal analysis with various measurement techniques. We have investigated the integration of different techniques into a biophotonic workstation that can provide biological researchers with these capabilities. The combination of a micromanipulation tool with three different imaging principles is accomplished in a single inverted microscope which makes the results from all the techniques directly comparable. Chinese Hamster Ovary (CHO) cells were manipulated by optical tweezers while the feedback was directly analyzed by fluorescence lifetime imaging, digital holographic microscopy and dynamic phase-contrast microscopy. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Monitoring femtosecond laser microscopic photothermolysis with multimodal microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Huang, Yimei; Lui, Harvey; Zhao, Jianhua; McLean, David I.; Zeng, Haishan

2016-02-01

Photothermolysis induced by femtosecond (fs) lasers may be a promising modality in dermatology because of its advantages of high precision due to multiphoton absorption and deeper penetration due to the use of near infrared wavelengths. Although multiphoton absorption nonlinear effects are capable of precision targeting, the femtosecond laser photothermolysis could still have effects beyond the targeted area if a sufficiently high dose of laser light is used. Such unintended effects could be minimized by real time monitoring photothermolysis during the treatment. Targeted photothermolytic treatment of ex vivo mouse skin dermis was performed with tightly focused fs laser beams. Images of reflectance confocal microscopy (RCM), second harmonic generation (SHG), and two-photon fluorescence (TPF) of the mouse skins were obtained with integrated multimodal microscopy before, during, and after the laser treatment. The RCM, SHG, and TPF signal intensities of the treatment areas changed after high power femtosecond laser irradiation. The intensities of the RCM and SHG signals decreased when the tissue was damaged, while the intensity of the TPF signal increased when the photothermolysis was achieved. Moreover, the TPF signal was more susceptible to the degree of the photothermolysis than the RCM and SHG signals. The results suggested that multimodal microscopy is a potentially useful tool to monitor and assess the femtosecond laser treatment of the skin to achieve microscopic photothermolysis with high precision.

Label-free imaging of acanthamoeba using multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Kobayashi, Tsubasa; Cha, Yu-Rok; Kaji, Yuichi; Oshika, Tetsuro; Leproux, Philippe; Couderc, Vincent; Kano, Hideaki

2018-02-01

Acanthamoeba keratitis is a disease in which amoebae named Acanthamoeba invade the cornea of an eye. To diagnose this disease before it becomes serious, it is important to detect the cyst state of Acanthamoeba in the early stage of infection. In the present study, we explored spectroscopic signitures of the cyst state of Acanthamoeba using multimodal nonlinear optical microscopy with the channels of multiplex coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and third harmonic generation (THG). A sharp band at around 1603 cm-1 in the CARS (Im[χ(3)]) spectrum was found at the cyst state of Acanthamoeba, which possibly originates from ergosterol and/or 7-dehydrostigmasterol. It can be used as a maker band of Acanthamoeba for medical treatment. Keyword: Acanthamoeba keratitis, coherent anti-Stokes Raman scattering, CARS, second harmonic generation, SHG, microspectroscopy, multiphoton microscopy

Noninvasive Spatially Offset and Transmission Raman Mapping of Breast Tissue: A Multimodal Approach Towards the In Vivo Assessment of Tissue Pathology

DTIC Science & Technology

2013-06-01

spectroscopy on tissue biopsies to correlate spectral bands with healthy and diseased breast tissue. Observed spectral changes are compared to infrared...capabilities and performance. Additionally, we conduct spectroscopy on tissue biopsies to correlate spectral bands with healthy and diseased ... disease states, ie hyperplasia, dysplasia, malignant, benign. The instrumentation has been built and characterized using archived tissue that was

Enabling the detection of UV signal in multimodal nonlinear microscopy with catalogue lens components.

PubMed

Vogel, Martin; Wingert, Axel; Fink, Rainer H A; Hagl, Christian; Ganikhanov, Feruz; Pfeffer, Christian P

2015-10-01

Using an optical system made from fused silica catalogue optical components, third-order nonlinear microscopy has been enabled on conventional Ti:sapphire laser-based multiphoton microscopy setups. The optical system is designed using two lens groups with straightforward adaptation to other microscope stands when one of the lens groups is exchanged. Within the theoretical design, the optical system collects and transmits light with wavelengths between the near ultraviolet and the near infrared from an object field of at least 1 mm in diameter within a resulting numerical aperture of up to 0.56. The numerical aperture can be controlled with a variable aperture stop between the two lens groups of the condenser. We demonstrate this new detection capability in third harmonic generation imaging experiments at the harmonic wavelength of ∼300 nm and in multimodal nonlinear optical imaging experiments using third-order sum frequency generation and coherent anti-Stokes Raman scattering microscopy so that the wavelengths of the detected signals range from ∼300 nm to ∼660 nm. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Label-free hyperspectral nonlinear optical microscopy of the biofuel micro-algae Haematococcus Pluvialis

PubMed Central

Barlow, Aaron M.; Slepkov, Aaron D.; Ridsdale, Andrew; McGinn, Patrick J.; Stolow, Albert

2014-01-01

We consider multi-modal four-wave mixing microscopies to be ideal tools for the in vivo study of carotenoid distributions within the important biofuel microalgae Haematococcus pluvialis. We show that hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy generates non-invasive, quantitative real-time concentrations maps of intracellular carotenoid distributions in live algae. PMID:25360358

Microscopy illumination engineering using a low-cost liquid crystal display.

PubMed

Guo, Kaikai; Bian, Zichao; Dong, Siyuan; Nanda, Pariksheet; Wang, Ying Min; Zheng, Guoan

2015-02-01

Illumination engineering is critical for obtaining high-resolution, high-quality images in microscope settings. In a typical microscope, the condenser lens provides sample illumination that is uniform and free from glare. The associated condenser diaphragm can be manually adjusted to obtain the optimal illumination numerical aperture. In this paper, we report a programmable condenser lens for active illumination control. In our prototype setup, we used a $15 liquid crystal display as a transparent spatial light modulator and placed it at the back focal plane of the condenser lens. By setting different binary patterns on the display, we can actively control the illumination and the spatial coherence of the microscope platform. We demonstrated the use of such a simple scheme for multimodal imaging, including bright-field microscopy, darkfield microscopy, phase-contrast microscopy, polarization microscopy, 3D tomographic imaging, and super-resolution Fourier ptychographic imaging. The reported illumination engineering scheme is cost-effective and compatible with most existing platforms. It enables a turnkey solution with high flexibility for researchers in various communities. From the engineering point-of-view, the reported illumination scheme may also provide new insights for the development of multimodal microscopy and Fourier ptychographic imaging.

Adaptive wavefront shaping for controlling nonlinear multimode interactions in optical fibres

NASA Astrophysics Data System (ADS)

Tzang, Omer; Caravaca-Aguirre, Antonio M.; Wagner, Kelvin; Piestun, Rafael

2018-06-01

Recent progress in wavefront shaping has enabled control of light propagation inside linear media to focus and image through scattering objects. In particular, light propagation in multimode fibres comprises complex intermodal interactions and rich spatiotemporal dynamics. Control of physical phenomena in multimode fibres and its applications are in their infancy, opening opportunities to take advantage of complex nonlinear modal dynamics. Here, we demonstrate a wavefront shaping approach for controlling nonlinear phenomena in multimode fibres. Using a spatial light modulator at the fibre input, real-time spectral feedback and a genetic algorithm optimization, we control a highly nonlinear multimode stimulated Raman scattering cascade and its interplay with four-wave mixing via a flexible implicit control on the superposition of modes coupled into the fibre. We show versatile spectrum manipulations including shifts, suppression, and enhancement of Stokes and anti-Stokes peaks. These demonstrations illustrate the power of wavefront shaping to control and optimize nonlinear wave propagation.

Laser a balayage spectral double-bande pour l'imagerie biomedicale multimodale

NASA Astrophysics Data System (ADS)

Goulamhoussen, Nadir

A novel swept laser providing simultaneous dual-band (780nm and 1 300 nm) wavelength scanning has been designed for use in multimodal imaging systems. The swept laser is based on two gain media : a fibered semiconductor optical amplifier (SOA) centered at 1 300nm and a free-space laser diode centered at 780 nm. Simultaneous wavelength tuning for both bands is obtained by separate wavelength filters set up around the same rotating polygonal mirror. For each band, a telescope in an infinite conjugate setup converges the wavelengths dispersed by a grating on the polygon. The polygon reflects back a narrow band of wavelengths for amplification in the gain medium. Rotating the polygon enables wavelength tuning and imaging at a rate of 6 000 to 30 000 spectral lines/s, or A-lines/s in Optical Coherence Tomography (OCT). The 780nm source has a bandwidth of 37 nm, a fibered output power of 54 mW and a coherence length of 11 mm. The 1 300nm source has a bandwidth of 75 nm, a fibered output power of 17mW and a coherence length of 7.2 mm. Three multimodal systems were designed to test the potential of the swept laser in biomedical imaging. A two color OCT which allows three-dimensional in depth imaging of biological tissues with good morphological contrast was first designed, including a novel arrangement for balanced detection in both bands. A simultaneous OCT and SECM instrument was also built in which spectrally encoded confocal microscopy (SECM) provides en face images of subcellular features with high resolution on top of the 3D high penetration image obtained by OCT. Finally, a system combining OCT with fluorescence was designed, thus adding functional imaging to structural OCT images. There are many prospective paths for these three modalities, first among them the adaptation of the systems such that they may be used with imaging probes. One potential solution would be the development of novel fiber components to combine the illumination of theses modalities while demultiplexing their detection, and as would be the development of new optomechanics to enable 3D real-time in vivo imaging.

Tunable all-fiber dissipative-soliton laser with a multimode interference filter.

PubMed

Zhang, Lei; Hu, Jinmeng; Wang, Jianhua; Feng, Yan

2012-09-15

We report on a tunable all-fiber dissipative-soliton laser with a multimode interference filter that consists of a multimode fiber spliced between two single-mode fibers. By carefully selecting the fiber parameters, a filter with a central wavelength at 1032 nm and a bandwidth of 7.6 nm is constructed and used for spectral filtering in an all-normal-dispersion mode-locked ytterbium-doped fiber laser based on nonlinear polarization evolution. The laser delivers 31 mW of average output power with positively chirped 7 ps pulses. The repetition rate of the pulses is 15.3 MHz, and pulse energy is 2.1 nJ. Tunable dissipative-soliton over 12 nm is achieved by applying tension to the single-mode-multimode-single-mode filter.

Single and low order mode interrogation of a multimode sapphire fibre Bragg grating sensor with tapered fibres

NASA Astrophysics Data System (ADS)

Grobnic, D.; Mihailov, S. J.; Ding, H.; Bilodeau, F.; Smelser, C. W.

2006-05-01

Multimode sapphire fibre Bragg gratings (SFBG) made with an ultrafast Ti:sapphire 800 nm laser and a phase mask were probed using a tapered single mode fibre of different taper diameters to produce single and low order mode reflection/transmission responses. A configuration made of an input single mode tapered fibre and multimode silica fibre used for output coupling was also tested and has delivered a filtered multimode transmission spectrum. The tapered coupling improved the spectral resolution of the SFBG. Such improvements facilitate the utilization of the SFBG as a high temperature sensor. Wavelength shifts of the single mode response were monitored as a function of temperature up to 1500 °C with no detectable degradation in the grating strength or hysteresis in the Bragg resonance.

Microscopy with multimode fibers

NASA Astrophysics Data System (ADS)

Moser, Christophe; Papadopoulos, Ioannis; Farahi, Salma; Psaltis, Demetri

2013-04-01

Microscopes are usually thought of comprising imaging elements such as objectives and eye-piece lenses. A different type of microscope, used for endoscopy, consists of waveguiding elements such as fiber bundles, where each fiber in the bundle transports the light corresponding to one pixel in the image. Recently a new type of microscope has emerged that exploits the large number of propagating modes in a single multimode fiber. We have successfully produced fluorescence images of neural cells with sub-micrometer resolution via a 200 micrometer core multimode fiber. The method for achieving imaging consists of using digital phase conjugation to reproduce a focal spot at the tip of the multimode fiber. The image is formed by scanning the focal spot digitally and collecting the fluorescence point by point.

Multimodal optical workstation for simultaneous linear, nonlinear microscopy and nanomanipulation: upgrading a commercial confocal inverted microscope.

PubMed

Mathew, Manoj; Santos, Susana I C O; Zalvidea, Dobryna; Loza-Alvarez, Pablo

2009-07-01

In this work we propose and build a multimodal optical workstation that extends a commercially available confocal microscope (Nikon Confocal C1-Si) to include nonlinear/multiphoton microscopy and optical manipulation/stimulation tools such as nanosurgery. The setup allows both subsystems (confocal and nonlinear) to work independently and simultaneously. The workstation enables, for instance, nanosurgery along with simultaneous confocal and brightfield imaging. The nonlinear microscopy capabilities are added around the commercial confocal microscope by exploiting all the flexibility offered by this microscope and without need for any mechanical or electronic modification of the confocal microscope systems. As an example, the standard differential interference contrast condenser and diascopic detector in the confocal microscope are readily used as a forward detection mount for second harmonic generation imaging. The various capabilities of this workstation, as applied directly to biology, are demonstrated using the model organism Caenorhabditis elegans.

Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei

2010-02-01

Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

Passive athermalization of multimode interference devices for wavelength-locking applications.

PubMed

Ruiz-Perez, Victor I; May-Arrioja, Daniel A; Guzman-Sepulveda, Jose R

2017-03-06

In this paper we demonstrate the passive, material-based athermalization of all-fiber architectures by cascading multimode interference (MMI) devices. In-line thermal compensation is achieved by including a liquid-core multimode section of variable length that allows ensuring temperature-independent operation while preserving the inherent filter-like spectral response of the MMI devices. The design of the temperature compensation unit is straightforward and its fabrication is simple. The applicability of our approach is experimentally verified by fabricating a wavelength-locked MMI laser with sensitivity of only -0.1 pm/°C, which is at least one order of magnitude lower than that achieved with other fiber optics devices.

Spectral embedding-based registration (SERg) for multimodal fusion of prostate histology and MRI

NASA Astrophysics Data System (ADS)

Hwuang, Eileen; Rusu, Mirabela; Karthigeyan, Sudha; Agner, Shannon C.; Sparks, Rachel; Shih, Natalie; Tomaszewski, John E.; Rosen, Mark; Feldman, Michael; Madabhushi, Anant

2014-03-01

Multi-modal image registration is needed to align medical images collected from different protocols or imaging sources, thereby allowing the mapping of complementary information between images. One challenge of multimodal image registration is that typical similarity measures rely on statistical correlations between image intensities to determine anatomical alignment. The use of alternate image representations could allow for mapping of intensities into a space or representation such that the multimodal images appear more similar, thus facilitating their co-registration. In this work, we present a spectral embedding based registration (SERg) method that uses non-linearly embedded representations obtained from independent components of statistical texture maps of the original images to facilitate multimodal image registration. Our methodology comprises the following main steps: 1) image-derived textural representation of the original images, 2) dimensionality reduction using independent component analysis (ICA), 3) spectral embedding to generate the alternate representations, and 4) image registration. The rationale behind our approach is that SERg yields embedded representations that can allow for very different looking images to appear more similar, thereby facilitating improved co-registration. Statistical texture features are derived from the image intensities and then reduced to a smaller set by using independent component analysis to remove redundant information. Spectral embedding generates a new representation by eigendecomposition from which only the most important eigenvectors are selected. This helps to accentuate areas of salience based on modality-invariant structural information and therefore better identifies corresponding regions in both the template and target images. The spirit behind SERg is that image registration driven by these areas of salience and correspondence should improve alignment accuracy. In this work, SERg is implemented using Demons to allow the algorithm to more effectively register multimodal images. SERg is also tested within the free-form deformation framework driven by mutual information. Nine pairs of synthetic T1-weighted to T2-weighted brain MRI were registered under the following conditions: five levels of noise (0%, 1%, 3%, 5%, and 7%) and two levels of bias field (20% and 40%) each with and without noise. We demonstrate that across all of these conditions, SERg yields a mean squared error that is 81.51% lower than that of Demons driven by MRI intensity alone. We also spatially align twenty-six ex vivo histology sections and in vivo prostate MRI in order to map the spatial extent of prostate cancer onto corresponding radiologic imaging. SERg performs better than intensity registration by decreasing the root mean squared distance of annotated landmarks in the prostate gland via both Demons algorithm and mutual information-driven free-form deformation. In both synthetic and clinical experiments, the observed improvement in alignment of the template and target images suggest the utility of parametric eigenvector representations and hence SERg for multimodal image registration.

Mechanisms of murine cerebral malaria: Multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites

PubMed Central

Hackett, Mark J.; Aitken, Jade B.; El-Assaad, Fatima; McQuillan, James A.; Carter, Elizabeth A.; Ball, Helen J.; Tobin, Mark J.; Paterson, David; de Jonge, Martin D.; Siegele, Rainer; Cohen, David D.; Vogt, Stefan; Grau, Georges E.; Hunt, Nicholas H.; Lay, Peter A.

2015-01-01

Using a multimodal biospectroscopic approach, we settle several long-standing controversies over the molecular mechanisms that lead to brain damage in cerebral malaria, which is a major health concern in developing countries because of high levels of mortality and permanent brain damage. Our results provide the first conclusive evidence that important components of the pathology of cerebral malaria include peroxidative stress and protein oxidation within cerebellar gray matter, which are colocalized with elevated nonheme iron at the site of microhemorrhage. Such information could not be obtained previously from routine imaging methods, such as electron microscopy, fluorescence, and optical microscopy in combination with immunocytochemistry, or from bulk assays, where the level of spatial information is restricted to the minimum size of tissue that can be dissected. We describe the novel combination of chemical probe–free, multimodal imaging to quantify molecular markers of disturbed energy metabolism and peroxidative stress, which were used to provide new insights into understanding the pathogenesis of cerebral malaria. In addition to these mechanistic insights, the approach described acts as a template for the future use of multimodal biospectroscopy for understanding the molecular processes involved in a range of clinically important acute and chronic (neurodegenerative) brain diseases to improve treatment strategies. PMID:26824064

Fused oblique incidence reflectometry and confocal fluorescence microscopy

NASA Astrophysics Data System (ADS)

Risi, Matthew D.; Rouse, Andrew R.; Gmitro, Arthur F.

2011-03-01

Confocal microendoscopy provides real-time high resolution cellular level images via a minimally invasive procedure, but relies on exogenous fluorophores, has a relatively limited penetration depth (100 μm) and field of view (700 μm), and produces a high rate of detailed information to the user. A new catheter based multi-modal system has been designed that combines confocal imaging and oblique incidence reflectometry (OIR), which is a non-invasive method capable of rapidly extracting tissue absorption, μa, and reduced scattering, μ's, spectra from tissue. The system builds on previous developments of a custom slit-scan multi-spectral confocal microendoscope and is designed to rapidly switch between diffuse spectroscopy and confocal fluorescence imaging modes of operation. An experimental proof-of-principle catheter has been developed that consists of a fiber bundle for traditional confocal fluorescence imaging and a single OIR source fiber which is manually redirected at +/- 26 degrees. Diffusely scattered light from each orientation of the source fiber is collected via the fiber bundle, with a frame of data representing spectra collected at a range of distances from the OIR source point. Initial results with intralipid phantoms show good agreement to published data over the 550-650 nm spectral range. We successfully imaged and measured the optical properties of rodent cardiac muscle.

Multimode optical dermoscopy (SkinSpect) analysis for skin with melanocytic nevus

NASA Astrophysics Data System (ADS)

Vasefi, Fartash; MacKinnon, Nicholas; Saager, Rolf; Kelly, Kristen M.; Maly, Tyler; Chave, Robert; Booth, Nicholas; Durkin, Anthony J.; Farkas, Daniel L.

2016-04-01

We have developed a multimode dermoscope (SkinSpect™) capable of illuminating human skin samples in-vivo with spectrally-programmable linearly-polarized light at 33 wavelengths between 468nm and 857 nm. Diffusely reflected photons are separated into collinear and cross-polarized image paths and images captured for each illumination wavelength. In vivo human skin nevi (N = 20) were evaluated with the multimode dermoscope and melanin and hemoglobin concentrations were compared with Spatially Modulated Quantitative Spectroscopy (SMoQS) measurements. Both systems show low correlation between their melanin and hemoglobin concentrations, demonstrating the ability of the SkinSpect™ to separate these molecular signatures and thus act as a biologically plausible device capable of early onset melanoma detection.

A meta-classifier for detecting prostate cancer by quantitative integration of in vivo magnetic resonance spectroscopy and magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Viswanath, Satish; Tiwari, Pallavi; Rosen, Mark; Madabhushi, Anant

2008-03-01

Recently, in vivo Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) have emerged as promising new modalities to aid in prostate cancer (CaP) detection. MRI provides anatomic and structural information of the prostate while MRS provides functional data pertaining to biochemical concentrations of metabolites such as creatine, choline and citrate. We have previously presented a hierarchical clustering scheme for CaP detection on in vivo prostate MRS and have recently developed a computer-aided method for CaP detection on in vivo prostate MRI. In this paper we present a novel scheme to develop a meta-classifier to detect CaP in vivo via quantitative integration of multimodal prostate MRS and MRI by use of non-linear dimensionality reduction (NLDR) methods including spectral clustering and locally linear embedding (LLE). Quantitative integration of multimodal image data (MRI and PET) involves the concatenation of image intensities following image registration. However multimodal data integration is non-trivial when the individual modalities include spectral and image intensity data. We propose a data combination solution wherein we project the feature spaces (image intensities and spectral data) associated with each of the modalities into a lower dimensional embedding space via NLDR. NLDR methods preserve the relationships between the objects in the original high dimensional space when projecting them into the reduced low dimensional space. Since the original spectral and image intensity data are divorced from their original physical meaning in the reduced dimensional space, data at the same spatial location can be integrated by concatenating the respective embedding vectors. Unsupervised consensus clustering is then used to partition objects into different classes in the combined MRS and MRI embedding space. Quantitative results of our multimodal computer-aided diagnosis scheme on 16 sets of patient data obtained from the ACRIN trial, for which corresponding histological ground truth for spatial extent of CaP is known, show a marginally higher sensitivity, specificity, and positive predictive value compared to corresponding CAD results with the individual modalities.

Mode synthesizing atomic force microscopy and mode-synthesizing sensing

DOEpatents

Passian, Ali; Thundat, Thomas George; Tetard, Laurene

2013-05-17

A method of analyzing a sample that includes applying a first set of energies at a first set of frequencies to a sample and applying, simultaneously with the applying the first set of energies, a second set of energies at a second set of frequencies, wherein the first set of energies and the second set of energies form a multi-mode coupling. The method further includes detecting an effect of the multi-mode coupling.

Mode-synthesizing atomic force microscopy and mode-synthesizing sensing

DOEpatents

Passain, Ali; Thundat, Thomas George; Tetard, Laurene

2014-07-22

A method of analyzing a sample that includes applying a first set of energies at a first set of frequencies to a sample and applying, simultaneously with the applying the first set of energies, a second set of energies at a second set of frequencies, wherein the first set of energies and the second set of energies form a multi-mode coupling. The method further includes detecting an effect of the multi-mode coupling.

Exploring the cellular and tissue uptake of nanomaterials in a range of biological samples using multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Johnston, Helinor J.; Mouras, Rabah; Brown, David M.; Elfick, Alistair; Stone, Vicki

2015-12-01

The uptake of nanomaterials (NMs) by cells is critical in determining their potential biological impact, whether beneficial or detrimental. Thus, investigation of NM internalization by cells is a common consideration in hazard and efficacy studies. There are currently a number of approaches that are routinely used to investigate NM-cell interactions, each of which have their own advantages and limitations. Ideally, imaging modalities used to investigate NM uptake by cells should not require the NM to be labelled (e.g. with fluorophores) to facilitate its detection. We present a multimodal imaging approach employing a combination of label-free microscopies that can be used to investigate NM-cell interactions. Coherent anti-Stokes Raman scattering microscopy was used in combination with either two-photon photoluminescence or four-wave mixing (FWM) to visualize the uptake of gold or titanium dioxide NMs respectively. Live and fixed cell imaging revealed that NMs were internalized by J774 macrophage and C3A hepatocyte cell lines (15-31 μg ml-1). Sprague Dawley rats were exposed to NMs (intratracheal instillation, 62 μg) and NMs were detected in blood and lung leucocytes, lung and liver tissue, demonstrating that NMs could translocate from the exposure site. Obtained data illustrate that multimodal nonlinear optical microscopy may help overcome current challenges in the assessment of NM cellular uptake and biodistribution. It is therefore a powerful tool that can be used to investigate unlabelled NM cellular and tissue uptake in three dimensions, requires minimal sample preparation, and is applicable to live and fixed cells.

Microspectroscopic analysis of green fluorescent proteins infiltrated into mesoporous silica nanochannels.

PubMed

Ma, Yujie; Rajendran, Prayanka; Blum, Christian; Cesa, Yanina; Gartmann, Nando; Brühwiler, Dominik; Subramaniam, Vinod

2011-04-01

The infiltration of enhanced green fluorescent protein (EGFP) into nanochannels of different diameters in mesoporous silica particles was studied in detail by fluorescence microspectroscopy at room temperature. Silica particles from the MCM-41, ASNCs and SBA-15 families possessing nanometer-sized (3-8 nm in diameter) channels, comparable to the dimensions of the infiltrated guest protein EGFP (barrel structure with dimensions of 2.4 nm × 4.2 nm), were used as hosts. We found that it is necessary to first functionalize the surfaces of the silica particles with an amino-silane for effective encapsulation of EGFP. We demonstrated successful infiltration of the protein into the nanochannels based on fluorescence microspectroscopy and loading capacity calculations, even for nanochannel diameters approaching the protein dimensions. We studied the spatial distributions of the EGFPs within the silica particles by confocal laser scanning microscopy (CLSM) and multimode microscopy. Upon infiltration, the fluorescence lifetime drops as expected for an emitter embedded in a high refractive index medium. Further, the spectral properties of EGFP are preserved, confirming the structural integrity of the infiltrated protein. This inorganic-protein host-guest system is an example of a nanobiophotonic hybrid system that may lead to composite materials with novel optical properties. Copyright © 2010 Elsevier Inc. All rights reserved.

A tunable comb filter using single-mode/multimode/polarization-maintaining-fiber-based Sagnac fiber loop

NASA Astrophysics Data System (ADS)

Ruan, Juan; Zhang, Wei-Gang; Zhang, Hao; Geng, Peng-Cheng; Bai, Zhi-Yong

2013-06-01

A novel tunable comb filter composed of a single-mode/multimode/polarization-maintaining-fiber-based Sagnac fiber loop is proposed and experimentally demonstrated. The filter tunability is achieved by rotating the polarization controller. The spectral shift is dependent on rotation direction and the position of the polarization controller. In addition, the adjustable range achieved by rotating the half-wave-plate polarization controller is twice higher than that of the quarter-wave-plate one.

Nonlinear dynamics and control of a vibrating rectangular plate

NASA Technical Reports Server (NTRS)

Shebalin, J. V.

1983-01-01

The von Karman equations of nonlinear elasticity are solved for the case of a vibrating rectangular plate by meams of a Fourier spectral transform method. The amplification of a particular Fourier mode by nonlinear transfer of energy is demonstrated for this conservative system. The multi-mode system is reduced to a minimal (two mode) system, retaining the qualitative features of the multi-mode system. The effect of a modal control law on the dynamics of this minimal nonlinear elastic system is examined.

A Versatile High-Vacuum Cryo-transfer System for Cryo-microscopy and Analytics

PubMed Central

Tacke, Sebastian; Krzyzanek, Vladislav; Nüsse, Harald; Wepf, Roger Albert; Klingauf, Jürgen; Reichelt, Rudolf

2016-01-01

Cryogenic microscopy methods have gained increasing popularity, as they offer an unaltered view on the architecture of biological specimens. As a prerequisite, samples must be handled under cryogenic conditions below their recrystallization temperature, and contamination during sample transfer and handling must be prevented. We present a high-vacuum cryo-transfer system that streamlines the entire handling of frozen-hydrated samples from the vitrification process to low temperature imaging for scanning transmission electron microscopy and transmission electron microscopy. A template for cryo-electron microscopy and multimodal cryo-imaging approaches with numerous sample transfer steps is presented. PMID:26910419

Interactive multi-spectral analysis of more than one Sonrai village in Niger, West Africa

NASA Technical Reports Server (NTRS)

Reining, P.; Egbert, D. D.

1975-01-01

Use of LANDSAT data and an interaction system is considered for identifying and measuring small scale compact human settlements (villages) for demographic and anthropological studies. Because village components are not uniformly distributed within any one village, they apparently are multimodal, spectrally. Therefore, the functions of location and enumeration are kept separate. Measurement of a known village is compared with CCT response.

In-fiber modal interferometer based on multimode and double cladding fiber segments for tunable fiber laser applications

NASA Astrophysics Data System (ADS)

Prieto-Cortés, P.; Álvarez-Tamayo, R. I.; Durán-Sánchez, M.; Castillo-Guzmán, A.; Salceda-Delgado, G.; Ibarra-Escamilla, B.; Kuzin, E. A.; Barcelata-Pinzón, A.; Selvas-Aguilar, R.

2018-02-01

We report an in-fiber structure based on the use of a multimode fiber segment and a double cladding fiber segment, and its application as spectral filter in an erbium-doped fiber laser for selection and tuning of the laser line wavelength. The output transmission of the proposed device exhibit spectrum modulation of the input signal with free spectral range of 21 nm and maximum visibility enhanced to more than 20 dB. The output spectrum of the in-fiber filter is wavelength displaced by bending application which allows a wavelength tuning of the generated laser line in a range of 12 nm. The use of the proposed in-fiber structure is demonstrated as a reliable, simple, and low-cost wavelength filter for tunable fiber lasers design and optical instrumentation applications.

Toward in vivo diagnosis of skin cancer using multimode imaging dermoscopy: (II) molecular mapping of highly pigmented lesions

NASA Astrophysics Data System (ADS)

Vasefi, Fartash; MacKinnon, Nicholas; Farkas, Daniel L.

2014-03-01

We have developed a multimode imaging dermoscope that combines polarization and hyperspectral imaging with a computationally rapid analytical model. This approach employs specific spectral ranges of visible and near infrared wavelengths for mapping the distribution of specific skin bio-molecules. This corrects for the melanin-hemoglobin misestimation common to other systems, without resorting to complex and computationally intensive tissue optical models that are prone to inaccuracies due to over-modeling. Various human skin measurements including a melanocytic nevus, and venous occlusion conditions were investigated and compared with other ratiometric spectral imaging approaches. Access to the broad range of hyperspectral data in the visible and near-infrared range allows our algorithm to flexibly use different wavelength ranges for chromophore estimation while minimizing melanin-hemoglobin optical signature cross-talk.

Multimodal swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography at 400 kHz

NASA Astrophysics Data System (ADS)

El-Haddad, Mohamed T.; Joos, Karen M.; Patel, Shriji N.; Tao, Yuankai K.

2017-02-01

Multimodal imaging systems that combine scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) have demonstrated the utility of concurrent en face and volumetric imaging for aiming, eye tracking, bulk motion compensation, mosaicking, and contrast enhancement. However, this additional functionality trades off with increased system complexity and cost because both SLO and OCT generally require dedicated light sources, galvanometer scanners, relay and imaging optics, detectors, and control and digitization electronics. We previously demonstrated multimodal ophthalmic imaging using swept-source spectrally encoded SLO and OCT (SS-SESLO-OCT). Here, we present system enhancements and a new optical design that increase our SS-SESLO-OCT data throughput by >7x and field-of-view (FOV) by >4x. A 200 kHz 1060 nm Axsun swept-source was optically buffered to 400 kHz sweep-rate, and SESLO and OCT were simultaneously digitized on dual input channels of a 4 GS/s digitizer at 1.2 GS/s per channel using a custom k-clock. We show in vivo human imaging of the anterior segment out to the limbus and retinal fundus over a >40° FOV. In addition, nine overlapping volumetric SS-SESLO-OCT volumes were acquired under video-rate SESLO preview and guidance. In post-processing, all nine SESLO images and en face projections of the corresponding OCT volumes were mosaicked to show widefield multimodal fundus imaging with a >80° FOV. Concurrent multimodal SS-SESLO-OCT may have applications in clinical diagnostic imaging by enabling aiming, image registration, and multi-field mosaicking and benefit intraoperative imaging by allowing for real-time surgical feedback, instrument tracking, and overlays of computationally extracted image-based surrogate biomarkers of disease.

Investigating the Strain, Temperature and Humidity Sensitivity of a Multimode Graded-Index Perfluorinated Polymer Optical Fiber with Bragg Grating

PubMed Central

Zheng, Yulong; Bremer, Kort

2018-01-01

In this work we investigate the strain, temperature and humidity sensitivity of a Fiber Bragg Grating (FBG) inscribed in a near infrared low-loss multimode perfluorinated polymer optical fiber based on cyclic transparent optical polymer (CYTOP). For this purpose, FBGs were inscribed into the multimode CYTOP fiber with a core diameter of 50 µm by using a krypton fluoride (KrF) excimer laser and the phase mask method. The evolution of the reflection spectrum of the FBG detected with a multimode interrogation technique revealed a single reflection peak with a full width at half maximum (FHWM) bandwidth of about 9 nm. Furthermore, the spectral envelope of the single FBG reflection peak can be optimized depending on the KrF excimer laser irradiation time. A linear shift of the Bragg wavelength due to applied strain, temperature and humidity was measured. Furthermore, depending on irradiation time of the KrF excimer laser, both the failure strain and strain sensitivity of the multimode fiber with FBG can be controlled. The inherent low light attenuation in the near infrared wavelength range (telecommunication window) of the multimode CYTOP fiber and the single FBG reflection peak when applying the multimode interrogation set-up will allow for new applications in the area of telecommunication and optical sensing. PMID:29734734

Investigating the Strain, Temperature and Humidity Sensitivity of a Multimode Graded-Index Perfluorinated Polymer Optical Fiber with Bragg Grating.

PubMed

Zheng, Yulong; Bremer, Kort; Roth, Bernhard

2018-05-05

In this work we investigate the strain, temperature and humidity sensitivity of a Fiber Bragg Grating (FBG) inscribed in a near infrared low-loss multimode perfluorinated polymer optical fiber based on cyclic transparent optical polymer (CYTOP). For this purpose, FBGs were inscribed into the multimode CYTOP fiber with a core diameter of 50 µm by using a krypton fluoride (KrF) excimer laser and the phase mask method. The evolution of the reflection spectrum of the FBG detected with a multimode interrogation technique revealed a single reflection peak with a full width at half maximum (FHWM) bandwidth of about 9 nm. Furthermore, the spectral envelope of the single FBG reflection peak can be optimized depending on the KrF excimer laser irradiation time. A linear shift of the Bragg wavelength due to applied strain, temperature and humidity was measured. Furthermore, depending on irradiation time of the KrF excimer laser, both the failure strain and strain sensitivity of the multimode fiber with FBG can be controlled. The inherent low light attenuation in the near infrared wavelength range (telecommunication window) of the multimode CYTOP fiber and the single FBG reflection peak when applying the multimode interrogation set-up will allow for new applications in the area of telecommunication and optical sensing.

Narrow-linewidth broadly tunable Yb-doped Q-switched fiber laser using multimode interference filter.

PubMed

Chakravarty, Usha; Mukhopadhyay, P K; Kuruvilla, A; Upadhyaya, B N; Bindra, K S

2017-05-01

A narrow-linewidth broadly tunable Yb-doped Q-switched fiber laser using an acousto-optic modulator and multimode interference filter (MMIF) in the linear bulk cavity resonator and an all-fiber ring cavity resonator has been demonstrated. Insertion of an MMIF in the linear cavity resonator using bulk components decreased the spectral bandwidth of the Q-switched signal by two orders of magnitude from 11 to less than 0.1 nm. Spectral tunability of more than 16 nm in the range from 1057 to 1073 nm has also been achieved by the combination of MMIF and a standard polarization controller (SPC). A decrease in the pulse duration with a decrease in the spectral bandwidth of the output signal has also been recorded. The pulse duration of the Q-switched signal was reduced from ∼305 to ∼240  ns by the introduction of the MMIF in the resonator at the same value of the input pump power. In the case of the all-fiber Q-switched ring cavity resonator, the spectral bandwidth of the Q-switched signal was reduced by two orders of magnitude from ∼17 to less than 0.1 nm due to the introduction of the MMIF in the resonator. The spectral tunability of more than 12 nm in the range from 1038 to 1050 nm was achieved by an MMIF and an SPC.

A portable microscopy system for fluorescence, polarized, and brightfield imaging

NASA Astrophysics Data System (ADS)

Gordon, Paul; Wattinger, Rolla; Lewis, Cody; Venancio, Vinicius Paula; Mertens-Talcott, Susanne U.; Coté, Gerard

2018-02-01

The use of mobile phones to conduct diagnostic microscopy at the point-of-care presents intriguing possibilities for the advancement of high-quality medical care in remote settings. However, it is challenging to create a single device that can adapt to the ever-varying camera technologies in phones or that can image with the customization that multiple modalities require for applications such as malaria diagnosis. A portable multi-modal microscope system is presented that utilizes a Raspberry Pi to collect and transmit data wirelessly to a myriad of electronic devices for image analysis. The microscopy system is capable of providing to the user correlated brightfield, polarized, and fluorescent images of samples fixed on traditional microscopy slides. The multimodal diagnostic capabilities of the microscope were assessed by measuring parasitemia of Plasmodium falciparum-infected thin blood smears. The device is capable of detecting fluorescently-labeled DNA using FITC excitation (490 nm) and emission (525 nm), the birefringent P. falciparum byproduct hemozoin, and detecting brightfield absorption with a resolution of 0.78 micrometers (element 9-3 of a 1951 Air Force Target). This microscopy system is a novel portable imaging tool that may be a viable candidate for field implementation if challenges of system durability, cost considerations, and full automation can be overcome.

Spectral response of fiber-coupled Fabry-Perot etalons.

PubMed

Ionov, Pavel

2014-03-01

In many remote sensing applications one or multiple Fabry-Perot etalons are used as high-spectral-resolution filter elements. These etalons are often coupled to a receiving telescope with a multimode fiber, leading to subtle effects of the fiber mode order on the overall spectral response of the system. A theoretical model is developed to treat the spectral response of the combined system: fiber, collimator, and etalon. The method is based on a closed-form expression of the diffracted mode in terms of a Hankel transform. In this representation, it is shown how the spectral effect of the fiber and collimator can be separated from the details of the etalon and can be viewed as a mode-dependent spectral broadening and shift.

Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

PubMed Central

Coughlin, Andrew J.; Ananta, Jeyarama S.; Deng, Nanfu; Larina, Irina V.; Decuzzi, Paolo

2014-01-01

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, we have engineered gadolinium-conjugated gold nanoshells and demonstrated that they enhance contrast for magnetic resonance imaging, X-Ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation. PMID:24115690

Spectral characteristics of multimode semiconductor lasers with a high-order surface diffraction grating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zolotarev, V V; Leshko, A Yu; Pikhtin, N A

2014-10-31

We have studied the spectral characteristics of multimode semiconductor lasers with high-order surface diffraction gratings based on asymmetric separate-confinement heterostructures grown by metalorganic vapour phase epitaxy (λ = 1070 nm). Experimental data demonstrate that, in the temperature range ±50 °C, the laser emission spectrum is ∼5 Å in width and contains a fine structure of longitudinal and transverse modes. A high-order (m = 15) surface diffraction grating is shown to ensure a temperature stability of the lasing spectrum dλ/dT = 0.9 Å K{sup -1} in this temperature range. From analysis of the fine structure of the lasing spectrum, we havemore » evaluated the mode spacing and, thus, experimentally determined the effective length of the Bragg diffraction grating, which was ∼400 μm in our samples. (lasers)« less

Brightness enhancement limits in pulsed cladding-pumped fiber Raman amplifiers

NASA Astrophysics Data System (ADS)

Ji, Junhua; Codemard, Christophe A.; Nilsson, Johan

2010-02-01

We analyze theoretically limitations on brightness enhancement of a multimode pump beam into a diffraction-limited Stokes beam in efficient cladding-pumped fiber Raman amplifiers. Firstly, the power-scaling of the 1st Stokes (hence the brightness enhancement) is limited by the generation of the 2nd order Stokes. Thus using a spectral waveguide filter such as a W-type fiber core, it is possible to improve this limit to nearly five times that of a normal fiber without spectral filter. Secondly, we analyze limits set by glass damage, propagation loss, and pump-signal pulse walk-off in the multimode fiber. We show that a well-designed fiber with a propagation loss of 3.5 dB/km allows for a pump-to-signal brightness improvement of over 1000 times for pulses longer than 40 ns and up to 3500 times in the cw regime.

Hyper-Spectral Communications, Networking and ATM as Foundation for Safe and Efficient Future Flight: Transcending Aviation Operational Limitations with Diverse and Secure Multi-Band, Multi-Mode, and mmWave Wireless Links: Project Overview, Aviation Communications and New Signaling

NASA Technical Reports Server (NTRS)

Matolak, David W.

2017-01-01

NASA's Aeronautics Research Mission Directorate (ARMD) has recently solicited proposals and awarded funds for research and development to achieve and exceed the goals envisioned in the ARMD Strategic Implementation Plan (SIP). The Hyper-Spectral Communications and Networking for Air Traffic Management (ATM) (HSCNA) project is the only University Leadership Initiative (ULI) program to address communications and networking (and to a degree, navigation and surveillance). This paper will provide an overview of the HSCNA project, and specifically describe two of the project's technical challenges: comprehensive aviation communications and networking assessment, and proposed multi-band and multimode communications and networking. The primary goals will be described, as will be research and development aimed to achieve and exceed these goals. Some example initial results are also provided.

Pancreatic tissue assessment using fluorescence and reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Chandra, Malavika; Heidt, David; Simeone, Diane; McKenna, Barbara; Scheiman, James; Mycek, Mary-Ann

2007-07-01

The ability of multi-modal optical spectroscopy to detect signals from pancreatic tissue was demonstrated by studying human pancreatic cancer xenografts in mice and freshly excised human pancreatic tumor tissue. Measured optical spectra and fluorescence decays were correlated with tissue morphological and biochemical properties. The measured spectral features and decay times correlated well with expected pathological differences in normal, pancreatitis and adenocarcinoma tissue states. The observed differences between the fluorescence and reflectance properties of normal, pancreatitis and adenocarcinoma tissue indicate a possible application of multi-modal optical spectroscopy to differentiating between the three tissue classifications.

Multimodal ophthalmic imaging using swept source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Malone, Joseph D.; El-Haddad, Mohamed T.; Tye, Logan A.; Majeau, Lucas; Godbout, Nicolas; Rollins, Andrew M.; Boudoux, Caroline; Tao, Yuankai K.

2016-03-01

Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) benefit clinical diagnostic imaging in ophthalmology by enabling in vivo noninvasive en face and volumetric visualization of retinal structures, respectively. Spectrally encoding methods enable confocal imaging through fiber optics and reduces system complexity. Previous applications in ophthalmic imaging include spectrally encoded confocal scanning laser ophthalmoscopy (SECSLO) and a combined SECSLO-OCT system for image guidance, tracking, and registration. However, spectrally encoded imaging suffers from speckle noise because each spectrally encoded channel is effectively monochromatic. Here, we demonstrate in vivo human retinal imaging using a swept source spectrally encoded scanning laser ophthalmoscope and OCT (SSSESLO- OCT) at 1060 nm. SS-SESLO-OCT uses a shared 100 kHz Axsun swept source, shared scanner and imaging optics, and are detected simultaneously on a shared, dual channel high-speed digitizer. SESLO illumination and detection was performed using the single mode core and multimode inner cladding of a double clad fiber coupler, respectively, to preserve lateral resolution while improving collection efficiency and reducing speckle contrast at the expense of confocality. Concurrent en face SESLO and cross-sectional OCT images were acquired with 1376 x 500 pixels at 200 frames-per-second. Our system design is compact and uses a shared light source, imaging optics, and digitizer, which reduces overall system complexity and ensures inherent co-registration between SESLO and OCT FOVs. En face SESLO images acquired concurrent with OCT cross-sections enables lateral motion tracking and three-dimensional volume registration with broad applications in multivolume OCT averaging, image mosaicking, and intraoperative instrument tracking.

A high throughput spectral image microscopy system

NASA Astrophysics Data System (ADS)

Gesley, M.; Puri, R.

2018-01-01

A high throughput spectral image microscopy system is configured for rapid detection of rare cells in large populations. To overcome flow cytometry rates and use of fluorophore tags, a system architecture integrates sample mechanical handling, signal processors, and optics in a non-confocal version of light absorption and scattering spectroscopic microscopy. Spectral images with native contrast do not require the use of exogeneous stain to render cells with submicron resolution. Structure may be characterized without restriction to cell clusters of differentiation.

A multimodal image sensor system for identifying water stress in grapevines

NASA Astrophysics Data System (ADS)

Zhao, Yong; Zhang, Qin; Li, Minzan; Shao, Yongni; Zhou, Jianfeng; Sun, Hong

2012-11-01

Water stress is one of the most common limitations of fruit growth. Water is the most limiting resource for crop growth. In grapevines, as well as in other fruit crops, fruit quality benefits from a certain level of water deficit which facilitates to balance vegetative and reproductive growth and the flow of carbohydrates to reproductive structures. A multi-modal sensor system was designed to measure the reflectance signature of grape plant surfaces and identify different water stress levels in this paper. The multi-modal sensor system was equipped with one 3CCD camera (three channels in R, G, and IR). The multi-modal sensor can capture and analyze grape canopy from its reflectance features, and identify the different water stress levels. This research aims at solving the aforementioned problems. The core technology of this multi-modal sensor system could further be used as a decision support system that combines multi-modal sensory data to improve plant stress detection and identify the causes of stress. The images were taken by multi-modal sensor which could output images in spectral bands of near-infrared, green and red channel. Based on the analysis of the acquired images, color features based on color space and reflectance features based on image process method were calculated. The results showed that these parameters had the potential as water stress indicators. More experiments and analysis are needed to validate the conclusion.

Coherent noise reduction in digital holographic microscopy by averaging multiple holograms recorded with a multimode laser.

PubMed

Pan, Feng; Yang, Lizhi; Xiao, Wen

2017-09-04

In digital holographic microscopy (DHM), it is undesirable to observe coherent noise in the reconstructed images. The sources of the noise are mainly the parasitic interference fringes caused by multiple reflections and the speckle pattern caused by the optical scattering on the object surface. Here we propose a noise reduction approach in DHM by averaging multiple holograms recorded with a multimode laser. Based on the periodicity of the temporal coherence of a multimode semiconductor laser, we acquire a series of holograms by changing the optical path length difference between the reference beam and object beam. Because of the use of low coherence light, we can remove the parasitic interference fringes caused by multiple reflections in the holograms. In addition, the coherent noise patterns change in this process due to the different optical paths. Therefore, the coherent noise can be reduced by averaging the multiple reconstructions with uncorrelated noise patterns. Several experiments have been carried out to validate the effectiveness of the proposed approach for coherent noise reduction in DHM. It is shown a remarkable improvement both in amplitude imaging quality and phase measurement accuracy.

Multimodal Broadband Vibrational Sum Frequency Generation (MM-BB-V-SFG) Spectrometer and Microscope.

PubMed

Lee, Christopher M; Kafle, Kabindra; Huang, Shixin; Kim, Seong H

2016-01-14

A broadband sum frequency generation (BB-SFG) spectrometer with multimodal (MM) capabilities was constructed, which could be routinely reconfigured for tabletop experiments in reflection, transmission, and total internal reflection (TIR) geometries, as well as microscopic imaging. The system was constructed using a Ti:sapphire amplifier (800 nm, pulse width = 85 fs, repetition rate = 2 kHz), an optical parameter amplification (OPA) system for production of broadband IR pulses tunable between 1000 and 4000 cm(-1), and two Fabry-Pérot etalons arranged in series for production of narrowband 800 nm pulses. The key feature allowing the MM operation was the nearly collinear alignment of the visible (fixed, 800 nm) and infrared (tunable, 1000-4000 cm(-1)) pulses which were spatially separated. Physical insights discussed in this paper include the comparison of spectral bandwidth produced with 40 and 85 fs pump beams, the improvement of spectral resolution using etalons, the SFG probe volume in bulk analysis, the normalization of SFG signals, the stitching of multiple spectral segments, and the operation in different modes for air/liquid and adsorbate/solid interfaces, bulk samples, as well as spectral imaging combined with principle component analysis (PCA). The SFG spectral features obtained with the MM-BB-SFG system were compared with those obtained with picosecond-scanning-SFG system and high-resolution BB-SFG system (HR-BB-SFG) for dimethyl sulfoxide, α-pinene, and various samples containing cellulose (purified commercial products, Cladophora cell wall, cotton and flax fibers, and onion epidermis cell wall).

Development of fiber lasers and devices for coherent Raman scattering microscopy

NASA Astrophysics Data System (ADS)

Lamb, Erin Stranford

As ultrafast laser technology has found expanding application in machining, spectroscopy, microscopy, surgery, and numerous other areas, the desire for inexpensive and robust laser sources has grown. Until recently, nonlinear effects in fiber systems due to the tight confinement of the light in the core have limited their performance. However, with advances in managing nonlinearity through pulse propagation physics and the use of large core fibers, the performance of fiber lasers can compete with that of their solid-state counterparts. As specific applications, such as coherent Raman scattering microscopy, emerge that stand to benefit from fiber technology, new performance challenges in areas such as laser noise are anticipated. This thesis studies nonlinear pulse propagation in fiber lasers and fiber parametric devices. Applications of dissipative solitons and self-similar pulse propagation to low-repetition rate oscillators that have the potential to simplify short-pulse amplification schemes will be examined. The rest of this thesis focuses on topics relevant to fiber laser development for coherent Raman scattering microscopy sources. Coherent pulse division and recombination inside the laser cavity will be introduced as an energy-scaling mechanism and demonstrated for a fiber soliton laser. The relative intensity noise properties of mode-locked fiber lasers, with a particular emphasis on normal dispersion lasers, will be explored in simulation and experiment. A fiber optical parametric oscillator will be studied in detail for low noise frequency conversion of picosecond pulses, and its utility for coherent Raman imaging will be demonstrated. Spectral compression of femtosecond pulses is used to generate picosecond pulses to pump this device, and this technique provides a route to future noise reduction in the system. Furthermore, this device forms a multimodal source capable of providing the picosecond pulses for coherent Raman scattering microscopy and the high energy femtosecond pulses for other multiphoton imaging techniques. Finally, ideas for future extensions of this work will be discussed.

Multiplexed single-mode wavelength-to-time mapping of multimode light

PubMed Central

Chandrasekharan, Harikumar K; Izdebski, Frauke; Gris-Sánchez, Itandehui; Krstajić, Nikola; Walker, Richard; Bridle, Helen L.; Dalgarno, Paul A.; MacPherson, William N.; Henderson, Robert K.; Birks, Tim A.; Thomson, Robert R.

2017-01-01

When an optical pulse propagates along an optical fibre, different wavelengths travel at different group velocities. As a result, wavelength information is converted into arrival-time information, a process known as wavelength-to-time mapping. This phenomenon is most cleanly observed using a single-mode fibre transmission line, where spatial mode dispersion is not present, but the use of such fibres restricts possible applications. Here we demonstrate that photonic lanterns based on tapered single-mode multicore fibres provide an efficient way to couple multimode light to an array of single-photon avalanche detectors, each of which has its own time-to-digital converter for time-correlated single-photon counting. Exploiting this capability, we demonstrate the multiplexed single-mode wavelength-to-time mapping of multimode light using a multicore fibre photonic lantern with 121 single-mode cores, coupled to 121 detectors on a 32 × 32 detector array. This work paves the way to efficient multimode wavelength-to-time mapping systems with the spectral performance of single-mode systems. PMID:28120822

Spectral Demultiplexing in Holographic and Fluorescent On-chip Microscopy

NASA Astrophysics Data System (ADS)

Sencan, Ikbal; Coskun, Ahmet F.; Sikora, Uzair; Ozcan, Aydogan

2014-01-01

Lensfree on-chip imaging and sensing platforms provide compact and cost-effective designs for various telemedicine and lab-on-a-chip applications. In this work, we demonstrate computational solutions for some of the challenges associated with (i) the use of broadband, partially-coherent illumination sources for on-chip holographic imaging, and (ii) multicolor detection for lensfree fluorescent on-chip microscopy. Specifically, we introduce spectral demultiplexing approaches that aim to digitally narrow the spectral content of broadband illumination sources (such as wide-band light emitting diodes or even sunlight) to improve spatial resolution in holographic on-chip microscopy. We also demonstrate the application of such spectral demultiplexing approaches for wide-field imaging of multicolor fluorescent objects on a chip. These computational approaches can be used to replace e.g., thin-film interference filters, gratings or other optical components used for spectral multiplexing/demultiplexing, which can form a desirable solution for cost-effective and compact wide-field microscopy and sensing needs on a chip.

Mixture-Tuned, Clutter Matched Filter for Remote Detection of Subpixel Spectral Signals

NASA Technical Reports Server (NTRS)

Thompson, David R.; Mandrake, Lukas; Green, Robert O.

2013-01-01

Mapping localized spectral features in large images demands sensitive and robust detection algorithms. Two aspects of large images that can harm matched-filter detection performance are addressed simultaneously. First, multimodal backgrounds may thwart the typical Gaussian model. Second, outlier features can trigger false detections from large projections onto the target vector. Two state-of-the-art approaches are combined that independently address outlier false positives and multimodal backgrounds. The background clustering models multimodal backgrounds, and the mixture tuned matched filter (MT-MF) addresses outliers. Combining the two methods captures significant additional performance benefits. The resulting mixture tuned clutter matched filter (MT-CMF) shows effective performance on simulated and airborne datasets. The classical MNF transform was applied, followed by k-means clustering. Then, each cluster s mean, covariance, and the corresponding eigenvalues were estimated. This yields a cluster-specific matched filter estimate as well as a cluster- specific feasibility score to flag outlier false positives. The technology described is a proof of concept that may be employed in future target detection and mapping applications for remote imaging spectrometers. It is of most direct relevance to JPL proposals for airborne and orbital hyperspectral instruments. Applications include subpixel target detection in hyperspectral scenes for military surveillance. Earth science applications include mineralogical mapping, species discrimination for ecosystem health monitoring, and land use classification.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype.

PubMed

Liu, Tin Yan Alvin; Han, Ian C; Goldberg, Morton F; Linz, Marguerite O; Chen, Connie J; Scott, Adrienne W

2018-05-01

Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

Development of stable, narrow spectral line-width, fiber delivered laser source for spin exchange optical pumping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Bo; Tong, Xin; Jiang, Chenyang

2015-06-05

In this study, we developed a stable, narrow spectral line-width, fiber delivered laser source for spin exchange optical pumping. An optimized external cavity equipped with an off-the-shelf volume holographic grating narrowed the spectral line-width of a 100 W high-power diode laser and stabilized the laser spectrum. The laser spectrum showed a high side mode suppression ratio of >30 dB and good long-term stability (center wavelength drifting within ±0.002 nm during 220 h of operation). Finally, our laser is delivered by a multimode fiber with power ~70 W, center wavelength of 794.77 nm, and spectral bandwidth of ~0.12 nm.

Investigation of multimodal forward scatter phenotyping from bacterial colonies

NASA Astrophysics Data System (ADS)

Kim, Huisung

A rapid, label-free, and elastic light scattering (ELS) based bacterial colony phenotyping technology, bacterial rapid detection using optical scattering technology (BARDOT) provides a successful classification of several bacterial genus and species. For a thorough understanding of the phenomena and overcoming the limitations of the previous design, five additional modalities from a bacterial colony: 3D morphology, spatial optical density (OD) distribution, spectral forward scattering pattern, spectral OD, and surface backward reflection pattern are proposed to enhance the classification/identification ratio, and the feasibilities of each modality are verified. For the verification, three different instruments: integrated colony morphology analyzer (ICMA), multi-spectral BARDOT (MS-BARDOT) , and multi-modal BARDOT (MM-BARDOT) are proposed and developed. The ICMA can measure 3D morphology and spatial OD distribution of the colony simultaneously. A commercialized confocal displacement meter is used to measure the profiles of the bacterial colonies, together with a custom built optical density measurement unit to interrogate the biophysics behind the collective behavior of a bacterial colony. The system delivers essential information related to the quantitative growth dynamics (height, diameter, aspect ratio, optical density) of the bacterial colony, as well as, a relationship in between the morphological characteristics of the bacterial colony and its forward scattering pattern. Two different genera: Escherichia coli O157:H7 EDL933, and Staphylococcus aureus ATCC 25923 are selected for the analysis of the spatially resolved growth dynamics, while, Bacillus spp. such as B. subtilis ATCC 6633, B. cereus ATCC 14579, B. thuringiensis DUP6044, B. polymyxa B719W, and B. megaterium DSP 81319, are interrogated since some of the Bacillus spp. provides strikingly different characteristics of ELS patterns, and the origin of the speckle patterns are successfully correlated with the 2-D spatial density map from the ICMA. The MS-BARDOT can measure multispectral elastic-light-scatter patterns of the bacterial colony and its spectral OD to overcome the inherent limits of the single-wavelength BARDOT. A theoretical model for spectral forward scatter patterns from a bacterial colony based on elastic light scatter is presented. The spectral forward scatter patterns are computed by scalar diffraction theory, and compared with experimental results of three discrete wavelengths (405 nm, 635 nm, and 904 nm). Both model and experiment results show an excellent agreement; a longer wavelength induces a wider ring width, a wider ring gap, a smaller pattern size, and smaller numbers of rings. Further analysis using spatial fast Fourier transform (SFFT) shows a good agreement; the spatial frequencies are increasing towards the inward direction, and the slope is inversely proportional to the incoming wavelength. Four major pathogenic bacterial genera (Escherichia coli O157:H7 EDL933, Listeria monocytogenes F4244, Salmonella enterica serovar Enteritidis PT21, and Staphylococcus aureus ATCC 25923) and the seven major Escherichia coli serovar (O26, O45, O103, O111, O121, O145, and O157) with 3-4 strains each are measured and analyzed with the proposed instrument and algorithm. The MM-BARDOT can measure six different modalities: 1) light microscopy, 2) 3D morphology map from confocal microscopy, 3) 3D optical density map, 4) spectral forward scattering pattern, 5) spectral OD, 6) surface backward reflection pattern, and 7) fluorescence of a bacterial colony without moving the specimen. A custom-built confocal microscope with a controller which can be easily attached to an infinity-corrected commercial microscope is designed and built. Since the current BARDOT needs additional information from a bacterial colony to enhance the identification/classification ratio for a lower hierarchy of bacterial taxonomy such as serovar or strain level, the approach can offer a series of coordinates matched and correlated bio-optical characteristics of a colony and enhance the classification accuracy of the previously introduced BARDOT system. Four major pathogenic bacterial genera: Escherichia coli O157:H7 EDL933, Listeria monocytogenes F4244, Salmonella enterica serovar Enteritidis PT21, and Staphylococcus aureus ATCC 25923 are measured and analyzed with the proposed instrument and algorithm. Also, a feasibility test for a smaller colony (up to 500 mum) classification utilizing a surface backward reflection pattern from the measurement is done, and shows a potential as an additional modality for the bacterial phenotyping.

Dual light-emitting diode-based multichannel microscopy for whole-slide multiplane, multispectral and phase imaging.

PubMed

Liao, Jun; Wang, Zhe; Zhang, Zibang; Bian, Zichao; Guo, Kaikai; Nambiar, Aparna; Jiang, Yutong; Jiang, Shaowei; Zhong, Jingang; Choma, Michael; Zheng, Guoan

2018-02-01

We report the development of a multichannel microscopy for whole-slide multiplane, multispectral and phase imaging. We use trinocular heads to split the beam path into 6 independent channels and employ a camera array for parallel data acquisition, achieving a maximum data throughput of approximately 1 gigapixel per second. To perform single-frame rapid autofocusing, we place 2 near-infrared light-emitting diodes (LEDs) at the back focal plane of the condenser lens to illuminate the sample from 2 different incident angles. A hot mirror is used to direct the near-infrared light to an autofocusing camera. For multiplane whole-slide imaging (WSI), we acquire 6 different focal planes of a thick specimen simultaneously. For multispectral WSI, we relay the 6 independent image planes to the same focal position and simultaneously acquire information at 6 spectral bands. For whole-slide phase imaging, we acquire images at 3 focal positions simultaneously and use the transport-of-intensity equation to recover the phase information. We also provide an open-source design to further increase the number of channels from 6 to 15. The reported platform provides a simple solution for multiplexed fluorescence imaging and multimodal WSI. Acquiring an instant focal stack without z-scanning may also enable fast 3-dimensional dynamic tracking of various biological samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

PubMed Central

Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

2014-01-01

Abstract. The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device. PMID:25375350

Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

NASA Astrophysics Data System (ADS)

Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

2014-11-01

The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%;/100%;, for SCC and BCC versus AK (57 versus 14 lesions) was 95%;/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

Label-Free, High Resolution, Multi-Modal Light Microscopy for Discrimination of Live Stem Cell Differentiation Status.

PubMed

Zhang, Jing; Moradi, Emilia; Somekh, Michael G; Mather, Melissa L

2018-01-15

A label-free microscopy method for assessing the differentiation status of stem cells is presented with potential application for characterization of therapeutic stem cell populations. The microscopy system is capable of characterizing live cells based on the use of evanescent wave microscopy and quantitative phase contrast (QPC) microscopy. The capability of the microscopy system is demonstrated by studying the differentiation of live immortalised neonatal mouse neural stem cells over a 15 day time course. Metrics extracted from microscope images are assessed and images compared with results from endpoint immuno-staining studies to illustrate the system's performance. Results demonstrate the potential of the microscopy system as a valuable tool for cell biologists to readily identify the differentiation status of unlabelled live cells.

Optical Biomarkers of Serous and Mucinous Human Ovarian Tumor Assessed with Nonlinear Optics Microscopies

PubMed Central

Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; Baratti, Mariana O.; Almeida, Diogo B.; Andrade, L. A. L. A.; Bottcher-Luiz, Fátima; Carvalho, Hernandes F.; Cesar, Carlos L.

2012-01-01

Background Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression. Methodology/Principal Findings We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells. Conclusions/Significance NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions. PMID:23056557

Multimodal confocal mosaicing microscopy: an emphasis on squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Chen, Nathaniel W.; Sensibaugh, Jordan; Ardeshiri, Ardaland; Blanchard, Adam; Jacques, Steven; Gareau, Daniel

2010-02-01

Our previous study reported a sensitivity of 96.6% and a specificity of 89.2% in rapidly detecting Basal Cell Carcinomas (BCCs) when nuclei were stained with acridine orange. Squamous Cell Carcinomas (SCCs) and infiltrative BCCs remain difficult to detect. More complete screening can be achieved utilizing both acridine orange for nuclei staining and eosin for cytoplasmic contrast, using two lasers to excite the two stains independently. Nuclear fluorescence is achieved by staining with acridine orange (0.5mM, 60 s), and cytoplasmic fluorescence is achieved by staining with eosin working solution (30 s). This work shows good morphological contrast of SCC and infiltrative BCC with eosin, acridine orange, and reflectance, and presents a means for rapid SCC and infiltrative BCC detection in fresh skin excisions using multimodal confocal microscopy. In addition, digital staining is shown to effectively simulate hematoxylin and eosin (H&E) histology with confocal mosaics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yin; Wang, Wen; Wysocki, Gerard, E-mail: gwysocki@princeton.edu

In this Letter, we present a method of performing broadband mid-infrared spectroscopy with conventional, free-running, continuous wave Fabry-Perot quantum cascade lasers (FP-QCLs). The measurement method is based on multi-heterodyne down-conversion of optical signals. The sample transmission spectrum probed by one multi-mode FP-QCL is down-converted to the radio-frequency domain through an optical multi-heterodyne process using a second FP-QCL as the local oscillator. Both a broadband multi-mode spectral measurement as well as high-resolution (∼15 MHz) spectroscopy of molecular absorption are demonstrated and show great potential for development of high performance FP-laser-based spectrometers for chemical sensing.

Mode power distribution effect in white-light multimode fiber extrinsic Fabry-Perot interferometric sensor systems.

PubMed

Han, Ming; Wang, Anbo

2006-05-01

Theoretical and experimental results have shown that mode power distribution (MPD) variations could significantly vary the phase of spectral fringes from multimode fiber extrinsic Fabry-Perot interferometric (MMF-EFPI) sensor systems, owing to the fact that different modes introduce different extra phase shifts resulting from the coupling of modes reflected at the second surface to the lead-in fiber end. This dependence of fringe pattern on MPD could cause measurement errors in signal demodulation methods of white-light MMF-EFPI sensors that implement the phase information of the fringes.

Cavity Quantum Acoustic Device in the Multimode Strong Coupling Regime

NASA Astrophysics Data System (ADS)

Moores, Bradley A.; Sletten, Lucas R.; Viennot, Jeremie J.; Lehnert, K. W.

2018-06-01

We demonstrate an acoustical analog of a circuit quantum electrodynamics system that leverages acoustic properties to enable strong multimode coupling in the dispersive regime while suppressing spontaneous emission to unconfined modes. Specifically, we fabricate and characterize a device that comprises a flux tunable transmon coupled to a 300 μ m long surface acoustic wave resonator. For some modes, the qubit-cavity coupling reaches 6.5 MHz, exceeding the cavity loss rate (200 kHz), qubit linewidth (1.1 MHz), and the cavity free spectral range (4.8 MHz), placing the device in both the strong coupling and strong multimode regimes. With the qubit detuned from the confined modes of the cavity, we observe that the qubit linewidth strongly depends on its frequency, as expected for spontaneous emission of phonons, and we identify operating frequencies where this emission rate is suppressed.

Internal Mirror Optical Fiber Couplers

NASA Astrophysics Data System (ADS)

Shin, Jong-Dug

A fusion splicing technique has been used to produce angled dielectric mirrors in multimode and single-mode silica fibers. These mirrored fiber couplers serve as compact directional couplers with low excess optical loss (~0.2 dB for multimode and 0.5 dB for single mode at 1.3 μm) and excellent mechanical properties. The reflectance is found to be wavelength dependent and strongly polarization dependent, as expected. Far-field scans of the reflected output power measured with a white-light source show a pattern which is almost circularly symmetric. The splitting ratio in a multimode coupler measured with a laser source is much less dependent on input coupling conditions than in conventional fused biconical-taper couplers. Spectral properties of multilayer fiber mirrors have been investigated experimentally, and a matrix analysis has been used to explain the results.

Focusing and imaging with increased numerical apertures through multimode fibers with micro-fabricated optics.

PubMed

Bianchi, S; Rajamanickam, V P; Ferrara, L; Di Fabrizio, E; Liberale, C; Di Leonardo, R

2013-12-01

The use of individual multimode optical fibers in endoscopy applications has the potential to provide highly miniaturized and noninvasive probes for microscopy and optical micromanipulation. A few different strategies have been proposed recently, but they all suffer from intrinsically low resolution related to the low numerical aperture of multimode fibers. Here, we show that two-photon polymerization allows for direct fabrication of micro-optics components on the fiber end, resulting in an increase of the numerical aperture to a value that is close to 1. Coupling light into the fiber through a spatial light modulator, we were able to optically scan a submicrometer spot (300 nm FWHM) over an extended region, facing the opposite fiber end. Fluorescence imaging with improved resolution is also demonstrated.

Compressive Coded-Aperture Multimodal Imaging Systems

NASA Astrophysics Data System (ADS)

Rueda-Chacon, Hoover F.

Multimodal imaging refers to the framework of capturing images that span different physical domains such as space, spectrum, depth, time, polarization, and others. For instance, spectral images are modeled as 3D cubes with two spatial and one spectral coordinate. Three-dimensional cubes spanning just the space domain, are referred as depth volumes. Imaging cubes varying in time, spectra or depth, are referred as 4D-images. Nature itself spans different physical domains, thus imaging our real world demands capturing information in at least 6 different domains simultaneously, giving turn to 3D-spatial+spectral+polarized dynamic sequences. Conventional imaging devices, however, can capture dynamic sequences with up-to 3 spectral channels, in real-time, by the use of color sensors. Capturing multiple spectral channels require scanning methodologies, which demand long time. In general, to-date multimodal imaging requires a sequence of different imaging sensors, placed in tandem, to simultaneously capture the different physical properties of a scene. Then, different fusion techniques are employed to mix all the individual information into a single image. Therefore, new ways to efficiently capture more than 3 spectral channels of 3D time-varying spatial information, in a single or few sensors, are of high interest. Compressive spectral imaging (CSI) is an imaging framework that seeks to optimally capture spectral imagery (tens of spectral channels of 2D spatial information), using fewer measurements than that required by traditional sensing procedures which follows the Shannon-Nyquist sampling. Instead of capturing direct one-to-one representations of natural scenes, CSI systems acquire linear random projections of the scene and then solve an optimization algorithm to estimate the 3D spatio-spectral data cube by exploiting the theory of compressive sensing (CS). To date, the coding procedure in CSI has been realized through the use of ``block-unblock" coded apertures, commonly implemented as chrome-on-quartz photomasks. These apertures block or permit to pass the entire spectrum from the scene at given spatial locations, thus modulating the spatial characteristics of the scene. In the first part, this thesis aims to expand the framework of CSI by replacing the traditional block-unblock coded apertures by patterned optical filter arrays, referred as ``color" coded apertures. These apertures are formed by tiny pixelated optical filters, which in turn, allow the input image to be modulated not only spatially but spectrally as well, entailing more powerful coding strategies. The proposed colored coded apertures are either synthesized through linear combinations of low-pass, high-pass and band-pass filters, paired with binary pattern ensembles realized by a digital-micromirror-device (DMD), or experimentally realized through thin-film color-patterned filter arrays. The optical forward model of the proposed CSI architectures will be presented along with the design and proof-of-concept implementations, which achieve noticeable improvements in the quality of the reconstructions compared with conventional block-unblock coded aperture-based CSI architectures. On another front, due to the rich information contained in the infrared spectrum as well as the depth domain, this thesis aims to explore multimodal imaging by extending the range sensitivity of current CSI systems to a dual-band visible+near-infrared spectral domain, and also, it proposes, for the first time, a new imaging device that captures simultaneously 4D data cubes (2D spatial+1D spectral+depth imaging) with as few as a single snapshot. Due to the snapshot advantage of this camera, video sequences are possible, thus enabling the joint capture of 5D imagery. It aims to create super-human sensing that will enable the perception of our world in new and exciting ways. With this, we intend to advance in the state of the art in compressive sensing systems to extract depth while accurately capturing spatial and spectral material properties. The applications of such a sensor are self-evident in fields such as computer/robotic vision because they would allow an artificial intelligence to make informed decisions about not only the location of objects within a scene but also their material properties.

Beam profile for the Herschel-SPIRE Fourier transform spectrometer.

PubMed

Makiwa, Gibion; Naylor, David A; Ferlet, Marc; Salji, Carl; Swinyard, Bruce; Polehampton, Edward; van der Wiel, Matthijs H D

2013-06-01

One of the instruments on board the Herschel Space Observatory is the Spectral and Photometric Imaging Receiver (SPIRE). SPIRE employs a Fourier transform spectrometer with feed-horn-coupled bolometers to provide imaging spectroscopy. To interpret the resultant spectral images requires knowledge of the wavelength-dependent beam, which in the case of SPIRE is complicated by the use of multimoded feed horns. In this paper we describe a series of observations and the analysis conducted to determine the wavelength dependence of the SPIRE spectrometer beam profile.

MULTIMODAL IMAGING OF ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ADAPTIVE OPTICS SCANNING LASER OPHTHALMOSCOPY.

PubMed

Skondra, Dimitra; Nesper, Peter L; Fawzi, Amani A

2017-05-16

To report a case of acute exudative polymorphous vitelliform maculopathy including the findings of optical coherence tomography angiography and adaptive optics scanning laser ophthalmoscopy. Findings on clinical examination, color fundus photography, spectral-domain optical coherence tomography, infrared reflectance, autofluorescence, optical coherence tomography angiography, and adaptive optics scanning laser ophthalmoscopy. A 54-year-old white man with no significant medical history and history of smoking presented with bilateral multiple serous and vitelliform detachments consistent with acute exudative polymorphous vitelliform maculopathy. Extensive infectious, inflammatory, and malignancy workup was negative. Spectral-domain optical coherence tomography showed thickened, hyperreflective ellipsoid zone, subretinal fluid, and focal as well as diffuse subretinal hyperreflective material corresponding to the vitelliform lesions. Optical coherence tomography angiography showed normal retinal and choroidal vasculature, whereas adaptive optics scanning laser ophthalmoscopy showed circular focal "target" lesions at the level of the photoreceptors in the area of foveal detachment. Multimodal imaging is valuable in evaluating patients with acute exudative polymorphous vitelliform maculopathy.

In-situ Multimodal Imaging and Spectroscopy of Mg Electrodeposition at Electrode-Electrolyte Interfaces

NASA Astrophysics Data System (ADS)

Wu, Yimin A.; Yin, Zuwei; Farmand, Maryam; Yu, Young-Sang; Shapiro, David A.; Liao, Hong-Gang; Liang, Wen-I.; Chu, Ying-Hao; Zheng, Haimei

2017-02-01

We report the study of Mg cathodic electrochemical deposition on Ti and Au electrode using a multimodal approach by examining the sample area in-situ using liquid cell transmission electron microscopy (TEM), scanning transmission X-ray microscopy (STXM) and X-ray absorption spectroscopy (XAS). Magnesium Aluminum Chloride Complex was synthesized and utilized as electrolyte, where non-reversible features during in situ charging-discharging cycles were observed. During charging, a uniform Mg film was deposited on the electrode, which is consistent with the intrinsic non-dendritic nature of Mg deposition in Mg ion batteries. The Mg thin film was not dissolvable during the following discharge process. We found that such Mg thin film is hexacoordinated Mg compounds by in-situ STXM and XAS. This study provides insights on the non-reversibility issue and failure mechanism of Mg ion batteries. Also, our method provides a novel generic method to understand the in situ battery chemistry without any further sample processing, which can preserve the original nature of battery materials or electrodeposited materials. This multimodal in situ imaging and spectroscopy provides many opportunities to attack complex problems that span orders of magnitude in length and time scale, which can be applied to a broad range of the energy storage systems.

In-situ Multimodal Imaging and Spectroscopy of Mg Electrodeposition at Electrode-Electrolyte Interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Yimin A.; Yin, Zuwei; Farmand, Maryam

We report the study of Mg cathodic electrochemical deposition on Ti and Au electrode using a multimodal approach by examining the sample area in-situ using liquid cell transmission electron microscopy (TEM), scanning transmission X-ray microscopy (STXM) and X-ray absorption spectroscopy (XAS). Magnesium Aluminum Chloride Complex was synthesized and utilized as electrolyte, where non-reversible features during in situ charging-discharging cycles were observed. During charging, a uniform Mg film was deposited on the electrode, which is consistent with the intrinsic non-dendritic nature of Mg deposition in Mg ion batteries. The Mg thin film was not dissolvable during the following discharge process. Wemore » found that such Mg thin film is hexacoordinated Mg compounds by in-situ STXM and XAS. This study provides insights on the non-reversibility issue and failure mechanism of Mg ion batteries. Also, our method provides a novel generic method to understand the in situ battery chemistry without any further sample processing, which can preserve the original nature of battery materials or electrodeposited materials. This multimodal in situ imaging and spectroscopy provides many opportunities to attack complex problems that span orders of magnitude in length and time scale, which can be applied to a broad range of the energy storage systems.« less

In-situ Multimodal Imaging and Spectroscopy of Mg Electrodeposition at Electrode-Electrolyte Interfaces

DOE PAGES

Wu, Yimin A.; Yin, Zuwei; Farmand, Maryam; ...

2017-02-10

We report the study of Mg cathodic electrochemical deposition on Ti and Au electrode using a multimodal approach by examining the sample area in-situ using liquid cell transmission electron microscopy (TEM), scanning transmission X-ray microscopy (STXM) and X-ray absorption spectroscopy (XAS). Magnesium Aluminum Chloride Complex was synthesized and utilized as electrolyte, where non-reversible features during in situ charging-discharging cycles were observed. During charging, a uniform Mg film was deposited on the electrode, which is consistent with the intrinsic non-dendritic nature of Mg deposition in Mg ion batteries. The Mg thin film was not dissolvable during the following discharge process. Wemore » found that such Mg thin film is hexacoordinated Mg compounds by in-situ STXM and XAS. This study provides insights on the non-reversibility issue and failure mechanism of Mg ion batteries. Also, our method provides a novel generic method to understand the in situ battery chemistry without any further sample processing, which can preserve the original nature of battery materials or electrodeposited materials. This multimodal in situ imaging and spectroscopy provides many opportunities to attack complex problems that span orders of magnitude in length and time scale, which can be applied to a broad range of the energy storage systems.« less

In-situ Multimodal Imaging and Spectroscopy of Mg Electrodeposition at Electrode-Electrolyte Interfaces.

PubMed

Wu, Yimin A; Yin, Zuwei; Farmand, Maryam; Yu, Young-Sang; Shapiro, David A; Liao, Hong-Gang; Liang, Wen-I; Chu, Ying-Hao; Zheng, Haimei

2017-02-10

We report the study of Mg cathodic electrochemical deposition on Ti and Au electrode using a multimodal approach by examining the sample area in-situ using liquid cell transmission electron microscopy (TEM), scanning transmission X-ray microscopy (STXM) and X-ray absorption spectroscopy (XAS). Magnesium Aluminum Chloride Complex was synthesized and utilized as electrolyte, where non-reversible features during in situ charging-discharging cycles were observed. During charging, a uniform Mg film was deposited on the electrode, which is consistent with the intrinsic non-dendritic nature of Mg deposition in Mg ion batteries. The Mg thin film was not dissolvable during the following discharge process. We found that such Mg thin film is hexacoordinated Mg compounds by in-situ STXM and XAS. This study provides insights on the non-reversibility issue and failure mechanism of Mg ion batteries. Also, our method provides a novel generic method to understand the in situ battery chemistry without any further sample processing, which can preserve the original nature of battery materials or electrodeposited materials. This multimodal in situ imaging and spectroscopy provides many opportunities to attack complex problems that span orders of magnitude in length and time scale, which can be applied to a broad range of the energy storage systems.

In-situ Multimodal Imaging and Spectroscopy of Mg Electrodeposition at Electrode-Electrolyte Interfaces

PubMed Central

Wu, Yimin A.; Yin, Zuwei; Farmand, Maryam; Yu, Young-Sang; Shapiro, David A.; Liao, Hong-Gang; Liang, Wen-I; Chu, Ying-Hao; Zheng, Haimei

2017-01-01

We report the study of Mg cathodic electrochemical deposition on Ti and Au electrode using a multimodal approach by examining the sample area in-situ using liquid cell transmission electron microscopy (TEM), scanning transmission X-ray microscopy (STXM) and X-ray absorption spectroscopy (XAS). Magnesium Aluminum Chloride Complex was synthesized and utilized as electrolyte, where non-reversible features during in situ charging-discharging cycles were observed. During charging, a uniform Mg film was deposited on the electrode, which is consistent with the intrinsic non-dendritic nature of Mg deposition in Mg ion batteries. The Mg thin film was not dissolvable during the following discharge process. We found that such Mg thin film is hexacoordinated Mg compounds by in-situ STXM and XAS. This study provides insights on the non-reversibility issue and failure mechanism of Mg ion batteries. Also, our method provides a novel generic method to understand the in situ battery chemistry without any further sample processing, which can preserve the original nature of battery materials or electrodeposited materials. This multimodal in situ imaging and spectroscopy provides many opportunities to attack complex problems that span orders of magnitude in length and time scale, which can be applied to a broad range of the energy storage systems. PMID:28186175

GRAFT-VERSUS-HOST DISEASE PANUVEITIS AND BILATERAL SEROUS DETACHMENTS: MULTIMODAL IMAGING ANALYSIS.

PubMed

Jung, Jesse J; Chen, Michael H; Rofagha, Soraya; Lee, Scott S

2017-01-01

To report the multimodal imaging findings and follow-up of a case of graft-versus-host disease-induced bilateral panuveitis and serous retinal detachments after allogenic bone marrow transplant for acute myeloid leukemia. A 75-year-old black man presented with acute decreased vision in both eyes for 1 week. Clinical examination and multimodal imaging, including spectral domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and swept-source optical coherence tomography angiography (Investigational Device; Carl Zeiss Meditec Inc) were performed. Clinical examination of the patient revealed anterior and posterior inflammation and bilateral serous retinal detachments. Ultra-widefield fundus autofluorescence demonstrated hyperautofluorescence secondary to subretinal fluid; and fluorescein angiography revealed multiple areas of punctate hyperfluorescence, leakage, and staining of the optic discs. Spectral domain and enhanced depth imaging optical coherence tomography demonstrated subretinal fluid, a thickened, undulating retinal pigment epithelium layer, and a thickened choroid in both eyes. En-face swept-source optical coherence tomography angiography did not show any retinal vascular abnormalities but did demonstrate patchy areas of decreased choriocapillaris flow. An extensive systemic infectious and malignancy workup was negative and the patient was treated with high-dose oral prednisone immunosuppression. Subsequent 6-month follow-up demonstrated complete resolution of the inflammation and bilateral serous detachments after completion of the prednisone taper over a 3-month period. Graft-versus-host disease panuveitis and bilateral serous retinal detachments are rare complications of allogenic bone marrow transplant for acute myeloid leukemia and can be diagnosed with clinical and multimodal imaging analysis. This form of autoimmune inflammation may occur after the recovery of T-cell activity within the donor graft targeting the host. Infectious and recurrent malignancy must be ruled out before initiation of immunosuppression, which can affectively treat this form of graft-versus-host disease.

Transfer function of radio over fiber multimode fiber optic links considering third-order dispersion.

PubMed

Capmany, J; Gasulla, Ivana

2007-08-20

Although a considerable number of multimode fiber (MMF) links operate in a wavelength region around 850 nm where chromatic dispersion of a given modal group mu is described adequately by the second derivative beta(mu) (2) of the propagation constant beta(mu)(omega), there is also an increasing interest in MMF links transmitting in the second spectral window (@1300nm) where this second derivative vanishes being thus necessary to consider the third derivative beta(mu) (3) in the evaluation of the transfer function of the multimode fiber link. We present in this paper, for the first time to our knowledge, an analytical model for the transfer function of a multimode fiber (MMF) optic link taken into account the impact of third-order dispersion. The model extends the operation of a previously reported one for second-order dispersion. Our results show that the performance of broadband radio over fiber transmission through middle-reach distances can be improved by working at the minimum-dispersion wavelength as long as low-linewidth lasers are employed.

Cavity Quantum Acoustic Device in the Multimode Strong Coupling Regime.

PubMed

Moores, Bradley A; Sletten, Lucas R; Viennot, Jeremie J; Lehnert, K W

2018-06-01

We demonstrate an acoustical analog of a circuit quantum electrodynamics system that leverages acoustic properties to enable strong multimode coupling in the dispersive regime while suppressing spontaneous emission to unconfined modes. Specifically, we fabricate and characterize a device that comprises a flux tunable transmon coupled to a 300  μm long surface acoustic wave resonator. For some modes, the qubit-cavity coupling reaches 6.5 MHz, exceeding the cavity loss rate (200 kHz), qubit linewidth (1.1 MHz), and the cavity free spectral range (4.8 MHz), placing the device in both the strong coupling and strong multimode regimes. With the qubit detuned from the confined modes of the cavity, we observe that the qubit linewidth strongly depends on its frequency, as expected for spontaneous emission of phonons, and we identify operating frequencies where this emission rate is suppressed.

All-Fiber Laser Curvature Sensor Using an In-Fiber Modal Interferometer Based on a Double Clad Fiber and a Multimode Fiber Structure

PubMed Central

Durán-Sánchez, Manuel; Prieto-Cortés, Patricia; Salceda-Delgado, Guillermo; Castillo-Guzmán, Arturo A.; Selvas-Aguilar, Romeo; Ibarra-Escamilla, Baldemar; Kuzin, Evgeny A.

2017-01-01

An all-fiber curvature laser sensor by using a novel modal interference in-fiber structure is proposed and experimentally demonstrated. The in-fiber device, fabricated by fusion splicing of multimode fiber and double-clad fiber segments, is used as wavelength filter as well as the sensing element. By including a multimode fiber in an ordinary modal interference structure based on a double-clad fiber, the fringe visibility of the filter transmission spectrum is significantly increased. By using the modal interferometer as a curvature sensitive wavelength filter within a ring cavity erbium-doped fiber laser, the spectral quality factor Q is considerably increased. The results demonstrate the reliability of the proposed curvature laser sensor with advantages of robustness, ease of fabrication, low cost, repeatability on the fabrication process and simple operation. PMID:29182527

Complete measurement of spatiotemporally complex multi-spatial-mode ultrashort pulses from multimode optical fibers using delay-scanned wavelength-multiplexed holography.

PubMed

Zhu, Ping; Jafari, Rana; Jones, Travis; Trebino, Rick

2017-10-02

We introduce a simple delay-scanned complete spatiotemporal intensity-and-phase measurement technique based on wavelength-multiplexed holography to characterize long, complex pulses in space and time. We demonstrate it using pulses emerging from multi-mode fiber. This technique extends the temporal range and spectral resolution of the single-frame STRIPED FISH technique without using an otherwise-required expensive ultranarrow-bandpass filter. With this technique, we measured the complete intensity and phase of up to ten fiber modes from a multi-mode fiber (normalized frequency V ≈10) over a ~3ps time range. Spatiotemporal complexities such as intermodal delay, modal dispersion, and material dispersion were also intuitively displayed by the retrieved results. Agreement between the reconstructed color movies and the monitored time-averaged spatial profiles confirms the validity to this delay-scanned STRIPED FISH method.

All-Fiber Laser Curvature Sensor Using an In-Fiber Modal Interferometer Based on a Double Clad Fiber and a Multimode Fiber Structure.

PubMed

Álvarez-Tamayo, Ricardo I; Durán-Sánchez, Manuel; Prieto-Cortés, Patricia; Salceda-Delgado, Guillermo; Castillo-Guzmán, Arturo A; Selvas-Aguilar, Romeo; Ibarra-Escamilla, Baldemar; Kuzin, Evgeny A

2017-11-28

An all-fiber curvature laser sensor by using a novel modal interference in-fiber structure is proposed and experimentally demonstrated. The in-fiber device, fabricated by fusion splicing of multimode fiber and double-clad fiber segments, is used as wavelength filter as well as the sensing element. By including a multimode fiber in an ordinary modal interference structure based on a double-clad fiber, the fringe visibility of the filter transmission spectrum is significantly increased. By using the modal interferometer as a curvature sensitive wavelength filter within a ring cavity erbium-doped fiber laser, the spectral quality factor Q is considerably increased. The results demonstrate the reliability of the proposed curvature laser sensor with advantages of robustness, ease of fabrication, low cost, repeatability on the fabrication process and simple operation.

Calibration for single multi-mode fiber digital scanning microscopy imaging system

NASA Astrophysics Data System (ADS)

Yin, Zhe; Liu, Guodong; Liu, Bingguo; Gan, Yu; Zhuang, Zhitao; Chen, Fengdong

2015-11-01

Single multimode fiber (MMF) digital scanning imaging system is a development tendency of modern endoscope. We concentrate on the calibration method of the imaging system. Calibration method comprises two processes, forming scanning focused spots and calibrating the couple factors varied with positions. Adaptive parallel coordinate algorithm (APC) is adopted to form the focused spots at the multimode fiber (MMF) output. Compare with other algorithm, APC contains many merits, i.e. rapid speed, small amount calculations and no iterations. The ratio of the optics power captured by MMF to the intensity of the focused spots is called couple factor. We setup the calibration experimental system to form the scanning focused spots and calculate the couple factors for different object positions. The experimental result the couple factor is higher in the center than the edge.

Mate choice in the eye and ear of the beholder? Female multimodal sensory configuration influences her preferences.

PubMed

Ronald, Kelly L; Fernández-Juricic, Esteban; Lucas, Jeffrey R

2018-05-16

A common assumption in sexual selection studies is that receivers decode signal information similarly. However, receivers may vary in how they rank signallers if signal perception varies with an individual's sensory configuration. Furthermore, receivers may vary in their weighting of different elements of multimodal signals based on their sensory configuration. This could lead to complex levels of selection on signalling traits. We tested whether multimodal sensory configuration could affect preferences for multimodal signals. We used brown-headed cowbird ( Molothrus ater ) females to examine how auditory sensitivity and auditory filters, which influence auditory spectral and temporal resolution, affect song preferences, and how visual spatial resolution and visual temporal resolution, which influence resolution of a moving visual signal, affect visual display preferences. Our results show that multimodal sensory configuration significantly affects preferences for male displays: females with better auditory temporal resolution preferred songs that were shorter, with lower Wiener entropy, and higher frequency; and females with better visual temporal resolution preferred males with less intense visual displays. Our findings provide new insights into mate-choice decisions and receiver signal processing. Furthermore, our results challenge a long-standing assumption in animal communication which can affect how we address honest signalling, assortative mating and sensory drive. © 2018 The Author(s).

Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy

NASA Astrophysics Data System (ADS)

Kühnemund, Malte; Wei, Qingshan; Darai, Evangelia; Wang, Yingjie; Hernández-Neuta, Iván; Yang, Zhao; Tseng, Derek; Ahlford, Annika; Mathot, Lucy; Sjöblom, Tobias; Ozcan, Aydogan; Nilsson, Mats

2017-01-01

Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies.

Correlative super-resolution fluorescence microscopy combined with optical coherence microscopy

NASA Astrophysics Data System (ADS)

Kim, Sungho; Kim, Gyeong Tae; Jang, Soohyun; Shim, Sang-Hee; Bae, Sung Chul

2015-03-01

Recent development of super-resolution fluorescence imaging technique such as stochastic optical reconstruction microscopy (STORM) and photoactived localization microscope (PALM) has brought us beyond the diffraction limits. It allows numerous opportunities in biology because vast amount of formerly obscured molecular structures, due to lack of spatial resolution, now can be directly observed. A drawback of fluorescence imaging, however, is that it lacks complete structural information. For this reason, we have developed a super-resolution multimodal imaging system based on STORM and full-field optical coherence microscopy (FF-OCM). FF-OCM is a type of interferometry systems based on a broadband light source and a bulk Michelson interferometer, which provides label-free and non-invasive visualization of biological samples. The integration between the two systems is simple because both systems use a wide-field illumination scheme and a conventional microscope. This combined imaging system gives us both functional information at a molecular level (~20nm) and structural information at the sub-cellular level (~1μm). For thick samples such as tissue slices, while FF-OCM is readily capable of imaging the 3D architecture, STORM suffer from aberrations and high background fluorescence that substantially degrade the resolution. In order to correct the aberrations in thick tissues, we employed an adaptive optics system in the detection path of the STORM microscope. We used our multimodal system to obtain images on brain tissue samples with structural and functional information.

Multimodal optical coherence tomography for in vivo imaging of brain tissue structure and microvascular network at glioblastoma

NASA Astrophysics Data System (ADS)

Yashin, Konstantin S.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Karabut, Maria M.; Elagin, Vadim V.; Sirotkina, Marina A.; Medyanik, Igor A.; Kravets, L. Y.; Gladkova, Natalia D.

2017-02-01

In the case of infiltrative brain tumors the surgeon faces difficulties in determining their boundaries to achieve total resection. The aim of the investigation was to evaluate the performance of multimodal OCT (MM OCT) for differential diagnostics of normal brain tissue and glioma using an experimental model of glioblastoma. The spectral domain OCT device that was used for the study provides simultaneously two modes: cross-polarization and microangiographic OCT. The comparative analysis of the both OCT modalities images from tumorous and normal brain tissue areas concurrently with histologic correlation shows certain difference between when accordingly to morphological and microvascular tissue features.

Multimode VCSEL model for wide frequency-range RIN simulation

NASA Astrophysics Data System (ADS)

Perchoux, Julien; Rissons, Angélique; Mollier, Jean-Claude

2008-01-01

In this paper, we present an equivalent circuit model for oxide-confined AlGaAs/GaAs VCSEL with the noise contribution adapted to optomicrowave links applications. This model is derived from the multimode rate equations. In order to understand the modal competition process, we restrain our description to a two-modes rate equations system affected by the spectral hole-burning. The relative intensity noise (RIN) measurements which were achieved on a prober in Faraday cage confirm the low frequency enhancement described by the model. We validate our model for a wide frequency-range [1 MHz-10 GHz] and high bias level up to six times the threshold current.

The multi-mode polarization modulation spectrometer: part 1: simultaneous detection of absorption, turbidity, and optical activity.

PubMed

Arvinte, Tudor; Bui, Tam T T; Dahab, Ali A; Demeule, Barthélemy; Drake, Alex F; Elhag, Dhia; King, Peter

2004-09-01

Circular dichroism (CD) is an important spectroscopic technique for monitoring chirality and biological macromolecule conformation. However, during a CD measurement, absorbance, light scattering/turbidity, and fluorescence can also be detected. The simultaneous measurement of these different spectral features for a single sample is the basis of a multi-mode optical spectrometer. This allows time-efficient gathering of complementary information and provides a scheme to ensure that CD measurements are reliable. Aspects of circular polarization differential light scattering, pH, and temperature variation of a protein (antibody) solution are described. A procedure to help ensure that CD measurements are reliable is described.

Multi-species detection using multi-mode absorption spectroscopy (MUMAS)

NASA Astrophysics Data System (ADS)

Northern, J. H.; Thompson, A. W. J.; Hamilton, M. L.; Ewart, P.

2013-06-01

The detection of multiple species using a single laser and single detector employing multi-mode absorption spectroscopy (MUMAS) is reported. An in-house constructed, diode-pumped, Er:Yb:glass micro-laser operating at 1,565 nm with 10 modes separated by 18 GHz was used to record MUMAS signals in a gas mixture containing C2H2, N2O and CO. The components of the mixture were detected simultaneously by identifying multiple transitions in each of the species. By using temperature- and pressure-dependent modelled spectral fits to the data, partial pressures of each species in the mixture were determined with an uncertainty of ±2 %.

CARS and SHG microscopy to follow collagen production in living human corneal fibroblasts and mesenchymal stem cells in fibrin hydrogel 3D cultures

NASA Astrophysics Data System (ADS)

Mortati, L.; Divieto, C.; Sassi, M. P.

2012-05-01

Coherent anti-Stokes Raman scattering (CARS) microscopy is combined with second harmonic generation (SHG) technique in order to follow the early stage of stem cell differentiation within a 3D scaffold. CARS microscopy can detect lipid membranes and droplet compartments in living cells and SHG microscopy enables a strong imaging contrast for molecules with a non-centrosymmetric ordered structure like collagen. One of the first evidence of hMSCs differentiation is the formation of an extracellular matrix (ECM) where the collagen protein is its main component. This work demonstrated the multimodal CARS and SHG microscopy as a powerful non-invasive label free technique to investigate the collagen production dynamic in living cell 3D cultures. Its ability to image the cell morphology and the produced collagen distribution on a long term (4 weeks) experiment allowed to obtain important information about the cell-scaffold interaction and the ECM production. The very low limit reached in detecting collagen has permitted to map even the small amount of collagen produced by the cells in few hours of culture. This demonstrates multimodal CARS and SHG microscopy as a novel method to follow cells collagen production and cells differentiation process. In addition the experiment shows that the technique is a powerful tool for imaging of very thick sections (about 4 mm). The study conducted on mesenchymal stem cell in fibrin gel cultures confirmed that differentiation stimulus is induced by the scaffold. The monitoring of stem cell differentiation within a scaffold in a non-destructive way will be an important advantage in regenerative medicine and tissue engineering field.

The multi-modal Australian ScienceS Imaging and Visualization Environment (MASSIVE) high performance computing infrastructure: applications in neuroscience and neuroinformatics research

PubMed Central

Goscinski, Wojtek J.; McIntosh, Paul; Felzmann, Ulrich; Maksimenko, Anton; Hall, Christopher J.; Gureyev, Timur; Thompson, Darren; Janke, Andrew; Galloway, Graham; Killeen, Neil E. B.; Raniga, Parnesh; Kaluza, Owen; Ng, Amanda; Poudel, Govinda; Barnes, David G.; Nguyen, Toan; Bonnington, Paul; Egan, Gary F.

2014-01-01

The Multi-modal Australian ScienceS Imaging and Visualization Environment (MASSIVE) is a national imaging and visualization facility established by Monash University, the Australian Synchrotron, the Commonwealth Scientific Industrial Research Organization (CSIRO), and the Victorian Partnership for Advanced Computing (VPAC), with funding from the National Computational Infrastructure and the Victorian Government. The MASSIVE facility provides hardware, software, and expertise to drive research in the biomedical sciences, particularly advanced brain imaging research using synchrotron x-ray and infrared imaging, functional and structural magnetic resonance imaging (MRI), x-ray computer tomography (CT), electron microscopy and optical microscopy. The development of MASSIVE has been based on best practice in system integration methodologies, frameworks, and architectures. The facility has: (i) integrated multiple different neuroimaging analysis software components, (ii) enabled cross-platform and cross-modality integration of neuroinformatics tools, and (iii) brought together neuroimaging databases and analysis workflows. MASSIVE is now operational as a nationally distributed and integrated facility for neuroinfomatics and brain imaging research. PMID:24734019

Biodistribution of arctigenin-loaded nanoparticles designed for multimodal imaging.

PubMed

Cui, Qingxin; Hou, Yuanyuan; Wang, Yanan; Li, Xu; Liu, Yang; Ma, Xiaoyao; Wang, Zengyong; Wang, Weiya; Tao, Jin; Wang, Qian; Jiang, Min; Chen, Dongyan; Feng, Xizeng; Bai, Gang

2017-04-07

Tracking targets of natural products is one of the most challenging issues in fields ranging from pharmacognosy to biomedicine. It is widely recognized that the biocompatible nanoparticle (NP) could function as a "key" that opens the target "lock". We report a functionalized poly-lysine NP technique that can monitor the target protein of arctigenin (ATG) in vivo non-invasively. The NPs were synthesized, and their morphologies and surface chemical properties were characterized by transmission electron microscopy (TEM), laser particle size analysis and atomic force microscopy (AFM). In addition, we studied the localization of ATG at the level of the cell and the whole animal (zebrafish and mice). We demonstrated that fluorescent NPs could be ideal carriers in the development of a feasible method for target identification. The distributions of the target proteins were found to be consistent with the pharmacological action of ATG at the cellular and whole-organism levels. The results indicated that functionalized poly-lysine NPs could be valuable in the multimodal imaging of arctigenin.

Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy

PubMed Central

Chowdhury, Shwetadwip; Eldridge, Will J.; Wax, Adam; Izatt, Joseph A.

2017-01-01

Sub-diffraction resolution imaging has played a pivotal role in biological research by visualizing key, but previously unresolvable, sub-cellular structures. Unfortunately, applications of far-field sub-diffraction resolution are currently divided between fluorescent and coherent-diffraction regimes, and a multimodal sub-diffraction technique that bridges this gap has not yet been demonstrated. Here we report that structured illumination (SI) allows multimodal sub-diffraction imaging of both coherent quantitative-phase (QP) and fluorescence. Due to SI’s conventionally fluorescent applications, we first demonstrate the principle of SI-enabled three-dimensional (3D) QP sub-diffraction imaging with calibration microspheres. Image analysis confirmed enhanced lateral and axial resolutions over diffraction-limited QP imaging, and established striking parallels between coherent SI and conventional optical diffraction tomography. We next introduce an optical system utilizing SI to achieve 3D sub-diffraction, multimodal QP/fluorescent visualization of A549 biological cells fluorescently tagged for F-actin. Our results suggest that SI has a unique utility in studying biological phenomena with significant molecular, biophysical, and biochemical components. PMID:28663887

Ratiometric wavelength monitor based on X-type spectral response using two edge filters

NASA Astrophysics Data System (ADS)

Hatta, Agus Muhamad; Rajan, Ginu; Farrell, Gerald; Semenova, Yuliya

2009-05-01

The performance of an all-fiber ratiometric wavelength measurement system is compared for the case of two edge filters and the case of one edge filter. The two fiber edge filters are used with overlapping and opposite slope spectral responses, a so called "X-type spectral response", each based on singlemode-multimode-singlemode (SMS) fiber structures. Noise and polarization dependent loss (PDL) are the two parameters that determine the resolution and an accuracy of the system. It is demonstrated that the use of two SMS edge filters for a ratiometric wavelength measurement system can increase the resolution and the accuracy when compared with a system using only one edge filter.

Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy

PubMed Central

Kühnemund, Malte; Wei, Qingshan; Darai, Evangelia; Wang, Yingjie; Hernández-Neuta, Iván; Yang, Zhao; Tseng, Derek; Ahlford, Annika; Mathot, Lucy; Sjöblom, Tobias; Ozcan, Aydogan; Nilsson, Mats

2017-01-01

Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies. PMID:28094784

Simultaneous off-axis multiplexed holography and regular fluorescence microscopy of biological cells.

PubMed

Nygate, Yoav N; Singh, Gyanendra; Barnea, Itay; Shaked, Natan T

2018-06-01

We present a new technique for obtaining simultaneous multimodal quantitative phase and fluorescence microscopy of biological cells, providing both quantitative phase imaging and molecular specificity using a single camera. Our system is based on an interferometric multiplexing module, externally positioned at the exit of an optical microscope. In contrast to previous approaches, the presented technique allows conventional fluorescence imaging, rather than interferometric off-axis fluorescence imaging. We demonstrate the presented technique for imaging fluorescent beads and live biological cells.

Rat brain imaging using full field optical coherence microscopy with short multimode fiber probe

NASA Astrophysics Data System (ADS)

Sato, Manabu; Saito, Daisuke; Kurotani, Reiko; Abe, Hiroyuki; Kawauchi, Satoko; Sato, Shunichi; Nishidate, Izumi

2017-02-01

We demonstrated FF OCM(full field optical coherence microscopy) using an ultrathin forward-imaging SMMF (short multimode fiber) probe of 50 μm core diameter, 125 μm diameter, and 7.4 mm length, which is a typical graded-index multimode fiber for optical communications. The axial resolution was measured to be 2.20 μm, which is close to the calculated axial resolution of 2.06 μm. The lateral resolution was evaluated to be 4.38 μm using a test pattern. Assuming that the FWHM of the contrast is the DOF (depth of focus), the DOF of the signal is obtained at 36 μm and that of the OCM is 66 μm. The contrast of the OCT images was 6.1 times higher than that of the signal images due to the coherence gate. After an euthanasia the rat brain was resected and cut at 2.6mm tail from Bregma. Contacting SMMF to the primary somatosensory cortex and the agranular insular cortex of ex vivo brain, OCM images of the brain were measured 100 times with 2μm step. 3D OCM images of the brain were measured, and internal structure information was obtained. The feasibility of an SMMF as an ultrathin forward-imaging probe in full-field OCM has been demonstrated.

Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging

NASA Astrophysics Data System (ADS)

Chernavskaia, Olga; Heuke, Sandro; Vieth, Michael; Friedrich, Oliver; Schürmann, Sebastian; Atreya, Raja; Stallmach, Andreas; Neurath, Markus F.; Waldner, Maximilian; Petersen, Iver; Schmitt, Michael; Bocklitz, Thomas; Popp, Jürgen

2016-07-01

Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit.

Enhanced EDX images by fusion of multimodal SEM images using pansharpening techniques.

PubMed

Franchi, G; Angulo, J; Moreaud, M; Sorbier, L

2018-01-01

The goal of this paper is to explore the potential interest of image fusion in the context of multimodal scanning electron microscope (SEM) imaging. In particular, we aim at merging the backscattered electron images that usually have a high spatial resolution but do not provide enough discriminative information to physically classify the nature of the sample, with energy-dispersive X-ray spectroscopy (EDX) images that have discriminative information but a lower spatial resolution. The produced images are named enhanced EDX. To achieve this goal, we have compared the results obtained with classical pansharpening techniques for image fusion with an original approach tailored for multimodal SEM fusion of information. Quantitative assessment is obtained by means of two SEM images and a simulated dataset produced by a software based on PENELOPE. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism

PubMed Central

Yaseen, Mohammad A.; Srinivasan, Vivek J.; Gorczynska, Iwona; Fujimoto, James G.; Boas, David A.; Sakadžić, Sava

2015-01-01

Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system’s design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence. PMID:26713212

Computational method for multi-modal microscopy based on transport of intensity equation

NASA Astrophysics Data System (ADS)

Li, Jiaji; Chen, Qian; Sun, Jiasong; Zhang, Jialin; Zuo, Chao

2017-02-01

In this paper, we develop the requisite theory to describe a hybrid virtual-physical multi-modal imaging system which yields quantitative phase, Zernike phase contrast, differential interference contrast (DIC), and light field moment imaging simultaneously based on transport of intensity equation(TIE). We then give the experimental demonstration of these ideas by time-lapse imaging of live HeLa cell mitosis. Experimental results verify that a tunable lens based TIE system, combined with the appropriate post-processing algorithm, can achieve a variety of promising imaging modalities in parallel with the quantitative phase images for the dynamic study of cellular processes.

Dynamics of a broad-band quantum cascade laser: from chaos to coherent dynamics and mode-locking

NASA Astrophysics Data System (ADS)

Columbo, L. L.; Barbieri, S.; Sirtori, C.; Brambilla, M.

2018-02-01

The dynamics of a multimode Quantum Cascade Laser, is studied in a model based on effective semiconductor Maxwell-Bloch equations, encompassing key features for the radiationmedium interaction such as an asymmetric, frequency dependent, gain and refractive index as well as the phase-amplitude coupling provided by the Henry factor. By considering the role of the free spectral range and Henry factor, we develop criteria suitable to identify the conditions which allow to destabilize, close to threshold, the traveling wave emitted by the laser and lead to chaotic or regular multimode dynamics. In the latter case our simulations show that the field oscillations are associated to self-confined structures which travel along the laser cavity, bridging mode-locking and solitary wave propagation. In addition, we show how a RF modulation of the bias current leads to active mode-locking yielding high-contrast, picosecond pulses. Our results compare well with recent experiments on broad-band THz-QCLs and may help understanding the conditions for the generation of ultrashort pulses and comb operation in Mid-IR and THz spectral regions

Multimodal Imaging in Diabetic Macular Edema.

PubMed

Acón, Dhariana; Wu, Lihteh

2018-01-01

Throughout ophthalmic history it has been shown that progress has gone hand in hand with technological breakthroughs. In the past, fluorescein angiography and fundus photographs were the most commonly used imaging modalities in the management of diabetic macular edema (DME). Today, despite the moderate correlation between macular thickness and functional outcomes, spectral domain optical coherence tomography (SD-OCT) has become the DME workhorse in clinical practice. Several SD-OCT biomarkers have been looked at including presence of epiretinal membrane, vitreomacular adhesion, disorganization of the inner retinal layers, central macular thickness, integrity of the ellipsoid layer, and subretinal fluid, among others. Emerging imaging modalities include fundus autofluorescence, macular pigment optical density, fluorescence lifetime imaging ophthalmoscopy, OCT angiography, and adaptive optics. Technological advances in imaging of the posterior segment of the eye have enabled ophthalmologists to develop hypotheses about pathological mechanisms of disease, monitor disease progression, and assess response to treatment. Spectral domain OCT is the most commonly performed imaging modality in the management of DME. However, reliable biomarkers have yet to be identified. Machine learning may provide treatment algorithms based on multimodal imaging. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

Observation of Geometric Parametric Instability Induced by the Periodic Spatial Self-Imaging of Multimode Waves

NASA Astrophysics Data System (ADS)

Krupa, Katarzyna; Tonello, Alessandro; Barthélémy, Alain; Couderc, Vincent; Shalaby, Badr Mohamed; Bendahmane, Abdelkrim; Millot, Guy; Wabnitz, Stefan

2016-05-01

Spatiotemporal mode coupling in highly multimode physical systems permits new routes for exploring complex instabilities and forming coherent wave structures. We present here the first experimental demonstration of multiple geometric parametric instability sidebands, generated in the frequency domain through resonant space-time coupling, owing to the natural periodic spatial self-imaging of a multimode quasi-continuous-wave beam in a standard graded-index multimode fiber. The input beam was launched in the fiber by means of an amplified microchip laser emitting sub-ns pulses at 1064 nm. The experimentally observed frequency spacing among sidebands agrees well with analytical predictions and numerical simulations. The first-order peaks are located at the considerably large detuning of 123.5 THz from the pump. These results open the remarkable possibility to convert a near-infrared laser directly into a broad spectral range spanning visible and infrared wavelengths, by means of a single resonant parametric nonlinear effect occurring in the normal dispersion regime. As further evidence of our strong space-time coupling regime, we observed the striking effect that all of the different sideband peaks were carried by a well-defined and stable bell-shaped spatial profile.

Multimodal instrument for high-sensitivity autofluorescence and spectral optical coherence tomography of the human eye fundus

PubMed Central

Komar, Katarzyna; Stremplewski, Patrycjusz; Motoczyńska, Marta; Szkulmowski, Maciej; Wojtkowski, Maciej

2013-01-01

In this paper we present a multimodal device for imaging fundus of human eye in vivo which combines functionality of autofluorescence by confocal SLO with Fourier domain OCT. Native fluorescence of human fundus was excited by modulated laser beam (λ = 473 nm, 20 MHz) and lock-in detection was applied resulting in improving sensitivity. The setup allows for acquisition of high resolution OCT and high contrast AF images using fluorescence excitation power of 50-65 μW without averaging consecutive images. Successful functioning of constructed device have been demonstrated for 8 healthy volunteers of different age ranging from 24 to 83 years old. PMID:24298426

The Impact Of Multimode Fiber Chromatic Dispersion On Data Communications

NASA Astrophysics Data System (ADS)

Hackert, Michael J.

1990-01-01

Capability for the lowest cost is the goal of contemporary communications managers. With all of the competitive pressures that modern businesses are experiencing these days, communications needs must be met with the most information carrying capacity for the lowest cost. Optical fiber communication systems meet these requirements while providing reliability, system integrity, and potential future upgradability. Consequently, optical fiber is finding numerous applications in addition to its traditional telephony plant. Fiber based systems are meeting these requirements in building networks and computer interconnects at a lower cost than copper based systems. A fiber type being chosen by industry to meet these needs in standard systems such as FDDI, is multimode fiber. Multimode fiber systems offer cost advantages over single-mode fiber through lower fiber connection costs. Also, system designers can gain savings by using low cost, high reliability, wide spectral width sources such as LEDs instead of lasers and by operating at higher bit rates than used for multimode systems in the past. However, in order to maximize the cost savings while ensuring the system will operate as intended, the chromatic dispersion of the fiber must be taken into account. This paper explains how to do that and shows how to calculate multimode chromatic dispersion for each of the standard fiber sizes (50 μm, 62.5 μm, 85 μm, and 100μm core diameter).

Multimodal fluorescence microscopy of prion strain specific PrP deposits stained by thiophene-based amyloid ligands.

PubMed

Magnusson, Karin; Simon, Rozalyn; Sjölander, Daniel; Sigurdson, Christina J; Hammarström, Per; Nilsson, K Peter R

2014-01-01

The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share an identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here, we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies.

Multimodal fluorescence microscopy of prion strain specific PrP deposits stained by thiophene-based amyloid ligands

PubMed Central

Magnusson, Karin; Simon, Rozalyn; Sjölander, Daniel; Sigurdson, Christina J; Hammarström, Per; Nilsson, K Peter R

2014-01-01

The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share an identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here, we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies. PMID:25495506

Fully integrated reflection-mode photoacoustic, two-photon, and second harmonic generation microscopy in vivo

NASA Astrophysics Data System (ADS)

Song, Wei; Xu, Qiang; Zhang, Yang; Zhan, Yang; Zheng, Wei; Song, Liang

2016-08-01

The ability to obtain comprehensive structural and functional information from intact biological tissue in vivo is highly desirable for many important biomedical applications, including cancer and brain studies. Here, we developed a fully integrated multimodal microscopy that can provide photoacoustic (optical absorption), two-photon (fluorescence), and second harmonic generation (SHG) information from tissue in vivo, with intrinsically co-registered images. Moreover, using a delicately designed optical-acoustic coupling configuration, a high-frequency miniature ultrasonic transducer was integrated into a water-immersion optical objective, thus allowing all three imaging modalities to provide a high lateral resolution of ~290 nm with reflection-mode imaging capability, which is essential for studying intricate anatomy, such as that of the brain. Taking advantage of the complementary and comprehensive contrasts of the system, we demonstrated high-resolution imaging of various tissues in living mice, including microvasculature (by photoacoustics), epidermis cells, cortical neurons (by two-photon fluorescence), and extracellular collagen fibers (by SHG). The intrinsic image co-registration of the three modalities conveniently provided improved visualization and understanding of the tissue microarchitecture. The reported results suggest that, by revealing complementary tissue microstructures in vivo, this multimodal microscopy can potentially facilitate a broad range of biomedical studies, such as imaging of the tumor microenvironment and neurovascular coupling.

Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

NASA Astrophysics Data System (ADS)

Roeder, Ryan K.; Curtis, Tyler E.; Nallathamby, Prakash D.; Irimata, Lisa E.; McGinnity, Tracie L.; Cole, Lisa E.; Vargo-Gogola, Tracy; Cowden Dahl, Karen D.

2017-03-01

Precision imaging is needed to realize precision medicine in cancer detection and treatment. Molecular imaging offers the ability to target and identify tumors, associated abnormalities, and specific cell populations with overexpressed receptors. Nuclear imaging and radionuclide probes provide high sensitivity but subject the patient to a high radiation dose and provide limited spatiotemporal information, requiring combined computed tomography (CT) for anatomic imaging. Therefore, nanoparticle contrast agents have been designed to enable molecular imaging and improve detection in CT alone. Core-shell nanoparticles provide a powerful platform for designing tailored imaging probes. The composition of the core is chosen for enabling strong X-ray contrast, multi-agent imaging with photon-counting spectral CT, and multimodal imaging. A silica shell is used for protective, biocompatible encapsulation of the core composition, volume-loading fluorophores or radionuclides for multimodal imaging, and facile surface functionalization with antibodies or small molecules for targeted delivery. Multi-agent (k-edge) imaging and quantitative molecular imaging with spectral CT was demonstrated using current clinical agents (iodine and BaSO4) and a proposed spectral library of contrast agents (Gd2O3, HfO2, and Au). Bisphosphonate-functionalized Au nanoparticles were demonstrated to enhance sensitivity and specificity for the detection of breast microcalcifications by conventional radiography and CT in both normal and dense mammary tissue using murine models. Moreover, photon-counting spectral CT enabled quantitative material decomposition of the Au and calcium signals. Immunoconjugated Au@SiO2 nanoparticles enabled highly-specific targeting of CD133+ ovarian cancer stem cells for contrast-enhanced detection in model tumors.

Multimodal backside imaging of a microcontroller using confocal laser scanning and optical-beam-induced current imaging

NASA Astrophysics Data System (ADS)

Finkeldey, Markus; Göring, Lena; Schellenberg, Falk; Brenner, Carsten; Gerhardt, Nils C.; Hofmann, Martin

2017-02-01

Microscopy imaging with a single technology is usually restricted to a single contrast mechanism. Multimodal imaging is a promising technique to improve the structural information that could be obtained about a device under test (DUT). Due to the different contrast mechanisms of laser scanning microscopy (LSM), confocal laser scanning microscopy (CLSM) and optical beam induced current microscopy (OBICM), a combination could improve the detection of structures in integrated circuits (ICs) and helps to reveal their layout. While OBIC imaging is sensitive to the changes between differently doped areas and to semiconductor-metal transitions, CLSM imaging is mostly sensitive to changes in absorption and reflection. In this work we present the implementation of OBIC imaging into a CLSM. We show first results using industry standard Atmel microcontrollers (MCUs) with a feature size of about 250nm as DUTs. Analyzing these types of microcontrollers helps to improve in the field of side-channel attacks to find hardware Trojans, possible spots for laser fault attacks and for reverse engineering. For the experimental results the DUT is placed on a custom circuit board that allows us to measure the current while imaging it in our in-house built stage scanning microscope using a near infrared (NIR) laser diode as light source. The DUT is thinned and polished, allowing backside imaging through the Si-substrate. We demonstrate the possibilities using this optical setup by evaluating OBIC, LSM and CLSM images above and below the threshold of the laser source.

Full optical model of micro-endoscope with optical coherence microscopy, multiphoton microscopy and visible capabilities

NASA Astrophysics Data System (ADS)

Vega, David; Kiekens, Kelli C.; Syson, Nikolas C.; Romano, Gabriella; Baker, Tressa; Barton, Jennifer K.

2018-02-01

While Optical Coherence Microscopy (OCM), Multiphoton Microscopy (MPM), and narrowband imaging are powerful imaging techniques that can be used to detect cancer, each imaging technique has limitations when used by itself. Combining them into an endoscope to work in synergy can help achieve high sensitivity and specificity for diagnosis at the point of care. Such complex endoscopes have an elevated risk of failure, and performing proper modelling ensures functionality and minimizes risk. We present full 2D and 3D models of a multimodality optical micro-endoscope to provide real-time detection of carcinomas, called a salpingoscope. The models evaluate the endoscope illumination and light collection capabilities of various modalities. The design features two optical paths with different numerical apertures (NA) through a single lens system with a scanning optical fiber. The dual path is achieved using dichroic coatings embedded in a triplet. A high NA optical path is designed to perform OCM and MPM while a low NA optical path is designed for the visible spectrum to navigate the endoscope to areas of interest and narrowband imaging. Different tests such as the reflectance profile of homogeneous epithelial tissue were performed to adjust the models properly. Light collection models for the different modalities were created and tested for efficiency. While it is challenging to evaluate the efficiency of multimodality endoscopes, the models ensure that the system is design for the expected light collection levels to provide detectable signal to work for the intended imaging.

Multiscale climate emulator of multimodal wave spectra: MUSCLE-spectra

NASA Astrophysics Data System (ADS)

Rueda, Ana; Hegermiller, Christie A.; Antolinez, Jose A. A.; Camus, Paula; Vitousek, Sean; Ruggiero, Peter; Barnard, Patrick L.; Erikson, Li H.; Tomás, Antonio; Mendez, Fernando J.

2017-02-01

Characterization of multimodal directional wave spectra is important for many offshore and coastal applications, such as marine forecasting, coastal hazard assessment, and design of offshore wave energy farms and coastal structures. However, the multivariate and multiscale nature of wave climate variability makes this complex problem tractable using computationally expensive numerical models. So far, the skill of statistical-downscaling model-based parametric (unimodal) wave conditions is limited in large ocean basins such as the Pacific. The recent availability of long-term directional spectral data from buoys and wave hindcast models allows for development of stochastic models that include multimodal sea-state parameters. This work introduces a statistical downscaling framework based on weather types to predict multimodal wave spectra (e.g., significant wave height, mean wave period, and mean wave direction from different storm systems, including sea and swells) from large-scale atmospheric pressure fields. For each weather type, variables of interest are modeled using the categorical distribution for the sea-state type, the Generalized Extreme Value (GEV) distribution for wave height and wave period, a multivariate Gaussian copula for the interdependence between variables, and a Markov chain model for the chronology of daily weather types. We apply the model to the southern California coast, where local seas and swells from both the Northern and Southern Hemispheres contribute to the multimodal wave spectrum. This work allows attribution of particular extreme multimodal wave events to specific atmospheric conditions, expanding knowledge of time-dependent, climate-driven offshore and coastal sea-state conditions that have a significant influence on local nearshore processes, coastal morphology, and flood hazards.

Multiscale Climate Emulator of Multimodal Wave Spectra: MUSCLE-spectra

NASA Astrophysics Data System (ADS)

Rueda, A.; Hegermiller, C.; Alvarez Antolinez, J. A.; Camus, P.; Vitousek, S.; Ruggiero, P.; Barnard, P.; Erikson, L. H.; Tomas, A.; Mendez, F. J.

2016-12-01

Characterization of multimodal directional wave spectra is important for many offshore and coastal applications, such as marine forecasting, coastal hazard assessment, and design of offshore wave energy farms and coastal structures. However, the multivariate and multiscale nature of wave climate variability makes this problem complex yet tractable using computationally-expensive numerical models. So far, the skill of statistical-downscaling models based parametric (unimodal) wave conditions is limited in large ocean basins such as the Pacific. The recent availability of long-term directional spectral data from buoys and wave hindcast models allows for development of stochastic models that include multimodal sea-state parameters. This work introduces a statistical-downscaling framework based on weather types to predict multimodal wave spectra (e.g., significant wave height, mean wave period, and mean wave direction from different storm systems, including sea and swells) from large-scale atmospheric pressure fields. For each weather type, variables of interest are modeled using the categorical distribution for the sea-state type, the Generalized Extreme Value (GEV) distribution for wave height and wave period, a multivariate Gaussian copula for the interdependence between variables, and a Markov chain model for the chronology of daily weather types. We apply the model to the Southern California coast, where local seas and swells from both the Northern and Southern Hemispheres contribute to the multimodal wave spectrum. This work allows attribution of particular extreme multimodal wave events to specific atmospheric conditions, expanding knowledge of time-dependent, climate-driven offshore and coastal sea-state conditions that have a significant influence on local nearshore processes, coastal morphology, and flood hazards.

Multimodal optical imaging database from tumour brain human tissue: endogenous fluorescence from glioma, metastasis and control tissues

NASA Astrophysics Data System (ADS)

Poulon, Fanny; Ibrahim, Ali; Zanello, Marc; Pallud, Johan; Varlet, Pascale; Malouki, Fatima; Abi Lahoud, Georges; Devaux, Bertrand; Abi Haidar, Darine

2017-02-01

Eliminating time-consuming process of conventional biopsy is a practical improvement, as well as increasing the accuracy of tissue diagnoses and patient comfort. We addressed these needs by developing a multimodal nonlinear endomicroscope that allows real-time optical biopsies during surgical procedure. It will provide immediate information for diagnostic use without removal of tissue and will assist the choice of the optimal surgical strategy. This instrument will combine several means of contrast: non-linear fluorescence, second harmonic generation signal, reflectance, fluorescence lifetime and spectral analysis. Multimodality is crucial for reliable and comprehensive analysis of tissue. Parallel to the instrumental development, we currently improve our understanding of the endogeneous fluorescence signal with the different modalities that will be implemented in the stated. This endeavor will allow to create a database on the optical signature of the diseased and control brain tissues. This proceeding will present the preliminary results of this database on three types of tissues: cortex, metastasis and glioblastoma.

Laser Microdissection and Atmospheric Pressure Chemical Ionization Mass Spectrometry Coupled for Multimodal Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lorenz, Matthias; Ovchinnikova, Olga S; Kertesz, Vilmos

2013-01-01

This paper describes the coupling of ambient laser ablation surface sampling, accomplished using a laser capture microdissection system, with atmospheric pressure chemical ionization mass spectrometry for high spatial resolution multimodal imaging. A commercial laser capture microdissection system was placed in close proximity to a modified ion source of a mass spectrometer designed to allow for sampling of laser ablated material via a transfer tube directly into the ionization region. Rhodamine 6G dye of red sharpie ink in a laser etched pattern as well as cholesterol and phosphatidylcholine in a cerebellum mouse brain thin tissue section were identified and imaged frommore » full scan mass spectra. A minimal spot diameter of 8 m was achieved using the 10X microscope cutting objective with a lateral oversampling pixel resolution of about 3.7 m. Distinguishing between features approximately 13 m apart in a cerebellum mouse brain thin tissue section was demonstrated in a multimodal fashion including co-registered optical and mass spectral chemical images.« less

Multi-Modal Nano-Probes for Radionuclide and 5-color Near Infrared Optical Lymphatic Imaging

PubMed Central

Kobayashi, Hisataka; Koyama, Yoshinori; Barrett, Tristan; Hama, Yukihiro; Regino, Celeste A. S.; Shin, In Soo; Jang, Beom-Su; Le, Nhat; Paik, Chang H.; Choyke, Peter L.; Urano, Yasuteru

2008-01-01

Current contrast agents generally have one function and can only be imaged in monochrome, therefore, the majority of imaging methods can only impart uniparametric information. A single nano-particle has the potential to be loaded with multiple payloads. Such multi-modality probes have the ability to be imaged by more than one imaging technique, which could compensate for the weakness or even combine the advantages of each individual modality. Furthermore, optical imaging using different optical probes enables us to achieve multi-color in vivo imaging, wherein multiple parameters can be read from a single image. To allow differentiation of multiple optical signals in vivo, each probe should have a close but different near infrared emission. To this end, we synthesized nano-probes with multi-modal and multi-color potential, which employed a polyamidoamine dendrimer platform linked to both radionuclides and optical probes, permitting dual-modality scintigraphic and 5-color near infrared optical lymphatic imaging using a multiple excitation spectrally-resolved fluorescence imaging technique. PMID:19079788

Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging.

PubMed

Kobayashi, Hisataka; Koyama, Yoshinori; Barrett, Tristan; Hama, Yukihiro; Regino, Celeste A S; Shin, In Soo; Jang, Beom-Su; Le, Nhat; Paik, Chang H; Choyke, Peter L; Urano, Yasuteru

2007-11-01

Current contrast agents generally have one function and can only be imaged in monochrome; therefore, the majority of imaging methods can only impart uniparametric information. A single nanoparticle has the potential to be loaded with multiple payloads. Such multimodality probes have the ability to be imaged by more than one imaging technique, which could compensate for the weakness or even combine the advantages of each individual modality. Furthermore, optical imaging using different optical probes enables us to achieve multicolor in vivo imaging, wherein multiple parameters can be read from a single image. To allow differentiation of multiple optical signals in vivo, each probe should have a close but different near-infrared emission. To this end, we synthesized nanoprobes with multimodal and multicolor potential, which employed a polyamidoamine dendrimer platform linked to both radionuclides and optical probes, permitting dual-modality scintigraphic and five-color near-infrared optical lymphatic imaging using a multiple-excitation spectrally resolved fluorescence imaging technique.

Compact fixed wavelength femtosecond oscillators as an add-on for tunable Ti:sapphire lasers extend the range of applications towards multimodal imaging and optogenetics

NASA Astrophysics Data System (ADS)

Hakulinen, T.; Klein, J.

2016-03-01

Two-photon (2P) microscopy based on tunable Ti:sapphire lasers has become a widespread tool for 3D imaging with sub-cellular resolution in living tissues. In recent years multi-photon microscopy with simpler fixed-wavelength femtosecond oscillators using Yb-doped tungstenates as gain material has raised increasing interest in life-sciences, because these lasers offer one order of magnitude more average power than Ti:sapphire lasers in the wavelength range around 1040 nm: Two-photon (2P) excitation of mainly red or yellow fluorescent dyes and proteins (e.g. YFP, mFruit series) simultaneously has been proven with a single IR laser wavelength. A new approach is to extend the usability of existing tunable Titanium sapphire lasers by adding a fixed IR wavelength with an Yb femtosecond oscillator. By that means a multitude of applications for multimodal imaging and optogenetics can be supported. Furthermore fs Yb-lasers are available with a repetition rate of typically 10 MHz and an average power of typically 5 W resulting in pulse energy of typically 500 nJ, which is comparably high for fs-oscillators. This makes them an ideal tool for two-photon spinning disk laser scanning microscopy and holographic patterning for simultaneous photoactivation of large cell populations. With this work we demonstrate that economical, small-footprint Yb fixed-wavelength lasers can present an interesting add-on to tunable lasers that are commonly used in multiphoton microscopy. The Yb fs-lasers hereby offer higher power for imaging of red fluorescent dyes and proteins, are ideally enhancing existing Ti:sapphire lasers with more power in the IR, and are supporting pulse energy and power hungry applications such as spinning disk microscopy and holographic patterning.

Complementary Imaging of Silver Nanoparticle Interactions with Green Algae: Dark-Field Microscopy, Electron Microscopy, and Nanoscale Secondary Ion Mass Spectrometry.

PubMed

Sekine, Ryo; Moore, Katie L; Matzke, Marianne; Vallotton, Pascal; Jiang, Haibo; Hughes, Gareth M; Kirby, Jason K; Donner, Erica; Grovenor, Chris R M; Svendsen, Claus; Lombi, Enzo

2017-11-28

Increasing consumer use of engineered nanomaterials has led to significantly increased efforts to understand their potential impact on the environment and living organisms. Currently, no individual technique can provide all the necessary information such as their size, distribution, and chemistry in complex biological systems. Consequently, there is a need to develop complementary instrumental imaging approaches that provide enhanced understanding of these "bio-nano" interactions to overcome the limitations of individual techniques. Here we used a multimodal imaging approach incorporating dark-field light microscopy, high-resolution electron microscopy, and nanoscale secondary ion mass spectrometry (NanoSIMS). The aim was to gain insight into the bio-nano interactions of surface-functionalized silver nanoparticles (Ag-NPs) with the green algae Raphidocelis subcapitata, by combining the fidelity, spatial resolution, and elemental identification offered by the three techniques, respectively. Each technique revealed that Ag-NPs interact with the green algae with a dependence on the size (10 nm vs 60 nm) and surface functionality (tannic acid vs branched polyethylenimine, bPEI) of the NPs. Dark-field light microscopy revealed the presence of strong light scatterers on the algal cell surface, and SEM imaging confirmed their nanoparticulate nature and localization at nanoscale resolution. NanoSIMS imaging confirmed their chemical identity as Ag, with the majority of signal concentrated at the cell surface. Furthermore, SEM and NanoSIMS provided evidence of 10 nm bPEI Ag-NP internalization at higher concentrations (40 μg/L), correlating with the highest toxicity observed from these NPs. This multimodal approach thus demonstrated an effective approach to complement dose-response studies in nano-(eco)-toxicological investigations.

Study of electromechanical and mechanical properties of bacteria using force microscopy

NASA Astrophysics Data System (ADS)

Reukov, Vladimir; Thompson, Gary; Nikiforov, Maxim; Guo, Senli; Ovchinnikov, Oleg; Jesse, Stephen; Kalinin, Sergei; Vertegel, Alexey

2010-03-01

The application of scanning probe microscopy (SPM) to biological systems has evolved over the past decade into a multimodal and spectroscopic instrument that provides multiple information channels at each spatial pixel acquired. Recently, functional recognition imaging based on differing electromechanical properties between Gram negative and Gram positive bacteria was achieved using artificial neural network analysis of band excitation piezoresponse force microscopy (BEPFM) data. The immediate goal of this project was to study mechanical and electromechanical properties of bacterial systems physiologically-relevant solutions using Band-width Excitation Piezoresponce Force Microscopy (BE PFM) in combination with Force Mapping. Electromechanical imaging in physiological environments will improve the versatility of functional recognition imaging and open the way for application of the rapid BEPFM line mode method to other living cell systems.

Multi-spectral digital holographic microscopy for enhanced quantitative phase imaging of living cells

NASA Astrophysics Data System (ADS)

Kemper, Björn; Kastl, Lena; Schnekenburger, Jürgen; Ketelhut, Steffi

2018-02-01

Main restrictions of using laser light in digital holographic microscopy (DHM) are coherence induced noise and parasitic reflections in the experimental setup which limit resolution and measurement accuracy. We explored, if coherence properties of partial coherent light sources can be generated synthetically utilizing spectrally tunable lasers. The concept of the method is demonstrated by label-free quantitative phase imaging of living pancreatic tumor cells and utilizing an experimental configuration including a commercial microscope and a laser source with a broad tunable spectral range of more than 200 nm.

Fiber-optic temperature sensors based on differential spectral transmittance/reflectivity and multiplexed sensing systems

NASA Astrophysics Data System (ADS)

Wang, Anbo; Wang, George Z.; Murphy, Kent A.; Claus, Richard O.

1995-05-01

Dielectric-multilayer-filter-based, optical-fiber temperature sensors based on differential spectral transmittance/reflectivity were shown experimentally. A resolution of 0.2 C was achieved over a measurement range of 30-120 C. The sensor was shown to possess low immunity to variations in light-source power and fiber-bending loss. A wavelength-division-multiplexed sensing system was also fabricated by cascading three such filters with distinct cutoff wavelengths along a single multimode fiber. A resolution of 0.5 C was achieved over a temperature spectrum of 50-100 C. Furthermore, cross talk between sensors was examined.

Total teleportation of a single-photon state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humble, Travis S; Bennink, Ryan S; Grice, Warren P

2008-01-01

Recent demonstrations of teleportation have transferred quantum information encoded into either polarization or field-quadrature degrees of freedom (DOFs), but an outstanding question is how to simultaneously teleport quantum information encoded into multiple DOFs. We describe how the transverse-spatial, spectral and polarization states of a single photon can be simultaneously teleported using a pair of multimode, polarization-entangled photons derived from spontaneous parametric down-conversion. Furthermore, when the initial photon pair is maximally entangled in the spatial, spectral, and polarization DOFs then the photon s full quantum state can be reliably teleported using a Bell-state measurement based on sum-frequency generation.

Multi-modal Registration for Correlative Microscopy using Image Analogies

PubMed Central

Cao, Tian; Zach, Christopher; Modla, Shannon; Powell, Debbie; Czymmek, Kirk; Niethammer, Marc

2014-01-01

Correlative microscopy is a methodology combining the functionality of light microscopy with the high resolution of electron microscopy and other microscopy technologies for the same biological specimen. In this paper, we propose an image registration method for correlative microscopy, which is challenging due to the distinct appearance of biological structures when imaged with different modalities. Our method is based on image analogies and allows to transform images of a given modality into the appearance-space of another modality. Hence, the registration between two different types of microscopy images can be transformed to a mono-modality image registration. We use a sparse representation model to obtain image analogies. The method makes use of corresponding image training patches of two different imaging modalities to learn a dictionary capturing appearance relations. We test our approach on backscattered electron (BSE) scanning electron microscopy (SEM)/confocal and transmission electron microscopy (TEM)/confocal images. We perform rigid, affine, and deformable registration via B-splines and show improvements over direct registration using both mutual information and sum of squared differences similarity measures to account for differences in image appearance. PMID:24387943

Emission spectra of a laser based on an In(Ga)As/GaAs quantum-dot superlattice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sobolev, M. M., E-mail: m.sobolev@mail.ioffe.ru; Buyalo, M. S.; Nevedomskiy, V. N.

2015-10-15

The spectral characteristics of a laser with an active region based on a ten-layer system of In(Ga)As/GaAs vertically correlated quantum dots with 4.5-nm GaAs spacer layers between InAs quantum dots are studied under the conditions of spontaneous and stimulated emission, depending on the current and the duration of pump pulses. Data obtained by transmission electron microscopy and electroluminescence and absorption polarization anisotropy measurements make it possible to demonstrate that the investigated system of tunnel-coupled InAs quantum dots separated by thin GaAs barriers represents a quantum-dot superlattice. With an increase in the laser pump current, the electroluminescence intensity increases linearly andmore » the spectral position of the electroluminescence maximum shifts to higher energies, which is caused by the dependence of the miniband density-of-states distribution on the pump current. Upon exceeding the threshold current, multimode lasing via the miniband ground state is observed. One of the lasing modes can be attributed to the zero-phonon line, and the other is determined by the longitudinal-optical phonon replica of quantum-dot emission. The results obtained give evidence that, under conditions of the laser pumping of an In(Ga)As/GaAs quantum-dot superlattice, strong coupling between the discrete electron states in the miniband and optical phonons takes place. This leads to the formation of quantum-dot polarons, resulting from the resonant mixing of electronic states whose energy separation is comparable to the optical-phonon energy.« less

Hybrid microscopy of human carotid atheroma by means of optical-resolution optoacoustic and non-linear optical microscopy

NASA Astrophysics Data System (ADS)

Seeger, Markus; Karlas, Angelos; Soliman, Dominik; Pelisek, Jaroslav; Ntziachristos, Vasilis

2017-03-01

Carotid atheromatosis is causally related to stroke, a leading cause of disability and death. We present the analysis of a human carotid atheroma using a novel hybrid microscopy system that combines optical-resolution optoacoustic (photoacoustic) microscopy and several non-linear optical microscopy modalities (second and third harmonic generation, as well as, two-photon excitation fluorescence) to achieve a multimodal examination of the extracted tissue within the same imaging framework. Our system enables the label-free investigation of atheromatous human carotid tissue with a resolution of about 1 μm and allows for the congruent interrogation of plaque morphology and clinically relevant constituents such as red blood cells, collagen, and elastin. Our data reveal mutual interactions between blood embeddings and connective tissue within the atheroma, offering comprehensive insights into its stage of evolution and severity, and potentially facilitating the further development of diagnostic tools, as well as treatment strategies.

Imaging Cellular Dynamics with Spectral Relaxation Imaging Microscopy: Distinct Spectral Dynamics in Golgi Membranes of Living Cells.

PubMed

Lajevardipour, Alireza; Chon, James W M; Chattopadhyay, Amitabha; Clayton, Andrew H A

2016-11-22

Spectral relaxation from fluorescent probes is a useful technique for determining the dynamics of condensed phases. To this end, we have developed a method based on wide-field spectral fluorescence lifetime imaging microscopy to extract spectral relaxation correlation times of fluorescent probes in living cells. We show that measurement of the phase and modulation of fluorescence from two wavelengths permit the identification and determination of excited state lifetimes and spectral relaxation correlation times at a single modulation frequency. For NBD fluorescence in glycerol/water mixtures, the spectral relaxation correlation time determined by our approach exhibited good agreement with published dielectric relaxation measurements. We applied this method to determine the spectral relaxation dynamics in membranes of living cells. Measurements of the Golgi-specific C 6 -NBD-ceramide probe in living HeLa cells revealed sub-nanosecond spectral dynamics in the intracellular Golgi membrane and slower nanosecond spectral dynamics in the extracellular plasma membrane. We interpret the distinct spectral dynamics as a result of structural plasticity of the Golgi membrane relative to more rigid plasma membranes. To the best of our knowledge, these results constitute one of the first measurements of Golgi rotational dynamics.

Multimodal lightsheet, structured illumination and Airyscan superresolution microscopy of chloroplast size and its impact on light propagation

USDA-ARS?s Scientific Manuscript database

Altering chloroplast size changes the way light propagates through a leaf by altering light reflectance and transmission as well as absorption by chlorophyll. Thus changing chloroplast size can used to manipulate leaf optical properties to optimize photosynthetic efficiency with the ultimate goal of...

Multimodal computational microscopy based on transport of intensity equation

NASA Astrophysics Data System (ADS)

Li, Jiaji; Chen, Qian; Sun, Jiasong; Zhang, Jialin; Zuo, Chao

2016-12-01

Transport of intensity equation (TIE) is a powerful tool for phase retrieval and quantitative phase imaging, which requires intensity measurements only at axially closely spaced planes without a separate reference beam. It does not require coherent illumination and works well on conventional bright-field microscopes. The quantitative phase reconstructed by TIE gives valuable information that has been encoded in the complex wave field by passage through a sample of interest. Such information may provide tremendous flexibility to emulate various microscopy modalities computationally without requiring specialized hardware components. We develop a requisite theory to describe such a hybrid computational multimodal imaging system, which yields quantitative phase, Zernike phase contrast, differential interference contrast, and light field moment imaging, simultaneously. It makes the various observations for biomedical samples easy. Then we give the experimental demonstration of these ideas by time-lapse imaging of live HeLa cell mitosis. Experimental results verify that a tunable lens-based TIE system, combined with the appropriate postprocessing algorithm, can achieve a variety of promising imaging modalities in parallel with the quantitative phase images for the dynamic study of cellular processes.

Near-field hyperspectral quantum probing of multimodal plasmonic resonators

NASA Astrophysics Data System (ADS)

Cuche, A.; Berthel, M.; Kumar, U.; Colas des Francs, G.; Huant, S.; Dujardin, E.; Girard, C.; Drezet, A.

2017-03-01

Quantum systems, excited by an external source of photons, display a photodynamics that is ruled by a subtle balance between radiative or nonradiative energy channels when interacting with metallic nanostructures. We apply and generalize this concept to achieve a quantum probing of multimodal plasmonic resonators by collecting and filtering the broad emission spectra generated by a nanodiamond (ND) hosting a small set of nitrogen-vacancy (NV) color centers attached at the apex of an optical tip. Spatially and spectrally resolved information on the photonic local density of states (ph-LDOS) can be recorded with this technique in the immediate vicinity of plasmonic resonators, paving the way for a complete near-field optical characterization of any kind of nanoresonators in the single photon regime.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PubMed

Duncker, Tobias; Lee, Winston; Jiang, Fan; Ramachandran, Rithambara; Hood, Donald C; Tsang, Stephen H; Sparrow, Janet R; Greenstein, Vivienne C

2018-01-01

To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

MULTIMODAL IMAGING OF MOSAIC RETINOPATHY IN CARRIERS OF HEREDITARY X-LINKED RECESSIVE DISEASES.

PubMed

Wu, An-Lun; Wang, Jung-Pan; Tseng, Yun-Ju; Liu, Laura; Kang, Yu-Chuan; Chen, Kuan-Jen; Chao, An-Ning; Yeh, Lung-Kun; Chen, Tun-Lu; Hwang, Yih-Shiou; Wu, Wei-Chi; Lai, Chi-Chun; Wang, Nan-Kai

2018-05-01

To investigate the clinical features in carriers of X-linked retinitis pigmentosa, X-linked ocular albinism, and choroideremia (CHM) using multimodal imaging and to assess their diagnostic value in these three mosaic retinopathies. We prospectively examined 14 carriers of 3 X-linked recessive disorders (X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM). Details of abnormalities of retinal morphology were evaluated using fundus photography, fundus autofluorescence (FAF) imaging, and spectral domain optical coherence tomography. In six X-linked retinitis pigmentosa carriers, fundus appearance varied from unremarkable to the presence of tapetal-like reflex and pigmentary changes. On FAF imaging, all carriers exhibited a bright radial reflex against a dark background. By spectral domain optical coherence tomography, loss of the ellipsoid zone in the macula was observed in 3 carriers (50%). Regarding the retinal laminar architecture, 4 carriers (66.7%) showed thinning of the outer nuclear layer and a dentate appearance of the outer plexiform layer. All five X-linked ocular albinism carriers showed a characteristic mud-splatter patterned fundus, dark radial streaks against a bright background on FAF imaging, and a normal-appearing retinal structure by spectral domain optical coherence tomography imaging. Two of the 3 CHM carriers (66.7%) showed a diffuse moth-eaten appearance of the fundus, and all 3 showed irregular hyper-FAF and hypo-FAF spots throughout the affected area. In the CHM carriers, the structural changes observed by spectral domain optical coherence tomography imaging were variable. Our findings in an Asian cohort suggest that FAF imaging is a practical diagnostic test for differentiating X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM carriers. Wide-field FAF is an easy and helpful adjunct to testing for the correct diagnosis and identification of lyonization in carriers of these three mosaic retinopathies.

Multimodal segmentation of optic disc and cup from stereo fundus and SD-OCT images

NASA Astrophysics Data System (ADS)

Miri, Mohammad Saleh; Lee, Kyungmoo; Niemeijer, Meindert; Abràmoff, Michael D.; Kwon, Young H.; Garvin, Mona K.

2013-03-01

Glaucoma is one of the major causes of blindness worldwide. One important structural parameter for the diagnosis and management of glaucoma is the cup-to-disc ratio (CDR), which tends to become larger as glaucoma progresses. While approaches exist for segmenting the optic disc and cup within fundus photographs, and more recently, within spectral-domain optical coherence tomography (SD-OCT) volumes, no approaches have been reported for the simultaneous segmentation of these structures within both modalities combined. In this work, a multimodal pixel-classification approach for the segmentation of the optic disc and cup within fundus photographs and SD-OCT volumes is presented. In particular, after segmentation of other important structures (such as the retinal layers and retinal blood vessels) and fundus-to-SD-OCT image registration, features are extracted from both modalities and a k-nearest-neighbor classification approach is used to classify each pixel as cup, rim, or background. The approach is evaluated on 70 multimodal image pairs from 35 subjects in a leave-10%-out fashion (by subject). A significant improvement in classification accuracy is obtained using the multimodal approach over that obtained from the corresponding unimodal approach (97.8% versus 95.2%; p < 0:05; paired t-test).

Proximal design for a multimodality endoscope with multiphoton microscopy, optical coherence microscopy and visual modalities

NASA Astrophysics Data System (ADS)

Kiekens, Kelli C.; Talarico, Olivia; Barton, Jennifer K.

2018-02-01

A multimodality endoscope system has been designed for early detection of ovarian cancer. Multiple illumination and detection systems must be integrated in a compact, stable, transportable configuration to meet the requirements of a clinical setting. The proximal configuration presented here supports visible light navigation with a large field of view and low resolution, high resolution multiphoton microscopy (MPM), and high resolution optical coherence microscopy (OCM). All modalities are integrated into a single optical system in the endoscope. The system requires two light sources: a green laser for visible light navigation and a compact fiber based femtosecond laser for MPM and OCM. Using an inline wavelength division multiplexer, the two sources are combined into a single mode fiber. To accomplish OCM, a fiber coupler is used to separate the femtosecond laser into a reference arm and signal arm. The reflected reference arm and the signal from the sample are interfered and wavelength separated by a reflection grating and detected using a linear array. The MPM signal is collimated and goes through a series of filters to separate the 2nd and 3rd harmonics as well as twophoton excitation florescence (2PEF) and 3PEF. Each signal is independently detected on a photo multiplier tube and amplified. The visible light is collected by multiple high numerical aperture fibers at the endoscope tip which are bundled into one SMA adapter at the proximal end and connected to a photodetector. This integrated system design is compact, efficient and meets both optical and mechanical requirements for clinical applications.

Hybrid of two-photon microscopy and optical multimodality imaging for multi-scale imaging of small animals

NASA Astrophysics Data System (ADS)

Li, Tianmeng; Hui, Hui; Ma, He; Yang, Xin; Tian, Jie

2018-02-01

Non-invasive imaging technologies, such as magnetic resonance imaging (MRI) and optical multimodality imaging methods, are commonly used for diagnosing and supervising the development of inflammatory bowel disease (IBD). These in vivo imaging methods can provide morphology changes information of IBD in macro-scale. However, it is difficult to investigate the intestinal wall in molecular and cellular level. State-of-art light-sheet and two-photon microscopy have the ability to acquire the changes for IBD in micro-scale. The aim of this work is to evaluate the size of the enterocoel and the thickness of colon wall using both MRI for in vivo imaging, and light-sheet and two-photon microscope for in vitro imaging. C57BL/6 mice were received 3.5% Dextran sodium sulfate (DSS) in the drinking water for 5 days to build IBD model. Mice were imaged with MRI on days 0, 6 to observe colitis progression. After MRI imaging, the mice were sacrificed to take colons for tissue clearing. Then, light-sheet and two-photon microscopies are used for in vitro imaging of the cleared samples. The experimental group showed symptoms of bloody stools, sluggishness and weight loss. It showed that the colon wall was thicker while the enterocoel was narrower compare to control group. The more details are observed using light-sheet and two-photon microscope. It is demonstrated that hybrid of MRI in macro-scale and light-sheet and two-photon microscopy in micro-scale imaging is feasible for colon inflammation diagnosing and supervising.

Peculiarities of spike multimode generation of a superradiant distributed feedback laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kocharovskaya, E R; Ginzburg, N S; Sergeev, A S

2011-08-31

Using one-dimensional semiclassical Maxwell - Bloch equations with account for the coherent polarisation dynamics, we have studied spike generation regimes of a superradiant distributed feedback laser in the case of inhomogeneous broadening of the spectral line of an active medium. By analysing the dynamic spectra of inversion of the active medium and laser radiation, we have revealed the relationship of individual spikes of radiation and their modulation with specific parts in the spectral line of the active medium and mode beatings. It has been shown that the broadening and shift of the lasing spectrum with respect to the initial electromagneticmore » Bragg-cavity modes is accompanied by a strong spectral gradient of inversion that is typical of the superradiant regimes. (control of radiation parameters)« less

Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice

PubMed Central

Imitola, Jaime; Côté, Daniel; Rasmussen, Stine; Xie, X. Sunney; Liu, Yingru; Chitnis, Tanuja; Sidman, Richard L.; Lin, Charles. P.; Khoury, Samia J.

2011-01-01

Myelin loss and axonal degeneration predominate in many neurological disorders; however, methods to visualize them simultaneously in live tissue are unavailable. We describe a new imaging strategy combining video rate reflectance and fluorescence confocal imaging with coherent anti-Stokes Raman scattering (CARS) microscopy tuned to CH2 vibration of myelin lipids, applied in live tissue of animals with chronic experimental autoimmune encephalomyelitis (EAE). Our method allows monitoring over time of demyelination and neurodegeneration in brain slices with high spatial resolution and signal-to-noise ratio. Local areas of severe loss of lipid signal indicative of demyelination and loss of the reflectance signal from axons were seen in the corpus callosum and spinal cord of EAE animals. Even in myelinated areas of EAE mice, the intensity of myelin lipid signals is significantly reduced. Using heterozygous knock-in mice in which green fluorescent protein replaces the CX3CR1 coding sequence that labels central nervous system microglia, we find areas of activated microglia colocalized with areas of altered reflectance and CARS signals reflecting axonal injury and demyelination. Our data demonstrate the use of multimodal CARS microscopy for characterization of demyelinating and neurodegenerative pathology in a mouse model of multiple sclerosis, and further confirm the critical role of microglia in chronic inflammatory neurodegeneration. PMID:21361672

Doppler flow imaging of cytoplasmic streaming using spectral domain phase microscopy

NASA Astrophysics Data System (ADS)

Choma, Michael A.; Ellerbee, Audrey K.; Yazdanfar, Siavash; Izatt, Joseph A.

2006-03-01

Spectral domain phase microscopy (SDPM) is a function extension of spectral domain optical coherence tomography. SDPM achieves exquisite levels of phase stability by employing common-path interferometry. We discuss the theory and limitations of Doppler flow imaging using SDPM, demonstrate monitoring the thermal contraction of a glass sample with nanometer per second velocity sensitivity, and apply this technique to measurement of cytoplasmic streaming in an Amoeba proteus pseudopod. We observe reversal of cytoplasmic flow induced by extracellular CaCl2, and report results that suggest parabolic flow of cytoplasm in the A. proteus pseudopod.

Improved spatial resolution for spot sampling in thermal desorption atomic force microscopy – mass spectrometry via rapid heating functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somnath, Suhas; Jesse, Stephen; Van Berkel, Gary J.

The key to advancing materials is to understand and control their structure and chemistry. However, thorough chemical characterization is challenging since existing techniques characterize only a few properties of the specimen, thereby necessitating multiple measurement platforms to acquire the necessary information. The multimodal combination of atomic force microscopy (AFM) and mass spectrometry (MS) transcends existing analytical capabilities for nanometer scale spatially resolved correlation of the chemical and physical properties of a sample surface. One such hybrid system employs heated AFM cantilevers for thermal desorption (TD) sampling of molecules from a surface and subsequent gas phase ionization and detection of themore » liberated species by MS. Here in this paper, we report on the use of voltage pulse trains to tailor cantilever heating such that spot sampling size was reduced and mass spectral signal was improved compared to constant voltage, static heating of the cantilever. Desorption efficiency (DE), defined as the quotient of the mass spectral signal intensity and the volume of the desorption crater, was used to judge the effectiveness of a particular tailored heating function. To guide the development and optimization of the heating functions and aid in interpreting experimental results, a 1D finite element model was developed that predicted the cantilever response to different heating functions. Three tailored heating functions that used different combinations, magnitudes, and durations of rectangular voltage pulses, were used for surface spot sampling. The resultant sampling spot size and DE were compared to the same metrics obtained with the conventional method that uses a single voltage pulse. Using a model system composed of a thin film of ink containing pigment yellow 74 as a model system, desorption craters shrunk from 2 μm, using the conventional approach, to 310 nm using the optimum tailored heating function. This same pulsed heating function produced a 381× improvement in the DE and an 8× improvement in spatial resolution compared to the conventional heating approach showing that signal/amount of material sampled was improved significantly by this new cantilever heating strategy.« less

Improved spatial resolution for spot sampling in thermal desorption atomic force microscopy – mass spectrometry via rapid heating functions

DOE PAGES

Somnath, Suhas; Jesse, Stephen; Van Berkel, Gary J.; ...

2017-04-17

The key to advancing materials is to understand and control their structure and chemistry. However, thorough chemical characterization is challenging since existing techniques characterize only a few properties of the specimen, thereby necessitating multiple measurement platforms to acquire the necessary information. The multimodal combination of atomic force microscopy (AFM) and mass spectrometry (MS) transcends existing analytical capabilities for nanometer scale spatially resolved correlation of the chemical and physical properties of a sample surface. One such hybrid system employs heated AFM cantilevers for thermal desorption (TD) sampling of molecules from a surface and subsequent gas phase ionization and detection of themore » liberated species by MS. Here in this paper, we report on the use of voltage pulse trains to tailor cantilever heating such that spot sampling size was reduced and mass spectral signal was improved compared to constant voltage, static heating of the cantilever. Desorption efficiency (DE), defined as the quotient of the mass spectral signal intensity and the volume of the desorption crater, was used to judge the effectiveness of a particular tailored heating function. To guide the development and optimization of the heating functions and aid in interpreting experimental results, a 1D finite element model was developed that predicted the cantilever response to different heating functions. Three tailored heating functions that used different combinations, magnitudes, and durations of rectangular voltage pulses, were used for surface spot sampling. The resultant sampling spot size and DE were compared to the same metrics obtained with the conventional method that uses a single voltage pulse. Using a model system composed of a thin film of ink containing pigment yellow 74 as a model system, desorption craters shrunk from 2 μm, using the conventional approach, to 310 nm using the optimum tailored heating function. This same pulsed heating function produced a 381× improvement in the DE and an 8× improvement in spatial resolution compared to the conventional heating approach showing that signal/amount of material sampled was improved significantly by this new cantilever heating strategy.« less

Dynamics of a broad-band quantum cascade laser: from chaos to coherent dynamics and mode-locking.

PubMed

Columbo, L L; Barbieri, S; Sirtori, C; Brambilla, M

2018-02-05

The dynamics of a multimode quantum cascade laser, are studied in a model based on effective semiconductor Maxwell-Bloch equations, encompassing key features for the radiation-medium interaction such as an asymmetric frequency dependent gain and refractive index as well as the phase-amplitude coupling provided by the linewidth enhancement factor. By considering its role and that of the free spectral range, we find the conditions in which the traveling wave emitted by the laser at the threshold can be destabilized by adjacent modes, thus leading the laser emission towards chaotic or regular multimode dynamics. In the latter case our simulations show that the field oscillations are associated to self-confined structures which travel along the laser cavity, bridging mode-locking and solitary wave propagation. In addition, we show how a RF modulation of the bias current leads to active mode-locking yielding high-contrast, picosecond pulses. Our results compare well with recent experiments on broad-band THz-QCLs and may help in the understanding of the conditions for the generation of ultrashort pulses and comb operation in mid-IR and THz spectral regions.

PANRETINAL DEGENERATION ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE AND HETEROZYGOUS USH2A MUTATION.

PubMed

Katsman, Diana; Sanfilippo, Christian; Sarraf, David

2017-01-01

To report a case of bilateral panretinal degeneration in a patient with long-term hydroxychloroquine exposure and positive for a heterozygous mutation in the USH2A gene. Retrospective case report. Multimodal imaging including spectral-domain optical coherence tomography, fundus autofluorescence, and fluorescein angiography was performed and the results are presented. Electroretinography findings are also described. The authors report a 39-year-old patient with a history of hydroxychloroquine therapy for 20 years (cumulative dose of 2,774 g). Multimodal retinal imaging demonstrated bilateral paracentral outer retinal atrophy with spectral-domain optical coherence tomography and characteristic of hydroxychloroquine toxicity. Full-field electroretinography showed bilateral panretinal depression of the rod and cone responses. Mutational analysis revealed that the patient was a carrier for an autosomal recessive mutation in the USH2A gene. We report a case of panretinal degeneration but with features characteristic of hydroxychloroquine retinopathy in a patient who was found to be a heterozygous carrier of the USH2A gene, a cause of recessive retinitis pigmentosa without hearing loss. Carrier status for a retinal degenerative mutation may have rendered this patient more susceptible to the retinotoxic effects of long-term hydroxychloroquine therapy.

Compact spectrometer for precision studies of multimode behavior in an extended-cavity diode laser

NASA Astrophysics Data System (ADS)

Roach, Timothy; Golemi, Josian; Krueger, Thomas

2016-05-01

We have built a compact, inexpensive, high-precision spectrometer and used it to investigate the tuning behavior of a grating stabilized extended-cavity diode laser (ECDL). A common ECDL design uses a laser chip with an uncoated (partially reflecting) front facet, and the laser output exhibits a complicated pattern of mode hops as the frequency is tuned, in some cases even showing chaotic dynamics. Our grating spectrometer (based on a design by White & Scholten) monitors a span of 4000 GHz (8 nm at 780 nm) with a linewidth of 3 GHz, which with line-splitting gives a precision of 0.02 GHz in determining the frequency of a laser mode. We have studied multimode operation of the ECDL, tracking two or three simultaneous chip cavity modes (spacing ~ 30 GHz) during tuning via current or piezo control of the external cavity. Simultaneous output on adjacent external cavity modes (spacing ~ 5 GHz) is monitored by measuring an increase in the spectral linewidth. Computer-control of the spectrometer (for line-fitting and averaging) and of the ECDL (electronic tuning) allows rapid collection of spectral data sets, which we will use to test mathematical simulation models of the non-linear laser cavity interactions.

Multi-modal molecular diffuse optical tomography system for small animal imaging

PubMed Central

Guggenheim, James A.; Basevi, Hector R. A.; Frampton, Jon; Styles, Iain B.; Dehghani, Hamid

2013-01-01

A multi-modal optical imaging system for quantitative 3D bioluminescence and functional diffuse imaging is presented, which has no moving parts and uses mirrors to provide multi-view tomographic data for image reconstruction. It is demonstrated that through the use of trans-illuminated spectral near infrared measurements and spectrally constrained tomographic reconstruction, recovered concentrations of absorbing agents can be used as prior knowledge for bioluminescence imaging within the visible spectrum. Additionally, the first use of a recently developed multi-view optical surface capture technique is shown and its application to model-based image reconstruction and free-space light modelling is demonstrated. The benefits of model-based tomographic image recovery as compared to 2D planar imaging are highlighted in a number of scenarios where the internal luminescence source is not visible or is confounding in 2D images. The results presented show that the luminescence tomographic imaging method produces 3D reconstructions of individual light sources within a mouse-sized solid phantom that are accurately localised to within 1.5mm for a range of target locations and depths indicating sensitivity and accurate imaging throughout the phantom volume. Additionally the total reconstructed luminescence source intensity is consistent to within 15% which is a dramatic improvement upon standard bioluminescence imaging. Finally, results from a heterogeneous phantom with an absorbing anomaly are presented demonstrating the use and benefits of a multi-view, spectrally constrained coupled imaging system that provides accurate 3D luminescence images. PMID:24954977

3D imaging of intrinsic crystalline defects in zinc oxide by spectrally resolved two-photon fluorescence microscopy

NASA Astrophysics Data System (ADS)

Al-Tabich, A.; Inami, W.; Kawata, Y.; Jablonski, R.; Worasawat, S.; Mimura, H.

2017-05-01

We present a method for three-dimensional intrinsic defect imaging in zinc oxide (ZnO) by spectrally resolved two-photon fluorescence microscopy, based on the previously presented method of observing a photoluminescence distribution in wide-gap semiconductor crystals [Noor et al., Appl. Phys. Lett. 92(16), 161106 (2008)]. A tightly focused light beam radiated by a titanium-sapphire laser is used to obtain a two-photon excitation of selected area of the ZnO sample. Photoluminescence intensity of a specific spectral range is then selected by optical band pass filters and measured by a photomultiplier tube. Reconstruction of the specimen image is done by scanning the volume of interest by a piezoelectric positioning stage and measuring the spectrally resolved photoluminescence intensity at each point. The method has been proved to be effective at locating intrinsic defects of the ZnO crystalline structure in the volume of the crystal. The method was compared with other defect imaging and 3D imaging techniques like scanning tunneling microscopy and confocal microscopy. In both cases, our method shows superior penetration abilities and, as the only method, allows location of the defects of the chosen type in 3D. In this paper, we present the results of oxygen vacancies and zinc antisites imaging in ZnO nanorods.

Institute for Science and Engineering Simulation (ISES)

DTIC Science & Technology

2015-12-18

performance and other functionalities such as electrical , magnetic, optical, thermal, biological, chemical, and so forth. Structural integrity...transmission electron microscopy (HRSTEM) and three-dimensional atom probe (3DAP) tomography , the true atomic scale structure and change in chemical...atom probe tomography (3DAP) techniques, has permitted characterizing and quantifying the multimodal size distribution of different generations of γ

Spectral modification of the laser emission of a terahertz quantum cascade laser induced by broad-band double pulse injection seeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markmann, Sergej, E-mail: sergej.markmann@ruhr-uni-bochum.de; Nong, Hanond, E-mail: nong.hanond@ruhr-uni-bochum.de; Hekmat, Negar

2015-09-14

We demonstrate by injection seeding that the spectral emission of a terahertz (THz) quantum cascade laser (QCL) can be modified with broad-band THz pulses whose bandwidths are greater than the QCL bandwidth. Two broad-band THz pulses delayed in time imprint a modulation on the single THz pulse spectrum. The resulting spectrum is used to injection seed the THz QCL. By varying the time delay between the THz pulses, the amplitude distribution of the QCL longitudinal modes is modified. By applying this approach, the QCL emission is reversibly switched from multi-mode to single mode emission.

A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors.

PubMed

Kempen, Paul J; Kircher, Moritz F; de la Zerda, Adam; Zavaleta, Cristina L; Jokerst, Jesse V; Mellinghoff, Ingo K; Gambhir, Sanjiv S; Sinclair, Robert

2015-01-01

The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spectroscopic photon localization microscopy: breaking the resolution limit of single molecule localization microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dong, Biqin; Almassalha, Luay Matthew; Urban, Ben E.; Nguyen, The-Quyen; Khuon, Satya; Chew, Teng-Leong; Backman, Vadim; Sun, Cheng; Zhang, Hao F.

2017-02-01

Distinguishing minute differences in spectroscopic signatures is crucial for revealing the fluorescence heterogeneity among fluorophores to achieve a high molecular specificity. Here we report spectroscopic photon localization microscopy (SPLM), a newly developed far-field spectroscopic imaging technique, to achieve nanoscopic resolution based on the principle of single-molecule localization microscopy while simultaneously uncovering the inherent molecular spectroscopic information associated with each stochastic event (Dong et al., Nature Communications 2016, in press). In SPLM, by using a slit-less monochromator, both the zero-order and the first-order diffractions from a grating were recorded simultaneously by an electron multiplying charge-coupled device to reveal the spatial distribution and the associated emission spectra of individual stochastic radiation events, respectively. As a result, the origins of photon emissions from different molecules can be identified according to their spectral differences with sub-nm spectral resolution, even when the molecules are within close proximity. With the newly developed algorithms including background subtraction and spectral overlap unmixing, we established and tested a method which can significantly extend the fundamental spatial resolution limit of single molecule localization microscopy by molecular discrimination through spectral regression. Taking advantage of this unique capability, we demonstrated improvement in spatial resolution of PALM/STORM up to ten fold with selected fluorophores. This technique can be readily adopted by other research groups to greatly enhance the optical resolution of single molecule localization microscopy without the need to modify their existing staining methods and protocols. This new resolving capability can potentially provide new insights into biological phenomena and enable significant research progress to be made in the life sciences.

A multimodal instrument for real-time in situ study of ultrasound and cavitation mediated drug delivery.

PubMed

Bian, Shuning; Seth, Anjali; Daly, Dan; Carlisle, Robert; Stride, Eleanor

2017-03-01

The development of a multimodal instrument capable of real-time in situ measurements of cavitation activity and effect in tissue mimicking phantoms during ultrasound and cavitation mediated drug delivery experiments is described here. The instrument features an acoustic arm that can expose phantoms to high-intensity focused-ultrasound while measuring cavitation activity and an optical arm that monitors cavitation effect using confocal microscopy. This combination of modalities allows real-time in situ characterisation of drug delivery in tissue and tissue mimicking phantoms during ultrasound and cavitation mediated drug delivery experiments. A representative result, obtained with a tissue mimicking phantom and acoustically activated droplets, is presented here as a demonstration of the instrument's capabilities and potential applications.

Multimodality hard-x-ray imaging of a chromosome with nanoscale spatial resolution

DOE PAGES

Yan, Hanfei; Nazaretski, Evgeny; Lauer, Kenneth R.; ...

2016-02-05

Here, we developed a scanning hard x-ray microscope using a new class of x-ray nano-focusing optic called a multilayer Laue lens and imaged a chromosome with nanoscale spatial resolution. The combination of the hard x-ray's superior penetration power, high sensitivity to elemental composition, high spatial-resolution and quantitative analysis creates a unique tool with capabilities that other microscopy techniques cannot provide. Using this microscope, we simultaneously obtained absorption-, phase-, and fluorescence-contrast images of Pt-stained human chromosome samples. The high spatial-resolution of the microscope and its multi-modality imaging capabilities enabled us to observe the internal ultra-structures of a thick chromosome without sectioningmore » it.« less

Multimodality hard-x-ray imaging of a chromosome with nanoscale spatial resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Hanfei; Nazaretski, Evgeny; Lauer, Kenneth R.

Here, we developed a scanning hard x-ray microscope using a new class of x-ray nano-focusing optic called a multilayer Laue lens and imaged a chromosome with nanoscale spatial resolution. The combination of the hard x-ray's superior penetration power, high sensitivity to elemental composition, high spatial-resolution and quantitative analysis creates a unique tool with capabilities that other microscopy techniques cannot provide. Using this microscope, we simultaneously obtained absorption-, phase-, and fluorescence-contrast images of Pt-stained human chromosome samples. The high spatial-resolution of the microscope and its multi-modality imaging capabilities enabled us to observe the internal ultra-structures of a thick chromosome without sectioningmore » it.« less

Simultaneous measurement of temperature and magnetic field based on a long period grating concatenated with multimode fiber

NASA Astrophysics Data System (ADS)

Miao, Yinping; Zhang, Hao; Lin, Jichao; Song, Binbin; Zhang, Kailiang; Lin, Wei; Liu, Bo; Yao, Jianquan

2015-03-01

A dual-parameter measurement scheme based on a long-period fiber grating (LPFG) concatenated with a multimode fiber (MMF) has been proposed and experimentally demonstrated for simultaneous measurement of magnetic field and temperature. Splicing the LPFG with the etched MMF enables the coupling between the core modes and different cladding modes of the LPFG as well as the interferences between higher-order modes in the MMF. Due to different transmission mechanisms of the LPFG and mode interference, the proposed sensor shows transmission dip wavelength sensitivities of 0.02878 nm/Oe and -0.04048 nm/°C for multi-mode interference (MMI) and -0.0024 nm/Oe and 0.03929 nm/°C for the LPFG, respectively. By monitoring the opposite behaviors of resonance wavelength shift corresponding to the LPFG and MMI, the magnetic field and environmental temperature can be simultaneously measured. The spectral characteristics of the proposed sensor that could be tuned through control of both environmental temperature and applied magnetic field, which would provide a promising candidate for dual-channel filtering applications as well as multi-parameter measurement applications.

TeraSCREEN: multi-frequency multi-mode Terahertz screening for border checks

NASA Astrophysics Data System (ADS)

Alexander, Naomi E.; Alderman, Byron; Allona, Fernando; Frijlink, Peter; Gonzalo, Ramón; Hägelen, Manfred; Ibáñez, Asier; Krozer, Viktor; Langford, Marian L.; Limiti, Ernesto; Platt, Duncan; Schikora, Marek; Wang, Hui; Weber, Marc Andree

2014-06-01

The challenge for any security screening system is to identify potentially harmful objects such as weapons and explosives concealed under clothing. Classical border and security checkpoints are no longer capable of fulfilling the demands of today's ever growing security requirements, especially with respect to the high throughput generally required which entails a high detection rate of threat material and a low false alarm rate. TeraSCREEN proposes to develop an innovative concept of multi-frequency multi-mode Terahertz and millimeter-wave detection with new automatic detection and classification functionalities. The system developed will demonstrate, at a live control point, the safe automatic detection and classification of objects concealed under clothing, whilst respecting privacy and increasing current throughput rates. This innovative screening system will combine multi-frequency, multi-mode images taken by passive and active subsystems which will scan the subjects and obtain complementary spatial and spectral information, thus allowing for automatic threat recognition. The TeraSCREEN project, which will run from 2013 to 2016, has received funding from the European Union's Seventh Framework Programme under the Security Call. This paper will describe the project objectives and approach.

Spatiotemporal mode-locking in multimode fiber lasers

NASA Astrophysics Data System (ADS)

Wright, Logan G.; Christodoulides, Demetrios N.; Wise, Frank W.

2017-10-01

A laser is based on the electromagnetic modes of its resonator, which provides the feedback required for oscillation. Enormous progress has been made toward controlling the interactions of longitudinal modes in lasers with a single transverse mode. For example, the field of ultrafast science has been built on lasers that lock many longitudinal modes together to form ultrashort light pulses. However, coherent superposition of longitudinal and transverse modes in a laser has received little attention. We show that modal and chromatic dispersions in fiber lasers can be counteracted by strong spatial and spectral filtering. This allows locking of multiple transverse and longitudinal modes to create ultrashort pulses with a variety of spatiotemporal profiles. Multimode fiber lasers thus open new directions in studies of nonlinear wave propagation and capabilities for applications.

Multi-Modal Ultra-Widefield Imaging Features in Waardenburg Syndrome

PubMed Central

Choudhry, Netan; Rao, Rajesh C.

2015-01-01

Background Waardenburg syndrome is characterized by a group of features including; telecanthus, a broad nasal root, synophrys of the eyebrows, piedbaldism, heterochromia irides, and deaf-mutism. Hypopigmentation of the choroid is a unique feature of this condition examined with multi-modal Ultra-Widefield Imaging in this report. Material/Methods Report of a single case. Results Bilateral symmetric choroidal hypopigmentation was observed with hypoautofluorescence in the region of hypopigmentation. Fluorescein angiography revealed a normal vasculature, however a thickened choroid was seen on Enhanced-Depth Imaging Spectral-Domain OCT (EDI SD-OCT). Conclusion(s) Choroidal hypopigmentation is a unique feature of Waardenburg syndrome, which can be visualized with ultra-widefield fundus autofluorescence. The choroid may also be thickened in this condition and its thickness measured with EDI SD-OCT. PMID:26114849

High energy supercontinuum sources using tapered photonic crystal fibers for multispectral photoacoustic microscopy.

PubMed

Bondu, Magalie; Brooks, Christopher; Jakobsen, Christian; Oakes, Keith; Moselund, Peter Morten; Leick, Lasse; Bang, Ole; Podoleanu, Adrian

2016-06-01

We demonstrate a record bandwidth high energy supercontinuum source suitable for multispectral photoacoustic microscopy. The source has more than 150  nJ/10  nm bandwidth over a spectral range of 500 to 1600 nm. This performance is achieved using a carefully designed fiber taper with large-core input for improved power handling and small-core output that provides the desired spectral range of the supercontinuum source.

Multimode simulations of a wide field of view double-Fourier far-infrared spatio-spectral interferometer

NASA Astrophysics Data System (ADS)

Bracken, Colm P.; Lightfoot, John; O'Sullivan, Creidhe; Murphy, J. Anthony; Donohoe, Anthony; Savini, Giorgio; Juanola-Parramon, Roser; The Fisica Consortium, On Behalf Of

2018-01-01

In the absence of 50-m class space-based observatories, subarcsecond astronomy spanning the full far-infrared wavelength range will require space-based long-baseline interferometry. The long baselines of up to tens of meters are necessary to achieve subarcsecond resolution demanded by science goals. Also, practical observing times command a field of view toward an arcminute (1‧) or so, not achievable with a single on-axis coherent detector. This paper is concerned with an application of an end-to-end instrument simulator PyFIInS, developed as part of the FISICA project under funding from the European Commission's seventh Framework Programme for Research and Technological Development (FP7). Predicted results of wide field of view spatio-spectral interferometry through simulations of a long-baseline, double-Fourier, far-infrared interferometer concept are presented and analyzed. It is shown how such an interferometer, illuminated by a multimode detector can recover a large field of view at subarcsecond angular resolution, resulting in similar image quality as that achieved by illuminating the system with an array of coherent detectors. Through careful analysis, the importance of accounting for the correct number of higher-order optical modes is demonstrated, as well as accounting for both orthogonal polarizations. Given that it is very difficult to manufacture waveguide and feed structures at sub-mm wavelengths, the larger multimode design is recommended over the array of smaller single mode detectors. A brief note is provided in the conclusion of this paper addressing a more elegant solution to modeling far-infrared interferometers, which holds promise for improving the computational efficiency of the simulations presented here.

Spectrally resolved modal characteristics of leaky-wave-coupled quantum cascade phase-locked laser arrays

NASA Astrophysics Data System (ADS)

Sigler, Chris; Gibson, Ricky; Boyle, Colin; Kirch, Jeremy D.; Lindberg, Donald; Earles, Thomas; Botez, Dan; Mawst, Luke J.; Bedford, Robert

2018-01-01

The modal characteristics of nonresonant five-element phase-locked arrays of 4.7-μm emitting quantum cascade lasers (QCLs) have been studied using spectrally resolved near- and far-field measurements and correlated with results of device simulation. Devices are fabricated by a two-step metal-organic chemical vapor deposition process and operate predominantly in an in-phase array mode near threshold, although become multimode at higher drive levels. The wide spectral bandwidth of the QCL's core region is found to be a factor in promoting multispatial-mode operation at high drive levels above threshold. An optimized resonant-array design is identified to allow sole in-phase array-mode operation to high drive levels above threshold, and indicates that for phase-locked laser arrays full spatial coherence to high output powers does not require full temporal coherence.

Second-harmonic patterned polarization-analyzed reflection confocal microscope

NASA Astrophysics Data System (ADS)

Okoro, Chukwuemeka; Toussaint, Kimani C.

2017-08-01

We introduce the second-harmonic patterned polarization-analyzed reflection confocal (SPPARC) microscope-a multimodal imaging platform that integrates Mueller matrix polarimetry with reflection confocal and second-harmonic generation (SHG) microscopy. SPPARC microscopy provides label-free three-dimensional (3-D), SHG-patterned confocal images that lend themselves to spatially dependent, linear polarimetric analysis for extraction of rich polarization information based on the Mueller calculus. To demonstrate its capabilities, we use SPPARC microscopy to analyze both porcine tendon and ligament samples and find differences in both circular degree-of-polarization and depolarization parameters. Moreover, using the collagen-generated SHG signal as an endogenous counterstain, we show that the technique can be used to provide 3-D polarimetric information of the surrounding extrafibrillar matrix plus cells or EFMC region. The unique characteristics of SPPARC microscopy holds strong potential for it to more accurately and quantitatively describe microstructural changes in collagen-rich samples in three spatial dimensions.

Correlative Fluorescence and Electron Microscopy

PubMed Central

Schirra, Randall T.; Zhang, Peijun

2014-01-01

Correlative fluorescence and electron microscopy (CFEM) is a multimodal technique that combines dynamic and localization information from fluorescence methods with ultrastructural data from electron microscopy, to give new information about how cellular components change relative to the spatiotemporal dynamics within their environment. In this review, we will discuss some of the basic techniques and tools of the trade for utilizing this attractive research method, which is becoming a very powerful tool for biology labs. The information obtained from correlative methods has proven to be invaluable in creating consensus between the two types of microscopy, extending the capability of each, and cutting the time and expense associate with using each method separately for comparative analysis. The realization of the advantages of these methods in cell biology have led to rapid improvement in the protocols and have ushered in a new generation of instruments to reach the next level of correlation – integration. PMID:25271959

A study approach on ferroelectric domains in BaTiO{sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocha, L.S.R.; Cavalcanti, C.S.

Atomic Force Acoustic Microscopy (AFAM) and Piezoresponse Force Microscopy (PFM) were used to study local elastic and electromechanical response in BaTiO{sub 3} ceramics. A commercial multi-mode Scanning Probe Microscopy (SPM) and AFAM mode to image contact stiffness were employed to accomplish the aforementioned purposes. Stiffness parameters along with Young's moduli and piezo coefficients were quantitatively determined. PFM studies were based on electrostatic and electromechanical response from localized tip-surface contact. Comparison was made regarding the Young's moduli obtained by AFAM and PFM. In addition, phase and amplitude images were analyzed based on poling behavior, obtained via the application of − 10more » V to + 10 V local voltage. - Highlights: •Nanoscale behavior of piezo domains in BaTiO{sub 3} ferroelectric materials •Use of Atomic Force Acoustic Microscopy (AFAM) and Piezo Force Microscopy (PFM) •Local elastic and electromechanical response in BaTiO{sub 3} ceramics •The young's moduli obtained from AFAM and PFM.« less

Identifying Nanoscale Structure-Function Relationships Using Multimodal Atomic Force Microscopy, Dimensionality Reduction, and Regression Techniques.

PubMed

Kong, Jessica; Giridharagopal, Rajiv; Harrison, Jeffrey S; Ginger, David S

2018-05-31

Correlating nanoscale chemical specificity with operational physics is a long-standing goal of functional scanning probe microscopy (SPM). We employ a data analytic approach combining multiple microscopy modes, using compositional information in infrared vibrational excitation maps acquired via photoinduced force microscopy (PiFM) with electrical information from conductive atomic force microscopy. We study a model polymer blend comprising insulating poly(methyl methacrylate) (PMMA) and semiconducting poly(3-hexylthiophene) (P3HT). We show that PiFM spectra are different from FTIR spectra, but can still be used to identify local composition. We use principal component analysis to extract statistically significant principal components and principal component regression to predict local current and identify local polymer composition. In doing so, we observe evidence of semiconducting P3HT within PMMA aggregates. These methods are generalizable to correlated SPM data and provide a meaningful technique for extracting complex compositional information that are impossible to measure from any one technique.

Integrated Raman and angular scattering microscopy reveals chemical and morphological differences between activated and nonactivated CD8+ T lymphocytes

PubMed Central

Smith, Zachary J.; Wang, Jyh-Chiang E.; Quataert, Sally A.; Berger, Andrew J.

2010-01-01

Integrated Raman and angular-scattering microscopy (IRAM) is a multimodal platform capable of noninvasively probing both the chemistry and morphology of a single cell without prior labeling. Using this system, we are able to detect activation-dependent changes in the Raman and elastic-scattering signals from CD8+ T cells stimulated with either Staphylococcal enterotoxin B (SEB) or phorbol myristate acetate (PMA). In both cases, results obtained from the IRAM instrument correlate well with results obtained from traditional fluorescence-based flow cytometry for paired samples. SEB-mediated activation was distinguished from resting state in CD8+ T cells by an increase in the number and mean size of small (∼500-nm) elastic scatterers as well as a decrease in Raman bands, indicating changes in nuclear content. PMA-mediated activation induced a different profile in CD8+ T cells from SEB, showing a similar increase in small elastic scatterers but a different Raman change, with elevation of cellular protein and lipid bands. These results suggest the potential of this multimodal, label-free optical technique for studying processes in single cells. PMID:20615023

Ultrathin forward-imaging short multimode fiber probe for full-field optical coherence microscopy

NASA Astrophysics Data System (ADS)

Sato, Manabu; Saito, Daisuke; Shouji, Kou; Kurotani, Reiko; Abe, Hiroyuki; Nishidate, Izumi

2016-12-01

To extend the applications of optical coherence tomography (OCT) to the fields of physiology and clinical medicine, less invasive, robust, and reliable optical probes are required. Thus, we demonstrate an ultrathin forward-imaging short multimode fiber (SMMF) optical coherence microscopy (OCM) probe with a 50 μm core diameter, 125 μm total diameter, and 5.12 mm length. Imaging conditions and magnification were analyzed, and they correspond closely to the measured results. The dispersion of the SMMF was investigated, and the modal dispersion coefficient was found to be 2.3% of the material dispersion coefficient. The axial resolution was minimized at 2.15 μm using a 0.885-mm-thick dispersion compensator. The lateral resolution was evaluated to be 4.38 μm using a test pattern. The contrast of the OCM images was 5.7 times higher than that of the signal images owing to the coherence gate. The depth of focus and diameter of the field of view were measured to be 60 μm and 40-50 μm, respectively. OCM images of the dried fins of small fish (Medaka) were measured and internal structures could be recognized.

Divergent receiver responses to components of multimodal signals in two foot-flagging frog species.

PubMed

Preininger, Doris; Boeckle, Markus; Sztatecsny, Marc; Hödl, Walter

2013-01-01

Multimodal communication of acoustic and visual signals serves a vital role in the mating system of anuran amphibians. To understand signal evolution and function in multimodal signal design it is critical to test receiver responses to unimodal signal components versus multimodal composite signals. We investigated two anuran species displaying a conspicuous foot-flagging behavior in addition to or in combination with advertisement calls while announcing their signaling sites to conspecifics. To investigate the conspicuousness of the foot-flagging signals, we measured and compared spectral reflectance of foot webbings of Micrixalus saxicola and Staurois parvus using a spectrophotometer. We performed behavioral field experiments using a model frog including an extendable leg combined with acoustic playbacks to test receiver responses to acoustic, visual and combined audio-visual stimuli. Our results indicated that the foot webbings of S. parvus achieved a 13 times higher contrast against their visual background than feet of M. saxicola. The main response to all experimental stimuli in S. parvus was foot flagging, whereas M. saxicola responded primarily with calls but never foot flagged. Together these across-species differences suggest that in S. parvus foot-flagging behavior is applied as a salient and frequently used communicative signal during agonistic behavior, whereas we propose it constitutes an evolutionary nascent state in ritualization of the current fighting behavior in M. saxicola.

Application of a reflective microscope objective for multiphoton microscopy.

PubMed

Kabir, Mohammad M; Choubal, Aakash M; Toussaint, Kimani C

2018-04-20

Reflective objectives (ROs) mitigate chromatic aberration across a broad wavelength range. Yet, a systematic performance characterisation of ROs has not been done. In this paper, we compare the performance of a 0.5 numerical-aperture (NA) reflective objective (RO) with a 0.55 NA standard glass objective (SO), using two-photon fluorescence (TPF) and second-harmonic generation (SHG). For experiments spanning ∼1 octave in the visible and NIR wavelengths, the SO leads to defocusing errors of 25-40% for TPF images of subdiffraction fluorescent beads and 10-12% for SHG images of collagen fibres. The corresponding error for the RO is ∼4% for both imaging modalities. This work emphasises the potential utility of ROs for multimodal multiphoton microscopy applications. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

Double-clad photonic crystal fiber coupler for compact nonlinear optical microscopy imaging.

PubMed

Fu, Ling; Gu, Min

2006-05-15

A 1 x 2 double-clad photonic crystal fiber coupler is fabricated by the fused tapered method, showing a low excess loss of 1.1 dB and a splitting ratio of 97/3 over the entire visible and near-infrared wavelength range. In addition to the property of splitting the laser power, the double-clad feature of the coupler facilitates the separation of a near-infrared single-mode beam from a visible multimode beam, which is ideal for nonlinear optical microscopy imaging. In conjunction with a gradient-index lens, this coupler is used to construct a miniaturized microscope based on two-photon fluorescence and second-harmonic generation. Three-dimensional nonlinear optical images demonstrate potential applications of the coupler to compact all-fiber and nonlinear optical microscopy and endoscopy.

Multimodal non-linear optical imaging for the investigation of drug nano-/microcrystal-cell interactions.

PubMed

Darville, Nicolas; Saarinen, Jukka; Isomäki, Antti; Khriachtchev, Leonid; Cleeren, Dirk; Sterkens, Patrick; van Heerden, Marjolein; Annaert, Pieter; Peltonen, Leena; Santos, Hélder A; Strachan, Clare J; Van den Mooter, Guy

2015-10-01

Drug nano-/microcrystals are being used for sustained parenteral drug release, but safety and efficacy concerns persist as the knowledge of the in vivo fate of long-living particulates is limited. There is a need for techniques enabling the visualization of drug nano-/microcrystals in biological matrices. The aim of this work was to explore the potential of coherent anti-Stokes Raman scattering (CARS) microscopy, supported by other non-linear optical methods, as an emerging tool for the investigation of cellular and tissue interactions of unlabeled and non-fluorescent nano-/microcrystals. Raman and CARS spectra of the prodrug paliperidone palmitate (PP), paliperidone (PAL) and several suspension stabilizers were recorded. PP nano-/microcrystals were incubated with RAW 264.7 macrophages in vitro and their cellular disposition was investigated using a fully-integrated multimodal non-linear optical imaging platform. Suitable anti-Stokes shifts (CH stretching) were identified for selective CARS imaging. CARS microscopy was successfully applied for the selective three-dimensional, non-perturbative and real-time imaging of unlabeled PP nano-/microcrystals having dimensions larger than the optical lateral resolution of approximately 400nm, in relation to the cellular framework in cell cultures and ex vivo in histological sections. In conclusion, CARS microscopy enables the non-invasive and label-free imaging of (sub)micron-sized (pro-)drug crystals in complex biological matrices and could provide vital information on poorly understood nano-/microcrystal-cell interactions in future. Copyright © 2015 Elsevier B.V. All rights reserved.

Colocalization of cellular nanostructure using confocal fluorescence and partial wave spectroscopy.

PubMed

Chandler, John E; Stypula-Cyrus, Yolanda; Almassalha, Luay; Bauer, Greta; Bowen, Leah; Subramanian, Hariharan; Szleifer, Igal; Backman, Vadim

2017-03-01

A new multimodal confocal microscope has been developed, which includes a parallel Partial Wave Spectroscopic (PWS) microscopy path. This combination of modalities allows molecular-specific sensing of nanoscale intracellular structure using fluorescent labels. Combining molecular specificity and sensitivity to nanoscale structure allows localization of nanostructural intracellular changes, which is critical for understanding the mechanisms of diseases such as cancer. To demonstrate the capabilities of this multimodal instrument, we imaged HeLa cells treated with valinomycin, a potassium ionophore that uncouples oxidative phosphorylation. Colocalization of fluorescence images of the nuclei (Hoechst 33342) and mitochondria (anti-mitochondria conjugated to Alexa Fluor 488) with PWS measurements allowed us to detect a significant decrease in nuclear nanoscale heterogeneity (Σ), while no significant change in Σ was observed at mitochondrial sites. In addition, application of the new multimodal imaging approach was demonstrated on human buccal samples prepared using a cancer screening protocol. These images demonstrate that nanoscale intracellular structure can be studied in healthy and diseased cells at molecular-specific sites. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fiber Optic Sensor System Using Birefringent Filters For Spectral Encoding

NASA Astrophysics Data System (ADS)

Dorsch, Friedhelm; Ulrich, Reinhard

1989-02-01

A system of multimode fiber optic sensors is described for the remote measurement of position, angle, force, pressure and other measurands that can be converted into a rotation of polarization. A birefringent filter encodes the polarization angle into the power ratio of two interleaved comb spectra or, in a modified implementation, into the absolute spectral position of a comb spectrum. By using identical filters in all transducers and in the evaluation unit, transducers for the same or different measurands become interchange-able. All sensors are of the incremental type, with accuracies reaching 0.5 % of one period of the measurand, independent of variations in the attenuation of the fiber link of up to 20dB.

Multi-species sensing using multi-mode absorption spectroscopy with mid-infrared interband cascade lasers

NASA Astrophysics Data System (ADS)

O'Hagan, S.; Northern, J. H.; Gras, B.; Ewart, P.; Kim, C. S.; Kim, M.; Merritt, C. D.; Bewley, W. W.; Canedy, C. L.; Vurgaftman, I.; Meyer, J. R.

2016-06-01

The application of an interband cascade laser, ICL, to multi-mode absorption spectroscopy, MUMAS, in the mid-infrared region is reported. Measurements of individual mode linewidths of the ICL, derived from the pressure dependence of lineshapes in MUMAS signatures of single, isolated, lines in the spectrum of HCl, were found to be in the range 10-80 MHz. Multi-line spectra of methane were recorded using spectrally limited bandwidths, of approximate width 27 cm-1, defined by an interference filter, and consist of approximately 80 modes at spectral locations spanning the 100 cm-1 bandwidth of the ICL output. Calibration of the methane pressures derived from MUMAS data using a capacitance manometer provided measurements with an uncertainty of 1.1 %. Multi-species sensing is demonstrated by the simultaneous detection of methane, acetylene and formaldehyde in a gas mixture. Individual partial pressures of the three gases are derived from best fits of model MUMAS signatures to the data with an experimental error of 10 %. Using an ICL, with an inter-mode interval of ~10 GHz, MUMAS spectra were recorded at pressures in the range 1-10 mbar, and, based on the data, a potential minimum detection limit of the order of 100 ppmv is estimated for MUMAS at atmospheric pressure using an inter-mode interval of 80 GHz.

Artifact mitigation of ptychography integrated with on-the-fly scanning probe microscopy

DOE PAGES

Huang, Xiaojing; Yan, Hanfei; Ge, Mingyuan; ...

2017-07-11

In this paper, we report our experiences with conducting ptychography simultaneously with the X-ray fluorescence measurement using the on-the-fly mode for efficient multi-modality imaging. We demonstrate that the periodic artifact inherent to the raster scan pattern can be mitigated using a sufficiently fine scan step size to provide an overlap ratio of >70%. This allows us to obtain transmitted phase contrast images with enhanced spatial resolution from ptychography while maintaining the fluorescence imaging with continuous-motion scans on pixelated grids. Lastly, this capability will greatly improve the competence and throughput of scanning probe X-ray microscopy.

Laser pulse power transmission limits of silica fibers with antireflective coating

NASA Astrophysics Data System (ADS)

Meister, St.; Wosniok, A.; Seewald, G.; Scharfenorth, Ch.; Eichler, H. J.

2005-04-01

Multimode optical fibers are used for the transmission of high power laser pulses and as phase conjugated mirrors by stimulated Brillouin scattering. Both applications are enhanced by antireflection coatings on the fiber end-faces. Fiber transmissions reach more than 99.5% for pulse energies below the threshold of stimulated Brillouin scattering. Laser-induced damage thresholds of the fibers coated with Ta2O5 / SiO2 were measured at 1064 nm and 24 ns pulse duration. A damage threshold of up to 101 J/cm2 could be achieved. The damage morphology was investigated using atomic force microscopy and scanning electron microscopy.

Observation of the immune response of cells and tissue through multimodal label-free microscopy

NASA Astrophysics Data System (ADS)

Pavillon, Nicolas; Smith, Nicholas I.

2017-02-01

We present applications of a label-free approach to assess the immune response based on the combination of interferometric microscopy and Raman spectroscopy, which makes it possible to simultaneously acquire morphological and molecular information of live cells. We employ this approach to derive statistical models for predicting the activation state of macrophage cells based both on morphological parameters extracted from the high-throughput full-field quantitative phase imaging, and on the molecular content information acquired through Raman spectroscopy. We also employ a system for 3D imaging based on coherence gating, enabling specific targeting of the Raman channel to structures of interest within tissue.

Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report.

PubMed

Hua, Rui; Chen, Kang; Hu, Yuedong; Wang, Xinling; Chen, Lei

2015-11-01

Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included visualization of the lesion's regression with spectral domain optical coherence tomography (SD-OCT). However, at 3 months after the injection, the CNV reoccurred. To the best of our knowledge, this is the first time that a case of CNV secondary to retinitis pigmentosa, in which the diagnosis was confirmed via multimodality imaging and the therapeutic efficacy was evaluated by SD-OCT, has been reported in China.

Combining near-field scanning optical microscopy with spectral interferometry for local characterization of the optical electric field in photonic structures.

PubMed

Trägårdh, Johanna; Gersen, Henkjan

2013-07-15

We show how a combination of near-field scanning optical microscopy with crossed beam spectral interferometry allows a local measurement of the spectral phase and amplitude of light propagating in photonic structures. The method only requires measurement at the single point of interest and at a reference point, to correct for the relative phase of the interferometer branches, to retrieve the dispersion properties of the sample. Furthermore, since the measurement is performed in the spectral domain, the spectral phase and amplitude could be retrieved from a single camera frame, here in 70 ms for a signal power of less than 100 pW limited by the dynamic range of the 8-bit camera. The method is substantially faster than most previous time-resolved NSOM methods that are based on time-domain interferometry, which also reduced problems with drift. We demonstrate how the method can be used to measure the refractive index and group velocity in a waveguide structure.

Multiplex CARS imaging with spectral notch shaped laser pulses delivered by optical fibers.

PubMed

Oh, Seung Ryeol; Park, Joo Hyun; Kim, Kyung-Soo; Lee, Jae Yong; Kim, Soohyun

2017-12-11

We present an experimental demonstration of single-pulse coherent anti-Stokes Raman spectroscopy (CARS) using a spectrally shaped broadband laser that is delivered by an optical fiber to a sample at its distal end. The optical fiber consists of a fiber Bragg grating component to serve as a narrowband notch filter and a combined large-mode-area fiber to transmit such shaped ultrashort laser pulses without spectral distortion in a long distance. Experimentally, our implementation showed a capability to measure CARS spectra of various samples with molecular vibrations in the fingerprint region. Furthermore, CARS imaging of poly(methyl methacrylate) bead samples was carried out successfully under epi-CARS geometry in which backward-scattered CARS signals were collected into a multimode optical fiber. A compatibility of single-pulse CARS scheme with fiber optics, verified in this study, implies a potential for future realization of compact all-fiber CARS spectroscopic imaging systems.

In vivo features of melanocytic lesions: multimode hyperspectral dermoscopy, reflectance confocal microscopy, and histopathologic correlates (Conference Presentation)

NASA Astrophysics Data System (ADS)

Vasefi, Fartash; MacKinnon, Nicholas B.; Jain, Manu; Cordova, Miguel A.; Kose, Kivanc; Rajadhyaksha, Milind; Halpern, Allan C.; Farkas, Daniel L.

2017-02-01

Motivation and background: Melanoma, the fastest growing cancer worldwide, kills more than one person every hour in the United States. Determining the depth and distribution of dermal melanin and hemoglobin adds physio-morphologic information to the current diagnostic standard, cellular morphology, to further develop noninvasive methods to discriminate between melanoma and benign skin conditions. Purpose: To compare the performance of a multimode dermoscopy system (SkinSpect), which is designed to quantify and map in three dimensions, in vivo melanin and hemoglobin in skin, and to validate this with histopathology and three dimensional reflectance confocal microscopy (RCM) imaging. Methods: Sequentially capture SkinSpect and RCM images of suspect lesions and nearby normal skin and compare this with histopathology reports, RCM imaging allows noninvasive observation of nuclear, cellular and structural detail in 1-5 μm-thin optical sections in skin, and detection of pigmented skin lesions with sensitivity of 90-95% and specificity of 70-80%. The multimode imaging dermoscope combines polarization (cross and parallel), autofluorescence and hyperspectral imaging to noninvasively map the distribution of melanin, collagen and hemoglobin oxygenation in pigmented skin lesions. Results: We compared in vivo features of ten melanocytic lesions extracted by SkinSpect and RCM imaging, and correlated them to histopathologic results. We present results of two melanoma cases (in situ and invasive), and compare with in vivo features from eight benign lesions. Melanin distribution at different depths and hemodynamics, including abnormal vascularity, detected by both SkinSpect and RCM will be discussed. Conclusion: Diagnostic features such as dermal melanin and hemoglobin concentration provided in SkinSpect skin analysis for melanoma and normal pigmented lesions can be compared and validated using results from RCM and histopathology.

Metabolic Mapping of Breast Cancer with Multiphoton Spectral and Lifetime Imaging

DTIC Science & Technology

2007-03-01

spectral and lifetime characterization of NADH may be used to reveal metabolic changes in vivo and has potential to be used as an early diagnostic...combined spectral lifetime imaging modality will help for 5 characterization of breast cancer cells from cell culture based models to a relevant in... spectral and lifetime system and integrated into a multiphoton fluorescence excitation microscopy system 7 • Calibrated and characterized this

Spectral interferometric microscopy reveals absorption by individual optical nanoantennas from extinction phase

PubMed Central

Gennaro, Sylvain D.; Sonnefraud, Yannick; Verellen, Niels; Van Dorpe, Pol; Moshchalkov, Victor V.; Maier, Stefan A.; Oulton, Rupert F.

2014-01-01

Optical antennas transform light from freely propagating waves into highly localized excitations that interact strongly with matter. Unlike their radio frequency counterparts, optical antennas are nanoscopic and high frequency, making amplitude and phase measurements challenging and leaving some information hidden. Here we report a novel spectral interferometric microscopy technique to expose the amplitude and phase response of individual optical antennas across an octave of the visible to near-infrared spectrum. Although it is a far-field technique, we show that knowledge of the extinction phase allows quantitative estimation of nanoantenna absorption, which is a near-field quantity. To verify our method we characterize gold ring-disk dimers exhibiting Fano interference. Our results reveal that Fano interference only cancels a bright mode’s scattering, leaving residual extinction dominated by absorption. Spectral interference microscopy has the potential for real-time and single-shot phase and amplitude investigations of isolated quantum and classical antennas with applications across the physical and life sciences. PMID:24781663

Daniell method for power spectral density estimation in atomic force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Labuda, Aleksander

An alternative method for power spectral density (PSD) estimation—the Daniell method—is revisited and compared to the most prevalent method used in the field of atomic force microscopy for quantifying cantilever thermal motion—the Bartlett method. Both methods are shown to underestimate the Q factor of a simple harmonic oscillator (SHO) by a predictable, and therefore correctable, amount in the absence of spurious deterministic noise sources. However, the Bartlett method is much more prone to spectral leakage which can obscure the thermal spectrum in the presence of deterministic noise. By the significant reduction in spectral leakage, the Daniell method leads to amore » more accurate representation of the true PSD and enables clear identification and rejection of deterministic noise peaks. This benefit is especially valuable for the development of automated PSD fitting algorithms for robust and accurate estimation of SHO parameters from a thermal spectrum.« less

High spectral resolution lidar based on quad mach zehnder interferometer for aerosols and wind measurements on board space missions

NASA Astrophysics Data System (ADS)

Mariscal, Jean-François; Bruneau, Didier; Pelon, Jacques; Van Haecke, Mathilde; Blouzon, Frédéric; Montmessin, Franck; Chepfer, Hélène

2018-04-01

We present the measurement principle and the optical design of a Quad Mach Zehnder (QMZ) interferometer as HSRL technique, allowing simultaneous measurements of particle backscattering and wind velocity. Key features of this concept is to operate with a multimodal laser and do not require any frequency stabilization. These features are relevant especially for space applications for which high technical readiness level is required.

New developments in multimodal clinical multiphoton tomography

NASA Astrophysics Data System (ADS)

König, Karsten

2011-03-01

80 years ago, the PhD student Maria Goeppert predicted in her thesis in Goettingen, Germany, two-photon effects. It took 30 years to prove her theory, and another three decades to realize the first two-photon microscope. With the beginning of this millennium, first clinical multiphoton tomographs started operation in research institutions, hospitals, and in the cosmetic industry. The multiphoton tomograph MPTflexTM with its miniaturized flexible scan head became the Prism-Award 2010 winner in the category Life Sciences. Multiphoton tomographs with its superior submicron spatial resolution can be upgraded to 5D imaging tools by adding spectral time-correlated single photon counting units. Furthermore, multimodal hybrid tomographs provide chemical fingerprinting and fast wide-field imaging. The world's first clinical CARS studies have been performed with a hybrid multimodal multiphoton tomograph in spring 2010. In particular, nonfluorescent lipids and water as well as mitochondrial fluorescent NAD(P)H, fluorescent elastin, keratin, and melanin as well as SHG-active collagen have been imaged in patients with dermatological disorders. Further multimodal approaches include the combination of multiphoton tomographs with low-resolution imaging tools such as ultrasound, optoacoustic, OCT, and dermoscopy systems. Multiphoton tomographs are currently employed in Australia, Japan, the US, and in several European countries for early diagnosis of skin cancer (malignant melanoma), optimization of treatment strategies (wound healing, dermatitis), and cosmetic research including long-term biosafety tests of ZnO sunscreen nanoparticles and the measurement of the stimulated biosynthesis of collagen by anti-ageing products.

Side-detecting optical fiber coated with Zn(OH)2 nanorods for ultraviolet sensing applications

NASA Astrophysics Data System (ADS)

Azad, S.; Parvizi, R.; Sadeghi, E.

2017-09-01

This paper presents an improved coupling efficiency and side detecting of UV radiation induced by light scattering and luminescent features of Zn(OH)2 nanorods coated multimode optical fibers. Uniform and high density Zn(OH)2 nanorods were grown hydrothermally on the core of chemically etched multimode optical fibers. The prepared samples were characterized through x-ray diffraction patterns, scanning electron microscopy and photoluminescence spectroscopy. The detecting technique was based on the intensity modulation of the side coupled light through the Zn(OH)2 nanorods. A simple and cost-effective UV radiation detecting setup has been designed. Experimentally estimated coupling efficiency of the proposed setup was obtained near 11%. The proposed device exhibited stable and reversible responses with a fast rising and decaying time of about 1.4 s and 0.85 s, respectively.

Tissue imaging using full field optical coherence microscopy with short multimode fiber probe

NASA Astrophysics Data System (ADS)

Sato, Manabu; Eto, Kai; Goto, Tetsuhiro; Kurotani, Reiko; Abe, Hiroyuki; Nishidate, Izumi

2018-03-01

In achieving minimally invasive accessibility to deeply located regions the size of the imaging probes is important. We demonstrated full-field optical coherence tomography (FF-OCM) using an ultrathin forward-imaging short multimode fiber (SMMF) probe of 50 μm core diameter, 125 μm diameter, and 7.4 mm length for optical communications. The axial resolution was measured to be 2.14 μm and the lateral resolution was also evaluated to be below 4.38 μm using a test pattern (TP). The spatial mode and polarization characteristics of SMMF were evaluated. Inserting SMMF to in vivo rat brain, 3D images were measured and 2D information of nerve fibers was obtained. The feasibility of an SMMF as an ultrathin forward-imaging probe in FF-OCM has been demonstrated.

Design and installation of a multimode microscopy system

NASA Astrophysics Data System (ADS)

Helm, Johannes P.; Haug, Finn-Mogens S.; Storm, Johan F.; Ottersen, Ole-Petter

2001-04-01

We describe design and installation of a multi-mode microscopy core facility in an environment of varied research activity in life-sciences. The experimentators can select any combination of a) microscopes (upright, upright fixed-stage, inverted), b) microscopy modes (widefield, DIC, IRDIC, widefield epifluorescence, transmission LSM, reflection and fluorescence CLSM, MPLSM), c) imaging techniques (direct observation, video observation, photography, quantitative camera-recording, flying spot scanning), d) auxiliary systems (equipment for live specimen imaging, electrophysiology, time-coordinated laser-scanning and electrophysiology, patch-clamp). The equipment is installed on one large vibration-isolating optical table (3m X 1.5m X 0.3m). Electronics, auxiliary equipment, and a fiber-coupled, remotely controlled Ar+-Kr+ laser are mounted in a rack system fixed to the ceiling. The design of the shelves allows the head of the CSLM to be moved to any of the microscopes without increasing critical cable lengths. At the same time easy access to all the units is preserved. The beam of a Titanium-Sapphire laser, controlled by means of an EOM and a prism GVD, is coupled directly to the microscopes. Three mirrors mounted on a single precision translation table are integrated into the beam steering system so that the beam can easily be redirected to any of the microscopes. All the available instruments can be operated by the educated and trained user. The system is popular among researchers in neuroanatomy, embryology, cell biology, molecular biology - including the study of protein interactions, e.g. by means of FRET, and electrophysiology. Its colocalization with an EM facility promises to provide considerable synergy effects.

Investigation of an angiogenesis-promoting topical treatment for diabetic wounds using multimodal microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, Joanne; Bower, Andrew J.; Arp, Zane A.; Olson, Eric; Holland, Claire; Chaney, Eric J.; Marjanovic, Marina; Boppart, Stephen A.

2016-02-01

Impaired skin wound healing is a significant co-morbid condition of diabetes that is caused by poor microcirculation among other factors. Hypoxia-inducible factors (HIFs) are transcription factors that mediate the effects of decreased levels of oxygen in biological environments. Inducing mild hypoxia in the tissue could promote angiogenesis, a critical step in the wound healing process in diabetic wounds. To investigate the relationship between hypoxia and diabetic wound healing, a topical treatment consisting of a HIF-activating prolyl-hydroxylase inhibitor was administered to the wounded skin of diabetic (db/db) mice. Studies were conducted in accordance with the GSK Policy on the Care, Welfare and Treatment of Laboratory Animals and were reviewed at GSK or by the ethical review process at the institution where the work was performed. The wounded area was tracked in vivo for 28 days utilizing a custom-built multimodal microscopy system. An increase in vascular density around the wounds of treated animals was observed using phase-variance optical coherence tomography (PV-OCT), in comparison to normal controls. In addition, second harmonic generation (SHG) and fluorescence lifetime imaging microscopy (FLIM) were utilized to examine the collagen regeneration and cellular metabolic activity, respectively, in the wounded skin. The utilization of these light based methods can follow metabolic and morphologic changes in the wound healing process in ways not possible with current evaluation processes. Insights demonstrated in these studies could lead to new endpoints for evaluation of the efficacy of drugs and lead to more direct ways of detecting patient response to treatment.

Correlative imaging of biological tissues with apertureless scanning near-field optical microscopy and confocal laser scanning microscopy

PubMed Central

Stanciu, Stefan G.; Tranca, Denis E.; Hristu, Radu; Stanciu, George A.

2017-01-01

Apertureless scanning near-field optical microscopy (ASNOM) has attracted considerable interest over the past years as a result of its valuable contrast mechanisms and capabilities for optical resolutions in the nanoscale range. However, at this moment the intersections between ASNOM and the realm of bioimaging are scarce, mainly due to data interpretation difficulties linked to the limited body of work performed so far in this field and hence the reduced volume of supporting information. We propose an imaging approach that holds significant potential for alleviating this issue, consisting of correlative imaging of biological specimens using a multimodal system that incorporates ASNOM and confocal laser scanning microscopy (CLSM), which allows placing near-field data into a well understood context of anatomical relevance. We demonstrate this approach on zebrafish retinal tissue. The proposed method holds important implications for the in-depth understanding of biological items through the prism of ASNOM and CLSM data complementarity. PMID:29296474

Multimodal imaging of human cerebellum - merging X-ray phase microtomography, magnetic resonance microscopy and histology

NASA Astrophysics Data System (ADS)

Schulz, Georg; Waschkies, Conny; Pfeiffer, Franz; Zanette, Irene; Weitkamp, Timm; David, Christian; Müller, Bert

2012-11-01

Imaging modalities including magnetic resonance imaging and X-ray computed tomography are established methods in daily clinical diagnosis of human brain. Clinical equipment does not provide sufficient spatial resolution to obtain morphological information on the cellular level, essential for applying minimally or non-invasive surgical interventions. Therefore, generic data with lateral sub-micrometer resolution have been generated from histological slices post mortem. Sub-cellular spatial resolution, lost in the third dimension as a result of sectioning, is obtained using magnetic resonance microscopy and micro computed tomography. We demonstrate that for human cerebellum grating-based X-ray phase tomography shows complementary contrast to magnetic resonance microscopy and histology. In this study, the contrast-to-noise values of magnetic resonance microscopy and phase tomography were comparable whereas the spatial resolution in phase tomography is an order of magnitude better. The registered data with their complementary information permit the distinct segmentation of tissues within the human cerebellum.

Ultrasonic imaging of seismic physical models using a fringe visibility enhanced fiber-optic Fabry-Perot interferometric sensor.

PubMed

Zhang, Wenlu; Chen, Fengyi; Ma, Wenwen; Rong, Qiangzhou; Qiao, Xueguang; Wang, Ruohui

2018-04-16

A fringe visibility enhanced fiber-optic Fabry-Perot interferometer based ultrasonic sensor is proposed and experimentally demonstrated for seismic physical model imaging. The sensor consists of a graded index multimode fiber collimator and a PTFE (polytetrafluoroethylene) diaphragm to form a Fabry-Perot interferometer. Owing to the increase of the sensor's spectral sideband slope and the smaller Young's modulus of the PTFE diaphragm, a high response to both continuous and pulsed ultrasound with a high SNR of 42.92 dB in 300 kHz is achieved when the spectral sideband filter technique is used to interrogate the sensor. The ultrasonic reconstructed images can clearly differentiate the shape of models with a high resolution.

A device for multimodal imaging of skin

NASA Astrophysics Data System (ADS)

Spigulis, Janis; Garancis, Valerijs; Rubins, Uldis; Zaharans, Eriks; Zaharans, Janis; Elste, Liene

2013-03-01

A compact prototype device for diagnostic imaging of skin has been developed and tested. Polarized LED light at several spectral regions is used for illumination, and round skin spot of diameter 30mm is imaged by a CMOS sensor via crossoriented polarizing filter. Four consecutive imaging series are performed: (1) RGB image at white LED illumination for revealing subcutaneous structures; (2) four spectral images at narrowband LED illumination (450nm, 540nm, 660nm, 940nm) for mapping of the main skin chromophores; (3) video-imaging under green LED illumination for mapping of skin blood perfusion; (4) autofluorescence video-imaging under UV (365nm) LED irradiation for mapping of the skin fluorophores. Design details of the device as well as preliminary results of clinical tests are presented.

Spectrally encoded optical fibre sensor systems and their application in process control, environmental and structural monitoring

NASA Astrophysics Data System (ADS)

Willsch, Reinhardt; Ecke, Wolfgang; Schwotzer, Gunter

2005-09-01

Different types of advanced optical fibre sensor systems using similar spectral interrogation principles and potential low-cost polychromator optoelectronic signal processing instrumentation will be presented, and examples of their industrial application are demonstrated. These are such sensors as multimode fibre based humidity, temperature, and pressure sensors with extrinsic microoptical Fabry-Perot transducers for process control in gas industry, UV absorption evanescent field sensors for organic pollution monitoring in groundwater, and single mode fibre Bragg grating (FBG) multiplexed strain & vibration and temperature sensor networks for structural health monitoring applications in electric power facilities, aerospace, railways, geotechnical and civil engineering. Recent results of current investigations applying FBGs and microstructured fibres for chemical sensing will be discussed.

2  μm laser oscillation of Ho3+:Tm3+-codoped silica microspheres.

PubMed

Peng, Longxiang; Huang, Yantang; Duan, Yafan; Zhuang, Shijian; Liao, Tingdi; Xu, Canhua

2017-09-10

2 μm laser oscillation with a low threshold has been achieved in Ho 3+ :Tm 3+ -codoped silica microspheres (HTCSMs). Ho 3+ :Tm 3+ -codoped solgel functionalization film is applied to the surface of a silica microsphere, and an optical tapered fiber is adopted to couple an 808 nm continuous-wave laser to serve as the pump light source. Multimode and single-mode laser oscillations around 2 μm within the eye-safe wave band are observed due to the I 7 5→I 8 5 transitions of Ho 3+ ions sensitized by Tm 3+ . The morphology characteristics of microspheres determine the multimode laser oscillation spectrum. The free spectral range is in good accordance with the calculated value based on Mie scattering theory. The HTCSM laser oscillation shows characteristics of good capability, simple process, high flexibility, and low cost.

Multimode nonlinear optical imaging of the dermis in ex vivo human skin based on the combination of multichannel mode and Lambda mode.

PubMed

Zhuo, Shuangmu; Chen, Jianxin; Luo, Tianshu; Zou, Dingsong

2006-08-21

A Multimode nonlinear optical imaging technique based on the combination of multichannel mode and Lambda mode is developed to investigate human dermis. Our findings show that this technique not only improves the image contrast of the structural proteins of extracellular matrix (ECM) but also provides an image-guided spectral analysis method to identify both cellular and ECM intrinsic components including collagen, elastin, NAD(P)H and flavin. By the combined use of multichannel mode and Lambda mode in tandem, the obtained in-depth two photon-excited fluorescence (TPEF) and second-harmonic generation (SHG) imaging and TPEF/SHG signals depth-dependence decay can offer a sensitive tool for obtaining quantitative tissue structural and biochemical information. These results suggest that the technique has the potential to provide more accurate information for determining tissue physiological and pathological states.

Dual-wavelength nano-engineered Thulium-doped fiber laser via bending of singlemode-multimode-singlemode fiber structure

NASA Astrophysics Data System (ADS)

Zulkifli, A. Z.; Latiff, A. A.; Paul, M. C.; Yasin, M.; Ahmad, H.; Harun, S. W.

2016-12-01

In this paper, a dual-wavelength fiber laser (DWFL) using nano-engineered Thulium-doped fiber as a gain medium with a bent singlemode-multimode-singlemode fiber structure (SMS) is demonstrated. The SMS structure is packaged systematically using Cr-39 polymer plates to provide linear bending via applied load. Experimental results have proved that the bent SMS is capable to provide highly effective wavelength filter and wavelengths stabilizer by balancing the net cavity gain between the two wavelengths. The DWFL provides very narrow spacing of 0.9 nm, narrow 3 dB spectral linewidth of ∼0.07 nm and SNR of ∼42 dB. Based on stability test, very small mode hopping is observed at the two wavelengths having deviations of ±0 nm and ±0.04 nm respectively. In conjunction, the DWFL provides very stable relative wavelength spacing with a deviation of ±0.04 nm.

Fiber Fabry-Perot tip sensor based on multimode photonic crystal fiber

NASA Astrophysics Data System (ADS)

Wu, Di; Huang, Yu; Fu, Jian-Yu; Wang, Guo-Yin

2015-03-01

We propose a novel Fabry-Perot interferometer (FPI) sensor for simultaneous measurement of refractive index (RI) and temperature based on Fresnel reflection and the thermo-optic effect of silica. The sensor head consists of a short section of multimode photonic crystal fiber (MPCF) and a conventional single mode fiber (SMF), where two thin films are formed by collapsing the air holes of MPCF with a commercialized fusion splicer. Experimental results show that such a device has a linear RI sensitivity of ~21.52 dB/RIU (RI unit) and a linear optical path difference (OPD) temperature sensitivity of ~25 nm/°C. In addition, a high RI resolution of about ~1.7×10-5 is obtained by using the Fourier transformation to decompose the spectral response in different spatial frequencies. Low-cost, easy fabrication and high resolution make it appropriate for practical applications.

Stereoscopic Integrated Imaging Goggles for Multimodal Intraoperative Image Guidance

PubMed Central

Mela, Christopher A.; Patterson, Carrie; Thompson, William K.; Papay, Francis; Liu, Yang

2015-01-01

We have developed novel stereoscopic wearable multimodal intraoperative imaging and display systems entitled Integrated Imaging Goggles for guiding surgeries. The prototype systems offer real time stereoscopic fluorescence imaging and color reflectance imaging capacity, along with in vivo handheld microscopy and ultrasound imaging. With the Integrated Imaging Goggle, both wide-field fluorescence imaging and in vivo microscopy are provided. The real time ultrasound images can also be presented in the goggle display. Furthermore, real time goggle-to-goggle stereoscopic video sharing is demonstrated, which can greatly facilitate telemedicine. In this paper, the prototype systems are described, characterized and tested in surgeries in biological tissues ex vivo. We have found that the system can detect fluorescent targets with as low as 60 nM indocyanine green and can resolve structures down to 0.25 mm with large FOV stereoscopic imaging. The system has successfully guided simulated cancer surgeries in chicken. The Integrated Imaging Goggle is novel in 4 aspects: it is (a) the first wearable stereoscopic wide-field intraoperative fluorescence imaging and display system, (b) the first wearable system offering both large FOV and microscopic imaging simultaneously, (c) the first wearable system that offers both ultrasound imaging and fluorescence imaging capacities, and (d) the first demonstration of goggle-to-goggle communication to share stereoscopic views for medical guidance. PMID:26529249

Multimodal ophthalmic imaging using handheld spectrally encoded coherence tomography and reflectometry (SECTR)

NASA Astrophysics Data System (ADS)

Leeburg, Kelsey C.; El-Haddad, Mohamed T.; Malone, Joseph D.; Terrones, Benjamin D.; Tao, Yuankai K.

2018-02-01

Scanning laser ophthalmoscopy (SLO) provides high-speed, noninvasive en face imaging of the retinal fundus. Optical coherence tomography (OCT) is the current "gold-standard" for ophthalmic diagnostic imaging and enables depth-resolved visualization of ophthalmic structures and image-based surrogate biomarkers of disease. We present a compact optical and mechanical design for handheld spectrally encoded coherence tomography and reflectometry (SECTR) for multimodality en face spectrally encoded reflectometry (SER) and cross-sectional OCT imaging. We custom-designed a double-pass telecentric scan lens, which halves the size of 4-f optical relays and allowed us to reduce the footprint of our SECTR scan-head by a factor of >2.7x (volume) over our previous design. The double-pass scan lens was optimized for diffraction-limited performance over a +/-10° scan field. SECTR optics and optomechanics were combined in a compact rapid-prototyped enclosure with dimensions 87 x 141.8 x 137 mm (w x h x d). SECTR was implemented using a custom-built 400 kHz 1050 nm swept-source. OCT and SER were simultaneously digitized on dual input channels of a 4 GS/s digitizer at 1.4 GS/s per channel. In vivo human en face SER and cross-sectional OCT images were acquired at 350 fps. OCT volumes of 1000 B-scans were acquired in 2.86 s. We believe clinical translation of our compact handheld design will benefit point-of-care ophthalmic diagnostics in patients who are unable to be imaged on conventional slit-lamp based systems, such as infants and the bedridden. When combined with multi-volumetric registration methods, handheld SECTR will have advantages in motion-artifact free imaging over existing handheld technologies.

Rapid microscopy measurement of very large spectral images.

PubMed

Lindner, Moshe; Shotan, Zav; Garini, Yuval

2016-05-02

The spectral content of a sample provides important information that cannot be detected by the human eye or by using an ordinary RGB camera. The spectrum is typically a fingerprint of the chemical compound, its environmental conditions, phase and geometry. Thus measuring the spectrum at each point of a sample is important for a large range of applications from art preservation through forensics to pathological analysis of a tissue section. To date, however, there is no system that can measure the spectral image of a large sample in a reasonable time. Here we present a novel method for scanning very large spectral images of microscopy samples even if they cannot be viewed in a single field of view of the camera. The system is based on capturing information while the sample is being scanned continuously 'on the fly'. Spectral separation implements Fourier spectroscopy by using an interferometer mounted along the optical axis. High spectral resolution of ~5 nm at 500 nm could be achieved with a diffraction-limited spatial resolution. The acquisition time is fairly high and takes 6-8 minutes for a sample size of 10mm x 10mm measured under a bright-field microscope using a 20X magnification.

Spectral interferometry for morphological imaging in in vitro fertilization (IVF) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhu, Yizheng; Li, Chengshuai

2016-03-01

Morphological assessment of spermatozoa is of critical importance for in vitro fertilization (IVF), especially intracytoplasmic sperm injection (ICSI)-based IVF. In ICSI, a single sperm cell is selected and injected into an egg to achieve fertilization. The quality of the sperm cell is found to be highly correlated to IVF success. Sperm morphology, such as shape, head birefringence and motility, among others, are typically evaluated under a microscope. Current observation relies on conventional techniques such as differential interference contrast microscopy and polarized light microscopy. Their qualitative nature, however, limits the ability to provide accurate quantitative analysis. Here, we demonstrate quantitative morphological measurement of sperm cells using two types of spectral interferometric techniques, namely spectral modulation interferometry and spectral multiplexing interferometry. Both are based on spectral-domain low coherence interferometry, which is known for its exquisite phase determination ability. While spectral modulation interferometry encodes sample phase in a single spectrum, spectral multiplexing interferometry does so for sample birefringence. Therefore they are capable of highly sensitive phase and birefringence imaging. These features suit well in the imaging of live sperm cells, which are small, dynamic objects with only low to moderate levels of phase and birefringence contrast. We will introduce the operation of both techniques and demonstrate their application to measuring the phase and birefringence morphology of sperm cells.

Use of Raman microscopy and band-target entropy minimization analysis to identify dyes in a commercial stamp. Implications for authentication and counterfeit detection.

PubMed

Widjaja, Effendi; Garland, Marc

2008-02-01

Raman microscopy was used in mapping mode to collect more than 1000 spectra in a 100 microm x 100 microm area from a commercial stamp. Band-target entropy minimization (BTEM) was then employed to unmix the mixture spectra in order to extract the pure component spectra of the samples. Three pure component spectral patterns with good signal-to-noise ratios were recovered, and their spatial distributions were determined. The three pure component spectral patterns were then identified as copper phthalocyanine blue, calcite-like material, and yellow organic dye material by comparison to known spectral libraries. The present investigation, consisting of (1) advanced curve resolution (blind-source separation) followed by (2) spectral data base matching, readily suggests extensions to authenticity and counterfeit studies of other types of commercial objects. The presence or absence of specific observable components form the basis for assessment. The present spectral analysis (BTEM) is applicable to highly overlapping spectral information. Since a priori information such as the number of components present and spectral libraries are not needed in BTEM, and since minor signals arising from trace components can be reconstructed, this analysis offers a robust approach to a wide variety of material problems involving authenticity and counterfeit issues.

Spectrally resolved laser interference microscopy

NASA Astrophysics Data System (ADS)

Butola, Ankit; Ahmad, Azeem; Dubey, Vishesh; Senthilkumaran, P.; Singh Mehta, Dalip

2018-07-01

We developed a new quantitative phase microscopy technique, namely, spectrally resolved laser interference microscopy (SR-LIM), with which it is possible to quantify multi-spectral phase information related to biological specimens without color crosstalk using a color CCD camera. It is a single shot technique where sequential switched on/off of red, green, and blue (RGB) wavelength light sources are not required. The method is implemented using a three-wavelength interference microscope and a customized compact grating based imaging spectrometer fitted at the output port. The results of the USAF resolution chart while employing three different light sources, namely, a halogen lamp, light emitting diodes, and lasers, are discussed and compared. The broadband light sources like the halogen lamp and light emitting diodes lead to stretching in the spectrally decomposed images, whereas it is not observed in the case of narrow-band light sources, i.e. lasers. The proposed technique is further successfully employed for single-shot quantitative phase imaging of human red blood cells at three wavelengths simultaneously without color crosstalk. Using the present technique, one can also use a monochrome camera, even though the experiments are performed using multi-color light sources. Finally, SR-LIM is not only limited to RGB wavelengths, it can be further extended to red, near infra-red, and infra-red wavelengths, which are suitable for various biological applications.

The influence of compressibility on nonlinear spectral energy transfer - Part 1: Fundamental mechanisms

NASA Astrophysics Data System (ADS)

Praturi, Divya Sri; Girimaji, Sharath

2017-11-01

Nonlinear spectral energy transfer by triadic interactions is one of the foundational processes in fluid turbulence. Much of our current knowledge of this process is contingent upon pressure being a Lagrange multiplier with the only function of re-orienting the velocity wave vector. In this study, we examine how the nonlinear spectral transfer is affected in compressible turbulence when pressure is a true thermodynamic variable with a wave character. We perform direct numerical simulations of multi-mode evolution at different turbulent Mach numbers of Mt = 0.03 , 0.6 . Simulations are performed with initial modes that are fully solenoidal, fully dilatational and mixed solenoidal-dilatational. It is shown that solenoidal-solenoidal interactions behave in canonical manner at all Mach numbers. However, dilatational and mixed mode interactions are profoundly different. This is due to the fact that wave-pressure leads to kinetic-internal energy exchange via the pressure-dilatation mechanism. An important consequence of this exchange is that the triple correlation term, responsible for spectral transfer, experiences non-monotonic behavior resulting in inefficient energy transfer to other modes.

Systems and methods for selective detection and imaging in coherent Raman microscopy by spectral excitation shaping

DOEpatents

Xie, Xiaoliang Sunney; Freudiger, Christian; Min, Wei

2016-03-15

A microscopy imaging system is disclosed that includes a light source system, a spectral shaper, a modulator system, an optics system, an optical detector and a processor. The light source system is for providing a first train of pulses and a second train of pulses. The spectral shaper is for spectrally modifying an optical property of at least some frequency components of the broadband range of frequency components such that the broadband range of frequency components is shaped producing a shaped first train of pulses to specifically probe a spectral feature of interest from a sample, and to reduce information from features that are not of interest from the sample. The modulator system is for modulating a property of at least one of the shaped first train of pulses and the second train of pulses at a modulation frequency. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of a train of pulses of interest transmitted or reflected through the common focal volume. The processor is for detecting a modulation at the modulation frequency of the integrated intensity of substantially all of the optical frequency components of the train of pulses of interest due to the non-linear interaction of the shaped first train of pulses with the second train of pulses as modulated in the common focal volume, and for providing an output signal for a pixel of an image for the microscopy imaging system.

Spatial and spectral imaging of point-spread functions using a spatial light modulator

NASA Astrophysics Data System (ADS)

Munagavalasa, Sravan; Schroeder, Bryce; Hua, Xuanwen; Jia, Shu

2017-12-01

We develop a point-spread function (PSF) engineering approach to imaging the spatial and spectral information of molecular emissions using a spatial light modulator (SLM). We show that a dispersive grating pattern imposed upon the emission reveals spectral information. We also propose a deconvolution model that allows the decoupling of the spectral and 3D spatial information in engineered PSFs. The work is readily applicable to single-molecule measurements and fluorescent microscopy.

Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy

NASA Astrophysics Data System (ADS)

Bélanger, Erik; Crépeau, Joël; Laffray, Sophie; Vallée, Réal; De Koninck, Yves; Côté, Daniel

2012-02-01

In vivo imaging of cellular dynamics can be dramatically enabling to understand the pathophysiology of nervous system diseases. To fully exploit the power of this approach, the main challenges have been to minimize invasiveness and maximize the number of concurrent optical signals that can be combined to probe the interplay between multiple cellular processes. Label-free coherent anti-Stokes Raman scattering (CARS) microscopy, for example, can be used to follow demyelination in neurodegenerative diseases or after trauma, but myelin imaging alone is not sufficient to understand the complex sequence of events that leads to the appearance of lesions in the white matter. A commercially available microendoscope is used here to achieve minimally invasive, video-rate multimodal nonlinear imaging of cellular processes in live mouse spinal cord. The system allows for simultaneous CARS imaging of myelin sheaths and two-photon excitation fluorescence microendoscopy of microglial cells and axons. Morphometric data extraction at high spatial resolution is also described, with a technique for reducing motion-related imaging artifacts. Despite its small diameter, the microendoscope enables high speed multimodal imaging over wide areas of tissue, yet at resolution sufficient to quantify subtle differences in myelin thickness and microglial motility.

Passive microrheology of soft materials with atomic force microscopy: A wavelet-based spectral analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez-Torres, C.; Streppa, L.; Arneodo, A.

2016-01-18

Compared to active microrheology where a known force or modulation is periodically imposed to a soft material, passive microrheology relies on the spectral analysis of the spontaneous motion of tracers inherent or external to the material. Passive microrheology studies of soft or living materials with atomic force microscopy (AFM) cantilever tips are rather rare because, in the spectral densities, the rheological response of the materials is hardly distinguishable from other sources of random or periodic perturbations. To circumvent this difficulty, we propose here a wavelet-based decomposition of AFM cantilever tip fluctuations and we show that when applying this multi-scale methodmore » to soft polymer layers and to living myoblasts, the structural damping exponents of these soft materials can be retrieved.« less

RELIABILITY OF CONFOCAL MICROSCOPY SPECTRAL IMAGING SYSTEMS: USE OF MULTISPECTRAL BEADS

EPA Science Inventory

Background: There is a need for a standardized, impartial calibration, and validation protocol on confocal spectral imaging (CSI) microscope systems. To achieve this goal, it is necessary to have testing tools to provide a reproducible way to evaluate instrument performance. ...

Automated multimodal spectral histopathology for quantitative diagnosis of residual tumour during basal cell carcinoma surgery.

PubMed

Boitor, Radu; Kong, Kenny; Shipp, Dustin; Varma, Sandeep; Koloydenko, Alexey; Kulkarni, Kusum; Elsheikh, Somaia; Schut, Tom Bakker; Caspers, Peter; Puppels, Gerwin; van der Wolf, Martin; Sokolova, Elena; Nijsten, T E C; Salence, Brogan; Williams, Hywel; Notingher, Ioan

2017-12-01

Multimodal spectral histopathology (MSH), an optical technique combining tissue auto-fluorescence (AF) imaging and Raman micro-spectroscopy (RMS), was previously proposed for detection of residual basal cell carcinoma (BCC) at the surface of surgically-resected skin tissue. Here we report the development of a fully-automated prototype instrument based on MSH designed to be used in the clinic and operated by a non-specialist spectroscopy user. The algorithms for the AF image processing and Raman spectroscopy classification had been first optimised on a manually-operated laboratory instrument and then validated on the automated prototype using skin samples from independent patients. We present results on a range of skin samples excised during Mohs micrographic surgery, and demonstrate consistent diagnosis obtained in repeat test measurement, in agreement with the reference histopathology diagnosis. We also show that the prototype instrument can be operated by clinical users (a skin surgeon and a core medical trainee, after only 1-8 hours of training) to obtain consistent results in agreement with histopathology. The development of the new automated prototype and demonstration of inter-instrument transferability of the diagnosis models are important steps on the clinical translation path: it allows the testing of the MSH technology in a relevant clinical environment in order to evaluate its performance on a sufficiently large number of patients.

Integral refractive index imaging of flowing cell nuclei using quantitative phase microscopy combined with fluorescence microscopy.

PubMed

Dardikman, Gili; Nygate, Yoav N; Barnea, Itay; Turko, Nir A; Singh, Gyanendra; Javidi, Barham; Shaked, Natan T

2018-03-01

We suggest a new multimodal imaging technique for quantitatively measuring the integral (thickness-average) refractive index of the nuclei of live biological cells in suspension. For this aim, we combined quantitative phase microscopy with simultaneous 2-D fluorescence microscopy. We used 2-D fluorescence microscopy to localize the nucleus inside the quantitative phase map of the cell, as well as for measuring the nucleus radii. As verified offline by both 3-D confocal fluorescence microscopy and 2-D fluorescence microscopy while rotating the cells during flow, the nucleus of cells in suspension that are not during division can be assumed to be an ellipsoid. The entire shape of a cell in suspension can be assumed to be a sphere. Then, the cell and nucleus 3-D shapes can be evaluated based on their in-plain radii available from the 2-D phase and fluorescent measurements, respectively. Finally, the nucleus integral refractive index profile is calculated. We demonstrate the new technique on cancer cells, obtaining nucleus refractive index values that are lower than those of the cytoplasm, coinciding with recent findings. We believe that the proposed technique has the potential to be used for flow cytometry, where full 3-D refractive index tomography is too slow to be implemented during flow.

Hyperspectral imaging with laser-scanning sum-frequency generation microscopy

PubMed Central

Hanninen, Adam; Shu, Ming Wai; Potma, Eric O.

2017-01-01

Vibrationally sensitive sum-frequency generation (SFG) microscopy is a chemically selective imaging technique sensitive to non-centrosymmetric molecular arrangements in biological samples. The routine use of SFG microscopy has been hampered by the difficulty of integrating the required mid-infrared excitation light into a conventional, laser-scanning nonlinear optical (NLO) microscope. In this work, we describe minor modifications to a regular laser-scanning microscope to accommodate SFG microscopy as an imaging modality. We achieve vibrationally sensitive SFG imaging of biological samples with sub-μm resolution at image acquisition rates of 1 frame/s, almost two orders of magnitude faster than attained with previous point-scanning SFG microscopes. Using the fast scanning capability, we demonstrate hyperspectral SFG imaging in the CH-stretching vibrational range and point out its use in the study of molecular orientation and arrangement in biologically relevant samples. We also show multimodal imaging by combining SFG microscopy with second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) on the same imaging platfrom. This development underlines that SFG microscopy is a unique modality with a spatial resolution and image acquisition time comparable to that of other NLO imaging techniques, making point-scanning SFG microscopy a valuable member of the NLO imaging family. PMID:28966861

An approach to estimate spatial distribution of analyte within cells using spectrally-resolved fluorescence microscopy.

PubMed

Sharma, Dharmendar Kumar; Irfanullah, Mir; Basu, Santanu Kumar; Madhu, Sheri; De, Suman; Jadhav, Sameer; Ravikanth, Mangalampalli; Chowdhury, Arindam

2017-01-18

While fluorescence microscopy has become an essential tool amongst chemists and biologists for the detection of various analyte within cellular environments, non-uniform spatial distribution of sensors within cells often restricts extraction of reliable information on relative abundance of analytes in different subcellular regions. As an alternative to existing sensing methodologies such as ratiometric or FRET imaging, where relative proportion of analyte with respect to the sensor can be obtained within cells, we propose a methodology using spectrally-resolved fluorescence microscopy, via which both the relative abundance of sensor as well as their relative proportion with respect to the analyte can be simultaneously extracted for local subcellular regions. This method is exemplified using a BODIPY sensor, capable of detecting mercury ions within cellular environments, characterized by spectral blue-shift and concurrent enhancement of emission intensity. Spectral emission envelopes collected from sub-microscopic regions allowed us to compare the shift in transition energies as well as integrated emission intensities within various intracellular regions. Construction of a 2D scatter plot using spectral shifts and emission intensities, which depend on the relative amount of analyte with respect to sensor and the approximate local amounts of the probe, respectively, enabled qualitative extraction of relative abundance of analyte in various local regions within a single cell as well as amongst different cells. Although the comparisons remain semi-quantitative, this approach involving analysis of multiple spectral parameters opens up an alternative way to extract spatial distribution of analyte in heterogeneous systems. The proposed method would be especially relevant for fluorescent probes that undergo relatively nominal shift in transition energies compared to their emission bandwidths, which often restricts their usage for quantitative ratiometric imaging in cellular media due to strong cross-talk between energetically separated detection channels.

An approach to estimate spatial distribution of analyte within cells using spectrally-resolved fluorescence microscopy

NASA Astrophysics Data System (ADS)

Sharma, Dharmendar Kumar; Irfanullah, Mir; Basu, Santanu Kumar; Madhu, Sheri; De, Suman; Jadhav, Sameer; Ravikanth, Mangalampalli; Chowdhury, Arindam

2017-03-01

While fluorescence microscopy has become an essential tool amongst chemists and biologists for the detection of various analyte within cellular environments, non-uniform spatial distribution of sensors within cells often restricts extraction of reliable information on relative abundance of analytes in different subcellular regions. As an alternative to existing sensing methodologies such as ratiometric or FRET imaging, where relative proportion of analyte with respect to the sensor can be obtained within cells, we propose a methodology using spectrally-resolved fluorescence microscopy, via which both the relative abundance of sensor as well as their relative proportion with respect to the analyte can be simultaneously extracted for local subcellular regions. This method is exemplified using a BODIPY sensor, capable of detecting mercury ions within cellular environments, characterized by spectral blue-shift and concurrent enhancement of emission intensity. Spectral emission envelopes collected from sub-microscopic regions allowed us to compare the shift in transition energies as well as integrated emission intensities within various intracellular regions. Construction of a 2D scatter plot using spectral shifts and emission intensities, which depend on the relative amount of analyte with respect to sensor and the approximate local amounts of the probe, respectively, enabled qualitative extraction of relative abundance of analyte in various local regions within a single cell as well as amongst different cells. Although the comparisons remain semi-quantitative, this approach involving analysis of multiple spectral parameters opens up an alternative way to extract spatial distribution of analyte in heterogeneous systems. The proposed method would be especially relevant for fluorescent probes that undergo relatively nominal shift in transition energies compared to their emission bandwidths, which often restricts their usage for quantitative ratiometric imaging in cellular media due to strong cross-talk between energetically separated detection channels. Dedicated to Professor Kankan Bhattacharyya.

Probing Cytoskeletal Structures by Coupling Optical Superresolution and AFM Techniques for a Correlative Approach

PubMed Central

Chacko, Jenu Varghese; Zanacchi, Francesca Cella; Diaspro, Alberto

2013-01-01

In this article, we describe and show the application of some of the most advanced fluorescence superresolution techniques, STED AFM and STORM AFM microscopy towards imaging of cytoskeletal structures, such as microtubule filaments. Mechanical and structural properties can play a relevant role in the investigation of cytoskeletal structures of interest, such as microtubules, that provide support to the cell structure. In fact, the mechanical properties, such as the local stiffness and the elasticity, can be investigated by AFM force spectroscopy with tens of nanometers resolution. Force curves can be analyzed in order to obtain the local elasticity (and the Young's modulus calculation by fitting the force curves from every pixel of interest), and the combination with STED/STORM microscopy integrates the measurement with high specificity and yields superresolution structural information. This hybrid modality of superresolution-AFM working is a clear example of correlative multimodal microscopy. PMID:24027190

Multimodality optical imaging of embryonic heart microstructure

PubMed Central

Yelin, Ronit; Yelin, Dvir; Oh, Wang-Yuhl; Yun, Seok H.; Boudoux, Caroline; Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.

2009-01-01

Study of developmental heart defects requires the visualization of the microstructure and function of the embryonic myocardium, ideally with minimal alterations to the specimen. We demonstrate multiple endogenous contrast optical techniques for imaging the Xenopus laevis tadpole heart. Each technique provides distinct and complementary imaging capabilities, including: 1. 3-D coherence microscopy with subcellular (1 to 2 µm) resolution in fixed embryos, 2. real-time reflectance confocal microscopy with large penetration depth in vivo, and 3. ultra-high speed (up to 900 frames per second) that enables real-time 4-D high resolution imaging in vivo. These imaging modalities can provide a comprehensive picture of the morphologic and dynamic phenotype of the embryonic heart. The potential of endogenous-contrast optical microscopy is demonstrated for investigation of the teratogenic effects of ethanol. Microstructural abnormalities associated with high levels of ethanol exposure are observed, including compromised heart looping and loss of ventricular trabecular mass. PMID:18163837

Multimodality optical imaging of embryonic heart microstructure.

PubMed

Yelin, Ronit; Yelin, Dvir; Oh, Wang-Yuhl; Yun, Seok H; Boudoux, Caroline; Vakoc, Benjamin J; Bouma, Brett E; Tearney, Guillermo J

2007-01-01

Study of developmental heart defects requires the visualization of the microstructure and function of the embryonic myocardium, ideally with minimal alterations to the specimen. We demonstrate multiple endogenous contrast optical techniques for imaging the Xenopus laevis tadpole heart. Each technique provides distinct and complementary imaging capabilities, including: 1. 3-D coherence microscopy with subcellular (1 to 2 microm) resolution in fixed embryos, 2. real-time reflectance confocal microscopy with large penetration depth in vivo, and 3. ultra-high speed (up to 900 frames per second) that enables real-time 4-D high resolution imaging in vivo. These imaging modalities can provide a comprehensive picture of the morphologic and dynamic phenotype of the embryonic heart. The potential of endogenous-contrast optical microscopy is demonstrated for investigation of the teratogenic effects of ethanol. Microstructural abnormalities associated with high levels of ethanol exposure are observed, including compromised heart looping and loss of ventricular trabecular mass.

Experimental verification of the spectral shift between near- and far-field peak intensities of plasmonic infrared nanoantennas.

PubMed

Alonso-González, P; Albella, P; Neubrech, F; Huck, C; Chen, J; Golmar, F; Casanova, F; Hueso, L E; Pucci, A; Aizpurua, J; Hillenbrand, R

2013-05-17

Theory predicts a distinct spectral shift between the near- and far-field optical response of plasmonic antennas. Here we combine near-field optical microscopy and far-field spectroscopy of individual infrared-resonant nanoantennas to verify experimentally this spectral shift. Numerical calculations corroborate our experimental results. We furthermore discuss the implications of this effect in surface-enhanced infrared spectroscopy.

Calibration and analysis of a multimodal micro-CT and structured light imaging system for the evaluation of excised breast tissue

NASA Astrophysics Data System (ADS)

McClatchy, David M., III; Rizzo, Elizabeth J.; Meganck, Jeff; Kempner, Josh; Vicory, Jared; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.

2017-12-01

A multimodal micro-computed tomography (CT) and multi-spectral structured light imaging (SLI) system is introduced and systematically analyzed to test its feasibility to aid in margin delineation during breast conserving surgery (BCS). Phantom analysis of the micro-CT yielded a signal-to-noise ratio of 34, a contrast of 1.64, and a minimum detectable resolution of 240 μm for a 1.2 min scan. The SLI system, spanning wavelengths 490 nm to 800 nm and spatial frequencies up to 1.37 mm-1 , was evaluated with aqueous tissue simulating phantoms having variations in particle size distribution, scatter density, and blood volume fraction. The reduced scattering coefficient, μs\\prime and phase function parameter, γ, were accurately recovered over all wavelengths independent of blood volume fractions from 0% to 4%, assuming a flat sample geometry perpendicular to the imaging plane. The resolution of the optical system was tested with a step phantom, from which the modulation transfer function was calculated yielding a maximum resolution of 3.78 cycles per mm. The three dimensional spatial co-registration between the CT and optical imaging space was tested and shown to be accurate within 0.7 mm. A freshly resected breast specimen, with lobular carcinoma, fibrocystic disease, and adipose, was imaged with the system. The micro-CT provided visualization of the tumor mass and its spiculations, and SLI yielded superficial quantification of light scattering parameters for the malignant and benign tissue types. These results appear to be the first demonstration of SLI combined with standard medical tomography for imaging excised tumor specimens. While further investigations are needed to determine and test the spectral, spatial, and CT features required to classify tissue, this study demonstrates the ability of multimodal CT/SLI to quantify, visualize, and spatially navigate breast tumor specimens, which could potentially aid in the assessment of tumor margin status during BCS.

EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.

PubMed

Boś-Liedke, Agnieszka; Walawender, Magdalena; Woźniak, Anna; Flak, Dorota; Gapiński, Jacek; Jurga, Stefan; Kucińska, Małgorzata; Plewiński, Adam; Murias, Marek; Elewa, Marwa; Lampp, Lisa; Imming, Peter; Tadyszak, Krzysztof

2018-06-01

Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.

Ultrabroadband infrared nanospectroscopic imaging

PubMed Central

Bechtel, Hans A.; Muller, Eric A.; Olmon, Robert L.; Martin, Michael C.; Raschke, Markus B.

2014-01-01

Characterizing and ultimately controlling the heterogeneity underlying biomolecular functions, quantum behavior of complex matter, photonic materials, or catalysis requires large-scale spectroscopic imaging with simultaneous specificity to structure, phase, and chemical composition at nanometer spatial resolution. However, as with any ultrahigh spatial resolution microscopy technique, the associated demand for an increase in both spatial and spectral bandwidth often leads to a decrease in desired sensitivity. We overcome this limitation in infrared vibrational scattering-scanning probe near-field optical microscopy using synchrotron midinfrared radiation. Tip-enhanced localized light–matter interaction is induced by low-noise, broadband, and spatially coherent synchrotron light of high spectral irradiance, and the near-field signal is sensitively detected using heterodyne interferometric amplification. We achieve sub-40-nm spatially resolved, molecular, and phonon vibrational spectroscopic imaging, with rapid spectral acquisition, spanning the full midinfrared (700–5,000 cm−1) with few cm−1 spectral resolution. We demonstrate the performance of synchrotron infrared nanospectroscopy on semiconductor, biomineral, and protein nanostructures, providing vibrational chemical imaging with subzeptomole sensitivity. PMID:24803431

[Cornea imagery and keratitis caused by processionary caterpillar hairs].

PubMed

Fournier, I; Saleh, M; Beynat, J; Creuzot-Garcher, C; Bourcier, T; Speeg-Schatz, C

2011-03-01

With their ability to migrate into the cornea and release toxins, caterpillar hairs can induce different clinical presentations such as conjunctivitis, keratoconjunctivitis, uveitis, and less frequently vitreoretinal inflammation (hyalitis, papillitis, macular edema). We report a case that occurred in Alsace (France) in a 13-years-old boy presenting with keratitis caused by caterpillar hairs. We localized them in the cornea, for the first time, using confocal microscopy and anterior segment spectral optical coherence tomography. Confocal microscopy and spectral optical coherence tomography can be useful for diagnosis and follow-up of this disease. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Exploiting chromatic aberration to spectrally encode depth in reflectance confocal microscopy

NASA Astrophysics Data System (ADS)

Carrasco-Zevallos, Oscar; Shelton, Ryan L.; Olsovsky, Cory; Saldua, Meagan; Applegate, Brian E.; Maitland, Kristen C.

2011-06-01

We present chromatic confocal microscopy as a technique to axially scan the sample by spectrally encoding depth information to avoid mechanical scanning of the lens or sample. We have achieved an 800 μm focal shift over a range of 680-1080 nm using a hyperchromat lens as the imaging lens. A more complex system that incorporates a water immersion objective to improve axial resolution was built and tested. We determined that increasing objective magnification decreases chromatic shift while improving axial resolution. Furthermore, collimating after the hyperchromat at longer wavelengths yields an increase in focal shift.

Biocompatible magnetofluorescent probes: luminescent silicon quantum dots coupled with superparamagnetic iron(III) oxide.

PubMed

Erogbogbo, Folarin; Yong, Ken-Tye; Hu, Rui; Law, Wing-Cheung; Ding, Hong; Chang, Ching-Wen; Prasad, Paras N; Swihart, Mark T

2010-09-28

Luminescent silicon quantum dots (SiQDs) are gaining momentum in bioimaging applications, based on their unique combination of optical properties and biocompatibility. Here, we report the development of a multimodal probe that combines the optical properties of silicon quantum dots with the superparamagnetic properties of iron oxide nanoparticles to create biocompatible magnetofluorescent nanoprobes. Multiple nanoparticles of each type are coencapsulated within the hydrophobic core of biocompatible phospholipid-polyethyleneglycol (DSPE-PEG) micelles. The size distribution and composition of the magnetofluorescent nanoprobes were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). Enhanced cellular uptake of these probes in the presence of a magnetic field was demonstrated in vitro. Their luminescence stability in a prostate cancer tumor model microenvironment was demonstrated in vivo. This paves the way for multimodal silicon quantum-dot-based nanoplatforms for a variety of imaging and delivery applications.

Exploring photoreceptor reflectivity via multimodal imaging of outer retinal tubulation in advanced age-related macular degeneration

PubMed Central

Litts, Katie M.; Wang, Xiaolin; Clark, Mark E.; Owsley, Cynthia; Freund, K. Bailey; Curcio, Christine A.; Zhang, Yuhua

2016-01-01

Purpose To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO). Methods Four eyes of 4 subjects with advanced AMD underwent color fundus photography, infrared reflectance imaging, SD-OCT, and AOSLO with a high-resolution research instrument. ORT was identified in closely spaced (11 μm) SD-OCT volume scans. Results ORT in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by AOSLO was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. Conclusion Lack of ORT cone reflectivity by AOSLO indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in OCT. PMID:27584549

Dual spherical single-mode-multimode-single-mode optical fiber temperature sensor based on a Mach–Zehnder interferometer

NASA Astrophysics Data System (ADS)

Tan, Jianchang; Feng, Guoying; Zhang, Shulin; Liang, Jingchuan; Li, Wei; Luo, Yun

2018-07-01

A dual spherical single-mode-multimode-single-mode (DSSMS) optical fiber temperature sensor based on a Mach–Zehnder interferometer (MZI) was designed and implemented in this paper. Theoretical and experimental results indicated that the LP01 mode in the core and the LP09 mode excited by the spherical structure were maintained and transmitted via multimode fiber and interfered at the second spherical structure, resulting in the interference spectrum. An increase or decrease in temperature can cause significant red-shift or blue-shift of the spectrum, respectively. The linearity of the spectral shift due to the temperature change is ~0.999, the sensitivity at 30 °C–540 °C is ~37.372 pm °C‑3, and at  ‑25 °C–25 °C is ~37.28 pm °C‑1. The reproducibility error of this all-fiber temperature sensor at 30 °C–540 °C is less than 0.15%. Compared with the optical fiber sensor with a tapered structure and fiber core offset structure, this MZI-based DSSMS optical fiber temperature sensor has higher mechanical strength. Moreover, benefiting from low-cost and environmentally friendly materials, it is expected to be a novel micro-nano all-fiber sensor.

CONFOCAL MICROSCOPY SYSTEM PERFORMANCE: FOUNDATIONS FOR MEASUREMENTS, QUANTITATION AND SPECTROSCOPY

EPA Science Inventory

The confocal laser-scanning microscopy (CLSM) has enormous potential in many biological fields. The goal of a CLSM is to acquire and quantify fluorescence and in some instruments acquire spectral characterization of the emitted signal. The accuracy of these measurements demands t...

Hyperspectral microscopy to identify foodborne bacteria with optimum lighting source

USDA-ARS?s Scientific Manuscript database

Hyperspectral microscopy is an emerging technology for rapid detection of foodborne pathogenic bacteria. Since scattering spectral signatures from hyperspectral microscopic images (HMI) vary with lighting sources, it is important to select optimal lights. The objective of this study is to compare t...

Real-time dynamic display of registered 4D cardiac MR and ultrasound images using a GPU

NASA Astrophysics Data System (ADS)

Zhang, Q.; Huang, X.; Eagleson, R.; Guiraudon, G.; Peters, T. M.

2007-03-01

In minimally invasive image-guided surgical interventions, different imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and real-time three-dimensional (3D) ultrasound (US), can provide complementary, multi-spectral image information. Multimodality dynamic image registration is a well-established approach that permits real-time diagnostic information to be enhanced by placing lower-quality real-time images within a high quality anatomical context. For the guidance of cardiac procedures, it would be valuable to register dynamic MRI or CT with intraoperative US. However, in practice, either the high computational cost prohibits such real-time visualization of volumetric multimodal images in a real-world medical environment, or else the resulting image quality is not satisfactory for accurate guidance during the intervention. Modern graphics processing units (GPUs) provide the programmability, parallelism and increased computational precision to begin to address this problem. In this work, we first outline our research on dynamic 3D cardiac MR and US image acquisition, real-time dual-modality registration and US tracking. Then we describe image processing and optimization techniques for 4D (3D + time) cardiac image real-time rendering. We also present our multimodality 4D medical image visualization engine, which directly runs on a GPU in real-time by exploiting the advantages of the graphics hardware. In addition, techniques such as multiple transfer functions for different imaging modalities, dynamic texture binding, advanced texture sampling and multimodality image compositing are employed to facilitate the real-time display and manipulation of the registered dual-modality dynamic 3D MR and US cardiac datasets.

Quantitative photoacoustic microscopy of optical absorption coefficients from acoustic spectra in the optical diffusive regime

NASA Astrophysics Data System (ADS)

Guo, Zijian; Favazza, Christopher; Garcia-Uribe, Alejandro; Wang, Lihong V.

2012-06-01

Photoacoustic (PA) microscopy (PAM) can image optical absorption contrast with ultrasonic spatial resolution in the optical diffusive regime. Conventionally, accurate quantification in PAM requires knowledge of the optical fluence attenuation, acoustic pressure attenuation, and detection bandwidth. We circumvent this requirement by quantifying the optical absorption coefficients from the acoustic spectra of PA signals acquired at multiple optical wavelengths. With the acoustic spectral method, the absorption coefficients of an oxygenated bovine blood phantom at 560, 565, 570, and 575 nm were quantified with errors of <3%. We also quantified the total hemoglobin concentration and hemoglobin oxygen saturation in a live mouse. Compared with the conventional amplitude method, the acoustic spectral method provides greater quantification accuracy in the optical diffusive regime. The limitations of the acoustic spectral method was also discussed.

Quantitative photoacoustic microscopy of optical absorption coefficients from acoustic spectra in the optical diffusive regime

PubMed Central

Guo, Zijian; Favazza, Christopher; Garcia-Uribe, Alejandro

2012-01-01

Abstract. Photoacoustic (PA) microscopy (PAM) can image optical absorption contrast with ultrasonic spatial resolution in the optical diffusive regime. Conventionally, accurate quantification in PAM requires knowledge of the optical fluence attenuation, acoustic pressure attenuation, and detection bandwidth. We circumvent this requirement by quantifying the optical absorption coefficients from the acoustic spectra of PA signals acquired at multiple optical wavelengths. With the acoustic spectral method, the absorption coefficients of an oxygenated bovine blood phantom at 560, 565, 570, and 575 nm were quantified with errors of <3%. We also quantified the total hemoglobin concentration and hemoglobin oxygen saturation in a live mouse. Compared with the conventional amplitude method, the acoustic spectral method provides greater quantification accuracy in the optical diffusive regime. The limitations of the acoustic spectral method was also discussed. PMID:22734767

Quantitative photoacoustic microscopy of optical absorption coefficients from acoustic spectra in the optical diffusive regime.

PubMed

Guo, Zijian; Favazza, Christopher; Garcia-Uribe, Alejandro; Wang, Lihong V

2012-06-01

Photoacoustic (PA) microscopy (PAM) can image optical absorption contrast with ultrasonic spatial resolution in the optical diffusive regime. Conventionally, accurate quantification in PAM requires knowledge of the optical fluence attenuation, acoustic pressure attenuation, and detection bandwidth. We circumvent this requirement by quantifying the optical absorption coefficients from the acoustic spectra of PA signals acquired at multiple optical wavelengths. With the acoustic spectral method, the absorption coefficients of an oxygenated bovine blood phantom at 560, 565, 570, and 575 nm were quantified with errors of <3%. We also quantified the total hemoglobin concentration and hemoglobin oxygen saturation in a live mouse. Compared with the conventional amplitude method, the acoustic spectral method provides greater quantification accuracy in the optical diffusive regime. The limitations of the acoustic spectral method was also discussed.

Lobster eye as a collector for water window microscopy

NASA Astrophysics Data System (ADS)

Pina, L.; Maršíková, V.; Inneman, A.; Nawaz, M. F.; Jančárek, A.; Havlíková, R.

2017-08-01

Imaging in EUV, SXR and XR spectral bands of radiation is of increasing interest. Material science, biology and hot plasma are examples of relevant fast developing areas. Applications include spectroscopy, astrophysics, Soft X-ray Ray metrology, Water Window microscopy, radiography and tomography. Especially Water Window imaging has still not fully recognized potential in biology and medicine microscopy applications. Theoretical study and design of Lobster Eye (LE) optics as a collector for water window (WW) microscopy and comparison with a similar size ellipsoidal mirror condensor are presented.

A new design approach to MMI-based (de)multiplexers

NASA Astrophysics Data System (ADS)

Yueyu, Xiao; Sailing, He

2004-09-01

A novel design method of the wavelength (de)multiplexer is presented. The output spectral response of a (de)multiplexer is designed from the view of FIR filters. Avoiding laborious mathematic analysis, the (de)multiplexer is analyzed and designed in this explicit and simple method. A four channel (de)multiplexer based on multimode interference (MMI) is designed as an example. The result obtained agrees with that of the commonly used method, and is verified by a finite difference beam propagation method (FDBPM) simulation.

Spectral Structure Of Phase-Induced Intensity Noise In Recirculating Delay Lines

NASA Astrophysics Data System (ADS)

Tur, M.; Moslehi, B.; Bowers, J. E.; Newton, S. A.; Jackson, K. P.; Goodman, J. W.; Cutler, C. C.; Shaw, H. J.

1983-09-01

The dynamic range of fiber optic signal processors driven by relatively incoherent multimode semiconductor lasers is shown to be severely limited by laser phase-induced noise. It is experimentally demonstrated that while the noise power spectrum of differential length fiber filters is approximately flat, processors with recirculating loops exhibit noise with a periodically structured power spectrum with notches at zero frequency as well as at all other multiples of 1/(loop delay). The experimental results are aug-mented by a theoretical analysis.

Optical fibers for the distribution of frequency and timing references

NASA Technical Reports Server (NTRS)

Lutes, G. F.

1981-01-01

An optical fiber communications link was installed for the purpose of evaluating the applicability of optical fiber technology to the distribution of frequency and timing reference signals. It incorporated a 1.5km length of optical fiber cable containing two multimode optical fibers. The two fibers were welded together at one end of the cable to attain a path length of 3km. Preliminary measurements made on this link, including Allan variance and power spectral density of phase noise are reported.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budagovsky, A V; Solovykh, N V; Budagovskaya, O N

By the example of vegetable organisms differing in structure and functional properties it is shown that their response to the action of quasi-monochromatic light from laser sources does not obey the Bunsen – Roscoe dose law. The dependence of biological effect on the irradiation time has the multimodal (multiextremal) form with alternating maxima and minima of the stimulating effect. Such a property manifests itself in the spectral ranges, corresponding to photoinduced conversion of chromoproteins of photocontrol systems and is probably related to the cyclic variations of metabolic activity in vegetable cells. (biophotonics)

Screening photoswitching properties of synthesized BODIPY-based fluorophores for multispectral superresolution microscopy (MSSRM) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bittel, Amy M.; Saldivar, Isaac S.; Nan, Xiaolin; Gibbs, Summer L.

2016-02-01

Single-molecule localization microscopy (SMLM) utilizes photoswitchable fluorophores to detect biological entities with 10-20 nm resolution. Multispectral superresolution microscopy (MSSRM) extends SMLM functionality by improving its spectral resolution up to 5 fold facilitating imaging of multicomponent cellular structures or signaling pathways. Current commercial fluorophores are not ideal for MSSRM as they are not designed to photoswitch and do not adequately cover the visible and far-red spectral regions required for MSSRM imaging. To obtain optimal MSSRM spatial and spectral resolution, fluorophores with narrow emission spectra and controllable photoswitching properties are necessary. Herein, a library of BODIPY-based fluorophores was synthesized and characterized to create optimal photoswitchable fluorophores for MSSRM. BODIPY was chosen as the core structure as it is photostable, has high quantum yield, and controllable photoswitching. The BODIPY core was modified through the addition of various aromatic moieties, resulting in a spectrally diverse library. Photoswitching properties were characterized using a novel polyvinyl alcohol (PVA) based film methodology to isolate single molecules. The PVA film methodology enabled photoswitching assessment without the need for protein conjugation, greatly improving screening efficiency of the BODIPY library. Additionally, image buffer conditions were optimized for the BODIPY-based fluorophores through systematic testing of oxygen scavenger systems, redox components, and additives. Through screening the photoswitching properties of BODIPY-based compounds in PVA films with optimized imaging buffer we identified novel fluorophores well suited for SMLM and MSSRM.

Multi-modality photoacoustic tomography, ultrasound, and light sheet microscopy for volumetric tumor margin detection

NASA Astrophysics Data System (ADS)

Sangha, Gurneet S.; Hu, Bihe; Bolus, Daniel; Wang, Mei; Skidmore, Shelby J.; Sholl, Andrew B.; Brown, J. Quincy; Goergen, Craig J.

2018-02-01

Current methods for breast tumor margin detection are invasive, time consuming, and typically result in a reoperative rate of over 25%. This marks a clear clinical need to develop improved tools to intraoperatively differentiate negative versus positive tumor margins. Here, we utilize photoacoustic tomography (PAT), ultrasound (US), and inverted Selective Plane Illumination Microscopy (iSPIM) to assess breast tumor margins in eight human breast biopsies. Our PAT/US system consists of a tunable Nd:YAG laser (NT 300, EKSPLA) coupled with a 40MHz central frequency US probe (Vevo2100, FUJIFILM Visual Sonics). This system allows for the delivery of 10Hz, 5ns pulses with fluence of 40mJ/cm2 to the tissue with PAT and US axial resolutions of 125μm and 40μm, respectively. For this study, we used a linear stepper motor to acquire volumetric PAT/US images of the breast biopsies using 1100nm light to identify bloodrich "tumor" regions and 1210nm light to identify lipid-rich "healthy" regions. iSPIM (Applied Scientific Instrumentation) is an advanced microscopy technique with lateral resolution of 1.5μm and axial resolution of 7μm. We used 488nm laser excitation and acridine orange as a general comprehensive histology stain. Our results show that PAT/US can be used to identify lipid-rich regions, dense areas of arterioles and arteries, and other internal structures such as ducts. iSPIM images correlate well with histopathology slides and can verify nuclear features, cell type and density, stromal features, and microcalcifications. Together, this multimodality approach has the potential to improve tumor margin detection with a high degree of sensitivity and specificity.

Characterization of a reflective objective with multiphoton microscopy

NASA Astrophysics Data System (ADS)

Kabir, Mohammad M.; Choubal, Aakash M.; Sivaguru, Mayandi; Toussaint, Kimani C.

2018-02-01

Reflective objectives (ROs) can reduce chromatic aberration across a wide wavelength range in multiphoton microscopy (MPM). However, a systematic characterization of the performance of ROs has not been carried out. In this paper, we analyze the performance of a 0.5 numerical-aperture (NA) RO and compare it with a 0.55 NA standard glass objective (SO), using two-photon fluorescence (TPF) and second-harmonic generation (SHG). For experiments extending 1 octave in visible and NIR wavelengths, the SO introduces defocusing errors of 25% for TPF images of sub-diffraction fluorescent beads and 10% for SHG images of collagen fibers. For both imaging systems, the RO provides a corresponding error of 4%. This work highlights the potential usefulness of ROs for multimodal MPM applications.

Frequency-domain photoacoustic and fluorescence microscopy: application on labeled and unlabeled cells

NASA Astrophysics Data System (ADS)

Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Pfeffer, Karoline; Wohlfarth, Sven; Hannesschläger, Günther; Klar, Thomas A.; Berer, Thomas

2018-02-01

In this paper, multimodal optical-resolution frequency-domain photoacoustic and fluorescence scanning microscopy is presented on labeled and unlabeled cells. In many molecules, excited electrons relax radiatively and non-radiatively, leading to fluorescence and photoacoustic signals, respectively. Both signals can then be detected simultaneously. There also exist molecules, e.g. hemoglobin, which do not exhibit fluorescence, but provide photoacoustic signals solely. Other molecules, especially fluorescent dyes, preferentially exhibit fluorescence. The fluorescence quantum yield of a molecule and with it the strength of photoacoustic and fluorescence signals depends on the local environment, e.g. on the pH. Therefore, the local distribution of the simultaneously recorded photoacoustic and fluorescence signals may be used in order to obtain information about the local chemistry.

Nanoparticle discrimination based on wavelength and lifetime-multiplexed cathodoluminescence microscopy.

PubMed

Garming, Mathijs W H; Weppelman, I Gerward C; de Boer, Pascal; Martínez, Felipe Perona; Schirhagl, Romana; Hoogenboom, Jacob P; Moerland, Robert J

2017-08-31

Nanomaterials can be identified in high-resolution electron microscopy images using spectrally-selective cathodoluminescence. Capabilities for multiplex detection can however be limited, e.g., due to spectral overlap or availability of filters. Also, the available photon flux may be limited due to degradation under electron irradiation. Here, we demonstrate single-pass cathodoluminescence-lifetime based discrimination of different nanoparticles, using a pulsed electron beam. We also show that cathodoluminescence lifetime is a robust parameter even when the nanoparticle cathodoluminescence intensity decays over an order of magnitude. We create lifetime maps, where the lifetime of the cathodoluminescence emission is correlated with the emission intensity and secondary-electron images. The consistency of lifetime-based discrimination is verified by also correlating the emission wavelength and the lifetime of nanoparticles. Our results show how cathodoluminescence lifetime provides an additional channel of information in electron microscopy.

Thin-film tunable filters for hyperspectral fluorescence microscopy

PubMed Central

Favreau, Peter; Hernandez, Clarissa; Lindsey, Ashley Stringfellow; Alvarez, Diego F.; Rich, Thomas; Prabhat, Prashant

2013-01-01

Abstract. Hyperspectral imaging is a powerful tool that acquires data from many spectral bands, forming a contiguous spectrum. Hyperspectral imaging was originally developed for remote sensing applications; however, hyperspectral techniques have since been applied to biological fluorescence imaging applications, such as fluorescence microscopy and small animal fluorescence imaging. The spectral filtering method largely determines the sensitivity and specificity of any hyperspectral imaging system. There are several types of spectral filtering hardware available for microscopy systems, most commonly acousto-optic tunable filters (AOTFs) and liquid crystal tunable filters (LCTFs). These filtering technologies have advantages and disadvantages. Here, we present a novel tunable filter for hyperspectral imaging—the thin-film tunable filter (TFTF). The TFTF presents several advantages over AOTFs and LCTFs, most notably, a high percentage transmission and a high out-of-band optical density (OD). We present a comparison of a TFTF-based hyperspectral microscopy system and a commercially available AOTF-based system. We have characterized the light transmission, wavelength calibration, and OD of both systems, and have then evaluated the capability of each system for discriminating between green fluorescent protein and highly autofluorescent lung tissue. Our results suggest that TFTFs are an alternative approach for hyperspectral filtering that offers improved transmission and out-of-band blocking. These characteristics make TFTFs well suited for other biomedical imaging devices, such as ophthalmoscopes or endoscopes. PMID:24077519

Application of Raman microscopy to biodegradable double-walled microspheres.

PubMed

Widjaja, Effendi; Lee, Wei Li; Loo, Say Chye Joachim

2010-02-15

Raman mapping measurements were performed on the cross section of the ternary-phase biodegradable double-walled microsphere (DWMS) of poly(D,L-lactide-co-glycolide) (50:50) (PLGA), poly(L-lactide) (PLLA), and poly(epsilon-caprolactone) (PCL), which was fabricated by a one-step solvent evaporation method. The collected Raman spectra were subjected to a band-target entropy minimization (BTEM) algorithm in order to reconstruct the pure component spectra of the species observed in this sample. Seven pure component spectral estimates were recovered, and their spatial distributions within DWMS were determined. The first three spectral estimates were identified as PLLA, PLGA 50:50, and PCL, which were the main components in DWMS. The last four spectral estimates were identified as semicrystalline polyglycolic acid (PGA), dichloromethane (DCM), copper-phthalocyanine blue, and calcite, which were the minor components in DWMS. PGA was the decomposition product of PLGA. DCM was the solvent used in DWMS fabrication. Copper-phthalocyanine blue and calcite were the unexpected contaminants. The current result showed that combined Raman microscopy and BTEM analysis can provide a sensitive characterization tool to DWMS, as it can give more specific information on the chemical species present as well as the spatial distributions. This novel analytical method for microsphere characterization can serve as a complementary tool to other more established analytical techniques, such as scanning electron microscopy and optical microscopy.

The study of documentary photographs of the early 20th century by the optical coherence microscopy method

NASA Astrophysics Data System (ADS)

Ryseva, Ekaterina; Zhukova, Ekaterina

2013-05-01

The wide field and spectral methods of optical coherence microscopy were used for extensive studying the photographs printed in the early 20th century. Tomographic images (B-scans) of photo and paper materials are presented and discussed.

CONFOCAL MICROSCOPY SYSTEM PERFORMANCE: FOUNDATIONS FOR QUANTIFYING CYTOMETRIC APPLICATIONS WITH SPECTROSCOPIC INSTRUMENTS

EPA Science Inventory

The confocal laser-scanning microscopy (CLSM) has enormous potential in many biological fields. The goal of a CLSM is to acquire and quantify fluorescence and in some instruments acquire spectral characterization of the emitted signal. The accuracy of these measurements demands t...

Efficient integration of spectral features for vehicle tracking utilizing an adaptive sensor

NASA Astrophysics Data System (ADS)

Uzkent, Burak; Hoffman, Matthew J.; Vodacek, Anthony

2015-03-01

Object tracking in urban environments is an important and challenging problem that is traditionally tackled using visible and near infrared wavelengths. By inserting extended data such as spectral features of the objects one can improve the reliability of the identification process. However, huge increase in data created by hyperspectral imaging is usually prohibitive. To overcome the complexity problem, we propose a persistent air-to-ground target tracking system inspired by a state-of-the-art, adaptive, multi-modal sensor. The adaptive sensor is capable of providing panchromatic images as well as the spectra of desired pixels. This addresses the data challenge of hyperspectral tracking by only recording spectral data as needed. Spectral likelihoods are integrated into a data association algorithm in a Bayesian fashion to minimize the likelihood of misidentification. A framework for controlling spectral data collection is developed by incorporating motion segmentation information and prior information from a Gaussian Sum filter (GSF) movement predictions from a multi-model forecasting set. An intersection mask of the surveillance area is extracted from OpenStreetMap source and incorporated into the tracking algorithm to perform online refinement of multiple model set. The proposed system is tested using challenging and realistic scenarios generated in an adverse environment.

A portable confocal hyperspectral microscope without any scan or tube lens and its application in fluorescence and Raman spectral imaging

NASA Astrophysics Data System (ADS)

Li, Jingwei; Cai, Fuhong; Dong, Yongjiang; Zhu, Zhenfeng; Sun, Xianhe; Zhang, Hequn; He, Sailing

2017-06-01

In this study, a portable confocal hyperspectral microscope is developed. In traditional confocal laser scanning microscopes, scan lens and tube lens are utilized to achieve a conjugate relationship between the galvanometer and the back focal plane of the objective, in order to achieve a better resolution. However, these lenses make it difficult to scale down the volume of the system. In our portable confocal hyperspectral microscope (PCHM), the objective is placed directly next to the galvomirror. Thus, scan lens and tube lens are not included in our system and the size of this system is greatly reduced. Furthermore, the resolution is also acceptable in many biomedical and food-safety applications. Through reducing the optical length of the system, the signal detection efficiency is enhanced. This is conducive to realizing both the fluorescence and Raman hyperspectral imaging. With a multimode fiber as a pinhole, an improved image contrast is also achieved. Fluorescent spectral images for HeLa cells/fingers and Raman spectral images of kumquat pericarp are present. The spectral resolution and spatial resolutions are about 0.4 nm and 2.19 μm, respectively. These results demonstrate that this portable hyperspectral microscope can be used in in-vivo fluorescence imaging and in situ Raman spectral imaging.

The MIND PALACE: A Multi-Spectral Imaging and Spectroscopy Database for Planetary Science

NASA Astrophysics Data System (ADS)

Eshelman, E.; Doloboff, I.; Hara, E. K.; Uckert, K.; Sapers, H. M.; Abbey, W.; Beegle, L. W.; Bhartia, R.

2017-12-01

The Multi-Instrument Database (MIND) is the web-based home to a well-characterized set of analytical data collected by a suite of deep-UV fluorescence/Raman instruments built at the Jet Propulsion Laboratory (JPL). Samples derive from a growing body of planetary surface analogs, mineral and microbial standards, meteorites, spacecraft materials, and other astrobiologically relevant materials. In addition to deep-UV spectroscopy, datasets stored in MIND are obtained from a variety of analytical techniques obtained over multiple spatial and spectral scales including electron microscopy, optical microscopy, infrared spectroscopy, X-ray fluorescence, and direct fluorescence imaging. Multivariate statistical analysis techniques, primarily Principal Component Analysis (PCA), are used to guide interpretation of these large multi-analytical spectral datasets. Spatial co-referencing of integrated spectral/visual maps is performed using QGIS (geographic information system software). Georeferencing techniques transform individual instrument data maps into a layered co-registered data cube for analysis across spectral and spatial scales. The body of data in MIND is intended to serve as a permanent, reliable, and expanding database of deep-UV spectroscopy datasets generated by this unique suite of JPL-based instruments on samples of broad planetary science interest.

Optical tweezers and multiphoton microscopies integrated photonic tool for mechanical and biochemical cell processes studies

NASA Astrophysics Data System (ADS)

de Thomaz, A. A.; Faustino, W. M.; Fontes, A.; Fernandes, H. P.; Barjas-Castro, M. d. L.; Metze, K.; Giorgio, S.; Barbosa, L. C.; Cesar, C. L.

2007-09-01

The research in biomedical photonics is clearly evolving in the direction of the understanding of biological processes at the cell level. The spatial resolution to accomplish this task practically requires photonics tools. However, an integration of different photonic tools and a multimodal and functional approach will be necessary to access the mechanical and biochemical cell processes. This way we can observe mechanicaly triggered biochemical events or biochemicaly triggered mechanical events, or even observe simultaneously mechanical and biochemical events triggered by other means, e.g. electricaly. One great advantage of the photonic tools is its easiness for integration. Therefore, we developed such integrated tool by incorporating single and double Optical Tweezers with Confocal Single and Multiphoton Microscopies. This system can perform 2-photon excited fluorescence and Second Harmonic Generation microscopies together with optical manipulations. It also can acquire Fluorescence and SHG spectra of specific spots. Force, elasticity and viscosity measurements of stretched membranes can be followed by real time confocal microscopies. Also opticaly trapped living protozoas, such as leishmania amazonensis. Integration with CARS microscopy is under way. We will show several examples of the use of such integrated instrument and its potential to observe mechanical and biochemical processes at cell level.

Confocal Rheology Probes the Structure and Mechanics of Collagen through the Sol-Gel Transition.

PubMed

Tran-Ba, Khanh-Hoa; Lee, Daniel J; Zhu, Jieling; Paeng, Keewook; Kaufman, Laura J

2017-10-17

Fibrillar type I collagen-based hydrogels are commonly used in tissue engineering and as matrices for biophysical studies. Mechanical and structural properties of these gels are known to be governed by the conditions under which fibrillogenesis occurs, exhibiting variation as a function of protein concentration, temperature, pH, and ionic strength. Deeper understanding of how macroscopic structure affects viscoelastic properties of collagen gels over the course of fibrillogenesis provides fundamental insight into biopolymer gel properties and promises enhanced control over the properties of such gels. Here, we investigate type I collagen fibrillogenesis using confocal rheology-simultaneous confocal reflectance microscopy, confocal fluorescence microscopy, and rheology. The multimodal approach allows direct comparison of how viscoelastic properties track the structural evolution of the gel on fiber and network length scales. Quantitative assessment and comparison of each imaging modality and the simultaneously collected rheological measurements show that the presence of a system-spanning structure occurs at a time similar to rheological determinants of gelation. Although this and some rheological measures are consistent with critical gelation through percolation, additional rheological and structural properties of the gel are found to be inconsistent with this theory. This study clarifies how structure sets viscoelasticity during collagen fibrillogenesis and more broadly highlights the utility of multimodal measurements as critical test-beds for theoretical descriptions of complex systems. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Antibody Conjugated, Raman Tagged Hollow Gold-Silver Nanospheres for Specific Targeting and Multimodal Dark-Field/SERS/Two Photon-FLIM Imaging of CD19(+) B Lymphoblasts.

PubMed

Nagy-Simon, Timea; Tatar, Andra-Sorina; Craciun, Ana-Maria; Vulpoi, Adriana; Jurj, Maria-Ancuta; Florea, Adrian; Tomuleasa, Ciprian; Berindan-Neagoe, Ioana; Astilean, Simion; Boca, Sanda

2017-06-28

In this Research Article, we propose a new class of contrast agents for the detection and multimodal imaging of CD19(+) cancer lymphoblasts. The agents are based on NIR responsive hollow gold-silver nanospheres conjugated with antiCD19 monoclonal antibodies and marked with Nile Blue (NB) SERS active molecules (HNS-NB-PEG-antiCD19). Proof of concept experiments on specificity of the complex for the investigated cells was achieved by transmission electron microscopy (TEM). The microspectroscopic investigations via dark field (DF), surface-enhanced Raman spectroscopy (SERS), and two-photon excited fluorescence lifetime imaging microscopy (TPE-FLIM) corroborate with TEM and demonstrate successful and preferential internalization of the antibody-nanocomplex. The combination of the microspectroscopic techniques enables contrast and sensitivity that competes with more invasive and time demanding cell imaging modalities, while depth sectioning images provide real time localization of the nanoparticles in the whole cytoplasm at the entire depth of the cells. Our findings prove that HNS-NB-PEG-antiCD19 represent a promising type of new contrast agents with great possibility of being detected by multiple, non invasive, rapid and accessible microspectroscopic techniques and real applicability for specific targeting of CD19(+) cancer cells. Such versatile nanocomplexes combine in one single platform the detection and imaging of cancer lymphoblasts by DF, SERS, and TPE-FLIM microspectroscopy.

Nanoscale simultaneous chemical and mechanical imaging via peak force infrared microscopy

PubMed Central

Wang, Le; Wang, Haomin; Wagner, Martin; Yan, Yong; Jakob, Devon S.; Xu, Xiaoji G.

2017-01-01

Nondestructive chemical and mechanical measurements of materials with ~10-nm spatial resolution together with topography provide rich information on the compositions and organizations of heterogeneous materials and nanoscale objects. However, multimodal nanoscale correlations are difficult to achieve because of the limitation on spatial resolution of optical microscopy and constraints from instrumental complexities. We report a novel noninvasive spectroscopic scanning probe microscopy method—peak force infrared (PFIR) microscopy—that allows chemical imaging, collection of broadband infrared spectra, and mechanical mapping at a spatial resolution of 10 nm. In our technique, chemical absorption information is directly encoded in the withdraw curve of the peak force tapping cycle after illumination with synchronized infrared laser pulses in a simple apparatus. Nanoscale phase separation in block copolymers and inhomogeneity in CH3NH3PbBr3 perovskite crystals are studied with correlative infrared/mechanical nanoimaging. Furthermore, we show that the PFIR method is sensitive to the presence of surface phonon polaritons in boron nitride nanotubes. PFIR microscopy will provide a powerful analytical tool for explorations at the nanoscale across wide disciplines. PMID:28691096

Effectiveness of Modal Decomposition for Tapping Atomic Force Microscopy Microcantilevers in Liquid Environment.

PubMed

Kim, Il Kwang; Lee, Soo Il

2016-05-01

The modal decomposition of tapping mode atomic force microscopy microcantilevers in liquid environments was studied experimentally. Microcantilevers with different lengths and stiffnesses and two sample surfaces with different elastic moduli were used in the experiment. The response modes of the microcantilevers were extracted as proper orthogonal modes through proper orthogonal decomposition. Smooth orthogonal decomposition was used to estimate the resonance frequency directly. The effects of the tapping setpoint and the elastic modulus of the sample under test were examined in terms of their multi-mode responses with proper orthogonal modes, proper orthogonal values, smooth orthogonal modes and smooth orthogonal values. Regardless of the stiffness of the microcantilever under test, the first mode was dominant in tapping mode atomic force microscopy under normal operating conditions. However, at lower tapping setpoints, the flexible microcantilever showed modal distortion and noise near the tip when tapping on a hard sample. The stiff microcantilever had a higher mode effect on a soft sample at lower tapping setpoints. Modal decomposition for tapping mode atomic force microscopy can thus be used to estimate the characteristics of samples in liquid environments.

Multiplane and Spectrally-Resolved Single Molecule Localization Microscopy with Industrial Grade CMOS cameras.

PubMed

Babcock, Hazen P

2018-01-29

This work explores the use of industrial grade CMOS cameras for single molecule localization microscopy (SMLM). We show that industrial grade CMOS cameras approach the performance of scientific grade CMOS cameras at a fraction of the cost. This makes it more economically feasible to construct high-performance imaging systems with multiple cameras that are capable of a diversity of applications. In particular we demonstrate the use of industrial CMOS cameras for biplane, multiplane and spectrally resolved SMLM. We also provide open-source software for simultaneous control of multiple CMOS cameras and for the reduction of the movies that are acquired to super-resolution images.

Development of a multi-scale and multi-modality imaging system to characterize tumours and their microenvironment in vivo

NASA Astrophysics Data System (ADS)

Rouffiac, Valérie; Ser-Leroux, Karine; Dugon, Emilie; Leguerney, Ingrid; Polrot, Mélanie; Robin, Sandra; Salomé-Desnoulez, Sophie; Ginefri, Jean-Christophe; Sebrié, Catherine; Laplace-Builhé, Corinne

2015-03-01

In vivo high-resolution imaging of tumor development is possible through dorsal skinfold chamber implantable on mice model. However, current intravital imaging systems are weakly tolerated along time by mice and do not allow multimodality imaging. Our project aims to develop a new chamber for: 1- long-term micro/macroscopic visualization of tumor (vascular and cellular compartments) and tissue microenvironment; and 2- multimodality imaging (photonic, MRI and sonography). Our new experimental device was patented in March 2014 and was primarily assessed on 75 mouse engrafted with 4T1-Luc tumor cell line, and validated in confocal and multiphoton imaging after staining the mice vasculature using Dextran 155KDa-TRITC or Dextran 2000kDa-FITC. Simultaneously, a universal stage was designed for optimal removal of respiratory and cardiac artifacts during microscopy assays. Experimental results from optical, ultrasound (Bmode and pulse subtraction mode) and MRI imaging (anatomic sequences) showed that our patented design, unlike commercial devices, improves longitudinal monitoring over several weeks (35 days on average against 12 for the commercial chamber) and allows for a better characterization of the early and late tissue alterations due to tumour development. We also demonstrated the compatibility for multimodality imaging and the increase of mice survival was by a factor of 2.9, with our new skinfold chamber. Current developments include: 1- defining new procedures for multi-labelling of cells and tissue (screening of fluorescent molecules and imaging protocols); 2- developing ultrasound and MRI imaging procedures with specific probes; 3- correlating optical/ultrasound/MRI data for a complete mapping of tumour development and microenvironment.

A multimodal spectroscopy system for real-time disease diagnosis

NASA Astrophysics Data System (ADS)

Šćepanović, Obrad R.; Volynskaya, Zoya; Kong, Chae-Ryon; Galindo, Luis H.; Dasari, Ramachandra R.; Feld, Michael S.

2009-04-01

The combination of reflectance, fluorescence, and Raman spectroscopy—termed multimodal spectroscopy (MMS)—provides complementary and depth-sensitive information about tissue composition. As such, MMS is a promising tool for disease diagnosis, particularly in atherosclerosis and breast cancer. We have developed an integrated MMS instrument and optical fiber spectral probe for simultaneous collection of all three modalities in a clinical setting. The MMS instrument multiplexes three excitation sources, a xenon flash lamp (370-740 nm), a nitrogen laser (337 nm), and a diode laser (830 nm), through the MMS probe to excite tissue and collect the spectra. The spectra are recorded on two spectrograph/charge-coupled device modules, one optimized for visible wavelengths (reflectance and fluorescence) and the other for the near-infrared (Raman), and processed to provide diagnostic parameters. We also describe the design and calibration of a unitary MMS optical fiber probe 2 mm in outer diameter, containing a single appropriately filtered excitation fiber and a ring of 15 collection fibers, with separate groups of appropriately filtered fibers for efficiently collecting reflectance, fluorescence, and Raman spectra from the same tissue location. A probe with this excitation/collection geometry has not been used previously to collect reflectance and fluorescence spectra, and thus physical tissue models ("phantoms") are used to characterize the probe's spectroscopic response. This calibration provides probe-specific modeling parameters that enable accurate extraction of spectral parameters. This clinical MMS system has been used recently to analyze artery and breast tissue in vivo and ex vivo.

Simultaneous frequency stabilization and high-power dense wavelength division multiplexing (HP-DWDM) using an external cavity based on volume Bragg gratings (VBGs)

NASA Astrophysics Data System (ADS)

Hengesbach, Stefan; Klein, Sarah; Holly, Carlo; Witte, Ulrich; Traub, Martin; Hoffmann, Dieter

2016-03-01

Multiplexing technologies enable the development of high-brightness diode lasers for direct industrial applications. We present a High-Power Dense Wavelength Division Multiplexer (HP-DWDM) with an average channel spacing of 1.7 (1.5) nm and a subsequent external cavity mirror to provide feedback for frequency stabilization and multiplexing in one step. The "self-optimizing" multiplexing unit consists of four reflective Volume Bragg Gratings (VBGs) with 99% diffraction efficiency and seven dielectric mirrors to overlay the radiation of five input channels with an adjustable channel spacing of 1-2 nm. In detail, we focus on the analysis of the overall optical efficiency, the change of the beam parameter product and the spectral width. The performance is demonstrated using five 90 μm multimode 9xx single emitters with M2<=17. Because of the feedback the lateral (multimodal) spatial and angular intensity distribution changes strongly and the beam parameter product decreases by a factor of 1.2 to 1.9. Thereby the angular intensity distribution is more affected than the width of the beam waist. The spectral width per emitter decreases to 3-200 pm (FWHM) depending on the injection current and the reflectance of the feedback mirror (0.75%, 1.5%, 4%, 6% or 8%). The overall optical multiplexing efficiency ranges between 77% and 86%. With some modifications (e.g. enhanced AR-coatings) we expect 90-95%.

Aerosol Size Distributions During ACE-Asia: Retrievals From Optical Thickness and Comparisons With In-situ Measurements

NASA Astrophysics Data System (ADS)

Kuzmanoski, M.; Box, M.; Box, G. P.; Schmidt, B.; Russell, P. B.; Redemann, J.; Livingston, J. M.; Wang, J.; Flagan, R. C.; Seinfeld, J. H.

2002-12-01

As part of the ACE-Asia experiment, conducted off the coast of China, Korea and Japan in spring 2001, measurements of aerosol physical, chemical and radiative characteristics were performed aboard the Twin Otter aircraft. Of particular importance for this paper were spectral measurements of aerosol optical thickness obtained at 13 discrete wavelengths, within 354-1558 nm wavelength range, using the AATS-14 sunphotometer. Spectral aerosol optical thickness can be used to obtain information about particle size distribution. In this paper, we use sunphotometer measurements to retrieve size distribution of aerosols during ACE-Asia. We focus on four cases in which layers influenced by different air masses were identified. Aerosol optical thickness of each layer was inverted using two different techniques - constrained linear inversion and multimodal. In the constrained linear inversion algorithm no assumption about the mathematical form of the distribution to be retrieved is made. Conversely, the multimodal technique assumes that aerosol size distribution is represented as a linear combination of few lognormal modes with predefined values of mode radii and geometric standard deviations. Amplitudes of modes are varied to obtain best fit of sum of optical thicknesses due to individual modes to sunphotometer measurements. In this paper we compare the results of these two retrieval methods. In addition, we present comparisons of retrieved size distributions with in situ measurements taken using an aerodynamic particle sizer and differential mobility analyzer system aboard the Twin Otter aircraft.

Nonspinning numerical relativity waveform surrogates: assessing the model

NASA Astrophysics Data System (ADS)

Field, Scott; Blackman, Jonathan; Galley, Chad; Scheel, Mark; Szilagyi, Bela; Tiglio, Manuel

2015-04-01

Recently, multi-modal gravitational waveform surrogate models have been built directly from data numerically generated by the Spectral Einstein Code (SpEC). I will describe ways in which the surrogate model error can be quantified. This task, in turn, requires (i) characterizing differences between waveforms computed by SpEC with those predicted by the surrogate model and (ii) estimating errors associated with the SpEC waveforms from which the surrogate is built. Both pieces can have numerous sources of numerical and systematic errors. We make an attempt to study the most dominant error sources and, ultimately, the surrogate model's fidelity. These investigations yield information about the surrogate model's uncertainty as a function of time (or frequency) and parameter, and could be useful in parameter estimation studies which seek to incorporate model error. Finally, I will conclude by comparing the numerical relativity surrogate model to other inspiral-merger-ringdown models. A companion talk will cover the building of multi-modal surrogate models.

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography.

PubMed

Garcia, Jose Mauricio Botto de Barros; Isaac, David Leonardo Cruvinel; Sardeiro, Tainara; Aquino, Érika; Avila, Marcos

2017-01-01

This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980), an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

A Multimode Optical Imaging System for Preclinical Applications In Vivo: Technology Development, Multiscale Imaging, and Chemotherapy Assessment

PubMed Central

Hwang, Jae Youn; Wachsmann-Hogiu, Sebastian; Ramanujan, V. Krishnan; Ljubimova, Julia; Gross, Zeev; Gray, Harry B.; Medina-Kauwe, Lali K.; Farkas, Daniel L.

2012-01-01

Purpose Several established optical imaging approaches have been applied, usually in isolation, to preclinical studies; however, truly useful in vivo imaging may require a simultaneous combination of imaging modalities to examine dynamic characteristics of cells and tissues. We developed a new multimode optical imaging system designed to be application-versatile, yielding high sensitivity, and specificity molecular imaging. Procedures We integrated several optical imaging technologies, including fluorescence intensity, spectral, lifetime, intravital confocal, two-photon excitation, and bioluminescence, into a single system that enables functional multiscale imaging in animal models. Results The approach offers a comprehensive imaging platform for kinetic, quantitative, and environmental analysis of highly relevant information, with micro-to-macroscopic resolution. Applied to small animals in vivo, this provides superior monitoring of processes of interest, represented here by chemo-/nanoconstruct therapy assessment. Conclusions This new system is versatile and can be optimized for various applications, of which cancer detection and targeted treatment are emphasized here. PMID:21874388

A multiplexed light-matter interface for fibre-based quantum networks

PubMed Central

Saglamyurek, Erhan; Grimau Puigibert, Marcelli; Zhou, Qiang; Giner, Lambert; Marsili, Francesco; Verma, Varun B.; Woo Nam, Sae; Oesterling, Lee; Nippa, David; Oblak, Daniel; Tittel, Wolfgang

2016-01-01

Processing and distributing quantum information using photons through fibre-optic or free-space links are essential for building future quantum networks. The scalability needed for such networks can be achieved by employing photonic quantum states that are multiplexed into time and/or frequency, and light-matter interfaces that are able to store and process such states with large time-bandwidth product and multimode capacities. Despite important progress in developing such devices, the demonstration of these capabilities using non-classical light remains challenging. Here, employing the atomic frequency comb quantum memory protocol in a cryogenically cooled erbium-doped optical fibre, we report the quantum storage of heralded single photons at a telecom-wavelength (1.53 μm) with a time-bandwidth product approaching 800. Furthermore, we demonstrate frequency-multimode storage and memory-based spectral-temporal photon manipulation. Notably, our demonstrations rely on fully integrated quantum technologies operating at telecommunication wavelengths. With improved storage efficiency, our light-matter interface may become a useful tool in future quantum networks. PMID:27046076

Single-Mode VCSELs

NASA Astrophysics Data System (ADS)

Larsson, Anders; Gustavsson, Johan S.

The only active transverse mode in a truly single-mode VCSEL is the fundamental mode with a near Gaussian field distribution. A single-mode VCSEL produces a light beam of higher spectral purity, higher degree of coherence and lower divergence than a multimode VCSEL and the beam can be more precisely shaped and focused to a smaller spot. Such beam properties are required in many applications. In this chapter, after discussing applications of single-mode VCSELs, we introduce the basics of fields and modes in VCSELs and review designs implemented for single-mode emission from VCSELs in different materials and at different wavelengths. This includes VCSELs that are inherently single-mode as well as inherently multimode VCSELs where higher-order modes are suppressed by mode selective gain or loss. In each case we present the current state-of-the-art and discuss pros and cons. At the end, a specific example with experimental results is provided and, as a summary, the most promising designs based on current technologies are identified.

Photonic bandpass filter characteristics of multimode SOI waveguides integrated with submicron gratings.

PubMed

Sah, Parimal; Das, Bijoy Krishna

2018-03-20

It has been shown that a fundamental mode adiabatically launched into a multimode SOI waveguide with submicron grating offers well-defined flat-top bandpass filter characteristics in transmission. The transmitted spectral bandwidth is controlled by adjusting both waveguide and grating design parameters. The bandwidth is further narrowed down by cascading two gratings with detuned parameters. A semi-analytical model is used to analyze the filter characteristics (1500  nm≤λ≤1650  nm) of the device operating in transverse-electric polarization. The proposed devices were fabricated with an optimized set of design parameters in a SOI substrate with a device layer thickness of 250 nm. The pass bandwidth of waveguide devices integrated with single-stage gratings are measured to be ∼24  nm, whereas the device with two cascaded gratings with slightly detuned periods (ΔΛ=2  nm) exhibits a pass bandwidth down to ∼10  nm.

A multiplexed light-matter interface for fibre-based quantum networks.

PubMed

Saglamyurek, Erhan; Grimau Puigibert, Marcelli; Zhou, Qiang; Giner, Lambert; Marsili, Francesco; Verma, Varun B; Woo Nam, Sae; Oesterling, Lee; Nippa, David; Oblak, Daniel; Tittel, Wolfgang

2016-04-05

Processing and distributing quantum information using photons through fibre-optic or free-space links are essential for building future quantum networks. The scalability needed for such networks can be achieved by employing photonic quantum states that are multiplexed into time and/or frequency, and light-matter interfaces that are able to store and process such states with large time-bandwidth product and multimode capacities. Despite important progress in developing such devices, the demonstration of these capabilities using non-classical light remains challenging. Here, employing the atomic frequency comb quantum memory protocol in a cryogenically cooled erbium-doped optical fibre, we report the quantum storage of heralded single photons at a telecom-wavelength (1.53 μm) with a time-bandwidth product approaching 800. Furthermore, we demonstrate frequency-multimode storage and memory-based spectral-temporal photon manipulation. Notably, our demonstrations rely on fully integrated quantum technologies operating at telecommunication wavelengths. With improved storage efficiency, our light-matter interface may become a useful tool in future quantum networks.

Deterministic Integration of Quantum Dots into on-Chip Multimode Interference Beamsplitters Using in Situ Electron Beam Lithography.

PubMed

Schnauber, Peter; Schall, Johannes; Bounouar, Samir; Höhne, Theresa; Park, Suk-In; Ryu, Geun-Hwan; Heindel, Tobias; Burger, Sven; Song, Jin-Dong; Rodt, Sven; Reitzenstein, Stephan

2018-04-11

The development of multinode quantum optical circuits has attracted great attention in recent years. In particular, interfacing quantum-light sources, gates, and detectors on a single chip is highly desirable for the realization of large networks. In this context, fabrication techniques that enable the deterministic integration of preselected quantum-light emitters into nanophotonic elements play a key role when moving forward to circuits containing multiple emitters. Here, we present the deterministic integration of an InAs quantum dot into a 50/50 multimode interference beamsplitter via in situ electron beam lithography. We demonstrate the combined emitter-gate interface functionality by measuring triggered single-photon emission on-chip with g (2) (0) = 0.13 ± 0.02. Due to its high patterning resolution as well as spectral and spatial control, in situ electron beam lithography allows for integration of preselected quantum emitters into complex photonic systems. Being a scalable single-step approach, it paves the way toward multinode, fully integrated quantum photonic chips.

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

DOE PAGES

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra; ...

2017-05-03

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

Efficient pump module coupling >1kW from a compact detachable fiber

NASA Astrophysics Data System (ADS)

Dogan, M.; Chin, R. H.; Fulghum, S.; Jacob, J. H.; Chin, A. K.

2018-02-01

In the most developed fiber amplifiers, optical pump power is introduced into the 400μm-diameter, 0.46NA first cladding of the double-clad, Yb-doped, gain fiber, using a (6+1):1 multi-mode fiber combiner. For this configuration, the core diameter and numerical aperture of the pump delivery fibers have maximum values of 225μm and 0.22, respectively. This paper presents the first fiber-coupled laser-diode pump module emitting more than 1kW of claddingmode- stripped power from a detachable 225μm, 0.22NA delivery fiber at 976nm. The electrical-to-optical power conversion efficiency at 1kW is 50%. The FWHM spectral width at 1kW output is 4nm and has an excellent overlap with the narrow absorption spectrum of ytterbium in glass. Six of these pump modules attached to a (6+1):1 multimode combiner enable a 5-6kW, single-mode, Yb-doped fiber amplifier.

Spectral domain phase microscopy: a new tool for measuring cellular dynamics and cytoplasmic flow

NASA Astrophysics Data System (ADS)

McDowell, Emily J.; Choma, Michael A.; Ellerbee, Audrey K.; Izatt, Joseph A.

2005-03-01

Broadband interferometry is an attractive technique for the detection of cellular motions because it provides depth-resolved interferometric phase information via coherence gating. Here a phase sensitive technique called spectral domain phase microscopy (SDPM) is presented. SDPM is a functional extension of spectral domain optical coherence tomography that allows for the detection of cellular motions and dynamics with nanometer-scale sensitivity. This sensitivity is made possible by the inherent phase stability of spectral domain OCT combined with common-path interferometry. The theory that underlies this technique is presented, the sensitivity of the technique is demonstrated by the measurement of the thermal expansion coefficient of borosilicate glass, and the response of an Amoeba proteus to puncture of its cell membrane is measured. We also exploit the phase stability of SDPM to perform Doppler flow imaging of cytoplasmic streaming in A. proteus. We show reversal of cytoplasmic flow in response to stimuli, and we show that the cytoplasmic flow is laminar (i.e. parabolic) in nature. We are currently investigating the use of SDPM in a variety of different cell types.

Combining total internal reflection sum frequency spectroscopy spectral imaging and confocal fluorescence microscopy.

PubMed

Allgeyer, Edward S; Sterling, Sarah M; Gunewardene, Mudalige S; Hess, Samuel T; Neivandt, David J; Mason, Michael D

2015-01-27

Understanding surface and interfacial lateral organization in material and biological systems is critical in nearly every field of science. The continued development of tools and techniques viable for elucidation of interfacial and surface information is therefore necessary to address new questions and further current investigations. Sum frequency spectroscopy (SFS) is a label-free, nonlinear optical technique with inherent surface specificity that can yield critical organizational information on interfacial species. Unfortunately, SFS provides no spatial information on a surface; small scale heterogeneities that may exist are averaged over the large areas typically probed. Over the past decade, this has begun to be addressed with the advent of SFS microscopy. Here we detail the construction and function of a total internal reflection (TIR) SFS spectral and confocal fluorescence imaging microscope directly amenable to surface investigations. This instrument combines, for the first time, sample scanning TIR-SFS imaging with confocal fluorescence microscopy.

Spectrally reconfigurable integrated multi-spot particle trap.

PubMed

Leake, Kaelyn D; Olson, Michael A B; Ozcelik, Damla; Hawkins, Aaron R; Schmidt, Holger

2015-12-01

Optical manipulation of small particles in the form of trapping, pushing, or sorting has developed into a vast field with applications in the life sciences, biophysics, and atomic physics. Recently, there has been increasing effort toward integration of particle manipulation techniques with integrated photonic structures on self-contained optofluidic chips. Here, we use the wavelength dependence of multi-spot pattern formation in multimode interference (MMI) waveguides to create a new type of reconfigurable, integrated optical particle trap. Interfering lateral MMI modes create multiple trapping spots in an intersecting fluidic channel. The number of trapping spots can be dynamically controlled by altering the trapping wavelength. This novel, spectral reconfigurability is utilized to deterministically move single and multiple particles between different trapping locations along the channel. This fully integrated multi-particle trap can form the basis of high throughput biophotonic assays on a chip.

Optical Measurement of Mass Flow of a Two-Phase Fluid

NASA Technical Reports Server (NTRS)

Wiley, John; Pedersen, Kevin; Koman, Valentin; Gregory, Don

2008-01-01

An optoelectronic system utilizes wavelength-dependent scattering of light for measuring the density and mass flow of a two-phase fluid in a pipe. The apparatus was invented for original use in measuring the mass flow of a two-phase cryogenic fluid (e.g., liquid hydrogen containing bubbles of hydrogen gas), but underlying principles of operation can readily be adapted to non-cryogenic two-phase fluids. The system (see figure) includes a laser module, which contains two or more laser diodes, each operating at a different wavelength. The laser module also contains beam splitters that combine the beams at the various wavelengths so as to produce two output beams, each containing all of the wavelengths. One of the multiwavelength output beams is sent, via a multimode fiberoptic cable, to a transmitting optical coupler. The other multiwavelength output beam is sent, via another multimode fiber-optic cable, to a reference detector module, wherein fiber-optic splitters split the light into several multiwavelength beams, each going to a photodiode having a spectral response that is known and that differs from the spectral responses of the other photodiodes. The outputs of these photodiodes are digitized and fed to a processor, which executes an algorithm that utilizes the known spectral responses to convert the photodiode outputs to obtain reference laser-power levels for the various wavelengths. The transmitting optical coupler is mounted in (and sealed to) a hole in the pipe and is oriented at a slant with respect to the axis of the pipe. The transmitting optical coupler contains a collimating lens and a cylindrical lens that form the light emerging from the end of the fiber-optic cable into a fan-shaped beam in a meridional plane of the pipe. Receiving optical couplers similar to the transmitting optical couplers are mounted in the same meridional plane at various longitudinal positions on the opposite side of the pipe, approximately facing the transmitting optical coupler along the same slant. Light collected by each receiving optical coupler is sent, via a multimode fiber-optic cable, to a detector module similar to the reference detector module. The outputs of the photodiodes in each detector module are digitized and processed, similarly to those of the reference detector module, to obtain indications of the amounts of light of each wavelength scattered to the corresponding receiving position. The value for each wavelength at each position is also normalized to the reference laser-power level for that wavelength. From these normalized values, the density and the mass flow rate of the fluid are estimated.

Drusen Characterization with Multimodal Imaging

PubMed Central

Spaide, Richard F.; Curcio, Christine A.

2010-01-01

Summary Multimodal imaging findings and histological demonstration of soft drusen, cuticular drusen, and subretinal drusenoid deposits provided information used to develop a model explaining their imaging characteristics. Purpose To characterize the known appearance of cuticular drusen, subretinal drusenoid deposits (reticular pseudodrusen), and soft drusen as revealed by multimodal fundus imaging; to create an explanatory model that accounts for these observations. Methods Reported color, fluorescein angiographic, autofluorescence, and spectral domain optical coherence tomography (SD-OCT) images of patients with cuticular drusen, soft drusen, and subretinal drusenoid deposits were reviewed, as were actual images from affected eyes. Representative histological sections were examined. The geometry, location, and imaging characteristics of these lesions were evaluated. A hypothesis based on the Beer-Lambert Law of light absorption was generated to fit these observations. Results Cuticular drusen appear as numerous uniform round yellow-white punctate accumulations under the retinal pigment epithelium (RPE). Soft drusen are larger yellow-white dome-shaped mounds of deposit under the RPE. Subretinal drusenoid deposits are polymorphous light-grey interconnected accumulations above the RPE. Based on the model, both cuticular and soft drusen appear yellow due to the removal of shorter wavelength light by a double pass through the RPE. Subretinal drusenoid deposits, which are located on the RPE, are not subjected to short wavelength attenuation and therefore are more prominent when viewed with blue light. The location and morphology of extracellular material in relationship to the RPE, and associated changes to RPE morphology and pigmentation, appeared to be primary determinants of druse appearance in different imaging modalities. Conclusion Although cuticular drusen, subretinal drusenoid deposits, and soft drusen are composed of common components, they are distinguishable by multimodal imaging due to differences in location, morphology, and optical filtering effects by drusenoid material and the RPE. PMID:20924263

Quasi-interferometric scheme improved by fiber Bragg grating written on macrostructure defect in silica multimode optical fiber operating in a few-mode regime

NASA Astrophysics Data System (ADS)

Evtushenko, Alexander S.; Faskhutdinov, Lenar M.; Kafarova, Anastasia M.; Kuznetzov, Artem A.; Minaeva, Alina Yu.; Sevruk, Nikita L.; Nureev, Ilnur I.; Vasilets, Alexander A.; Andreev, Vladimir A.; Morozov, Oleg G.; Burdin, Vladimir A.; Bourdine, Anton V.

2017-04-01

This work presents results of experimental approbation of earlier on proposed modified fiber optic stress sensor based on a few-mode effects occurring during laser-excited optical signal propagation over silica multimode optical fiber (MMF). Modification is concerned with a passage to quasi-interferometric scheme realized by two multimode Y-couplers with equalized arm lengths improved by fiber Bragg grating (FBG) written on preliminary formed precision macrostructure defects in silica multimode graded-index optical fibers and special offset launching conditions providing laser-based excitation of higher-order modes. The "arms" of quasi-interferometer are two equalized lengths of MMF Cat. OM2 with great central dip of refractive index profile and strong pulse splitting due to high differential mode delay (DMD). We tested FBGs with Bragg wavelength both 1310 nm and 1550 nm written over tapers or up-tapers preliminary formed in short pieces of MMF Cat. OM2+/OM3 and further jointed to the end of one of the arms before output Y-coupler. Researches were focused on comparison analysis of pulse responses under changing of selected excited mode mixing and power diffusion processes due to stress distributed action to sensor fiber depending. Here we considered FBGs not only as particular wavelength reflector during spectral response measurement but also as local periodic microstructure defect which strongly effects on few-mode signal components mixing process also improved by combination with macro-defect like taper or up-taper that should provide response variation. Some results pulse response measurements produced for different scheme configuration and their comparison analysis are represented.

Sparse-sampling with time-encoded (TICO) stimulated Raman scattering for fast image acquisition

NASA Astrophysics Data System (ADS)

Hakert, Hubertus; Eibl, Matthias; Karpf, Sebastian; Huber, Robert

2017-07-01

Modern biomedical imaging modalities aim to provide researchers a multimodal contrast for a deeper insight into a specimen under investigation. A very promising technique is stimulated Raman scattering (SRS) microscopy, which can unveil the chemical composition of a sample with a very high specificity. Although the signal intensities are enhanced manifold to achieve a faster acquisition of images if compared to standard Raman microscopy, there is a trade-off between specificity and acquisition speed. Commonly used SRS concepts either probe only very few Raman transitions as the tuning of the applied laser sources is complicated or record whole spectra with a spectrometer based setup. While the first approach is fast, it reduces the specificity and the spectrometer approach records whole spectra -with energy differences where no Raman information is present-, which limits the acquisition speed. Therefore, we present a new approach based on the TICO-Raman concept, which we call sparse-sampling. The TICO-sparse-sampling setup is fully electronically controllable and allows probing of only the characteristic peaks of a Raman spectrum instead of always acquiring a whole spectrum. By reducing the spectral points to the relevant peaks, the acquisition time can be greatly reduced compared to a uniformly, equidistantly sampled Raman spectrum while the specificity and the signal to noise ratio (SNR) are maintained. Furthermore, all laser sources are completely fiber based. The synchronized detection enables a full resolution of the Raman signal, whereas the analogue and digital balancing allows shot noise limited detection. First imaging results with polystyrene (PS) and polymethylmethacrylate (PMMA) beads confirm the advantages of TICO sparse-sampling. We achieved a pixel dwell time as low as 35 μs for an image differentiating both species. The mechanical properties of the applied voice coil stage for scanning the sample currently limits even faster acquisition.

Electron Energy Loss Spectral Imaging of TiC Formed by Supernovae: A Scanning Transmission Electron Microscopy Study of Grain Formation and Alteration Mechanisms

NASA Astrophysics Data System (ADS)

Daulton, T. L.; Bernatowicz, T. J.; Croat, T. K.

2012-03-01

Micrometer-sized spherules of graphite formed by supernovae contain numerous TiC and Fe-Ni subgrains. These subgrains often have disordered surface rims. The mechanism(s) of rim formation on these subgrains is studied by transmission electron microscopy.

Fiber-optic-bundle-based optical coherence tomography.

PubMed

Xie, Tuqiang; Mukai, David; Guo, Shuguang; Brenner, Matthew; Chen, Zhongping

2005-07-15

A fiber-optic-bundle-based optical coherence tomography (OCT) probe method is presented. The experimental results demonstrate this multimode optical fiber-bundle-based OCT system can achieve a lateral resolution of 12 microm and an axial resolution of 10 microm with a superluminescent diode source. This novel OCT imaging approach eliminates any moving parts in the probe and has a primary advantage for use in extremely compact and safe OCT endoscopes for imaging internal organs and great potential to be combined with confocal endoscopic microscopy.

Localization of protein-protein interactions among three fluorescent proteins in a single living cell: three-color FRET microscopy

NASA Astrophysics Data System (ADS)

Sun, Yuansheng; Booker, Cynthia F.; Day, Richard N.; Periasamy, Ammasi

2009-02-01

Förster resonance energy transfer (FRET) methodology has been used for over 30 years to localize protein-protein interactions in living specimens. The cloning and modification of various visible fluorescent proteins (FPs) has generated a variety of new probes that can be used as FRET pairs to investigate the protein associations in living cells. However, the spectral cross-talk between FRET donor and acceptor channels has been a major limitation to FRET microscopy. Many investigators have developed different ways to eliminate the bleedthrough signals in the FRET channel for one donor and one acceptor. We developed a novel FRET microscopy method for studying interactions among three chromophores: three-color FRET microscopy. We generated a genetic construct that directly links the three FPs - monomeric teal FP (mTFP), Venus and tandem dimer Tomato (tdTomato), and demonstrated the occurrence of mutually dependent energy transfers among the three FPs. When expressed in cells and excited with the 458 nm laser line, the mTFP-Venus-tdTomato fusion proteins yielded parallel (mTFP to Venus and mTFP to tdTomato) and sequential (mTFP to Venus and then to tdTomato) energy transfer signals. To quantify the FRET signals in the three-FP system in a single living cell, we developed an algorithm to remove all the spectral cross-talk components and also to separate different FRET signals at a same emission channel using the laser scanning spectral imaging and linear unmixing techniques on the Zeiss510 META system. Our results were confirmed with fluorescence lifetime measurements and using acceptor photobleaching FRET microscopy.

Quantitative chemical imaging with background-free multiplex coherent anti-Stokes Raman scattering by dual-soliton Stokes pulses

PubMed Central

Chen, Kun; Wu, Tao; Wei, Haoyun; Zhou, Tian; Li, Yan

2016-01-01

Coherent anti-Stokes Raman microscopy (CARS) is a quantitative, chemically specific, and label-free optical imaging technique for studying inhomogeneous systems. However, the complicating influence of the nonresonant response on the CARS signal severely limits its sensitivity and specificity and especially limits the extent to which CARS microscopy has been used as a fully quantitative imaging technique. On the basis of spectral focusing mechanism, we establish a dual-soliton Stokes based CARS microspectroscopy and microscopy scheme capable of quantifying the spatial information of densities and chemical composition within inhomogeneous samples, using a single fiber laser. Dual-soliton Stokes scheme not only removes the nonresonant background but also allows robust acquisition of multiple characteristic vibrational frequencies. This all-fiber based laser source can cover the entire fingerprint (800-2200 cm−1) region with a spectral resolution of 15 cm−1. We demonstrate that quantitative degree determination of lipid-chain unsaturation in the fatty acids mixture can be achieved by the characterization of C = C stretching and CH2 deformation vibrations. For microscopy purposes, we show that the spatially inhomogeneous distribution of lipid droplets can be further quantitatively visualized using this quantified degree of lipid unsaturation in the acyl chain for contrast in the hyperspectral CARS images. The combination of compact excitation source and background-free capability to facilitate extraction of quantitative composition information with multiplex spectral peaks will enable wider applications of quantitative chemical imaging in studying biological and material systems. PMID:27867704

Chemical imaging of molecular changes in a hydrated single cell by dynamic secondary ion mass spectrometry and super-resolution microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, Xin; Szymanski, Craig; Wang, Zhaoying

2016-01-01

Chemical imaging of single cells is important in capturing biological dynamics. Single cell correlative imaging is realized between structured illumination microscopy (SIM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) using System for Analysis at the Liquid Vacuum Interface (SALVI), a multimodal microreactor. SIM characterized cells and guided subsequent ToF-SIMS analysis. Dynamic ToF-SIMS provided time- and space-resolved cell molecular mapping. Lipid fragments were identified in the hydrated cell membrane. Principal component analysis was used to elucidate chemical component differences among mouse lung cells that uptake zinc oxide nanoparticles. Our results provided submicron chemical spatial mapping for investigations of cell dynamics atmore » the molecular level.« less

A multi-modal stereo microscope based on a spatial light modulator.

PubMed

Lee, M P; Gibson, G M; Bowman, R; Bernet, S; Ritsch-Marte, M; Phillips, D B; Padgett, M J

2013-07-15

Spatial Light Modulators (SLMs) can emulate the classic microscopy techniques, including differential interference (DIC) contrast and (spiral) phase contrast. Their programmability entails the benefit of flexibility or the option to multiplex images, for single-shot quantitative imaging or for simultaneous multi-plane imaging (depth-of-field multiplexing). We report the development of a microscope sharing many of the previously demonstrated capabilities, within a holographic implementation of a stereo microscope. Furthermore, we use the SLM to combine stereo microscopy with a refocusing filter and with a darkfield filter. The instrument is built around a custom inverted microscope and equipped with an SLM which gives various imaging modes laterally displaced on the same camera chip. In addition, there is a wide angle camera for visualisation of a larger region of the sample.

An integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique for liver disease diagnosis

NASA Astrophysics Data System (ADS)

Lin, Jian; Lu, Fake; Zheng, Wei; Yu, Hanry; Sheppard, Colin; Huang, Zhiwei

2012-03-01

Liver steatosis and fibrosis are two prevalence liver diseases and may eventually develop into hepatocellular carcinoma (HCC) Due to their prevalence and severity, much work has been done to develop efficient diagnostic methods and therapies. Nonlinear optical microscopy has high sensitivity and chemical specificity for major biochemical compounds, making it a powerful tool for tissue imaging without staining. In this study, three nonlinear microscopy imaging modalities are applied to the study of liver diseases in a bile duct ligation rat modal. CARS shows the distributions of fats or lipids quantitatively across the tissue; SHG visualizes the collagens; and TPEF reveals the morphology of hepatic cells. The results clearly show the development of liver steatosis and fibrosis with time, and the hepatic fat and collagen fibrils are quantified. This study demonstrates the ability of multimodal nonlinear optical microscopy for liver disease diagnosis, and may provide new insights into the understanding of the mechanisms of steatosis/fibrosis transformations at the cellular and molecular levels.

Combined FLIM and reflectance confocal microscopy for epithelial imaging

NASA Astrophysics Data System (ADS)

Jabbour, Joey M.; Cheng, Shuna; Shrestha, Sebina; Malik, Bilal; Jo, Javier A.; Applegate, Brian; Maitland, Kristen C.

2012-03-01

Current methods for detection of oral cancer lack the ability to delineate between normal and precancerous tissue with adequate sensitivity and specificity. The usual diagnostic mechanism involves visual inspection and palpation followed by tissue biopsy and histopathology, a process both invasive and time-intensive. A more sensitive and objective screening method can greatly facilitate the overall process of detection of early cancer. To this end, we present a multimodal imaging system with fluorescence lifetime imaging (FLIM) for wide field of view guidance and reflectance confocal microscopy for sub-cellular resolution imaging of epithelial tissue. Moving from a 12 x 12 mm2 field of view with 157 ìm lateral resolution using FLIM to 275 x 200 μm2 with lateral resolution of 2.2 μm using confocal microscopy, hamster cheek pouch model is imaged both in vivo and ex vivo. The results indicate that our dual modality imaging system can identify and distinguish between different tissue features, and, therefore, can potentially serve as a guide in early oral cancer detection..

Alignment-free, all-spliced fiber laser source for CARS microscopy based on four-wave-mixing.

PubMed

Baumgartl, Martin; Gottschall, Thomas; Abreu-Afonso, Javier; Díez, Antonio; Meyer, Tobias; Dietzek, Benjamin; Rothhardt, Manfred; Popp, Jürgen; Limpert, Jens; Tünnermann, Andreas

2012-09-10

An environmentally-stable low-repetition rate fiber oscillator is developed to produce narrow-bandwidth pulses with several tens of picoseconds duration. Based on this oscillator an alignment-free all-fiber laser for multi-photon microscopy is realized using in-fiber frequency conversion based on four-wave-mixing. Both pump and Stokes pulses for coherent anti-Stokes Raman scattering (CARS) microscopy are readily available from one fiber end, intrinsically overlapped in space and time, which drastically simplifies the experimental handling for the user. The complete laser setup is mounted on a home-built laser scanning microscope with small footprint. High-quality multimodal microscope images of biological tissue are presented probing the CH-stretching resonance of lipids at an anti-Stokes Raman-shift of 2845 cm(-1) and second-harmonic generation of collagen. Due to its simplicity, compactness, maintenance-free operation, and ease-of-use the presented low-cost laser is an ideal source for bio-medical applications outside laser laboratories and in particular inside clinics.

Comparing in vivo pump–probe and multiphoton fluorescence microscopy of melanoma and pigmented lesions

PubMed Central

Wilson, Jesse W.; Degan, Simone; Gainey, Christina S.; Mitropoulos, Tanya; Simpson, Mary Jane; Zhang, Jennifer Y.; Warren, Warren S.

2014-01-01

Abstract. We demonstrate a multimodal approach that combines a pump–probe with confocal reflectance and multiphoton autofluorescence microscopy. Pump–probe microscopy has been proven to be of great value in analyzing thin tissue sections of pigmented lesions, as it produces molecular contrast which is inaccessible by other means. However, the higher optical intensity required to overcome scattering in thick tissue leads to higher-order nonlinearities in the optical response of melanin (e.g., two-photon pump and one-photon probe) that present additional challenges for interpreting the data. We show that analysis of pigment composition in vivo must carefully account for signal terms that are nonlinear with respect to the pump and probe intensities. We find that pump–probe imaging gives useful contrast for pigmented structures over a large range of spatial scales (100  μm to 1 cm), making it a potentially useful tool for tracking the progression of pigmented lesions without the need to introduce exogenous contrast agents. PMID:25415567

Multimodal imaging in a case of bilateral outer retinitis associated with mumps infection.

PubMed

Kahloun, Rim; Ben Amor, Hager; Ksiaa, Imen; Zina, Sourour; Jelliti, Bechir; Ben Yahia, Salim; Khairallah, Moncef

2018-02-01

To report the results of multimodal imaging of acute outer retinitis associated to mumps infection. A patient with mumps-associated outer retinitis evaluated by color fundus photography, spectral domain optical coherence tomography (SD-OCT), optical coherence tomography angiography, fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA). We report a case of a 12-year-old boy who developed bilateral outer retinitis related to mumps. Ophthalmoscopy showed confluent areas of outer retinitis involving the posterior pole and the periphery with a centrifugal gyrate pattern. SD-OCT revealed a marked disorganization of the outer retinal layers with multiple highly reflective spicules. FA shows diffuse late hyperfluorescence with optic disk staining. ICGA shows macular and peripheral hyperfluorescent lesions with a geographical pattern in the late phases. The patient was treated with acyclovir and oral prednisone. Four weeks after presentation visual acuity remained unchanged, and retinal changes seen at the acute phase had resolved leading to extensive retinal atrophy and optic disk pallor. SD-OCT showed atrophy of the retinal pigment epithelial and outer retinal layers. FAF revealed scattered hyperautofluorescent lesions. Electrophysiology showed generalized retinal dysfunction. Mumps infection should be considered in the differential diagnosis of bilateral necrotizing outer retinitis in children and young adults. A multimodal imaging approach may help distinguish mumps-associated retinitis from other causes of viral retinitis and facilitate appropriate management.

A multimodal 3D framework for fire characteristics estimation

NASA Astrophysics Data System (ADS)

Toulouse, T.; Rossi, L.; Akhloufi, M. A.; Pieri, A.; Maldague, X.

2018-02-01

In the last decade we have witnessed an increasing interest in using computer vision and image processing in forest fire research. Image processing techniques have been successfully used in different fire analysis areas such as early detection, monitoring, modeling and fire front characteristics estimation. While the majority of the work deals with the use of 2D visible spectrum images, recent work has introduced the use of 3D vision in this field. This work proposes a new multimodal vision framework permitting the extraction of the three-dimensional geometrical characteristics of fires captured by multiple 3D vision systems. The 3D system is a multispectral stereo system operating in both the visible and near-infrared (NIR) spectral bands. The framework supports the use of multiple stereo pairs positioned so as to capture complementary views of the fire front during its propagation. Multimodal registration is conducted using the captured views in order to build a complete 3D model of the fire front. The registration process is achieved using multisensory fusion based on visual data (2D and NIR images), GPS positions and IMU inertial data. Experiments were conducted outdoors in order to show the performance of the proposed framework. The obtained results are promising and show the potential of using the proposed framework in operational scenarios for wildland fire research and as a decision management system in fighting.

Spectral confocal reflection microscopy using a white light source

NASA Astrophysics Data System (ADS)

Booth, M.; Juškaitis, R.; Wilson, T.

2008-08-01

We present a reflection confocal microscope incorporating a white light supercontinuum source and spectral detection. The microscope provides images resolved spatially in three-dimensions, in addition to spectral resolution covering the wavelength range 450-650nm. Images and reflection spectra of artificial and natural specimens are presented, showing features that are not normally revealed in conventional microscopes or confocal microscopes using discrete line lasers. The specimens include thin film structures on semiconductor chips, iridescent structures in Papilio blumei butterfly scales, nacre from abalone shells and opal gemstones. Quantitative size and refractive index measurements of transparent beads are derived from spectral interference bands.

Theoretical extension and experimental demonstration of spectral compression in second-harmonic generation by Fresnel-inspired binary phase shaping

NASA Astrophysics Data System (ADS)

Li, Baihong; Dong, Ruifang; Zhou, Conghua; Xiang, Xiao; Li, Yongfang; Zhang, Shougang

2018-05-01

Selective two-photon microscopy and high-precision nonlinear spectroscopy rely on efficient spectral compression at the desired frequency. Previously, a Fresnel-inspired binary phase shaping (FIBPS) method was theoretically proposed for spectral compression of two-photon absorption and second-harmonic generation (SHG) with a square-chirped pulse. Here, we theoretically show that the FIBPS can introduce a negative quadratic frequency phase (negative chirp) by analogy with the spatial-domain phase function of Fresnel zone plate. Thus, the previous theoretical model can be extended to the case where the pulse can be transformed limited and in any symmetrical spectral shape. As an example, we experimentally demonstrate spectral compression in SHG by FIBPS for a Gaussian transform-limited pulse and show good agreement with the theory. Given the fundamental pulse bandwidth, a narrower SHG bandwidth with relatively high intensity can be obtained by simply increasing the number of binary phases. The experimental results also verify that our method is superior to that proposed in [Phys. Rev. A 46, 2749 (1992), 10.1103/PhysRevA.46.2749]. This method will significantly facilitate the applications of selective two-photon microscopy and spectroscopy. Moreover, as it can introduce negative dispersion, hence it can also be generalized to other applications in the field of dispersion compensation.

Molecular Imaging for Breast Cancer Using Magnetic Resonance-Guided Positron Emission Mammography and Excitation-Resolved Near-Infrared Fluorescence Imaging

NASA Astrophysics Data System (ADS)

Cho, Jaedu

The aim of this work is to develop novel breast-specific molecular imaging techniques for management of breast cancer. In this dissertation, we describe two novel molecular imaging approaches for breast cancer management. In Part I, we introduce our multimodal molecular imaging approach for breast cancer therapy monitoring using magnetic resonance imaging and positron emission mammography (MR/PEM). We have focused on the therapy monitoring technique for aggressive cancer molecular subtypes, which is challenging due to time constraint. Breast cancer therapy planning relies on a fast and accurate monitoring of functional and anatomical change. We demonstrate a proof-of-concept of sequential dual-modal magnetic resonance and positron emission mammography (MR/PEM) for the cancer therapy monitoring. We have developed dedicated breast coils with breast compression mechanism equipped with MR-compatible PEM detector heads. We have designed a fiducial marker that allows straightforward image registration of data obtained from MRI and PEM. We propose an optimal multimodal imaging procedure for MR/PEM. In Part II, we have focused on the development of a novel intraoperative near-infrared fluorescence imaging system (NIRF) for image-guided breast cancer surgery. Conventional spectrally-resolved NIRF systems are unable to resolve various NIR fluorescence dyes for the following reasons. First, the fluorescence spectra of viable NIR fluorescence dyes are heavily overlapping. Second, conventional emission-resolved NIRF suffers from a trade-off between the fluence rate and the spectral resolution. Third, the multiple scattering in tissue degrades not only the spatial information but also the spectral contents by the red-shift. We develop a wavelength-swept laser-based NIRF system that can resolve the excitation shift of various NIR fluorescence dyes without substantial loss of the fluence rate. A linear ratiometric model is employed to measure the relative shift of the excitation spectrum of a fluorescence dye.

Quantitative comparison between full-spectrum and filter-based imaging in hyperspectral fluorescence microscopy

PubMed Central

GAO, L.; HAGEN, N.; TKACZYK, T.S.

2012-01-01

Summary We implement a filterless illumination scheme on a hyperspectral fluorescence microscope to achieve full-range spectral imaging. The microscope employs polarisation filtering, spatial filtering and spectral unmixing filtering to replace the role of traditional filters. Quantitative comparisons between full-spectrum and filter-based microscopy are provided in the context of signal dynamic range and accuracy of measured fluorophores’ emission spectra. To show potential applications, a five-colour cell immunofluorescence imaging experiment is theoretically simulated. Simulation results indicate that the use of proposed full-spectrum imaging technique may result in three times improvement in signal dynamic range compared to that can be achieved in the filter-based imaging. PMID:22356127

Hyperspectral light sheet microscopy

NASA Astrophysics Data System (ADS)

Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O.; Huisken, Jan

2015-09-01

To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5 nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos.

Hyperspectral light sheet microscopy.

PubMed

Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O; Huisken, Jan

2015-09-02

To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5 nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos.

Coupling radiative heat transfer in participating media with other heat transfer modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tencer, John; Howell, John R.

The common methods for finding the local radiative flux divergence in participating media through solution of the radiative transfer equation are outlined. The pros and cons of each method are discussed in terms of their speed, ability to handle spectral properties and scattering phenomena, as well as their accuracy in different ranges of media transport properties. The suitability of each method for inclusion in the energy equation to efficiently solve multi-mode thermal transfer problems is discussed. Lastly, remaining topics needing research are outlined.

Coupling radiative heat transfer in participating media with other heat transfer modes

DOE PAGES

Tencer, John; Howell, John R.

2015-09-28

The common methods for finding the local radiative flux divergence in participating media through solution of the radiative transfer equation are outlined. The pros and cons of each method are discussed in terms of their speed, ability to handle spectral properties and scattering phenomena, as well as their accuracy in different ranges of media transport properties. The suitability of each method for inclusion in the energy equation to efficiently solve multi-mode thermal transfer problems is discussed. Lastly, remaining topics needing research are outlined.

Joint quantum measurement using unbalanced array detection.

PubMed

Beck, M; Dorrer, C; Walmsley, I A

2001-12-17

We have measured the joint Q-function of a highly multimode field using unbalanced heterodyne detection with a charge-coupled device array detector. We use spectral interferometry between a weak signal field and a strong, 100 fs duration local oscillator pulse to reconstruct the joint quadrature amplitude statistics of about 25 temporal modes. By adjusting the time delay between the signal and local oscillator pulses we are able to shift all the classical noise to modes distinct from the signal. This obviates the need to use a balanced detector.

Mid-infrared two photon absorption sensitivity of commercial detectors

NASA Astrophysics Data System (ADS)

Boiko, D. L.; Antonov, A. V.; Kuritsyn, D. I.; Yablonskiy, A. N.; Sergeev, S. M.; Orlova, E. E.; Vaks, V. V.

2017-10-01

We report on broad-band two-photon absorption (TPA) in several commercially available MIR inter-band bulk semiconductor photodetectors with the spectral cutoff in the range of 4.5-6 μm. The highest TPA responsivity of 2 × 10-5 A.mm2/W2 is measured for a nitrogen-cooled InSb photovoltaic detector. Its performance as a two-photon detector is validated by measuring the second-order interferometric autocorrelation function of a multimode quantum cascade laser emitting at the wavelength of 8 μm.

Morphological and Spectral Characteristics of Hybrid Nanosystems Based on Mono- and Bimetallic Platinum Nanoparticles and Silver

NASA Astrophysics Data System (ADS)

Valueva, S. V.; Vylegzhanina, M. E.; Sukhanova, T. E.

2018-02-01

Morphological and spectral characteristics of hybrid nanosystems (NSes) based on mono- and bimetallic silver and platinum nanoparticles (NPs) stabilized by a cationic polyelectrolyte (CP), poly- N,N,N,N-trimethylmethacryloyloxyethylammonium methylsulfate, are determined via static/dynamic light scattering, UV spectroscopy, and atomic force microscopy. The formation of dense spherical polymolecular nanostructures is established. The possibility of controlling the morphological and spectral characteristics of the NS is shown by varying the nature and composition of NPs.

Open-Source Programming for Automated Generation of Graphene Raman Spectral Maps

NASA Astrophysics Data System (ADS)

Vendola, P.; Blades, M.; Pierre, W.; Jedlicka, S.; Rotkin, S. V.

Raman microscopy is a useful tool for studying the structural characteristics of graphene deposited onto substrates. However, extracting useful information from the Raman spectra requires data processing and 2D map generation. An existing home-built confocal Raman microscope was optimized for graphene samples and programmed to automatically generate Raman spectral maps across a specified area. In particular, an open source data collection scheme was generated to allow the efficient collection and analysis of the Raman spectral data for future use. NSF ECCS-1509786.

Investigation on the impact of irregular fringe patterns of a single-fiber Mach-Zehnder interferometer on its sensing capabilities

NASA Astrophysics Data System (ADS)

Kumar, Naveen; Kumar, Ashish

2018-07-01

A novel single-mode single-fiber (SMSF) MZI formed by cascading of two non-adiabatic fiber tapers, with stable and repeatable spectrum, has been found to be useful in sensing applications in recent times. A multimode interference based novel simulation approach is proposed to predict the sensing characteristics of SMSF-MZI and is validated with experimental observation. The proposed method includes solving of simultaneous non-homogenous equations for determining the amplitudes of the interfering modes excited in the tapered section of the interferometer. The simulated fringe pattern and the experimental spectral response converge to some important comprehension reported for the first time. A linear shift in output spectral response, of SMSF-MZI, due to change in optical path length induced by temperature/strain etc., is likely to be characterized by three modes interference occurring in the interference region of the interferometer. Whereas if the spectral shift starts saturating at moderately higher temperature/strain, then the formation of interference fringes are possibly governed by two modes interference. Further, it was also explained that a SMSF-MZI with variable fringe widths in its spectral pattern exhibits higher sensitivity than that of the SMSF-MZI having wavelength spectrum with uniform free spectral range. These findings are useful in selecting and predicting the sensitivity of a given SMSF-MZI, based on its spectrum, for sensing applications.

Control of the amplifications of large-band amplitude-modulated pulses in an Nd-glass amplifier chain

NASA Astrophysics Data System (ADS)

Videau, Laurent; Bar, Emmanuel; Rouyer, Claude; Gouedard, Claude; Garnier, Josselin C.; Migus, Arnold

1999-07-01

We study nonlinear effects in amplification of partially coherent pulses in a high power laser chain. We compare statistical models with experimental results for temporal and spatial effects. First we show the interplay between self-phase modulation which broadens spectrum bandwidth and gain narrowing which reduces output spectrum. Theoretical results are presented for spectral broadening and energy limitation in case of time-incoherent pulses. In a second part, we introduce spatial incoherence with a multimode optical fiber which provides a smoothed beam. We show with experimental result that spatial filter pinholes are responsible for additive energy losses in the amplification. We develop a statistical model which takes into account the deformation of the focused beam as a function of B integral. We estimate the energy transmission of the spatial filter pinholes and compare this model with experimental data. We find a good agreement between theory and experiments. As a conclusion, we present an analogy between temporal and spatial effects with spectral broadening and spectral filter. Finally, we propose some solutions to control energy limitations in smoothed pulses amplification.

Temperature stable oxide-confined 850-nm VCSELs operating at bit rates up to 25 Gbit/s at 150°C

NASA Astrophysics Data System (ADS)

Ledentsov, N.; Agustin, M.; Kropp, J.-R.; Shchukin, V. A.; Kalosha, V. P.; Chi, K. L.; Khan, Z.; Shi, J. W.; Ledentsov, N. N.

2018-02-01

New applications in industrial, automotive and datacom applications require vertical-cavity surface-emitting lasers (VCSELs) operating at very high ambient temperatures at ultrahigh speed. We discuss issues related to high temperature performance of the VCSELs including temperature response and spectral properties. The influence of the gain-to-cavity wavelength detuning on temperature performance and spectral width of the VCSELs is discussed. Performance of the oxide-confined 850 nm VCSELs with increased temperature stability capable of operating at bit rates up to 25 Gbit/s at heat sink temperature of 150°C and 35Gbit/s at 130°C. Furthermore, opposite to previous studies of VCSELs with large gain-to-cavity detuning, which demonstrated strongly increased spectral width and a strong redistribution of the mode intensities upon current increase. VCSELs demonstrated in this work show good reproducibility of a narrow spectrum in a wide range of currents and temperatures. Such performance strongly improves the transmission distance over multi-mode fiber and can reduce mode partition noise during high speed operation.

Quantum-cascade lasers in the 7-8 μm spectral range with full top metallization

NASA Astrophysics Data System (ADS)

Kurochkin, A. S.; Babichev, A. V.; Denisov, D. V.; Karachinsky, L. Ya; Novikov, I. I.; Sofronov, A. N.; Firsov, D. A.; Vorobjev, L. E.; Bousseksou, A.; Egorov, A. Yu

2018-03-01

The paper demonstrates the generation of multistage quantum-cascade lasers (QCL) in the 7-8 μm spectral range in the pulse generation mode. The active region structure we used is based on a two-phonon resonance scheme. The QCL heterostructure based on a heteropair of In0.53Ga0.47As/Al0.48In0.52As solid alloys was grown by molecular beam epitaxy and includes 50 identical stages. A waveguide geometry with top cladding with full top metallization (surface- plasmon quantum-cascade lasers) has been used. The developed QCLs have demonstrated multimodal generation in the 7-8 μm spectral range in the pulse mode in the 78-250 K temperature range. The threshold current density for a 1.6 mm long laser and a 20 μm ridge width amounted to ˜ 2.8 kA/cm2 at a temperature of 78 К. A temperature increase to 250 K causes a long-wave shift of the wavelength from 7.6 to 7.9 μm and a jth increase to 5.0 kA/cm2.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells.

PubMed

Hofemeier, Arne D; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F W; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-05-26

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO4(3-) symmetric stretch vibrations at 959 cm(-1) assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue-implant-interfaces or disease diagnosis.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells

NASA Astrophysics Data System (ADS)

Hofemeier, Arne D.; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F. W.; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-05-01

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43- symmetric stretch vibrations at 959 cm-1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue-implant-interfaces or disease diagnosis.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells

PubMed Central

Hofemeier, Arne D.; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F. W.; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

2016-01-01

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43− symmetric stretch vibrations at 959 cm−1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue–implant-interfaces or disease diagnosis. PMID:27225821

Three-dimensional holographic optical manipulation through a high-numerical-aperture soft-glass multimode fibre

NASA Astrophysics Data System (ADS)

Leite, Ivo T.; Turtaev, Sergey; Jiang, Xin; Šiler, Martin; Cuschieri, Alfred; Russell, Philip St. J.; Čižmár, Tomáš

2018-01-01

Holographic optical tweezers (HOT) hold great promise for many applications in biophotonics, allowing the creation and measurement of minuscule forces on biomolecules, molecular motors and cells. Geometries used in HOT currently rely on bulk optics, and their exploitation in vivo is compromised by the optically turbid nature of tissues. We present an alternative HOT approach in which multiple three-dimensional (3D) traps are introduced through a high-numerical-aperture multimode optical fibre, thus enabling an equally versatile means of manipulation through channels having cross-section comparable to the size of a single cell. Our work demonstrates real-time manipulation of 3D arrangements of micro-objects, as well as manipulation inside otherwise inaccessible cavities. We show that the traps can be formed over fibre lengths exceeding 100 mm and positioned with nanometric resolution. The results provide the basis for holographic manipulation and other high-numerical-aperture techniques, including advanced microscopy, through single-core-fibre endoscopes deep inside living tissues and other complex environments.

Multimodal assessment of spatial distribution of drug-tracer uptake by brain tissue after intra-arterial injections

NASA Astrophysics Data System (ADS)

Singh-Moon, Rajinder; Chaudhuri, Durba; Wang, Mei; Straubinger, Robert; Bigio, Irving J.; Joshi, Shailendra

2014-02-01

It is challenging to track the rapid changes in drug concentrations after intra-arterial (IA) administration to elucidate the pharmacokinetics of this method of drug delivery. Traditional pharmacokinetic parameters (such as protein binding) that are highly relevant to intravenous (IV) administration do not seem to apply to IA injections. Regional drug delivery is affected by the biomechanics of drug injection, resting blood flow, and local tissue extraction. In-vivo and ex-vivo, optical methods for spatial mapping of drug deposition can assist in visualizing drug distributions and aid in the screening of potential drugs and carrier candidates. We present a multimodal approach for the assessment of drug distribution in postmortem tissue specimens using diffuse reflectance spectroscopy, multispectral imaging, and confocal microscopy and demonstrate feasibility of distinguishing route of administration advantages of liposome-dye conjugate delivery. The results of this study suggest that insight on drug dynamics gained by this aggregated approach can be used to help screen and/or optimize potential drug candidates and drug delivery protocols.

Multimodal discrimination of immune cells using a combination of Raman spectroscopy and digital holographic microscopy

NASA Astrophysics Data System (ADS)

McReynolds, Naomi; Cooke, Fiona G. M.; Chen, Mingzhou; Powis, Simon J.; Dholakia, Kishan

2017-03-01

The ability to identify and characterise individual cells of the immune system under label-free conditions would be a significant advantage in biomedical and clinical studies where untouched and unmodified cells are required. We present a multi-modal system capable of simultaneously acquiring both single point Raman spectra and digital holographic images of single cells. We use this combined approach to identify and discriminate between immune cell populations CD4+ T cells, B cells and monocytes. We investigate several approaches to interpret the phase images including signal intensity histograms and texture analysis. Both modalities are independently able to discriminate between cell subsets and dual-modality may therefore be used a means for validation. We demonstrate here sensitivities achieved in the range of 86.8% to 100%, and specificities in the range of 85.4% to 100%. Additionally each modality provides information not available from the other providing both a molecular and a morphological signature of each cell.

Biocytin-Derived MRI Contrast Agent for Longitudinal Brain Connectivity Studies

PubMed Central

2011-01-01

To investigate the connectivity of brain networks noninvasively and dynamically, we have developed a new strategy to functionalize neuronal tracers and designed a biocompatible probe that can be visualized in vivo using magnetic resonance imaging (MRI). Furthermore, the multimodal design used allows combined ex vivo studies with microscopic spatial resolution by conventional histochemical techniques. We present data on the functionalization of biocytin, a well-known neuronal tract tracer, and demonstrate the validity of the approach by showing brain networks of cortical connectivity in live rats under MRI, together with the corresponding microscopic details, such as fibers and neuronal morphology under light microscopy. We further demonstrate that the developed molecule is the first MRI-visible probe to preferentially trace retrograde connections. Our study offers a new platform for the development of multimodal molecular imaging tools of broad interest in neuroscience, that capture in vivo the dynamics of large scale neural networks together with their microscopic characteristics, thereby spanning several organizational levels. PMID:22860157

A versatile clearing agent for multi-modal brain imaging

PubMed Central

Costantini, Irene; Ghobril, Jean-Pierre; Di Giovanna, Antonino Paolo; Mascaro, Anna Letizia Allegra; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Onofri, Leonardo; Conti, Valerio; Vanzi, Francesco; Sacconi, Leonardo; Guerrini, Renzo; Markram, Henry; Iannello, Giulio; Pavone, Francesco Saverio

2015-01-01

Extensive mapping of neuronal connections in the central nervous system requires high-throughput µm-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multi-modal optical techniques. Here, we introduce a versatile brain clearing agent (2,2′-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue. PMID:25950610

Separating Bulk and Surface Contributions to Electronic Excited-State Processes in Hybrid Mixed Perovskite Thin Films via Multimodal All-Optical Imaging.

PubMed

Simpson, Mary Jane; Doughty, Benjamin; Das, Sanjib; Xiao, Kai; Ma, Ying-Zhong

2017-07-20

A comprehensive understanding of electronic excited-state phenomena underlying the impressive performance of solution-processed hybrid halide perovskite solar cells requires access to both spatially resolved electronic processes and corresponding sample morphological characteristics. Here, we demonstrate an all-optical multimodal imaging approach that enables us to obtain both electronic excited-state and morphological information on a single optical microscope platform with simultaneous high temporal and spatial resolution. Specifically, images were acquired for the same region of interest in thin films of chloride containing mixed lead halide perovskites (CH 3 NH 3 PbI 3-x Cl x ) using femtosecond transient absorption, time-integrated photoluminescence, confocal reflectance, and transmission microscopies. Comprehensive image analysis revealed the presence of surface- and bulk-dominated contributions to the various images, which describe either spatially dependent electronic excited-state properties or morphological variations across the probed region of the thin films. These results show that PL probes effectively the species near or at the film surface.

Using multimodal information for the segmentation of fluorescent micrographs with application to virology and microbiology.

PubMed

Held, Christian; Wenzel, Jens; Webel, Rike; Marschall, Manfred; Lang, Roland; Palmisano, Ralf; Wittenberg, Thomas

2011-01-01

In order to improve reproducibility and objectivity of fluorescence microscopy based experiments and to enable the evaluation of large datasets, flexible segmentation methods are required which are able to adapt to different stainings and cell types. This adaption is usually achieved by the manual adjustment of the segmentation methods parameters, which is time consuming and challenging for biologists with no knowledge on image processing. To avoid this, parameters of the presented methods automatically adapt to user generated ground truth to determine the best method and the optimal parameter setup. These settings can then be used for segmentation of the remaining images. As robust segmentation methods form the core of such a system, the currently used watershed transform based segmentation routine is replaced by a fast marching level set based segmentation routine which incorporates knowledge on the cell nuclei. Our evaluations reveal that incorporation of multimodal information improves segmentation quality for the presented fluorescent datasets.

Development of a Multi-modal Tissue Diagnostic System Combining High Frequency Ultrasound and Photoacoustic Imaging with Lifetime Fluorescence Spectroscopy

PubMed Central

Sun, Yang; Stephens, Douglas N.; Park, Jesung; Sun, Yinghua; Marcu, Laura; Cannata, Jonathan M.; Shung, K. Kirk

2010-01-01

We report the development and validate a multi-modal tissue diagnostic technology, which combines three complementary techniques into one system including ultrasound backscatter microscopy (UBM), photoacoustic imaging (PAI), and time-resolved laser-induced fluorescence spectroscopy (TR-LIFS). UBM enables the reconstruction of the tissue microanatomy. PAI maps the optical absorption heterogeneity of the tissue associated with structure information and has the potential to provide functional imaging of the tissue. Examination of the UBM and PAI images allows for localization of regions of interest for TR-LIFS evaluation of the tissue composition. The hybrid probe consists of a single element ring transducer with concentric fiber optics for multi-modal data acquisition. Validation and characterization of the multi-modal system and ultrasonic, photoacoustic, and spectroscopic data coregistration were conducted in a physical phantom with properties of ultrasound scattering, optical absorption, and fluorescence. The UBM system with the 41 MHz ring transducer can reach the axial and lateral resolution of 30 and 65 μm, respectively. The PAI system with 532 nm excitation light from a Nd:YAG laser shows great contrast for the distribution of optical absorbers. The TR-LIFS system records the fluorescence decay with the time resolution of ~300 ps and a high sensitivity of nM concentration range. Biological phantom constructed with different types of tissues (tendon and fat) was used to demonstrate the complementary information provided by the three modalities. Fluorescence spectra and lifetimes were compared to differentiate chemical composition of tissues at the regions of interest determined by the coregistered high resolution UBM and PAI image. Current results demonstrate that the fusion of these techniques enables sequentially detection of functional, morphological, and compositional features of biological tissue, suggesting potential applications in diagnosis of tumors and atherosclerotic plaques. PMID:21894259

Development of a Multi-modal Tissue Diagnostic System Combining High Frequency Ultrasound and Photoacoustic Imaging with Lifetime Fluorescence Spectroscopy.

PubMed

Sun, Yang; Stephens, Douglas N; Park, Jesung; Sun, Yinghua; Marcu, Laura; Cannata, Jonathan M; Shung, K Kirk

2008-01-01

We report the development and validate a multi-modal tissue diagnostic technology, which combines three complementary techniques into one system including ultrasound backscatter microscopy (UBM), photoacoustic imaging (PAI), and time-resolved laser-induced fluorescence spectroscopy (TR-LIFS). UBM enables the reconstruction of the tissue microanatomy. PAI maps the optical absorption heterogeneity of the tissue associated with structure information and has the potential to provide functional imaging of the tissue. Examination of the UBM and PAI images allows for localization of regions of interest for TR-LIFS evaluation of the tissue composition. The hybrid probe consists of a single element ring transducer with concentric fiber optics for multi-modal data acquisition. Validation and characterization of the multi-modal system and ultrasonic, photoacoustic, and spectroscopic data coregistration were conducted in a physical phantom with properties of ultrasound scattering, optical absorption, and fluorescence. The UBM system with the 41 MHz ring transducer can reach the axial and lateral resolution of 30 and 65 μm, respectively. The PAI system with 532 nm excitation light from a Nd:YAG laser shows great contrast for the distribution of optical absorbers. The TR-LIFS system records the fluorescence decay with the time resolution of ~300 ps and a high sensitivity of nM concentration range. Biological phantom constructed with different types of tissues (tendon and fat) was used to demonstrate the complementary information provided by the three modalities. Fluorescence spectra and lifetimes were compared to differentiate chemical composition of tissues at the regions of interest determined by the coregistered high resolution UBM and PAI image. Current results demonstrate that the fusion of these techniques enables sequentially detection of functional, morphological, and compositional features of biological tissue, suggesting potential applications in diagnosis of tumors and atherosclerotic plaques.

Single-wavelength functional photoacoustic microscopy in biological tissue.

PubMed

Danielli, Amos; Favazza, Christopher P; Maslov, Konstantin; Wang, Lihong V

2011-03-01

Recently, we developed a reflection-mode relaxation photoacoustic microscope, based on saturation intensity, to measure picosecond relaxation times using a nanosecond laser. Here, using the different relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, the oxygen saturation was quantified in vivo with single-wavelength photoacoustic microscopy. All previous functional photoacoustic microscopy measurements required imaging with multiple-laser-wavelength measurements to quantify oxygen saturation. Eliminating the need for multiwavelength measurements removes the influence of spectral properties on oxygenation calculations and improves the portability and cost-effectiveness of functional or molecular photoacoustic microscopy.

Single-wavelength functional photoacoustic microscopy in biological tissue

PubMed Central

Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin; Wang, Lihong V.

2011-01-01

Recently, we developed a reflection-mode relaxation photoacoustic microscope, based on saturation intensity, to measure picosecond relaxation times using a nanosecond laser. Here, using the different relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, the oxygen saturation was quantified in vivo with single-wavelength photoacoustic microscopy. All previous functional photoacoustic microscopy measurements required imaging with multiple laser-wavelength measurements to quantify oxygen saturation. Eliminating the need for multi-wavelength measurements removes the influence of spectral properties on oxygenation calculations and improves the portability and cost-effectiveness of functional or molecular photoacoustic microscopy. PMID:21368977

Raman-based imaging uncovers the effects of alginate hydrogel implants in spinal cord injury

NASA Astrophysics Data System (ADS)

Galli, Roberta; Tamosaityte, Sandra; Koch, Maria; Sitoci-Ficici, Kerim H.; Later, Robert; Uckermann, Ortrud; Beiermeister, Rudolf; Gelinsky, Michael; Schackert, Gabriele; Kirsch, Matthias; Koch, Edmund; Steiner, Gerald

2015-07-01

The treatment of spinal cord injury by using implants that provide a permissive environment for axonal growth is in the focus of the research for regenerative therapies. Here, Raman-based label-free techniques were applied for the characterization of morphochemical properties of surgically induced spinal cord injury in the rat that received an implant of soft unfunctionalized alginate hydrogel. Raman microspectroscopy followed by chemometrics allowed mapping the different degenerative areas, while multimodal multiphoton microscopy (e.g. the combination of coherent anti-Stokes Raman scattering (CARS), endogenous two-photon fluorescence and second harmonic generation on the same platform) enabled to address the morphochemistry of the tissue at cellular level. The regions of injury, characterized by demyelination and scarring, were retrieved and the distribution of key tissue components was evaluated by Raman mapping. The alginate hydrogel was detected in the lesion up to six months after implantation and had positive effects on the nervous tissue. For instance, multimodal multiphoton microscopy complemented the results of Raman mapping, providing the micromorphology of lipid-rich tissue structures by CARS and enabling to discern lipid-rich regions that contained myelinated axons from degenerative regions characterized by myelin fragmentation and presence of foam cells. These findings demonstrate that Raman-based imaging methods provide useful information for the evaluation of alginate implant effects and have therefore the potential to contribute to new strategies for monitoring degenerative and regenerative processes induced in SCI, thereby improving the effectiveness of therapies.

Hierarchical multimodal tomographic x-ray imaging at a superbend

NASA Astrophysics Data System (ADS)

Stampanoni, M.; Marone, F.; Mikuljan, G.; Jefimovs, K.; Trtik, P.; Vila-Comamala, J.; David, C.; Abela, R.

2008-08-01

Over the last decade, synchrotron-based X-ray tomographic microscopy has established itself as a fundamental tool for non-invasive, quantitative investigations of a broad variety of samples, with application ranging from space research and materials science to biology and medicine. Thanks to the brilliance of modern third generation sources, voxel sizes in the micrometer range are routinely achieved by the major X-ray microtomography devices around the world, while the isotropic 100 nm barrier is reached and trespassed only by few instruments. The beamline for TOmographic Microscopy and Coherent rAdiology experiments (TOMCAT) of the Swiss Light Source at the Paul Scherrer Institut, operates a multimodal endstation which offers tomographic capabilities in the micrometer range in absorption contrast - of course - as well as phase contrast imaging. Recently, the beamline has been equipped with a full field, hard X-rays microscope with a theoretical pixel size down to 30 nm and a field of view of 50 microns. The nanoscope performs well at X-ray energies between 8 and 12 keV, selected from the white beam of a 2.9 T superbend by a [Ru/C]100 fixed exit multilayer monochromator. In this work we illustrate the experimental setup dedicated to the nanoscope, in particular the ad-hoc designed X-ray optics needed to produce a homogeneous, square illumination of the sample imaging plane as well as the magnifying zone plate. Tomographic reconstructions at 60 nm voxel size will be shown and discussed.

Aspergillus infection monitored by multimodal imaging in a rat model.

PubMed

Pluhacek, Tomas; Petrik, Milos; Luptakova, Dominika; Benada, Oldrich; Palyzova, Andrea; Lemr, Karel; Havlicek, Vladimir

2016-06-01

Although myriads of experimental approaches have been published in the field of fungal infection diagnostics, interestingly, in 21st century there is no satisfactory early noninvasive tool for Aspergillus diagnostics with good sensitivity and specificity. In this work, we for the first time described the fungal burden in rat lungs by multimodal imaging approach. The Aspergillus infection was monitored by positron emission tomography and light microscopy employing modified Grocott's methenamine silver staining and eosin counterstaining. Laser ablation inductively coupled plasma mass spectrometry imaging has revealed a dramatic iron increase in fungi-affected areas, which can be presumably attributed to microbial siderophores. Quantitative elemental data were inferred from matrix-matched standards prepared from rat lungs. The iron, silver, and gold MS images collected with variable laser foci revealed that particularly silver or gold can be used as excellent elements useful for sensitively tracking the Aspergillus infection. The limit of detection was determined for both (107) Ag and (197) Au as 0.03 μg/g (5 μm laser focus). The selective incorporation of (107) Ag and (197) Au into fungal cell bodies and low background noise from both elements were confirmed by energy dispersive X-ray scattering utilizing the submicron lateral resolving power of scanning electron microscopy. The low limits of detection and quantitation of both gold and silver make ICP-MS imaging monitoring a viable alternative to standard optical evaluation used in current clinical settings. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

3D widefield light microscope image reconstruction without dyes

NASA Astrophysics Data System (ADS)

Larkin, S.; Larson, J.; Holmes, C.; Vaicik, M.; Turturro, M.; Jurkevich, A.; Sinha, S.; Ezashi, T.; Papavasiliou, G.; Brey, E.; Holmes, T.

2015-03-01

3D image reconstruction using light microscope modalities without exogenous contrast agents is proposed and investigated as an approach to produce 3D images of biological samples for live imaging applications. Multimodality and multispectral imaging, used in concert with this 3D optical sectioning approach is also proposed as a way to further produce contrast that could be specific to components in the sample. The methods avoid usage of contrast agents. Contrast agents, such as fluorescent or absorbing dyes, can be toxic to cells or alter cell behavior. Current modes of producing 3D image sets from a light microscope, such as 3D deconvolution algorithms and confocal microscopy generally require contrast agents. Zernike phase contrast (ZPC), transmitted light brightfield (TLB), darkfield microscopy and others can produce contrast without dyes. Some of these modalities have not previously benefitted from 3D image reconstruction algorithms, however. The 3D image reconstruction algorithm is based on an underlying physical model of scattering potential, expressed as the sample's 3D absorption and phase quantities. The algorithm is based upon optimizing an objective function - the I-divergence - while solving for the 3D absorption and phase quantities. Unlike typical deconvolution algorithms, each microscope modality, such as ZPC or TLB, produces two output image sets instead of one. Contrast in the displayed image and 3D renderings is further enabled by treating the multispectral/multimodal data as a feature set in a mathematical formulation that uses the principal component method of statistics.

Investigation of Upconversion, downshifting and quantum –cutting behavior of Eu3+, Yb3+, Bi3+ co-doped LaNbO4 phosphor as a spectral conversion material

NASA Astrophysics Data System (ADS)

Dwivedi, A.; Mishra, K.; Rai, S. B.

2018-06-01

This work presents the spectral conversion characteristics [upconversion (UC), downshifting (DS) and quantum–cutting (QC) optical processes] of Eu3+, Yb3+ and Bi3+ co-doped LaNbO4 (LBO) phosphor samples synthesized by solid state reaction technique. The crystal structure and the pure phase formation have been confirmed by x-ray diffraction (XRD) measurements. The surface morphology and particle size are studied by scanning electron microscopy (SEM). The rarely observed intense red UC emission from Eu3+ ion has been successfully obtained in Eu3+/Yb3+ co-doped LaNbO4 phosphor (on excitation with 980 nm) by optimizing the concentrations of Eu3+ and Yb3+ ions. The downshifting (DS) behavior has been studied by photoluminescence (PL) measurements on excitation with 265 nm wavelength from a Xe lamp source. A broad blue emission in the region 300–550 nm with its maximum ∼415 nm due to charge transfer band (CTB) of the host and large number of sharp peaks due to f-f transitions of Eu3+ ion have been observed. The energy transfer has been observed from (NbO4)3‑ to Eu3+ ion and the fluorescence emission has been optimized by varying the concentration of Eu3+ ion. An intense red emission has also been observed corresponding to 5D0 → 7F2 transition of Eu3+ ion at 611 nm in LBO: 0.09Eu3+ phosphor on excitation with 394 nm. The luminescence properties of Eu3+ ion are enhanced further through the sensitization effect of Bi3+ ion. The near infra-red (NIR) quantum cutting (QC) behavior due to Yb3+ ion has been monitored on excitation with 265 as well as 394 nm. The NIR QC is observed due to 2F5/2 → 2F7/2 transition of Yb3+ ion via co-operative energy transfer (CET) process from (NbO4)3‑ as well as Eu3+ ions to Yb3+ ion. This multimodal behavior (UC, DS and QC) makes this a promising phosphor material for multi-purpose spectral converter.

Thermal investigation on high power dfb broad area lasers at 975 nm, with 60% efficiency

NASA Astrophysics Data System (ADS)

Mostallino, R.; Garcia, M.; Deshayes, Y.; Larrue, A.; Robert, Y.; Vinet, E.; Bechou, L.; Lecomte, M.; Parillaud, O.; Krakowski, M.

2016-03-01

The demand of high power diode lasers in the range of 910-980nm is regularly growing. This kind of device for many applications, such as fiber laser pumping [1], material processing [1], solid-state laser pumping [1], defense and medical/dental. The key role of this device lies in the efficiency (𝜂𝐸) of converting input electrical power into output optical power. The high value of 𝜂𝐸 allows high power level and reduces the need in heat dissipation. The requirement of wavelength stabilization with temperature is more obvious in the case of multimode 975nm diode lasers used for pumping Yb, Er and Yb/Er co-doped solid-state lasers, due to the narrow absorption line close to this wavelength. Such spectral width property (<1 nm), combined with wavelength thermal stabilization (0.07 𝑛𝑚 • °𝐶-1), provided by a uniform distributed feedback grating (DFB) introduced by etching and re-growth process techniques, is achievable in high power diode lasers using optical feedback. This paper reports on the development of the diode laser structure and the process techniques required to write the gratings taking into account of the thermal dissipation and optical performances. Performances are particularly determined in terms of experimental electro-optical characterizations. One of the main objectives is to determine the thermal resistance of the complete assembly to ensure the mastering of the diode laser temperature for operating condition. The classical approach to determine junction temperature is based on the infrared thermal camera, the spectral measurement and the pulse electrical method. In our case, we base our measurement on the spectral measurement but this approach is not well adapted to the high power diodes laser studied. We develop a new measurement based on the pulse electrical method and using the T3STERequipment. This method is well known for electronic devices and LEDs but is weakly developed for the high power diodes laser. This crucial measurement compared to spectral one is critical for understand the thermal management of diode laser device and improve the structure based on design for reliability. To have a perfect relation between structure, and their modification, and temperature, FEM simulations are performed using COMSOL software. In this case, we can understand the impact of structure on the isothermal distribution and then reveal the sensitive zones in the diode laser. To validate the simulation, we compare the simulation results to the experimental one and develop an analytical model to determine the different contributions of the thermal heating. This paper reports on the development laser structure and the process techniques required to write the gratings. Performances are particularly characterized in terms of experimental electro-optical characterization and spectral response. The extraction of thermal resistance (Rth) is particularly difficult, because of the implicit low value (Rth ≈ 2𝐾/𝑊) and the multimodal nature of the diode laser. In such a context, thermal resistance has been measured using a dedicated equipment namely T3STER©. The results have been compared with those given by the well-known technique achieved from the spectrum of the diode laser (central wavelength variations vs temperature) that is more difficult to apply for multimodal diodes laser. The last section deals with thermal simulations based on finite elements method (FEM) modeling in order to estimate junction temperature . This study represent a significant part of the general Design for Reliability (DfR) effort carried out on such devices to produce efficient and reliable high power devices at the industrial level.

Multiple speckle illumination for optical-resolution photoacoustic imaging

NASA Astrophysics Data System (ADS)

Poisson, Florian; Stasio, Nicolino; Moser, Christophe; Psaltis, Demetri; Bossy, Emmanuel

2017-03-01

Optical-resolution photoacoustic microscopy offers exquisite and specific contrast to optical absorption. Conventional approaches generally involves raster scanning a focused spot over the sample. Here, we demonstrate that a full-field illumination approach with multiple speckle illumination can also provide diffraction-limited optical-resolution photoacoustic images. Two different proof-of-concepts are demonstrated with micro-structured test samples. The first approach follows the principle of correlation/ghost imaging,1, 2 and is based on cross-correlating photoacoustic signals under multiple speckle illumination with known speckle patterns measured during a calibration step. The second approach is a speckle scanning microscopy technique, which adapts the technique proposed in fluorescence microscopy by Bertolotti and al.:3 in our work, spatially unresolved photoacoustic measurements are performed for various translations of unknown speckle patterns. A phase-retrieval algorithm is used to reconstruct the object from the knowledge of the modulus of its Fourier Transform yielded by the measurements. Because speckle patterns naturally appear in many various situations, including propagation through biological tissue or multi-mode fibers (for which focusing light is either very demanding if not impossible), speckle-illumination-based photoacoustic microscopy provides a powerful framework for the development of novel reconstruction approaches, well-suited to compressed sensing approaches.2

Photoswitchable non-fluorescent thermochromic dye-nanoparticle hybrid probes.

PubMed

Harrington, Walter N; Haji, Mwafaq R; Galanzha, Ekaterina I; Nedosekin, Dmitry A; Nima, Zeid A; Watanabe, Fumiya; Ghosh, Anindya; Biris, Alexandru S; Zharov, Vladimir P

2016-11-08

Photoswitchable fluorescent proteins with controllable light-dark states and spectral shifts in emission in response to light have led to breakthroughs in the study of cell biology. Nevertheless, conventional photoswitching is not applicable for weakly fluorescent proteins and requires UV light with low depth penetration in bio-tissue. Here we introduce a novel concept of photoswitchable hybrid probes consisting of thermochromic dye and absorbing nanoparticles, in which temperature-sensitive light-dark states and spectral shifts in absorption can be switched through controllable photothermal heating of doped nanoparticles. The proof-of-concept is demonstrated through the use of two different types of temperature-sensitive dyes doped with magnetic nanoparticles and reversibly photoswitched by a near-infrared laser. Photoacoustic imaging revealed the high contrast of these probes, which is sufficient for their visualization in cells and deep tissue. Our results suggest that these new photoswitchable multicolour probes can be used for multimodal cellular diagnostics and potentially for magnetic and photothermal therapy.

Optofluidic wavelength division multiplexing for single-virus detection

PubMed Central

Ozcelik, Damla; Parks, Joshua W.; Wall, Thomas A.; Stott, Matthew A.; Cai, Hong; Parks, Joseph W.; Hawkins, Aaron R.; Schmidt, Holger

2015-01-01

Optical waveguides simultaneously transport light at different colors, forming the basis of fiber-optic telecommunication networks that shuttle data in dozens of spectrally separated channels. Here, we reimagine this wavelength division multiplexing (WDM) paradigm in a novel context––the differentiated detection and identification of single influenza viruses on a chip. We use a single multimode interference (MMI) waveguide to create wavelength-dependent spot patterns across the entire visible spectrum and enable multiplexed single biomolecule detection on an optofluidic chip. Each target is identified by its time-dependent fluorescence signal without the need for spectral demultiplexing upon detection. We demonstrate detection of individual fluorescently labeled virus particles of three influenza A subtypes in two implementations: labeling of each virus using three different colors and two-color combinatorial labeling. By extending combinatorial multiplexing to three or more colors, MMI-based WDM provides the multiplexing power required for differentiated clinical tests and the growing field of personalized medicine. PMID:26438840

Label-Free Molecular Imaging of Biological Cells and Tissues by Linear and Nonlinear Raman Spectroscopic Approaches.

PubMed

Krafft, Christoph; Schmitt, Michael; Schie, Iwan W; Cialla-May, Dana; Matthäus, Christian; Bocklitz, Thomas; Popp, Jürgen

2017-04-10

Raman spectroscopy is an emerging technique in bioanalysis and imaging of biomaterials owing to its unique capability of generating spectroscopic fingerprints. Imaging cells and tissues by Raman microspectroscopy represents a nondestructive and label-free approach. All components of cells or tissues contribute to the Raman signals, giving rise to complex spectral signatures. Resonance Raman scattering and surface-enhanced Raman scattering can be used to enhance the signals and reduce the spectral complexity. Raman-active labels can be introduced to increase specificity and multimodality. In addition, nonlinear coherent Raman scattering methods offer higher sensitivities, which enable the rapid imaging of larger sampling areas. Finally, fiber-based imaging techniques pave the way towards in vivo applications of Raman spectroscopy. This Review summarizes the basic principles behind medical Raman imaging and its progress since 2012. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photoswitchable non-fluorescent thermochromic dye-nanoparticle hybrid probes

NASA Astrophysics Data System (ADS)

Harrington, Walter N.; Haji, Mwafaq R.; Galanzha, Ekaterina I.; Nedosekin, Dmitry A.; Nima, Zeid A.; Watanabe, Fumiya; Ghosh, Anindya; Biris, Alexandru S.; Zharov, Vladimir P.

2016-11-01

Photoswitchable fluorescent proteins with controllable light-dark states and spectral shifts in emission in response to light have led to breakthroughs in the study of cell biology. Nevertheless, conventional photoswitching is not applicable for weakly fluorescent proteins and requires UV light with low depth penetration in bio-tissue. Here we introduce a novel concept of photoswitchable hybrid probes consisting of thermochromic dye and absorbing nanoparticles, in which temperature-sensitive light-dark states and spectral shifts in absorption can be switched through controllable photothermal heating of doped nanoparticles. The proof-of-concept is demonstrated through the use of two different types of temperature-sensitive dyes doped with magnetic nanoparticles and reversibly photoswitched by a near-infrared laser. Photoacoustic imaging revealed the high contrast of these probes, which is sufficient for their visualization in cells and deep tissue. Our results suggest that these new photoswitchable multicolour probes can be used for multimodal cellular diagnostics and potentially for magnetic and photothermal therapy.

End coating on optical fibers for multiplexers-demultiplexers in optical communications

NASA Astrophysics Data System (ADS)

Richier, Robert; Grezes-Besset, Catherine; Pelletier, Emile P.

1993-03-01

Economical multiplexers-demultiplexers can be made from cut optical fibers coated at their ends with multidielectric filters and then put together. An optical multilayer deposited at the end of a fiber has a spectral response which is different from that obtained when the multilayer is classically used in oblique incidence. We show that it is possible to forecast the multi- demultiplexer performances on multimode fibers with a numerical model using a divergent beam of angular width `a' at a mean incidence `i.' As we know the design of the multilayer used, we can correctly predict the cross-talk and the losses of multi-demultiplexers. Then we show how a series of different experiments are exploited for this study. Nevertheless, the development of a higher selectivity spectral filter and the use of a single mode fiber necessitate further improvement concerning the test for the validity of the model used.

Alchemist multimodal workflows for diabetic retinopathy research, disease prevention and investigational drug discovery.

PubMed

Riposan, Adina; Taylor, Ian; Owens, David R; Rana, Omer; Conley, Edward C

2007-01-01

In this paper we present mechanisms for imaging and spectral data discovery, as applied to the early detection of pathologic mechanisms underlying diabetic retinopathy in research and clinical trial scenarios. We discuss the Alchemist framework, built using a generic peer-to-peer architecture, supporting distributed database queries and complex search algorithms based on workflow. The Alchemist is a domain-independent search mechanism that can be applied to search and data discovery scenarios in many areas. We illustrate Alchemist's ability to perform complex searches composed as a collection of peer-to-peer overlays, Grid-based services and workflows, e.g. applied to image and spectral data discovery, as applied to the early detection and prevention of retinal disease and investigational drug discovery. The Alchemist framework is built on top of decentralised technologies and uses industry standards such as Web services and SOAP for messaging.

Thermo-optic characteristic of DNA thin solid film and its application as a biocompatible optical fiber temperature sensor.

PubMed

Hong, Seongjin; Jung, Woohyun; Nazari, Tavakol; Song, Sanggwon; Kim, Taeoh; Quan, Chai; Oh, Kyunghwan

2017-05-15

We report unique thermo-optical characteristics of DNA-Cetyl tri-methyl ammonium (DNA-CTMA) thin solid film with a large negative thermo-optical coefficient of -3.4×10^-4/°C in the temperature range from 20°C to 70°C without any observable thermal hysteresis. By combining this thermo-optic DNA film and fiber optic multimode interference (MMI) device, we experimentally demonstrated a highly sensitive compact temperature sensor with a large spectral shift of 0.15 nm/°C. The fiber optic MMI device was a concatenated structure with single-mode fiber (SMF)-coreless silica fiber (CSF)-single mode fiber (SMF) and the DNA-CTMA film was deposited on the CSF. The spectral shifts of the device in experiments were compared with the beam propagation method, which showed a good agreement.

Raman-in-SEM, a multimodal and multiscale analytical tool: performance for materials and expertise.

PubMed

Wille, Guillaume; Bourrat, Xavier; Maubec, Nicolas; Lahfid, Abdeltif

2014-12-01

The availability of Raman spectroscopy in a powerful analytical scanning electron microscope (SEM) allows morphological, elemental, chemical, physical and electronic analysis without moving the sample between instruments. This paper documents the metrological performance of the SEMSCA commercial Raman interface operated in a low vacuum SEM. It provides multiscale and multimodal analyses as Raman/EDS, Raman/cathodoluminescence or Raman/STEM (STEM: scanning transmission electron microscopy) as well as Raman spectroscopy on nanomaterials. Since Raman spectroscopy in a SEM can be influenced by several SEM-related phenomena, this paper firstly presents a comparison of this new tool with a conventional micro-Raman spectrometer. Then, some possible artefacts are documented, which are due to the impact of electron beam-induced contamination or cathodoluminescence contribution to the Raman spectra, especially with geological samples. These effects are easily overcome by changing or adapting the Raman spectrometer and the SEM settings and methodology. The deletion of the adverse effect of cathodoluminescence is solved by using a SEM beam shutter during Raman acquisition. In contrast, this interface provides the ability to record the cathodoluminescence (CL) spectrum of a phase. In a second part, this study highlights the interest and efficiency of the coupling in characterizing micrometric phases at the same point. This multimodal approach is illustrated with various issues encountered in geosciences. Copyright © 2014 Elsevier Ltd. All rights reserved.

Individual Human Cell Responses to Low Doses of Chemicals and Radiation Studied by Synchrotron Infrared Spectromicroscopy

NASA Astrophysics Data System (ADS)

Martin, Michael C.; Holman, Hoi-Ying N.; Blakely, Eleanor A.; Goth-Goldstein, Regine; McKinney, Wayne R.

2000-03-01

Vibrational spectroscopy, when combined with synchrotron radiation-based (SR) microscopy, is a powerful new analytical tool with high spatial resolution for detecting biochemical changes in individual living cells. In contrast to other microscopy methods that require fixing, drying, staining or labeling, SR FTIR microscopy probes intact living cells providing a composite view of all of the molecular responses and the ability to monitor the responses over time in the same cell. Observed spectral changes include all types of lesions induced in that cell as well as cellular responses to external and internal stresses. These spectral changes combined with other analytical tools may provide a fundamental understanding of the key molecular mechanisms induced in response to stresses created by low-doses of radiation and chemicals. In this study we used high spatial-resolution SR FTIR vibrational spectromicroscopy at ALS Beamline 1.4.3 as a sensitive analytical tool to detect chemical- and radiation-induced changes in individual human cells. Our preliminary spectral measurements indicate that this technique is sensitive enough to detect changes in nucleic acids and proteins of cells treated with environmentally relevant concentrations of oxidative stresses: bleomycin, hydrogen peroxide, and X-rays. We observe spectral changes that are unique to each exogenous stressor. This technique has the potential to distinguish changes from exogenous or endogenous oxidative processes. Future development of this technique will allow rapid monitoring of cellular processes such as drug metabolism, early detection of disease, bio-compatibility of implant materials, cellular repair mechanisms, self assembly of cellular apparatus, cell differentiation and fetal development.

Accounting for tissue heterogeneity in infrared spectroscopic imaging for accurate diagnosis of thyroid carcinoma subtypes.

PubMed

Martinez-Marin, David; Sreedhar, Hari; Varma, Vishal K; Eloy, Catarina; Sobrinho-Simões, Manuel; Kajdacsy-Balla, André; Walsh, Michael J

2017-07-01

Fourier transform infrared (FT-IR) microscopy was used to image tissue samples from twenty patients diagnosed with thyroid carcinoma. The spectral data were then used to differentiate between follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma using principle component analysis coupled with linear discriminant analysis and a Naïve Bayesian classifier operating on a set of computed spectral metrics. Classification of patients' disease type was accomplished by using average spectra from a wide region containing follicular cells, colloid, and fibrosis; however, classification of disease state at the pixel level was only possible when the extracted spectra were limited to follicular epithelial cells in the samples, excluding the relatively uninformative areas of fibrosis. The results demonstrate the potential of FT-IR microscopy as a tool to assist in the difficult diagnosis of these subtypes of thyroid cancer, and also highlights the importance of selectively and separately analyzing spectral information from different features of a tissue of interest.

Experimental assessment and analysis of super-resolution in fluorescence microscopy based on multiple-point spread function fitting of spectrally demultiplexed images

NASA Astrophysics Data System (ADS)

Nishimura, Takahiro; Kimura, Hitoshi; Ogura, Yusuke; Tanida, Jun

2018-06-01

This paper presents an experimental assessment and analysis of super-resolution microscopy based on multiple-point spread function fitting of spectrally demultiplexed images using a designed DNA structure as a test target. For the purpose, a DNA structure was designed to have binding sites at a certain interval that is smaller than the diffraction limit. The structure was labeled with several types of quantum dots (QDs) to acquire their spatial information as spectrally encoded images. The obtained images are analyzed with a point spread function multifitting algorithm to determine the QD locations that indicate the binding site positions. The experimental results show that the labeled locations can be observed beyond the diffraction-limited resolution using three-colored fluorescence images that were obtained with a confocal fluorescence microscope. Numerical simulations show that labeling with eight types of QDs enables the positions aligned at 27.2-nm pitches on the DNA structure to be resolved with high accuracy.

Spectral characterization of Dictyostelium autofluorescence.

PubMed

Engel, Ruchira; Van Haastert, Peter J M; Visser, Antonie J W G

2006-03-01

Dictyostelium discoideum is used extensively as a model organism for the study of chemotaxis. In recent years, an increasing number of studies of Dictyostelium chemotaxis have made use of fluorescence-based techniques. One of the major factors that can interfere with the application of these techniques in cells is the cellular autofluorescence. In this study, the spectral properties of Dictyostelium autofluorescence have been characterized using fluorescence microscopy. Whole cell autofluorescence spectra obtained using spectral imaging microscopy show that Dictyostelium autofluorescence covers a wavelength range from approximately 500 to 650 nm with a maximum at approximately 510 nm, and thus, potentially interferes with measurements of green fluorescent protein (GFP) fusion proteins with fluorescence microscopy techniques. Further characterization of the spatial distribution, intensity, and brightness of the autofluorescence was performed with fluorescence confocal microscopy and fluorescence fluctuation spectroscopy (FFS). The autofluorescence in both chemotaxing and nonchemotaxing cells is localized in discrete areas. The high intensity seen in cells incubated in the growth medium HG5 reduces by around 50% when incubated in buffer, and can be further reduced by around 85% by photobleaching cells for 5-7 s. The average intensity and spatial distribution of the autofluorescence do not change with long incubations in the buffer. The cellular autofluorescence has a seven times lower molecular brightness than eGFP. The influence of autofluorescence in FFS measurements can be minimized by incubating cells in buffer during the measurements, pre-bleaching, and making use of low excitation intensities. The results obtained in this study thus offer guidelines to the design of future fluorescence studies of Dictyostelium. Microsc. Res. Tech. 69:168-174, 2006. (c) 2006 Wiley-Liss, Inc.

Thermal maturity of Tasmanites microfossils from confocal laser scanning fluorescence microscopy

USGS Publications Warehouse

Hackley, Paul C.; Kus, Jolanta

2015-01-01

We report here, for the first time, spectral properties of Tasmanites microfossils determined by confocal laser scanning fluorescence microscopy (CLSM, using Ar 458 nm excitation). The Tasmanites occur in a well-characterized natural maturation sequence (Ro 0.48–0.74%) of Devonian shale (n = 3 samples) from the Appalachian Basin. Spectral property λmax shows excellent agreement (r2 = 0.99) with extant spectra from interlaboratory studies which used conventional fluorescence microscopy techniques. This result suggests spectral measurements from CLSM can be used to infer thermal maturity of fluorescent organic materials in geologic samples. Spectra of regions with high fluorescence intensity at fold apices and flanks in individual Tasmanites are blue-shifted relative to less-deformed areas in the same body that have lower fluorescence intensity. This is interpreted to result from decreased quenching moiety concentration at these locations, and indicates caution is needed in the selection of measurement regions in conventional fluorescence microscopy, where it is common practice to select high intensity regions for improved signal intensity and better signal to noise ratios. This study also documents application of CLSM to microstructural characterization of Tasmanites microfossils. Finally, based on an extant empirical relation between conventional λmax values and bitumen reflectance, λmax values from CLSM of Tasmanites microfossils can be used to calculate a bitumen reflectance equivalent value. The results presented herein can be used as a basis to broaden the future application of CLSM in the geological sciences into hydrocarbon prospecting and basin analysis.

Efficient photonic reformatting of celestial light for diffraction-limited spectroscopy

NASA Astrophysics Data System (ADS)

MacLachlan, D. G.; Harris, R. J.; Gris-Sánchez, I.; Morris, T. J.; Choudhury, D.; Gendron, E.; Basden, A. G.; Spaleniak, I.; Arriola, A.; Birks, T. A.; Allington-Smith, J. R.; Thomson, R. R.

2017-02-01

The spectral resolution of a dispersive astronomical spectrograph is limited by the trade-off between throughput and the width of the entrance slit. Photonic guided wave transitions have been proposed as a route to bypass this trade-off, by enabling the efficient reformatting of incoherent seeing-limited light collected by the telescope into a linear array of single modes: a pseudo-slit which is highly multimode in one axis but diffraction-limited in the dispersion axis of the spectrograph. It is anticipated that the size of a single-object spectrograph fed with light in this manner would be essentially independent of the telescope aperture size. A further anticipated benefit is that such spectrographs would be free of `modal noise', a phenomenon that occurs in high-resolution multimode fibre-fed spectrographs due to the coherent nature of the telescope point spread function (PSF). We seek to address these aspects by integrating a multicore fibre photonic lantern with an ultrafast laser inscribed three-dimensional waveguide interconnect to spatially reformat the modes within the PSF into a diffraction-limited pseudo-slit. Using the CANARY adaptive optics (AO) demonstrator on the William Herschel Telescope, and 1530 ± 80 nm stellar light, the device exhibits a transmission of 47-53 per cent depending upon the mode of AO correction applied. We also show the advantage of using AO to couple light into such a device by sampling only the core of the CANARY PSF. This result underscores the possibility that a fully optimized guided-wave device can be used with AO to provide efficient spectroscopy at high spectral resolution.

Building an EEG-fMRI Multi-Modal Brain Graph: A Concurrent EEG-fMRI Study

PubMed Central

Yu, Qingbao; Wu, Lei; Bridwell, David A.; Erhardt, Erik B.; Du, Yuhui; He, Hao; Chen, Jiayu; Liu, Peng; Sui, Jing; Pearlson, Godfrey; Calhoun, Vince D.

2016-01-01

The topological architecture of brain connectivity has been well-characterized by graph theory based analysis. However, previous studies have primarily built brain graphs based on a single modality of brain imaging data. Here we develop a framework to construct multi-modal brain graphs using concurrent EEG-fMRI data which are simultaneously collected during eyes open (EO) and eyes closed (EC) resting states. FMRI data are decomposed into independent components with associated time courses by group independent component analysis (ICA). EEG time series are segmented, and then spectral power time courses are computed and averaged within 5 frequency bands (delta; theta; alpha; beta; low gamma). EEG-fMRI brain graphs, with EEG electrodes and fMRI brain components serving as nodes, are built by computing correlations within and between fMRI ICA time courses and EEG spectral power time courses. Dynamic EEG-fMRI graphs are built using a sliding window method, versus static ones treating the entire time course as stationary. In global level, static graph measures and properties of dynamic graph measures are different across frequency bands and are mainly showing higher values in eyes closed than eyes open. Nodal level graph measures of a few brain components are also showing higher values during eyes closed in specific frequency bands. Overall, these findings incorporate fMRI spatial localization and EEG frequency information which could not be obtained by examining only one modality. This work provides a new approach to examine EEG-fMRI associations within a graph theoretic framework with potential application to many topics. PMID:27733821

Toward automated face detection in thermal and polarimetric thermal imagery

NASA Astrophysics Data System (ADS)

Gordon, Christopher; Acosta, Mark; Short, Nathan; Hu, Shuowen; Chan, Alex L.

2016-05-01

Visible spectrum face detection algorithms perform pretty reliably under controlled lighting conditions. However, variations in illumination and application of cosmetics can distort the features used by common face detectors, thereby degrade their detection performance. Thermal and polarimetric thermal facial imaging are relatively invariant to illumination and robust to the application of makeup, due to their measurement of emitted radiation instead of reflected light signals. The objective of this work is to evaluate a government off-the-shelf wavelet based naïve-Bayes face detection algorithm and a commercial off-the-shelf Viola-Jones cascade face detection algorithm on face imagery acquired in different spectral bands. New classifiers were trained using the Viola-Jones cascade object detection framework with preprocessed facial imagery. Preprocessing using Difference of Gaussians (DoG) filtering reduces the modality gap between facial signatures across the different spectral bands, thus enabling more correlated histogram of oriented gradients (HOG) features to be extracted from the preprocessed thermal and visible face images. Since the availability of training data is much more limited in the thermal spectrum than in the visible spectrum, it is not feasible to train a robust multi-modal face detector using thermal imagery alone. A large training dataset was constituted with DoG filtered visible and thermal imagery, which was subsequently used to generate a custom trained Viola-Jones detector. A 40% increase in face detection rate was achieved on a testing dataset, as compared to the performance of a pre-trained/baseline face detector. Insights gained in this research are valuable in the development of more robust multi-modal face detectors.

Operating organic light-emitting diodes imaged by super-resolution spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, John T.; Granick, Steve

Super-resolution stimulated emission depletion (STED) microscopy is adapted here for materials characterization that would not otherwise be possible. With the example of organic light-emitting diodes (OLEDs), spectral imaging with pixel-by-pixel wavelength discrimination allows us to resolve local-chain environment encoded in the spectral response of the semi-conducting polymer, and correlate chain packing with local electroluminescence by using externally applied current as the excitation source. We observe nanoscopic defects that would be unresolvable by traditional microscopy. They are revealed in electroluminescence maps in operating OLEDs with 50 nm spatial resolution. We find that brightest emission comes from regions with more densely packedmore » chains. Conventional microscopy of an operating OLED would lack the resolution needed to discriminate these features, while traditional methods to resolve nanoscale features generally cannot be performed when the device is operating. As a result, this points the way towards real-time analysis of materials design principles in devices as they actually operate.« less

Phenol homeostasis is ensured in vanilla fruit by storage under solid form in a new chloroplast-derived organelle, the phenyloplast

PubMed Central

Conéjéro, Geneviève

2014-01-01

A multiple cell imaging approach combining immunofluorescence by confocal microscopy, fluorescence spectral analysis by multiphotonic microscopy, and transmission electron microscopy identified the site of accumulation of 4-O-(3-methoxybenzaldehyde) β-d-glucoside, a phenol glucoside massively stockpiled by vanilla fruit. The glucoside is sufficiently abundant to be detected by spectral analysis of its autofluorescence. The convergent results obtained by these different techniques demonstrated that the phenol glucoside accumulates in the inner volume of redifferentiating chloroplasts as solid amorphous deposits, thus ensuring phenylglucoside cell homeostasis. Redifferentiation starts with the generation of loculi between thylakoid membranes which are progressively filled with the glucoside until a fully matured organelle is obtained. This peculiar mode of storage of a phenolic secondary metabolite is suspected to occur in other plants and its generalization in the Plantae could be considered. This new chloroplast-derived organelle is referred to as a ‘phenyloplast’. PMID:24683183

Phenol homeostasis is ensured in vanilla fruit by storage under solid form in a new chloroplast-derived organelle, the phenyloplast.

PubMed

Brillouet, Jean-Marc; Verdeil, Jean-Luc; Odoux, Eric; Lartaud, Marc; Grisoni, Michel; Conéjéro, Geneviève

2014-06-01

A multiple cell imaging approach combining immunofluorescence by confocal microscopy, fluorescence spectral analysis by multiphotonic microscopy, and transmission electron microscopy identified the site of accumulation of 4-O-(3-methoxybenzaldehyde) β-d-glucoside, a phenol glucoside massively stockpiled by vanilla fruit. The glucoside is sufficiently abundant to be detected by spectral analysis of its autofluorescence. The convergent results obtained by these different techniques demonstrated that the phenol glucoside accumulates in the inner volume of redifferentiating chloroplasts as solid amorphous deposits, thus ensuring phenylglucoside cell homeostasis. Redifferentiation starts with the generation of loculi between thylakoid membranes which are progressively filled with the glucoside until a fully matured organelle is obtained. This peculiar mode of storage of a phenolic secondary metabolite is suspected to occur in other plants and its generalization in the Plantae could be considered. This new chloroplast-derived organelle is referred to as a 'phenyloplast'. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Operating organic light-emitting diodes imaged by super-resolution spectroscopy

DOE PAGES

King, John T.; Granick, Steve

2016-06-21

Super-resolution stimulated emission depletion (STED) microscopy is adapted here for materials characterization that would not otherwise be possible. With the example of organic light-emitting diodes (OLEDs), spectral imaging with pixel-by-pixel wavelength discrimination allows us to resolve local-chain environment encoded in the spectral response of the semi-conducting polymer, and correlate chain packing with local electroluminescence by using externally applied current as the excitation source. We observe nanoscopic defects that would be unresolvable by traditional microscopy. They are revealed in electroluminescence maps in operating OLEDs with 50 nm spatial resolution. We find that brightest emission comes from regions with more densely packedmore » chains. Conventional microscopy of an operating OLED would lack the resolution needed to discriminate these features, while traditional methods to resolve nanoscale features generally cannot be performed when the device is operating. As a result, this points the way towards real-time analysis of materials design principles in devices as they actually operate.« less

High-extinction virtually imaged phased array-based Brillouin spectroscopy of turbid biological media

NASA Astrophysics Data System (ADS)

Fiore, Antonio; Zhang, Jitao; Shao, Peng; Yun, Seok Hyun; Scarcelli, Giuliano

2016-05-01

Brillouin microscopy has recently emerged as a powerful technique to characterize the mechanical properties of biological tissue, cell, and biomaterials. However, the potential of Brillouin microscopy is currently limited to transparent samples, because Brillouin spectrometers do not have sufficient spectral extinction to reject the predominant non-Brillouin scattered light of turbid media. To overcome this issue, we combined a multi-pass Fabry-Perot interferometer with a two-stage virtually imaged phased array spectrometer. The Fabry-Perot etalon acts as an ultra-narrow band-pass filter for Brillouin light with high spectral extinction and low loss. We report background-free Brillouin spectra from Intralipid solutions and up to 100 μm deep within chicken muscle tissue.

Multiplex coherent anti-Stokes Raman scattering microspectroscopy of brain tissue with higher ranking data classification for biomedical imaging

NASA Astrophysics Data System (ADS)

Pohling, Christoph; Bocklitz, Thomas; Duarte, Alex S.; Emmanuello, Cinzia; Ishikawa, Mariana S.; Dietzeck, Benjamin; Buckup, Tiago; Uckermann, Ortrud; Schackert, Gabriele; Kirsch, Matthias; Schmitt, Michael; Popp, Jürgen; Motzkus, Marcus

2017-06-01

Multiplex coherent anti-Stokes Raman scattering (MCARS) microscopy was carried out to map a solid tumor in mouse brain tissue. The border between normal and tumor tissue was visualized using support vector machines (SVM) as a higher ranking type of data classification. Training data were collected separately in both tissue types, and the image contrast is based on class affiliation of the single spectra. Color coding in the image generated by SVM is then related to pathological information instead of single spectral intensities or spectral differences within the data set. The results show good agreement with the H&E stained reference and spontaneous Raman microscopy, proving the validity of the MCARS approach in combination with SVM.

Dual-color 3D superresolution microscopy by combined spectral-demixing and biplane imaging.

PubMed

Winterflood, Christian M; Platonova, Evgenia; Albrecht, David; Ewers, Helge

2015-07-07

Multicolor three-dimensional (3D) superresolution techniques allow important insight into the relative organization of cellular structures. While a number of innovative solutions have emerged, multicolor 3D techniques still face significant technical challenges. In this Letter we provide a straightforward approach to single-molecule localization microscopy imaging in three dimensions and two colors. We combine biplane imaging and spectral-demixing, which eliminates a number of problems, including color cross-talk, chromatic aberration effects, and problems with color registration. We present 3D dual-color images of nanoscopic structures in hippocampal neurons with a 3D compound resolution routinely achieved only in a single color. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Programmable LED-based integrating sphere light source for wide-field fluorescence microscopy.

PubMed

Rehman, Aziz Ul; Anwer, Ayad G; Goldys, Ewa M

2017-12-01

Wide-field fluorescence microscopy commonly uses a mercury lamp, which has limited spectral capabilities. We designed and built a programmable integrating sphere light (PISL) source which consists of nine LEDs, light-collecting optics, a commercially available integrating sphere and a baffle. The PISL source is tuneable in the range 365-490nm with a uniform spatial profile and a sufficient power at the objective to carry out spectral imaging. We retrofitted a standard fluorescence inverted microscope DM IRB (Leica) with a PISL source by mounting it together with a highly sensitive low- noise CMOS camera. The capabilities of the setup have been demonstrated by carrying out multispectral autofluorescence imaging of live BV2 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamics-Enabled Nanoelectromechanical Systems (NEMS) Oscillators

DTIC Science & Technology

2014-06-01

it becomes strongly nonlinear, and thus constitutes an archetypal candidate for nonlinear engineering • its fundamental resonant frequency...width of spectral peaks of atomic force microscopy (AFM) resonators as they are brought close to a surface. 39 Approved for public release...alternating current AD Allan Deviation AFM atomic force microscopy AFRL Air Force Research Laboratory AlN aluminum nitride APN Anomalous Phase

FRET-FLIM microscopy

NASA Astrophysics Data System (ADS)

Elangovan, Masilamani; Day, Richard N.; Periasamy, Ammasi

2002-06-01

Visualizing and quantifying protein-protein interactions is a recent trend in biomedical imaging. The current advances in fluorescence microscopy coupled with the development of new fluorescent probes provide the tools to study protein interactions in living specimens. Spectral bleed-through or cross talk is a problem in one- and two-photon microscopy to recognize whether one is observing the sensitized emission or the bleed-through signals. In contrast, FLIM (fluorescence lifetime imaging microscopy) or lifetime measurements are independent of excitation intensity or fluorophore concentration. The combination of FLIM and FRET will provide high spatial (nanometer) and temporal (nanoseconds) resolution when compared to steady state FRET imaging. Importantly, spectral bleed-through is not an issue in FLIM imaging because only the donor fluorophore lifetime is measured. The presence of acceptor molecules within the local environment of the donor that permit energy transfer will influence the fluorescence lifetime of the donor. By measuring the donor lifetime in the presence and the absence of acceptor one can accurately calculate the FRET efficiency and the distance between donor- and acceptor-labeled proteins. Moreover, the FRET-FLIM technique allows monitoring more than one pair of protein interactions in a single living cell.

Microscopy and microanalysis 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, G.W.; Corbett, J.M.; Dimlich, R.V.W.

1996-12-31

The Proceedings of this Annual Meeting contain paper of members from the three societies. These proceedings emphasizes the common research interests and attempts to eliminate some unwanted overlap. Topics covered are: microscopic analysis of animals with altered gene expression and in-situ gene and antibody localizations, high-resolution elemental mapping of nucleoprofein interactions, plant biology and pathology, quantitative HREM analysis of perfect and defected materials, computational methods for TEM image analysis, high-resolution FESM in materials research, frontiers in polymer microscopy and microanalysis, oxidation and corrosion, micro XRD and XRF, molecular microspectroscopy and spectral imaging, advances in confocal and multidimensional light microscopy, analyticalmore » electron microscopy in biology, correlative microscopy in biological sciences, grain-boundary microengineering, surfaces and interfaces, telepresence microscopy in education and research, MSA educational outreach, quantitative electron probe microanalysis, frontiers of analytical electron microscopy, critical issues in ceramic microstructures, dynamic organization of the cell, pathology, microbiology, high-resolution biological and cryo SEM, and scanning-probe microscopy.« less

Multispectral detection of cutaneous lesions using spectroscopy and microscopy approaches

NASA Astrophysics Data System (ADS)

Borisova, E.; Genova-Hristova, Ts.; Troyanova, P.; Pavlova, E.; Terziev, I.; Semyachkina-Glushkovskaya, O.; Lomova, M.; Genina, E.; Stanciu, G.; Tranca, D.; Avramov, L.

2018-02-01

Autofluorescence, diffuse-reflectance and transmission spectral, and microscopic measurements were made on different cutaneous neoplastic lesions, namely basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and dysplastic and benign lesions related. Spectroscopic measurements were made on ex vivo tissue samples, and confocal microscopy investigations were made on thin tissue slices. Fluorescence spectra obtained reveal statistically significant differences between the different benign, dysplastic and malignant lesions by the level of emission intensity, as well by spectral shape, which are fingerprints applicable for differentiation algorithms. In reflectance mode the most significant differences are related to the influence of skin pigments - melanin and hemoglobin. Transmission spectroscopy mode gave complementary optical properties information about the tissue samples investigated to that one of reflectance and absorption spectroscopy. Using autofluorescence detection of skin lesions we obtain very good diagnostic performance for distinguishing of nonmelanoma lesions. Using diffuse reflectance and transmission spectroscopy we obtain significant tool for pigmented pathologies differentiation, but it is a tool with moderate sensitivity for non-melanoma lesions detection. One could rapidly increase the diagnostic accuracy of the received combined "optical biopsy" method when several spectral detection techniques are applied in common algorithm for lesions' differentiation. Specific spectral features observed in each type of lesion investigated on micro and macro level would be presented and discussed. Correlation between the spectral data received and the microscopic features observed would be discussed in the report.

Dynamic calibration of higher eigenmode parameters of a cantilever in atomic force microscopy by using tip–surface interactions

DOE PAGES

Borysov, Stanislav S.; Forchheimer, Daniel; Haviland, David B.

2014-10-29

Here we present a theoretical framework for the dynamic calibration of the higher eigenmode parameters (stiffness and optical lever inverse responsivity) of a cantilever. The method is based on the tip–surface force reconstruction technique and does not require any prior knowledge of the eigenmode shape or the particular form of the tip–surface interaction. The calibration method proposed requires a single-point force measurement by using a multimodal drive and its accuracy is independent of the unknown physical amplitude of a higher eigenmode.

Multimodal optical imaging of microvessel network convective oxygen transport dynamics.

PubMed

Dedeugd, Casey; Wankhede, Mamta; Sorg, Brian S

2009-04-01

Convective oxygen transport by microvessels depends on several parameters, including red blood cell flux and oxygen saturation. We demonstrate the use of intravital microscopy techniques to measure hemoglobin saturations, red blood cell fluxes and velocities, and microvessel cross-sectional areas in regions of microvascular networks containing multiple vessels. With these methods, data can be obtained at high spatial and temporal resolution and correlations between oxygen transport and hemodynamic parameters can be assessed. In vivo data are presented for a mouse mammary adenocarcinoma grown in a dorsal skinfold window chamber model.

The plastic ear and perceptual relearning in auditory spatial perception

PubMed Central

Carlile, Simon

2014-01-01

The auditory system of adult listeners has been shown to accommodate to altered spectral cues to sound location which presumably provides the basis for recalibration to changes in the shape of the ear over a life time. Here we review the role of auditory and non-auditory inputs to the perception of sound location and consider a range of recent experiments looking at the role of non-auditory inputs in the process of accommodation to these altered spectral cues. A number of studies have used small ear molds to modify the spectral cues that result in significant degradation in localization performance. Following chronic exposure (10–60 days) performance recovers to some extent and recent work has demonstrated that this occurs for both audio-visual and audio-only regions of space. This begs the questions as to the teacher signal for this remarkable functional plasticity in the adult nervous system. Following a brief review of influence of the motor state in auditory localization, we consider the potential role of auditory-motor learning in the perceptual recalibration of the spectral cues. Several recent studies have considered how multi-modal and sensory-motor feedback might influence accommodation to altered spectral cues produced by ear molds or through virtual auditory space stimulation using non-individualized spectral cues. The work with ear molds demonstrates that a relatively short period of training involving audio-motor feedback (5–10 days) significantly improved both the rate and extent of accommodation to altered spectral cues. This has significant implications not only for the mechanisms by which this complex sensory information is encoded to provide spatial cues but also for adaptive training to altered auditory inputs. The review concludes by considering the implications for rehabilitative training with hearing aids and cochlear prosthesis. PMID:25147497

The three-hinged arch as an example of piezomechanic passive controlled structure

NASA Astrophysics Data System (ADS)

Pagnini, Luisa Carlotta; Piccardo, Giuseppe

2016-09-01

Although piezoelectric transducers are employed in a variety of fields, their application for vibration control of civil or industrial structures has not yet been fully developed, at the best of authors' knowledge. Thanks to a new generation of ever more performing piezoceramic materials and to the recent development of scientific proposals based on a very simple technology, this paper presents a step forward to engineering applications for the control of structural systems. A three-hinged arch controlled by piezoelectric stack actuators and passive RL electrical circuits is chosen as a simple structural model that may represent the starting point for a generalization to the most common typologies of civil and industrial engineering structures. Based on the concept of electromechanical analogy, the evolution equations are obtained through a consistent Lagrangian approach. A multimodal vibration suppression is guaranteed by the spectral analogy between the mechanical and electrical components. Preliminary applications related to free oscillations, with one or more actuators on each member, seem to lead to excellent performance in terms of multimodal damping and dissipated energy.

Minimally invasive multimode optical fiber microendoscope for deep brain fluorescence imaging

PubMed Central

Ohayon, Shay; Caravaca-Aguirre, Antonio; Piestun, Rafael; DiCarlo, James J.

2018-01-01

A major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive multi-photon approaches for deep (>2mm) structures, while gradient refractive index (GRIN) endoscopes are relatively thick and can cause significant damage upon insertion. Here, we present a novel micro-endoscope design to image neural activity at arbitrary depths via an ultra-thin multi-mode optical fiber (MMF) probe that has 5–10X thinner diameter than commercially available micro-endoscopes. We demonstrate micron-scale resolution, multi-spectral and volumetric imaging. In contrast to previous approaches, we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator (GCaMP). Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions. PMID:29675297

Demonstration of a stand-alone cylindrical fiber coil for optical amplifiers

NASA Astrophysics Data System (ADS)

Laxton, Steven R.; Bravo, Tyler; Madsen, Christi K.

2015-08-01

The design, fabrication and measurement of a cylindrical fiber coil structure is presented that has applications for compact fiber-optic amplifiers. A multimode fiber is used as a surrogate for a dual clad, rare-earth doped fiber for coil fabrication and optical testing. A ray trace algorithm, written in Python, was used to simulate the behavior of light travelling along the waveguide path. An in-house fabrication method was developed using 3D printed parts designed in SolidWorks and assembled with Arduino-controlled stepper motors for coil winding. Ultraviolet-cured epoxy was used to bind the coils into a rigid cylinder. Bend losses are introduced by the coil, and a measurement of the losses for two coil lengths was obtained experimentally. The measurements confirm that bend losses through a multimode fiber, representative of pump light propagating in a dual-clad rare-earth doped fiber, are relatively wavelength independent over a large spectral range and that higher order modes are extinguished quickly while lower order modes transmit through the windings with relatively low loss.

Technique for writing of fiber Bragg gratings over or near preliminary formed macro-structure defects in silica optical fibers

NASA Astrophysics Data System (ADS)

Evtushenko, Alexander S.; Faskhutdinov, Lenar M.; Kafarova, Anastasia M.; Kazakov, Vadim S.; Kuznetzov, Artem A.; Minaeva, Alina Yu.; Sevruk, Nikita L.; Nureev, Ilnur I.; Vasilets, Alexander A.; Andreev, Vladimir A.; Morozov, Oleg G.; Burdin, Vladimir A.; Bourdine, Anton V.

2017-04-01

This work presents method for performing precision macro-structure defects "tapers" and "up-tapers" written in conventional silica telecommunication multimode optical fibers by commercially available field fusion splicer with modified software settings and following writing fiber Bragg gratings over or near them. We developed technique for macrodefect geometry parameters estimation via analysis of photo-image performed after defect writing and displayed on fusion splicer screen. Some research results of defect geometry dependence on fusion current and fusion time values re-set in splicer program are represented that provided ability to choose their "the best" combination. Also experimental statistical researches concerned with "taper" and "up-taper" diameter stability as well as their insertion loss values during their writing under fixed corrected splicer program parameters were performed. We developed technique for FBG writing over or near macro-structure defect. Some results of spectral response measurements produced for short-length samples of multimode optical fiber with fiber Bragg gratings written over and near macro-defects prepared by using proposed technique are presented.

Detection of human brain tumor infiltration with multimodal multiscale optical analysis

NASA Astrophysics Data System (ADS)

Poulon, Fanny; Metais, Camille; Jamme, Frederic; Zanello, Marc; Varlet, Pascale; Devaux, Bertrand; Refregiers, Matthieu; Abi Haidar, Darine

2017-02-01

Brain tumor surgeries are facing major challenges to improve patients' quality of life. The extent of resection while preserving surrounding eloquent brain areas is necessary to equilibrate the onco-functional. A tool able to increase the accuracy of tissue analysis and to deliver an immediate diagnostic on tumor, could drastically improve actual surgeries and patient survival rates. To achieve such performances a complete optical study, ranging from ultraviolet to infrared, of biopsies has been started by our group. Four different contrasts were used: 1) spectral analysis covering the DUV to IR range, 2) two photon fluorescence lifetime imaging and one photon time domain measurement, 3) second harmonic generation imaging and 4) fluorescence imaging using DUV to IR, one and two photon excitation. All these measurements were done on the endogenous fluorescence of tissues to avoid any bias and further clinical complication due to the introduction of external markers. The different modalities are then crossed to build a matrix of criteria to discriminate tumorous tissues. The results of multimodal optical analysis on human biopsies were compared to the gold standard histopathology.

Deterministic Integration of Quantum Dots into on-Chip Multimode Interference Beamsplitters Using in Situ Electron Beam Lithography

NASA Astrophysics Data System (ADS)

Schnauber, Peter; Schall, Johannes; Bounouar, Samir; Höhne, Theresa; Park, Suk-In; Ryu, Geun-Hwan; Heindel, Tobias; Burger, Sven; Song, Jin-Dong; Rodt, Sven; Reitzenstein, Stephan

2018-04-01

The development of multi-node quantum optical circuits has attracted great attention in recent years. In particular, interfacing quantum-light sources, gates and detectors on a single chip is highly desirable for the realization of large networks. In this context, fabrication techniques that enable the deterministic integration of pre-selected quantum-light emitters into nanophotonic elements play a key role when moving forward to circuits containing multiple emitters. Here, we present the deterministic integration of an InAs quantum dot into a 50/50 multi-mode interference beamsplitter via in-situ electron beam lithography. We demonstrate the combined emitter-gate interface functionality by measuring triggered single-photon emission on-chip with $g^{(2)}(0) = 0.13\\pm 0.02$. Due to its high patterning resolution as well as spectral and spatial control, in-situ electron beam lithography allows for integration of pre-selected quantum emitters into complex photonic systems. Being a scalable single-step approach, it paves the way towards multi-node, fully integrated quantum photonic chips.

A multimodal approach in the diagnosis of patients with hematopoietic disorders.

PubMed

Mark, H F; Gray, Y; Mark, Y; Khorsand, J; Sikov, W

1999-02-01

Myelodysplastic syndromes (MDS) are a group of relatively ill-defined hematopoietic disorders in which both qualitative and quantitative defects of the hematopoietic cells cause bone marrow dysfunction. With an incidence estimated to be approximately 1 per 100,000 persons per year, MDS mainly affects the elderly. Myelodysplastic syndromes share many features with acute nonlymphocytic leukemia; in fact, a proportion of patients with MDS eventually develop acute myeloid leukemia. To illustrate a multimodal approach in the diagnosis of patients with hematopoietic disorders, we describe a 66-year-old patient with a question of myelodysplastic syndrome, leukemia, and two translocations involving chromosome 10:t(5;10) and t(7;10). These structural rearrangements effectively gave rise to monosomy for part of the long arm of chromosome 5 and for the long arm of chromosome 7. Findings of del(5q) and del(7) in MDS have been reported in the literature. The results of chromosome morphometry, which was conducted to compare the lengths of all relevant chromosome segments, are consistent with the hypothesized chromosomal abnormalities. The investigational technique of fluorescence in situ hybridization (FISH), using both painting and alpha-satellite probes, was used as an adjunct to conventional cytogenetics to further delineate the nature of the chromosome abnormalities observed in the GTG-banded studies. Confirmatory studies utilizing the new technique of spectral karyotyping (SKY) were also carried out. Thus, the multimodal approach of hematopathology, GTG-banding, chromosome morphometry, FISH, and SKY can be very useful for delineating complex cytogenetic cases.

NicoLase—An open-source diode laser combiner, fiber launch, and sequencing controller for fluorescence microscopy

PubMed Central

Walsh, James; Böcking, Till; Gaus, Katharina

2017-01-01

Modern fluorescence microscopy requires software-controlled illumination sources with high power across a wide range of wavelengths. Diode lasers meet the power requirements and combining multiple units into a single fiber launch expands their capability across the required spectral range. We present the NicoLase, an open-source diode laser combiner, fiber launch, and software sequence controller for fluorescence microscopy and super-resolution microscopy applications. Two configurations are described, giving four or six output wavelengths and one or two single-mode fiber outputs, with all CAD files, machinist drawings, and controller source code openly available. PMID:28301563

Photonic filtering of microwave signals in the frequency range of 0.01-20 GHz using a Fabry-Perot filter

NASA Astrophysics Data System (ADS)

Aguayo-Rodríguez, G.; Zaldívar-Huerta, I. E.; García-Juárez, A.; Rodríguez-Asomoza, J.; Larger, L.; Courjal, N.

2011-01-01

We demonstrate experimentally the efficiency of tuning of a photonic filter in the frequency range of 0.01 to 20 GHz. The presented work combines the use of a multimode optical source associated with a dispersive optical fiber to obtain the filtering effect. Tunability effect is achieved by the use of a Fabry-Perot filter that allows altering the spectral characteristics of the optical source. Experimental results are validated by means of numerical simulations. The scheme here proposed has a potential application in the field of optical telecommunications.

Impact and vibration detection in composite materials by using intermodal interference in multimode optical fibers

NASA Astrophysics Data System (ADS)

Malki, Abdelrafik; Gafsi, Rachid; Michel, Laurent; Labarrère, Michel; Lecoy, Pierre

1996-09-01

An optical fiber sensor based on the intermodal interference principle is integrated in a composite material to detect impacts and vibrations. Six fibers are integrated at the top of a carbon/epoxy composite panel so as to form a grid into the structure. Spectral and temporal responses to impacts and acoustic vibrations of the sensor are compared with a piezoelectric accelerometer. The tests proved the facility of integration and the high sensitivity of the device. The location of impacts is performed with this arrangement by measuring the arrival times of the front waves to the fibers.

FIBER OPTICS. ACOUSTOOPTICS: Amplification of semiconductor laser radiation in the wavelength range 1.24-1.3 μm by stimulated Raman scattering in an optical fiber

NASA Astrophysics Data System (ADS)

Belotitskiĭ, V. I.; Kuzin, E. A.; Ovsyannikov, D. V.; Petrov, Mikhail P.

1990-07-01

An investigation was made of the influence of weak semiconductor laser radiation on the spectrum of stimulated Raman scattering in a single-mode optical waveguide pumped by a YAG:Nd3+ laser emitting at 1.06 μm. The scattered radiation power increased by a factor exceeding 10 at the semiconductor laser wavelength. A small-signal dynamic gain reached 47 dB. Simultaneous amplification was observed of several modes of multimode semiconductor laser radiation with an intermode spectral interval of 1.3 nm.

Fast, cheap and in control: spectral imaging with handheld devices

NASA Astrophysics Data System (ADS)

Gooding, Edward A.; Deutsch, Erik R.; Huehnerhoff, Joseph; Hajian, Arsen R.

2017-05-01

Remote sensing has moved out of the laboratory and into the real world. Instruments using reflection or Raman imaging modalities become faster, cheaper and more powerful annually. Enabling technologies include virtual slit spectrometer design, high power multimode diode lasers, fast open-loop scanning systems, low-noise IR-sensitive array detectors and low-cost computers with touchscreen interfaces. High-volume manufacturing assembles these components into inexpensive portable or handheld devices that make possible sophisticated decision-making based on robust data analytics. Examples include threat, hazmat and narcotics detection; remote gas sensing; biophotonic screening; environmental remediation and a host of other applications.

Physics of frequency-modulated comb generation in quantum-well diode lasers

NASA Astrophysics Data System (ADS)

Dong, Mark; Cundiff, Steven T.; Winful, Herbert G.

2018-05-01

We investigate the physical origin of frequency-modulated combs generated from single-section semiconductor diode lasers based on quantum wells, isolating the essential physics necessary for comb generation. We find that the two effects necessary for comb generation—spatial hole burning (leading to multimode operation) and four-wave mixing (leading to phase locking)—are indeed present in some quantum-well systems. The physics of comb generation in quantum wells is similar to that in quantum dot and quantum cascade lasers. We discuss the nature of the spectral phase and some important material parameters of these diode lasers.

Ultrafast optical pulse delivery with fibers for nonlinear microscopy

PubMed Central

Kim, Daekeun; Choi, Heejin; Yazdanfar, Siavash; So, Peter T. C.

2008-01-01

Nonlinear microscopies including multiphoton excitation fluorescence microscopy and multiple-harmonic generation microscopy have recently gained popularity for cellular and tissue imaging. The optimization of these imaging methods for minimally invasive use will require optical fibers to conduct light into tight space where free space delivery is difficult. The delivery of high peak power laser pulses with optical fibers is limited by dispersion resulting from nonlinear refractive index responses. In this paper, we characterize a variety of commonly used optical fibers in terms of how they affect pulse profile and imaging performance of nonlinear microscopy; the following parameters are quantified: spectral bandwidth and temporal pulse width, two-photon excitation efficiency, and optical resolution. A theoretical explanation for the measured performance of these is also provided. PMID:18816597

Individual human cell responses to low doses of chemicals studied by synchrotron infrared spectromicroscopy

NASA Astrophysics Data System (ADS)

Holman, Hoi-Ying N.; Goth-Goldstein, Regine; Blakely, Elanor A.; Bjornstad, Kathy; Martin, Michael C.; McKinney, Wayne R.

2000-05-01

Vibrational spectroscopy, when combined with synchrotron radiation-based (SR) microscopy, is a powerful new analytical tool with high spatial resolution for detecting biochemical changes in the individual living cells. In contrast to other microscopy methods that require fixing, drying, staining or labeling, SR-FTIR microscopy probes intact living cells providing a composite view of all of the molecular response and the ability to monitor the response over time in the same cell. Observed spectral changes include all types of lesions induced in that cell as well as cellular responses to external and internal stresses. These spectral changes combined with other analytical tools may provide a fundamental understanding of the key molecular mechanisms induced in response to stresses created by low- doses of chemicals. In this study we used the high spatial - resolution SR-FTIR vibrational spectromicroscopy as a sensitive analytical tool to detect chemical- and radiation- induced changes in individual human cells. Our preliminary spectral measurements indicate that this technique is sensitive enough to detect changes in nucleic acids and proteins of cells treated with environmentally relevant concentrations of dioxin. This technique has the potential to distinguish changes from exogenous or endogenous oxidative processes. Future development of this technique will allow rapid monitoring of cellular processes such as drug metabolism, early detection of disease, bio- compatibility of implant materials, cellular repair mechanisms, self assembly of cellular apparatus, cell differentiation and fetal development.

Single-Shot Optical Sectioning Using Two-Color Probes in HiLo Fluorescence Microscopy

PubMed Central

Muro, Eleonora; Vermeulen, Pierre; Ioannou, Andriani; Skourides, Paris; Dubertret, Benoit; Fragola, Alexandra; Loriette, Vincent

2011-01-01

We describe a wide-field fluorescence microscope setup which combines HiLo microscopy technique with the use of a two-color fluorescent probe. It allows one-shot fluorescence optical sectioning of thick biological moving sample which is illuminated simultaneously with a flat and a structured pattern at two different wavelengths. Both homogenous and structured fluorescence images are spectrally separated at detection and combined similarly with the HiLo microscopy technique. We present optically sectioned full-field images of Xenopus laevis embryos acquired at 25 images/s frame rate. PMID:21641327

Determining the vibrations between sensor and sample in SQUID microscopy

NASA Astrophysics Data System (ADS)

Schiessl, Daniel; Kirtley, John R.; Paulius, Lisa; Rosenberg, Aaron J.; Palmstrom, Johanna C.; Ullah, Rahim R.; Holland, Connor M.; Fung, Y.-K.-K.; Ketchen, Mark B.; Gibson, Gerald W.; Moler, Kathryn A.

2016-12-01

Vibrations can cause noise in scanning probe microscopies. Relative vibrations between the scanning sensor and the sample are important but can be more difficult to determine than absolute vibrations or vibrations relative to the laboratory. We measure the noise spectral density in a scanning SQUID microscope as a function of position near a localized source of magnetic field and show that we can determine the spectra of all three components of the relative sensor-sample vibrations. This method is a powerful tool for diagnosing vibrational noise in scanning microscopies.

Automated processing of label-free Raman microscope images of macrophage cells with standardized regression for high-throughput analysis.

PubMed

Milewski, Robert J; Kumagai, Yutaro; Fujita, Katsumasa; Standley, Daron M; Smith, Nicholas I

2010-11-19

Macrophages represent the front lines of our immune system; they recognize and engulf pathogens or foreign particles thus initiating the immune response. Imaging macrophages presents unique challenges, as most optical techniques require labeling or staining of the cellular compartments in order to resolve organelles, and such stains or labels have the potential to perturb the cell, particularly in cases where incomplete information exists regarding the precise cellular reaction under observation. Label-free imaging techniques such as Raman microscopy are thus valuable tools for studying the transformations that occur in immune cells upon activation, both on the molecular and organelle levels. Due to extremely low signal levels, however, Raman microscopy requires sophisticated image processing techniques for noise reduction and signal extraction. To date, efficient, automated algorithms for resolving sub-cellular features in noisy, multi-dimensional image sets have not been explored extensively. We show that hybrid z-score normalization and standard regression (Z-LSR) can highlight the spectral differences within the cell and provide image contrast dependent on spectral content. In contrast to typical Raman imaging processing methods using multivariate analysis, such as single value decomposition (SVD), our implementation of the Z-LSR method can operate nearly in real-time. In spite of its computational simplicity, Z-LSR can automatically remove background and bias in the signal, improve the resolution of spatially distributed spectral differences and enable sub-cellular features to be resolved in Raman microscopy images of mouse macrophage cells. Significantly, the Z-LSR processed images automatically exhibited subcellular architectures whereas SVD, in general, requires human assistance in selecting the components of interest. The computational efficiency of Z-LSR enables automated resolution of sub-cellular features in large Raman microscopy data sets without compromise in image quality or information loss in associated spectra. These results motivate further use of label free microscopy techniques in real-time imaging of live immune cells.

Multi-mode optical fibers for connecting space-based spectrometers

NASA Astrophysics Data System (ADS)

Roberts, W. T.; Lindenmisth, C. A.; Bender, S.; Miller, E. A.; Motts, E.; Ott, M.; LaRocca, F.; Thomes, J.

2017-11-01

Laser spectral analysis systems are increasingly being considered for in situ analysis of the atomic and molecular composition of selected rock and soil samples on other planets [1][2][3]. Both Laser Induced Breakdown Spectroscopy (LIBS) and Raman spectroscopy are used to identify the constituents of soil and rock samples in situ. LIBS instruments use a high peak-power laser to ablate a minute area of the surface of a sample. The resulting plasma is observed with an optical head, which collects the emitted light for analysis by one or more spectrometers. By identifying the ion emission lines observed in the plasma, the constituent elements and their abundance can be deduced. In Raman spectroscopy, laser photons incident on the sample surface are scattered and experience a Raman shift, exchanging small amounts of energy with the molecules scattering the light. By observing the spectrum of the scattered light, it is possible to determine the molecular composition of the sample. For both types of instruments, there are advantages to physically separating the light collecting optics from the spectroscopy optics. The light collection system will often have articulating or rotating elements to facilitate the interrogation of multiple samples with minimum expenditure of energy and motion. As such, the optical head is often placed on a boom or an appendage allowing it to be pointed in different directions or easily positioned in different locations. By contrast, the spectrometry portion of the instrument is often well-served by placing it in a more static location. The detectors often operate more consistently in a thermally-controlled environment. Placing them deep within the spacecraft structure also provides some shielding from ionizing radiation, extending the instrument's useful life. Finally, the spectrometry portion of the instrument often contains significant mass, such that keeping it off of the moving portion of the platform, allowing that portion to be significantly smaller, less massive and less robust. Large core multi-mode optical fibers are often used to accommodate the optical connection of the two separated portions of such instrumentation. In some cases, significant throughput efficiency improvement can be realized by judiciously orienting the strands of multi-fiber cable, close-bunching them to accommodate a tight focus of the optical system on the optical side of the connection, and splaying them out linearly along a spectrometer slit on the other end. For such instrumentation to work effectively in identifying elements and molecules, and especially to produce accurate quantitative results, the spectral throughput of the optical fiber connection must be consistent over varying temperatures, over the range of motion of the optical head (and it's implied optical cable stresses), and over angle-aperture invariant of the total system. While the first two of these conditions have been demonstrated[4], spectral observations of the latter present a cause for concern, and may have an impact on future design of fiber-connected LIBS and Raman spectroscopy instruments. In short, we have observed that the shape of the spectral efficiency curve of a large multi-mode core optical fiber changes as a function of input angle.

Raman Microscopy: A Noninvasive Method to Visualize the Localizations of Biomolecules in the Cornea.

PubMed

Kaji, Yuichi; Akiyama, Toshihiro; Segawa, Hiroki; Oshika, Tetsuro; Kano, Hideaki

2017-11-01

In vivo and in situ visualization of biomolecules without pretreatment will be important for diagnosis and treatment of ocular disorders in the future. Recently, multiphoton microscopy, based on the nonlinear interactions between molecules and photons, has been applied to reveal the localizations of various molecules in tissues. We aimed to use multimodal multiphoton microscopy to visualize the localizations of specific biomolecules in rat corneas. Multiphoton images of the corneas were obtained from nonlinear signals of coherent anti-Stokes Raman scattering, third-order sum frequency generation, and second-harmonic generation. The localizations of the adhesion complex-containing basement membrane and Bowman layer were clearly visible in the third-order sum frequency generation images. The fine structure of type I collagen was observed in the corneal stroma in the second-harmonic generation images. The localizations of lipids, proteins, and nucleic acids (DNA/RNA) was obtained in the coherent anti-Stokes Raman scattering images. Imaging technologies have progressed significantly and been applied in medical fields. Optical coherence tomography and confocal microscopy are widely used but do not provide information on the molecular structure of the cornea. By contrast, multiphoton microscopy provides information on the molecular structure of living tissues. Using this technique, we successfully visualized the localizations of various biomolecules including lipids, proteins, and nucleic acids in the cornea. We speculate that multiphoton microscopy will provide essential information on the physiological and pathological conditions of the cornea, as well as molecular localizations in tissues without pretreatment.

Intravital multiphoton fluorescence imaging and optical manipulation of spinal cord in mice, using a compact fiber laser system.

PubMed

Oshima, Yusuke; Horiuch, Hideki; Honkura, Naoki; Hikita, Atsuhiko; Ogata, Tadanori; Miura, Hiromasa; Imamura, Takeshi

2014-09-01

Near-infrared ultrafast lasers are widely used for multiphoton excited fluorescence microscopy in living animals. Ti:Sapphire lasers are typically used for multiphoton excitation, but their emission wavelength is restricted below 1,000 nm. The aim of this study is to evaluate the performance of a compact Ytterbium-(Yb-) fiber laser at 1,045 nm for multiphoton excited fluorescence microscopy in spinal cord injury. In this study, we employed a custom-designed microscopy system with a compact Yb-fiber laser and evaluated the performance of this system in in vivo imaging of brain cortex and spinal cord in YFP-H transgenic mice. For in vivo imaging of brain cortex, sharp images of basal dendrites, and pyramidal cells expressing EYFP were successfully captured using the Yb-fiber laser in our microscopy system. We also performed in vivo imaging of axon fibers of spinal cord in the transgenic mice. The obtained images were almost as sharp as those obtained using a conventional ultrafast laser system. In addition, laser ablation and multi-color imaging could be performed simultaneously using the Yb-fiber laser. The high-peak pulse Yb-fiber laser is potentially useful for multimodal bioimaging methods based on a multiphoton excited fluorescence microscopy system that incorporates laser ablation techniques. Our results suggest that microscopy systems of this type could be utilized in studies of neuroscience and clinical use in diagnostics and therapeutic tool for spinal cord injury in the future. © 2014 Wiley Periodicals, Inc.

Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy

NASA Astrophysics Data System (ADS)

Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; D'Souza-Li, Lilia; Assunção, Maria do Carmo; Bottcher-Luiz, Fátima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

2012-08-01

We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.

Isometric multimodal photoacoustic microscopy based on optically transparent micro-ring ultrasonic detection.

PubMed

Dong, Biqin; Li, Hao; Zhang, Zhen; Zhang, Kevin; Chen, Siyu; Sun, Cheng; Zhang, Hao F

2015-01-01

Photoacoustic microscopy (PAM) is an attractive imaging tool complementary to established optical microscopic modalities by providing additional molecular specificities through imaging optical absorption contrast. While the development of optical resolution photoacoustic microscopy (ORPAM) offers high lateral resolution, the acoustically-determined axial resolution is limited due to the constraint in ultrasonic detection bandwidth. ORPAM with isometric spatial resolution along both axial and lateral direction is yet to be developed. Although recently developed sophisticated optical illumination and reconstruction methods offer improved axial resolution in ORPAM, the image acquisition procedures are rather complicated, limiting their capabilities for high-speed imaging and being easily integrated with established optical microscopic modalities. Here we report an isometric ORPAM based on an optically transparent micro-ring resonator ultrasonic detector and a commercial inverted microscope platform. Owing to the superior spatial resolution and the ease of integrating our ORPAM with established microscopic modalities, single cell imaging with extrinsic fluorescence staining, intrinsic autofluorescence, and optical absorption can be achieved simultaneously. This technique holds promise to greatly improve the accessibility of PAM to the broader biomedical researchers.

Nonlinear microscopy of collagen fibers

NASA Astrophysics Data System (ADS)

Strupler, M.; Pena, A.-M.; Hernest, M.; Tharaux, P.-L.; Fabre, A.; Marchal-Somme, J.; Crestani, B.; Débarre, D.; Martin, J.-L.; Beaurepaire, E.; Schanne-Klein, M.-C.

2007-02-01

We used intrinsic Second Harmonic Generation (SHG) by fibrillar collagen to visualize the three-dimensional architecture of collagen fibrosis at the micrometer scale using laser scanning nonlinear microscopy. We showed that SHG signals are highly specific to fibrillar collagen and provide a sensitive probe of the micrometer-scale structural organization of collagen in tissues. Moreover, recording simultaneously other nonlinear optical signals in a multimodal setup, we visualized the tissue morphology using Two-Photon Excited Fluorescence (2PEF) signals from endogenous chromophores such as NADH or elastin. We then compared different methods to determine accurate indexes of collagen fibrosis using nonlinear microscopy, given that most collagen fibrils are smaller than the microscope resolution and that second harmonic generation is a coherent process. In order to define a robust method to process our three-dimensional images, we either calculated the fraction of the images occupied by a significant SHG signal, or averaged SHG signal intensities. We showed that these scores provide an estimation of the extension of renal and pulmonary fibrosis in murine models, and that they clearly sort out the fibrotic mice.

Two-photon spectral fluorescence lifetime and second-harmonic generation imaging of the porcine cornea with a 12-femtosecond laser microscope

NASA Astrophysics Data System (ADS)

Batista, Ana; Breunig, Hans Georg; Uchugonova, Aisada; Morgado, António Miguel; König, Karsten

2016-03-01

Five dimensional microscopy with a 12-fs laser scanning microscope based on spectrally resolved two-photon autofluorescence lifetime and second-harmonic generation (SHG) imaging was used to characterize all layers of the porcine cornea. This setup allowed the simultaneous excitation of both metabolic cofactors, NAD(P)H and flavins, and their discrimination based on their spectral emission properties and fluorescence decay characteristics. Furthermore, the architecture of the stromal collagen fibrils was assessed by SHG imaging in both forward and backward directions. Information on the metabolic state and the tissue architecture of the porcine cornea were obtained with subcellular resolution, and high temporal and spectral resolutions.

Two-photon spectral fluorescence lifetime and second-harmonic generation imaging of the porcine cornea with a 12-femtosecond laser microscope.

PubMed

Batista, Ana; Breunig, Hans Georg; Uchugonova, Aisada; Morgado, António Miguel; König, Karsten

2016-03-01

Five dimensional microscopy with a 12-fs laser scanning microscope based on spectrally resolved two-photon autofluorescence lifetime and second-harmonic generation (SHG) imaging was used to characterize all layers of the porcine cornea. This setup allowed the simultaneous excitation of both metabolic cofactors, NAD(P)H and flavins, and their discrimination based on their spectral emission properties and fluorescence decay characteristics. Furthermore, the architecture of the stromal collagen fibrils was assessed by SHG imaging in both forward and backward directions. Information on the metabolic state and the tissue architecture of the porcine cornea were obtained with subcellular resolution, and high temporal and spectral resolutions.

Characterization of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

Herein, a commercial optical microscope, laser microdissection instrument was coupled with an electrospray ionization mass spectrometer via a low profile liquid vortex capture probe to yield a hybrid optical microscopy/mass spectrometry imaging system. The instrument has bright-field and fluorescence microscopy capabilities in addition to a highly focused UV laser beam that is utilized for laser ablation of samples. With this system, material laser ablated from a sample using the microscope was caught by a liquid vortex capture probe and transported in solution for analysis by electrospray ionization mass spectrometry. Both lane scanning and spot sampling mass spectral imaging modes weremore » used. The smallest area the system was able to ablate was ~0.544 μm × ~0.544 μm, achieved by oversampling of the smallest laser ablation spot size that could be obtained (~1.9 μm). With use of a model photoresist surface, known features as small as ~1.5 μm were resolved. The capabilities of the system with real world samples were demonstrated first with a blended polymer thin film containing poly(2-vinylpyridine) and poly(N-vinylcarbazole). Using spot sampling imaging, sub-micrometer sized features (0.62, 0.86, and 0.98 μm) visible by optical microscopy were clearly distinguished in the mass spectral images. A second real world example showed the imaging of trace amounts of cocaine in mouse brain thin tissue sections. Lastly, with use of a lane scanning mode with ~6 μm × ~6 μm data pixels, features in the tissue as small as 15 μm in size could be distinguished in both the mass spectral and optical images.« less

Characterization of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging

DOE PAGES

Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

2015-10-22

Herein, a commercial optical microscope, laser microdissection instrument was coupled with an electrospray ionization mass spectrometer via a low profile liquid vortex capture probe to yield a hybrid optical microscopy/mass spectrometry imaging system. The instrument has bright-field and fluorescence microscopy capabilities in addition to a highly focused UV laser beam that is utilized for laser ablation of samples. With this system, material laser ablated from a sample using the microscope was caught by a liquid vortex capture probe and transported in solution for analysis by electrospray ionization mass spectrometry. Both lane scanning and spot sampling mass spectral imaging modes weremore » used. The smallest area the system was able to ablate was ~0.544 μm × ~0.544 μm, achieved by oversampling of the smallest laser ablation spot size that could be obtained (~1.9 μm). With use of a model photoresist surface, known features as small as ~1.5 μm were resolved. The capabilities of the system with real world samples were demonstrated first with a blended polymer thin film containing poly(2-vinylpyridine) and poly(N-vinylcarbazole). Using spot sampling imaging, sub-micrometer sized features (0.62, 0.86, and 0.98 μm) visible by optical microscopy were clearly distinguished in the mass spectral images. A second real world example showed the imaging of trace amounts of cocaine in mouse brain thin tissue sections. Lastly, with use of a lane scanning mode with ~6 μm × ~6 μm data pixels, features in the tissue as small as 15 μm in size could be distinguished in both the mass spectral and optical images.« less

Synthesis and characterization of high-surface-area millimeter-sized silica beads with hierarchical multi-modal pore structure by the addition of agar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Yosep; Choi, Junhyun; Tong, Meiping, E-mail: tongmeiping@iee.pku.edu.cn

2014-04-01

Millimeter-sized spherical silica foams (SSFs) with hierarchical multi-modal pore structure featuring high specific surface area and ordered mesoporous frameworks were successfully prepared using aqueous agar addition, foaming and drop-in-oil processes. The pore-related properties of the prepared spherical silica (SSs) and SSFs were systematically characterized by field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), small-angle X-ray diffraction (SAXRD), Hg intrusion porosimetry, and N{sub 2} adsorption–desorption isotherm measurements. Improvements in the BET surface area and total pore volume were observed at 504 m{sup 2} g{sup −1} and 5.45 cm{sup 3} g{sup −1}, respectively, after an agar addition and foaming process. Despitemore » the increase in the BET surface area, the mesopore wall thickness and the pore size of the mesopores generated from the block copolymer with agar addition were unchanged based on the SAXRD, TEM, and BJH methods. The SSFs prepared in the present study were confirmed to have improved BET surface area and micropore volume through the agar loading, and to exhibit interconnected 3-dimensional network macropore structure leading to the enhancement of total porosity and BET surface area via the foaming process. - Highlights: • Millimeter-sized spherical silica foams (SSFs) are successfully prepared. • SSFs exhibit high BET surface area and ordered hierarchical pore structure. • Agar addition improves BET surface area and micropore volume of SSFs. • Foaming process generates interconnected 3-D network macropore structure of SSFs.« less

High-speed vibrational imaging and spectral analysis of lipid bodies by compound Raman microscopy.

PubMed

Slipchenko, Mikhail N; Le, Thuc T; Chen, Hongtao; Cheng, Ji-Xin

2009-05-28

Cells store excess energy in the form of cytoplasmic lipid droplets. At present, it is unclear how different types of fatty acids contribute to the formation of lipid droplets. We describe a compound Raman microscope capable of both high-speed chemical imaging and quantitative spectral analysis on the same platform. We used a picosecond laser source to perform coherent Raman scattering imaging of a biological sample and confocal Raman spectral analysis at points of interest. The potential of the compound Raman microscope was evaluated on lipid bodies of cultured cells and live animals. Our data indicate that the in vivo fat contains much more unsaturated fatty acids (FAs) than the fat formed via de novo synthesis in 3T3-L1 cells. Furthermore, in vivo analysis of subcutaneous adipocytes and glands revealed a dramatic difference not only in the unsaturation level but also in the thermodynamic state of FAs inside their lipid bodies. Additionally, the compound Raman microscope allows tracking of the cellular uptake of a specific fatty acid and its abundance in nascent cytoplasmic lipid droplets. The high-speed vibrational imaging and spectral analysis capability renders compound Raman microscopy an indispensible analytical tool for the study of lipid-droplet biology.

Multi-frequency tapping-mode atomic force microscopy beyond three eigenmodes in ambient air

PubMed Central

An, Sangmin; Long, Christian J

2014-01-01

Summary We present an exploratory study of multimodal tapping-mode atomic force microscopy driving more than three cantilever eigenmodes. We present tetramodal (4-eigenmode) imaging experiments conducted on a thin polytetrafluoroethylene (PTFE) film and computational simulations of pentamodal (5-eigenmode) cantilever dynamics and spectroscopy, focusing on the case of large amplitude ratios between the fundamental eigenmode and the higher eigenmodes. We discuss the dynamic complexities of the tip response in time and frequency space, as well as the average amplitude and phase response. We also illustrate typical images and spectroscopy curves and provide a very brief description of the observed contrast. Overall, our findings are promising in that they help to open the door to increasing sophistication and greater versatility in multi-frequency AFM through the incorporation of a larger number of driven eigenmodes, and in highlighting specific future research opportunities. PMID:25383276

Multimodal fiber-probe spectroscopy for the diagnostics and classification of bladder tumors

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Fantechi, Riccardo; Gacci, Mauro; Nesi, Gabriella; Carini, Marco; Pavone, Francesco S.

2017-02-01

The gold standard for the detection of bladder cancer is white light cystoscopy, followed by an invasive biopsy and pathological examination. Tissue pathology is time consuming and often prone to sampling errors. Recently, optical spectroscopy techniques have evolved as promising techniques for the detection of neoplasia. The specific goal of this study is to evaluate the application of combined auto-fluorescence (excited using 378 nm and 445 nm wavelengths) and diffuse reflectance spectroscopy to discriminate normal bladder tissue from tumor at different grades. The fluorescence spectrum at both excitation wavelengths showed an increased spectral intensity in tumors with respect to normal tissues. Reflectance data indicated an increased reflectance in the wavelength range 610 nm - 700 nm for different grades of tumors, compared to normal tissues. The spectral data were further analyzed using principal component analysis for evaluating the sensitivity and specificity for diagnosing tumor. The spectral differences observed between various grades of tumors provides a strong genesis for the future evaluation on a larger patient population to achieve statistical significance. This study indicates that a combined spectroscopic strategy, incorporating fluorescence and reflectance spectroscopy, could improve the capability for diagnosing bladder tumor as well as for differentiating tumors in different grades.

Simultaneous identification of optical constants and PSD of spherical particles by multi-wavelength scattering-transmittance measurement

NASA Astrophysics Data System (ADS)

Zhang, Jun-You; Qi, Hong; Ren, Ya-Tao; Ruan, Li-Ming

2018-04-01

An accurate and stable identification technique is developed to retrieve the optical constants and particle size distributions (PSDs) of particle system simultaneously from the multi-wavelength scattering-transmittance signals by using the improved quantum particle swarm optimization algorithm. The Mie theory are selected to calculate the directional laser intensity scattered by particles and the spectral collimated transmittance. The sensitivity and objective function distribution analysis were conducted to evaluate the mathematical properties (i.e. ill-posedness and multimodality) of the inverse problems under three different optical signals combinations (i.e. the single-wavelength multi-angle light scattering signal, the single-wavelength multi-angle light scattering and spectral transmittance signal, and the multi-angle light scattering and spectral transmittance signal). It was found the best global convergence performance can be obtained by using the multi-wavelength scattering-transmittance signals. Meanwhile, the present technique have been tested under different Gaussian measurement noise to prove its feasibility in a large solution space. All the results show that the inverse technique by using multi-wavelength scattering-transmittance signals is effective and suitable for retrieving the optical complex refractive indices and PSD of particle system simultaneously.

Assessing FRET using Spectral Techniques

PubMed Central

Leavesley, Silas J.; Britain, Andrea L.; Cichon, Lauren K.; Nikolaev, Viacheslav O.; Rich, Thomas C.

2015-01-01

Förster resonance energy transfer (FRET) techniques have proven invaluable for probing the complex nature of protein–protein interactions, protein folding, and intracellular signaling events. These techniques have traditionally been implemented with the use of one or more fluorescence band-pass filters, either as fluorescence microscopy filter cubes, or as dichroic mirrors and band-pass filters in flow cytometry. In addition, new approaches for measuring FRET, such as fluorescence lifetime and acceptor photobleaching, have been developed. Hyperspectral techniques for imaging and flow cytometry have also shown to be promising for performing FRET measurements. In this study, we have compared traditional (filter-based) FRET approaches to three spectral-based approaches: the ratio of acceptor-to-donor peak emission, linear spectral unmixing, and linear spectral unmixing with a correction for direct acceptor excitation. All methods are estimates of FRET efficiency, except for one-filter set and three-filter set FRET indices, which are included for consistency with prior literature. In the first part of this study, spectrofluorimetric data were collected from a CFP–Epac–YFP FRET probe that has been used for intracellular cAMP measurements. All comparisons were performed using the same spectrofluorimetric datasets as input data, to provide a relevant comparison. Linear spectral unmixing resulted in measurements with the lowest coefficient of variation (0.10) as well as accurate fits using the Hill equation. FRET efficiency methods produced coefficients of variation of less than 0.20, while FRET indices produced coefficients of variation greater than 8.00. These results demonstrate that spectral FRET measurements provide improved response over standard, filter-based measurements. Using spectral approaches, single-cell measurements were conducted through hyperspectral confocal microscopy, linear unmixing, and cell segmentation with quantitative image analysis. Results from these studies confirmed that spectral imaging is effective for measuring subcellular, time-dependent FRET dynamics and that additional fluorescent signals can be readily separated from FRET signals, enabling multilabel studies of molecular interactions. PMID:23929684

Assessing FRET using spectral techniques.

PubMed

Leavesley, Silas J; Britain, Andrea L; Cichon, Lauren K; Nikolaev, Viacheslav O; Rich, Thomas C

2013-10-01

Förster resonance energy transfer (FRET) techniques have proven invaluable for probing the complex nature of protein-protein interactions, protein folding, and intracellular signaling events. These techniques have traditionally been implemented with the use of one or more fluorescence band-pass filters, either as fluorescence microscopy filter cubes, or as dichroic mirrors and band-pass filters in flow cytometry. In addition, new approaches for measuring FRET, such as fluorescence lifetime and acceptor photobleaching, have been developed. Hyperspectral techniques for imaging and flow cytometry have also shown to be promising for performing FRET measurements. In this study, we have compared traditional (filter-based) FRET approaches to three spectral-based approaches: the ratio of acceptor-to-donor peak emission, linear spectral unmixing, and linear spectral unmixing with a correction for direct acceptor excitation. All methods are estimates of FRET efficiency, except for one-filter set and three-filter set FRET indices, which are included for consistency with prior literature. In the first part of this study, spectrofluorimetric data were collected from a CFP-Epac-YFP FRET probe that has been used for intracellular cAMP measurements. All comparisons were performed using the same spectrofluorimetric datasets as input data, to provide a relevant comparison. Linear spectral unmixing resulted in measurements with the lowest coefficient of variation (0.10) as well as accurate fits using the Hill equation. FRET efficiency methods produced coefficients of variation of less than 0.20, while FRET indices produced coefficients of variation greater than 8.00. These results demonstrate that spectral FRET measurements provide improved response over standard, filter-based measurements. Using spectral approaches, single-cell measurements were conducted through hyperspectral confocal microscopy, linear unmixing, and cell segmentation with quantitative image analysis. Results from these studies confirmed that spectral imaging is effective for measuring subcellular, time-dependent FRET dynamics and that additional fluorescent signals can be readily separated from FRET signals, enabling multilabel studies of molecular interactions. © 2013 International Society for Advancement of Cytometry. Copyright © 2013 International Society for Advancement of Cytometry.

Quantitative polarized light microscopy using spectral multiplexing interferometry.

PubMed

Li, Chengshuai; Zhu, Yizheng

2015-06-01

We propose an interferometric spectral multiplexing method for measuring birefringent specimens with simple configuration and high sensitivity. The retardation and orientation of sample birefringence are simultaneously encoded onto two spectral carrier waves, generated interferometrically by a birefringent crystal through polarization mixing. A single interference spectrum hence contains sufficient information for birefringence determination, eliminating the need for mechanical rotation or electrical modulation. The technique is analyzed theoretically and validated experimentally on cellulose film. System simplicity permits the possibility of mitigating system birefringence background. Further analysis demonstrates the technique's exquisite sensitivity as high as ∼20  pm for retardation measurement.

Powder metallurgy processing and deformation characteristics of bulk multimodal nickel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farbaniec, L., E-mail: lfarban1@jhu.edu; Dirras, G., E-mail: dirras@univ-paris13.fr; Krawczynska, A.

2014-08-15

Spark plasma sintering was used to process bulk nickel samples from a blend of three powder types. The resulting multimodal microstructure was made of coarse (average size ∼ 135 μm) spherical microcrystalline entities (the core) surrounded by a fine-grained matrix (average grain size ∼ 1.5 μm) or a thick rim (the shell) distinguishable from the matrix. Tensile tests revealed yield strength of ∼ 470 MPa that was accompanied by limited ductility (∼ 2.8% plastic strain). Microstructure observation after testing showed debonding at interfaces between the matrix and the coarse entities, but in many instances, shallow dimples within the rim weremore » observed indicating local ductile events in the shell. Dislocation emission and annihilation at grain boundaries and twinning at crack tip were the main deformation mechanisms taking place within the fine-grained matrix as revealed by in-situ transmission electron microscopy. Estimation of the stress from loop's curvature and dislocation pile-up indicates that dislocation emission from grain boundaries and grain boundary overcoming largely contributes to the flow stress. - Highlights: • Bulk multi-modal Ni was processed by SPS from a powder blend. • Ultrafine-grained matrix or rim observed around spherical microcrystalline entities • Yield strength (470 MPa) and ductility (2.8% plastic strain) were measured. • Debonding was found at the matrix/microcrystalline entity interfaces. • In-situ TEM showed twinning, dislocation emission and annihilation at grain boundaries.« less

Fluorescence labeled microbubbles for multimodal imaging.

PubMed

Barrefelt, Åsa; Zhao, Ying; Larsson, Malin K; Egri, Gabriella; Kuiper, Raoul V; Hamm, Jörg; Saghafian, Maryam; Caidahl, Kenneth; Brismar, Torkel B; Aspelin, Peter; Heuchel, Rainer; Muhammed, Mamoun; Dähne, Lars; Hassan, Moustapha

2015-08-28

Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-μCT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Rigorous quantitative elemental microanalysis by scanning electron microscopy/energy dispersive x-ray spectrometry (SEM/EDS) with spectrum processing by NIST DTSA-II

NASA Astrophysics Data System (ADS)

Newbury, Dale E.; Ritchie, Nicholas W. M.

2014-09-01

Quantitative electron-excited x-ray microanalysis by scanning electron microscopy/silicon drift detector energy dispersive x-ray spectrometry (SEM/SDD-EDS) is capable of achieving high accuracy and high precision equivalent to that of the high spectral resolution wavelength dispersive x-ray spectrometer even when severe peak interference occurs. The throughput of the SDD-EDS enables high count spectra to be measured that are stable in calibration and resolution (peak shape) across the full deadtime range. With this high spectral stability, multiple linear least squares peak fitting is successful for separating overlapping peaks and spectral background. Careful specimen preparation is necessary to remove topography on unknowns and standards. The standards-based matrix correction procedure embedded in the NIST DTSA-II software engine returns quantitative results supported by a complete error budget, including estimates of the uncertainties from measurement statistics and from the physical basis of the matrix corrections. NIST DTSA-II is available free for Java-platforms at: http://www.cstl.nist.gov/div837/837.02/epq/dtsa2/index.html).

Color digital lensless holographic microscopy: laser versus LED illumination.

PubMed

Garcia-Sucerquia, Jorge

2016-08-20

A comparison of the performance of color digital lensless holographic microscopy (CDLHM) as utilized for illumination of RGB lasers or a super-bright white-light LED with a set of spectral filters is presented. As the use of lasers in CDLHM conceals the possibility of having a compact, lightweight, portable, and low cost microscope, and additionally the limited available laser radiation wavelengths limit a real multispectral imaging microscope, here we present the use of super-bright white-light LED and spectral filters for illuminating the sample. The performance of RGB laser-CDLHM and LED-CDLHM is evaluated on imaging a section of the head of a Drosophila melanogaster fly. This comparison shows that there is trade-off between the spatial resolution of the microscope and the light sources utilized, which can be understood with regard to the coherence properties of the illuminating light. Despite the smaller spatial coherence features of LED-CDLHM in comparison with laser-CDLHM, the former shows promise as a portable RGB digital lensless holographic microscope that could be extended to other wavelengths by the use of different spectral filters.

Extended output phasor representation of multi-spectral fluorescence lifetime imaging microscopy

PubMed Central

Campos-Delgado, Daniel U.; Navarro, O. Gutiérrez; Arce-Santana, E. R.; Jo, Javier A.

2015-01-01

In this paper, we investigate novel low-dimensional and model-free representations for multi-spectral fluorescence lifetime imaging microscopy (m-FLIM) data. We depart from the classical definition of the phasor in the complex plane to propose the extended output phasor (EOP) and extended phasor (EP) for multi-spectral information. The frequency domain properties of the EOP and EP are analytically studied based on a multiexponential model for the impulse response of the imaged tissue. For practical implementations, the EOP is more appealing since there is no need to perform deconvolution of the instrument response from the measured m-FLIM data, as in the case of EP. Our synthetic and experimental evaluations with m-FLIM datasets of human coronary atherosclerotic plaques show that low frequency indexes have to be employed for a distinctive representation of the EOP and EP, and to reduce noise distortion. The tissue classification of the m-FLIM datasets by EOP and EP also improves with low frequency indexes, and does not present significant differences by using either phasor. PMID:26114031

Fast spectral coherent anti-Stokes Raman scattering microscopy with high-speed tunable picosecond laser.

PubMed

Cahyadi, Harsono; Iwatsuka, Junichi; Minamikawa, Takeo; Niioka, Hirohiko; Araki, Tsutomu; Hashimoto, Mamoru

2013-09-01

We develop a coherent anti-Stokes Raman scattering (CARS) microscopy system equipped with a tunable picosecond laser for high-speed wavelength scanning. An acousto-optic tunable filter (AOTF) is integrated in the laser cavity to enable wavelength scanning by varying the radio frequency waves applied to the AOTF crystal. An end mirror attached on a piezoelectric actuator and a pair of parallel plates driven by galvanometer motors are also introduced into the cavity to compensate for changes in the cavity length during wavelength scanning to allow synchronization with another picosecond laser. We demonstrate fast spectral imaging of 3T3-L1 adipocytes every 5  cm-1 in the Raman spectral region around 2850  cm-1 with an image acquisition time of 120 ms. We also demonstrate fast switching of Raman shifts between 2100 and 2850  cm-1, corresponding to CD2 symmetric stretching and CH2 symmetric stretching vibrations, respectively. The fast-switching CARS images reveal different locations of recrystallized deuterated and nondeuterated stearic acid.

A spectral approach for the quantitative description of cardiac collagen network from nonlinear optical imaging.

PubMed

Masè, Michela; Cristoforetti, Alessandro; Avogaro, Laura; Tessarolo, Francesco; Piccoli, Federico; Caola, Iole; Pederzolli, Carlo; Graffigna, Angelo; Ravelli, Flavia

2015-01-01

The assessment of collagen structure in cardiac pathology, such as atrial fibrillation (AF), is essential for a complete understanding of the disease. This paper introduces a novel methodology for the quantitative description of collagen network properties, based on the combination of nonlinear optical microscopy with a spectral approach of image processing and analysis. Second-harmonic generation (SHG) microscopy was applied to atrial tissue samples from cardiac surgery patients, providing label-free, selective visualization of the collagen structure. The spectral analysis framework, based on 2D-FFT, was applied to the SHG images, yielding a multiparametric description of collagen fiber orientation (angle and anisotropy indexes) and texture scale (dominant wavelength and peak dispersion indexes). The proof-of-concept application of the methodology showed the capability of our approach to detect and quantify differences in the structural properties of the collagen network in AF versus sinus rhythm patients. These results suggest the potential of our approach in the assessment of collagen properties in cardiac pathologies related to a fibrotic structural component.

Carotenoid Distribution in Living Cells of Haematococcus pluvialis (Chlorophyceae)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, Aaron M.; Jones, Howland D. T.; Han, Danxiang

Haematococcus pluvialis is a freshwater unicellular green microalga belonging to the class Chlorophyceae and is of commercial interest for its ability to accumulate massive amounts of the red ketocarotenoid astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione). Using confocal Raman microscopy and multivariate analysis, we demonstrate the ability to spectrally resolve resonance–enhanced Raman signatures associated with astaxanthin and β-carotene along with chlorophyll fluorescence. By mathematically isolating these spectral signatures, in turn, it is possible to locate these species independent of each other in living cells of H. pluvialis in various stages of the life cycle. Chlorophyll emission was found only in the chloroplast whereas astaxanthin wasmore » identified within globular and punctate regions of the cytoplasmic space. Moreover, we found evidence for β-carotene to be co-located with both the chloroplast and astaxanthin in the cytosol. These observations imply that β-carotene is a precursor for astaxanthin and the synthesis of astaxanthin occurs outside the chloroplast. Finally, our work demonstrates the broad utility of confocal Raman microscopy to resolve spectral signatures of highly similar chromophores in living cells.« less

Fluorescent magnetic hybrid nanoprobe for multimodal bioimaging

PubMed Central

Bright, Vanessa

2011-01-01

A fluorescent magnetic hybrid imaging nanoprobe (HINP) was fabricated by conjugation of superparamagnetic Fe3O4 nanoparticles and visible light-emitting (~600 nm) fluorescent CdTe/CdS quantum dots (QDs). The assembly strategy used the covalent linking of the oxidized dextran shell of magnetic particles to the glutathione ligands of QDs. Synthesized HINP formed stable water-soluble colloidal dispersions. The structure and properties of the particles were characterized by transmission electron and atomic force microscopy, energy dispersive X-ray analysis and inductively coupled plasma optical emission spectroscopy, dynamic light scattering analysis, optical absorption and photoluminescence spectroscopy, and fluorescent imaging. The luminescence imaging region of the nanoprobe was extended to the near-infrared (NIR) (~800 nm) by conjugation of superparamagnetic nanoparticles with synthesized CdHgTe/CdS QDs. Cadmium, mercury based QDs in HINP can be easily replaced by novel water soluble glutathione stabilized AgInS2/ZnS QDs to present a new class of cadmium-free multimodal imaging agents. Observed NIR photoluminescence of fluorescent magnetic nanocomposites supports their use for bioimaging. The developed HINP provides dual-imaging channels for simultaneous optical and magnetic resonance imaging. PMID:21597146

Minimizing Experimental Setup Time and Effort at APS beamline 1-ID through Instrumentation Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benda, Erika; Almer, Jonathan; Kenesei, Peter

2016-01-01

Sector 1-ID at the APS accommodates a number of dif-ferent experimental techniques in the same spatial enve-lope of the E-hutch end station. These include high-energy small and wide angle X-ray scattering (SAXS and WAXS), high-energy diffraction microscopy (HEDM, both near and far field modes) and high-energy X-ray tomography. These techniques are frequently combined to allow the users to obtain multimodal data, often attaining 1 μm spatial resolution and <0.05º angular resolution. Furthermore, these techniques are utilized while the sam-ple is thermo-mechanically loaded to mimic real operat-ing conditions. The instrumentation required for each of these techniques and environments has been designedmore » and configured in a modular way with a focus on stability and repeatability between changeovers. This approach allows the end station to be more versatile, capable of collecting multi-modal data in-situ while reducing time and effort typically required for set up and alignment, resulting in more efficient beam time use. Key instrumentation de-sign features and layout of the end station are presented.« less

Multifunctional PHPMA-Derived Polymer for Ratiometric pH Sensing, Fluorescence Imaging, and Magnetic Resonance Imaging.

PubMed

Su, Fengyu; Agarwal, Shubhangi; Pan, Tingting; Qiao, Yuan; Zhang, Liqiang; Shi, Zhengwei; Kong, Xiangxing; Day, Kevin; Chen, Meiwan; Meldrum, Deirdre; Kodibagkar, Vikram D; Tian, Yanqing

2018-01-17

In this paper, we report synthesis and characterization of a novel multimodality (MRI/fluorescence) probe for pH sensing and imaging. A multifunctional polymer was derived from poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and integrated with a naphthalimide-based-ratiometric fluorescence probe and a gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex (Gd-DOTA complex). The polymer was characterized using UV-vis absorption spectrophotometry, fluorescence spectrofluorophotometry, magnetic resonance imaging (MRI), and confocal microscopy for optical and MRI-based pH sensing and cellular imaging. In vitro labeling of macrophage J774 and esophageal CP-A cell lines shows the polymer's ability to be internalized in the cells. The transverse relaxation time (T 2 ) of the polymer was observed to be pH-dependent, whereas the spin-lattice relaxation time (T 1 ) was not. The pH probe in the polymer shows a strong fluorescence-based ratiometric pH response with emission window changes, exhibiting blue emission under acidic conditions and green emission under basic conditions, respectively. This study provides new materials with multimodalities for pH sensing and imaging.

Multimodal second harmonic generation and two photon fluorescence imaging of microdomain calcium contraction coupling in single cardiomyocytes

NASA Astrophysics Data System (ADS)

Chan, James; Awasthi, Samir; Izu, Leighton; Mao, Ziliang; Jian, Zhong; Landas, Trevor; Lerner, Aaron; Shimkunas, Rafael; Woldeyesus, Rahwa; Bossuyt, Julie; Wood, Brittani; Chen, Yi-Je; Matthews, Dennis; Lieu, Deborah; Chiamvimonvat, Nipavan; Lam, Kit; Chen-Izu, Ye

2016-11-01

The objective of this study was to develop a method for simultaneously measuring the calcium and contraction dynamics of single, live cardiomyocytes at high spatial resolutions. Such measurements are important to investigate local calcium release and the mechanical response at the sarcomere level (i.e. the basic unit of contraction), which have important implications in cardiac dysfunction and arrhythmias in conditions such as hypertension, atrial fibrillation, and myocardial infarction. Here, we describe a multimodal second harmonic generation (SHG) and two photon fluorescence (2PF) microscopy technique that is used to simultaneously measure subsarcomere calcium and contraction events at high spatial and temporal resolutions. The method takes advantage of the label-free nature of SHG for imaging the sarcomeres and the high spatial colocalization of the SHG signal and the fluorescence signal excited from calcium indicators. This microscope was used to measure calcium sparks and waves and associated contractions in subcellular microdomains, leading to the generation of subcellular strain. We anticipate this new imaging tool will play an important role in studying mechanical stress-induced heart disease.

Orbital angular momentum mode groups multiplexing transmission over 2.6-km conventional multi-mode fiber.

PubMed

Zhu, Long; Wang, Andong; Chen, Shi; Liu, Jun; Mo, Qi; Du, Cheng; Wang, Jian

2017-10-16

Twisted light carrying orbital angular momentum (OAM) is a special kind of structured light that has a helical phase front, a phase singularity, and a doughnut intensity profile. Beyond widespread developments in manipulation, microscopy, metrology, astronomy, nonlinear and quantum optics, OAM-carrying twisted light has seen emerging application of optical communications in free space and specially designed fibers. Instead of specialty fibers, here we show the direct use of a conventional graded-index multi-mode fiber (MMF) for OAM communications. By exploiting fiber-compatible mode exciting and filtering elements, we excite the first four OAM mode groups in an MMF. We demonstrate 2.6-km MMF transmission using four data-carrying OAM mode groups (OAM 0,1 , OAM +1,1 /OAM -1,1 , OAM +2,1 , OAM +3,1 ). Moreover, we demonstrate two data-carrying OAM mode groups multiplexing transmission over the 2.6-km MMF with low-level crosstalk free of multiple-input multiple-output digital signal processing (MIMO-DSP). The demonstrations may open up new perspectives to fiber-based OAM communication/non-communication applications using already existing conventional fibers.

Separating Bulk and Surface Contributions to Electronic Excited-State Processes in Hybrid Mixed Perovskite Thin Films via Multimodal All-Optical Imaging

DOE PAGES

Simpson, Mary Jane; Doughty, Benjamin; Das, Sanjib; ...

2017-07-04

A comprehensive understanding of electronic excited-state phenomena underlying the impressive performance of solution-processed hybrid halide perovskite solar cells requires access to both spatially resolved electronic processes and corresponding sample morphological characteristics. In this paper, we demonstrate an all-optical multimodal imaging approach that enables us to obtain both electronic excited-state and morphological information on a single optical microscope platform with simultaneous high temporal and spatial resolution. Specifically, images were acquired for the same region of interest in thin films of chloride containing mixed lead halide perovskites (CH 3NH 3PbI 3–xCl x) using femtosecond transient absorption, time-integrated photoluminescence, confocal reflectance, and transmissionmore » microscopies. Comprehensive image analysis revealed the presence of surface- and bulk-dominated contributions to the various images, which describe either spatially dependent electronic excited-state properties or morphological variations across the probed region of the thin films. Finally, these results show that PL probes effectively the species near or at the film surface.« less

Low-cost fluorescence microscopy for point-of-care cell imaging

NASA Astrophysics Data System (ADS)

Lochhead, Michael J.; Ives, Jeff; Givens, Monique; Delaney, Marie; Moll, Kevin; Myatt, Christopher J.

2010-02-01

Fluorescence microscopy has long been a standard tool in laboratory medicine. Implementation of fluorescence microscopy for near-patient diagnostics, however, has been limited due to cost and complexity associated with traditional fluorescence microscopy techniques. There is a particular need for robust, low-cost imaging in high disease burden areas in the developing world, where access to central laboratory facilities and trained staff is limited. Here we describe a point-of-care assay that combines a disposable plastic cartridge with an extremely low cost fluorescence imaging instrument. Based on a novel, multi-mode planar waveguide configuration, the system capitalizes on advances in volume-manufactured consumer electronic components to deliver an imaging system with minimal moving parts and low power requirements. A two-color cell imager is presented, with magnification optimized for enumeration of immunostained human T cells. To demonstrate the system, peripheral blood mononuclear cells were stained with fluorescently labeled anti-human-CD4 and anti-human-CD3 antibodies. Registered images were used to generate fractional CD4+ and CD3+ staining and enumeration results that show excellent correlation with flow cytometry. The cell imager is under development as a very low cost CD4+ T cell counter for HIV disease management in limited resource settings.

Next generation DIRCM for 2.1-2.3 micron wavelength based on direct-diode GaSb technology

NASA Astrophysics Data System (ADS)

Dvinelis, Edgaras; Naujokaitė, Greta; Greibus, Mindaugas; Trinkūnas, Augustinas; Vizbaras, Kristijonas; Vizbaras, Augustinas

2018-02-01

Continuous advances in low-cost MANPAD heat-seeking missile technology over the past 50 years remains the number one hostile threat to airborne platforms globally responsible for over 60 % of casualties. Laser based directional countermeasure (DIRCM) technology have been deployed to counter the threat. Ideally, a laser based DIRCM system must involve a number of lasers emitting at different spectral bands mimicking the spectral signature of the airborne platform. Up to now, near and mid infrared spectral bands have been covered with semiconductor laser technology and only SWIR band remained with bulky fiber laser technology. Recent technology developments on direct-diode GaSb laser technology at Brolis Semiconductors offer a replacement for the fiber laser source leading to significant improvements by few orders of magnitude in weight, footprint, efficiency and cost. We demonstrate that with careful engineering, several multimode emitters can be combined to provide a directional laser beam with radiant intensity from 10 kW/sr to 60 kW/sr in an ultra-compact hermetic package with weight < 30 g and overall efficiency of 15 % in the 2.1- 2.3 micron spectral band offering 150 times improvement in efficiency and reduction in footprint. We will discuss present results, challenges and future developments for such next-generation integrated direct diode DIRCM modules for SWIR band.

MULTIMODAL IMAGING OF DISEASE-ASSOCIATED PIGMENTARY CHANGES IN RETINITIS PIGMENTOSA.

PubMed

Schuerch, Kaspar; Marsiglia, Marcela; Lee, Winston; Tsang, Stephen H; Sparrow, Janet R

2016-12-01

Using multiple imaging modalities, we evaluated the changes in photoreceptor cells and retinal pigment epithelium (RPE) that are associated with bone spicule-shaped melanin pigmentation in retinitis pigmentosa. In a cohort of 60 patients with retinitis pigmentosa, short-wavelength autofluorescence, near-infrared autofluorescence (NIR-AF), NIR reflectance, spectral domain optical coherence tomography, and color fundus images were studied. Central AF rings were visible in both short-wavelength autofluorescence and NIR-AF images. Bone spicule pigmentation was nonreflective in NIR reflectance, hypoautofluorescent with short-wavelength autofluorescence and NIR-AF imaging, and presented as intraretinal hyperreflective foci in spectral domain optical coherence tomography images. In areas beyond the AF ring outer border, the photoreceptor ellipsoid zone band was absent in spectral domain optical coherence tomography and the visibility of choroidal vessels in short-wavelength autofluorescence, NIR-AF, and NIR reflectance images was indicative of reduced RPE pigmentation. Choroidal visibility was most pronounced in the zone approaching peripheral areas of bone spicule pigmentation; here RPE/Bruch membrane thinning became apparent in spectral domain optical coherence tomography. These findings are consistent with a process by which RPE cells vacate their monolayer and migrate into inner retina in response to photoreceptor cell degeneration. The remaining RPE spread undergo thinning and consequently become less pigmented. An explanation for the absence of NIR-AF melanin signal in relation to bone spicule pigmentation is not forthcoming.

Multimodal ophthalmic imaging using spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

El-Haddad, Mohamed T.; Malone, Joseph D.; Li, Jianwei D.; Bozic, Ivan; Arquitola, Amber M.; Joos, Karen M.; Patel, Shriji N.; Tao, Yuankai K.

2017-08-01

Ophthalmic surgery involves manipulation of delicate, layered tissue structures on milli- to micrometer scales. Traditional surgical microscopes provide an inherently two-dimensional view of the surgical field with limited depth perception which precludes accurate depth-resolved visualization of these tissue layers, and limits the development of novel surgical techniques. We demonstrate multimodal swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (SS-SESLO-OCT) to address current limitations of image-guided ophthalmic microsurgery. SS-SESLO-OCT provides inherently co-registered en face and cross-sectional field-of-views (FOVs) at a line rate of 400 kHz and >2 GPix/s throughput. We show in vivo imaging of the anterior segment and retinal fundus of a healthy volunteer, and preliminary results of multi-volumetric mosaicking for ultrawide-field retinal imaging with 90° FOV. Additionally, a scan-head was rapid-prototyped with a modular architecture which enabled integration of SS-SESLO-OCT with traditional surgical microscope and slit-lamp imaging optics. Ex vivo surgical maneuvers were simulated in cadaveric porcine eyes. The system throughput enabled volumetric acquisition at 10 volumes-per-second (vps) and allowed visualization of surgical dynamics in corneal sweeps, compressions, and dissections, and retinal sweeps, compressions, and elevations. SESLO en face images enabled simple real-time co-registration with the surgical microscope FOV, and OCT cross-sections provided depth-resolved visualization of instrument-tissue interactions. Finally, we demonstrate novel augmented-reality integration with the surgical view using segmentation overlays to aid surgical guidance. SS-SESLO-OCT may benefit clinical diagnostics by enabling aiming, registration, and mosaicking; and intraoperative imaging by allowing for real-time surgical feedback, instrument tracking, and overlays of computationally extracted biomarkers of disease.

Image-guided feedback for ophthalmic microsurgery using multimodal intraoperative swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Li, Jianwei D.; Malone, Joseph D.; El-Haddad, Mohamed T.; Arquitola, Amber M.; Joos, Karen M.; Patel, Shriji N.; Tao, Yuankai K.

2017-02-01

Surgical interventions for ocular diseases involve manipulations of semi-transparent structures in the eye, but limited visualization of these tissue layers remains a critical barrier to developing novel surgical techniques and improving clinical outcomes. We addressed limitations in image-guided ophthalmic microsurgery by using microscope-integrated multimodal intraoperative swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (iSS-SESLO-OCT). We previously demonstrated in vivo human ophthalmic imaging using SS-SESLO-OCT, which enabled simultaneous acquisition of en face SESLO images with every OCT cross-section. Here, we integrated our new 400 kHz iSS-SESLO-OCT, which used a buffered Axsun 1060 nm swept-source, with a surgical microscope and TrueVision stereoscopic viewing system to provide image-based feedback. In vivo human imaging performance was demonstrated on a healthy volunteer, and simulated surgical maneuvers were performed in ex vivo porcine eyes. Denselysampled static volumes and volumes subsampled at 10 volumes-per-second were used to visualize tissue deformations and surgical dynamics during corneal sweeps, compressions, and dissections, and retinal sweeps, compressions, and elevations. En face SESLO images enabled orientation and co-registration with the widefield surgical microscope view while OCT imaging enabled depth-resolved visualization of surgical instrument positions relative to anatomic structures-of-interest. TrueVision heads-up display allowed for side-by-side viewing of the surgical field with SESLO and OCT previews for real-time feedback, and we demonstrated novel integrated segmentation overlays for augmented-reality surgical guidance. Integration of these complementary imaging modalities may benefit surgical outcomes by enabling real-time intraoperative visualization of surgical plans, instrument positions, tissue deformations, and image-based surrogate biomarkers correlated with completion of surgical goals.

Microscopic and macroscopic spectral peculiarities of cutaneous tumours

NASA Astrophysics Data System (ADS)

Borisova, Ekaterina; Genova, Tsanislava; Troyanova, Petranka; Terziev, Ivan; Zakharov, Valery; Bratchenko, Ivan; Lomova, Maria; Gorin, Dmitry; Avramov, Latchezar

2017-12-01

Autofluorescence spectral and confocal microscopic measurements were made on different cutaneous neoplastic lesions, namely basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and their dysplastic forms - keratoacantoma, dysplastic nevi and benign lesions related - basal cell papiloma, seboreic keratosa and compound nevi using excitation at 405 nm. Spectroscopic investigations were made on in vivo and ex vivo tissue samples, and confocal microscopy investigations were made on ex vivo and eosin-haematoxilin stained thin slices of the tumours detected. Correlation between the spectral data received and the microscopic features observed was found, related to the morphological and biochemical alterations during neoplasia growth. Specific spectral features observed in each type of lesion investigated on micro and macro level would be presented and discussed.

Cross-phase modulation spectral shifting: nonlinear phase contrast in a pump-probe microscope

PubMed Central

Wilson, Jesse W.; Samineni, Prathyush; Warren, Warren S.; Fischer, Martin C.

2012-01-01

Microscopy with nonlinear phase contrast is achieved by a simple modification to a nonlinear pump-probe microscope. The technique measures cross-phase modulation by detecting a pump-induced spectral shift in the probe pulse. Images with nonlinear phase contrast are acquired both in transparent and absorptive media. In paraffin-embedded biopsy sections, cross-phase modulation complements the chemically-specific pump-probe images with structural context. PMID:22567580

Analysis of pigments in polychromes by use of laser induced breakdown spectroscopy and Raman microscopy

NASA Astrophysics Data System (ADS)

Castillejo, M.; Martín, M.; Silva, D.; Stratoudaki, T.; Anglos, D.; Burgio, L.; Clark, R. J. H.

2000-09-01

Two laser-based analytical techniques, Laser Induced Breakdown Spectroscopy (LIBS) and Raman microscopy, have been used for the identification of pigments on a polychrome from the Rococo period. Detailed spectral data are presented from analyses performed on a fragment of a gilded altarpiece from the church of Escatrón, Zaragoza, Spain. LIBS measurements yielded elemental analytical data which suggest the presence of certain pigments and, in addition, provide information on the stratigraphy of the paint layers. Identification of most pigments and of the materials used in the preparation layer was performed by Raman microscopy.

Spectral imaging perspective on cytomics.

PubMed

Levenson, Richard M

2006-07-01

Cytomics involves the analysis of cellular morphology and molecular phenotypes, with reference to tissue architecture and to additional metadata. To this end, a variety of imaging and nonimaging technologies need to be integrated. Spectral imaging is proposed as a tool that can simplify and enrich the extraction of morphological and molecular information. Simple-to-use instrumentation is available that mounts on standard microscopes and can generate spectral image datasets with excellent spatial and spectral resolution; these can be exploited by sophisticated analysis tools. This report focuses on brightfield microscopy-based approaches. Cytological and histological samples were stained using nonspecific standard stains (Giemsa; hematoxylin and eosin (H&E)) or immunohistochemical (IHC) techniques employing three chromogens plus a hematoxylin counterstain. The samples were imaged using the Nuance system, a commercially available, liquid-crystal tunable-filter-based multispectral imaging platform. The resulting data sets were analyzed using spectral unmixing algorithms and/or learn-by-example classification tools. Spectral unmixing of Giemsa-stained guinea-pig blood films readily classified the major blood elements. Machine-learning classifiers were also successful at the same task, as well in distinguishing normal from malignant regions in a colon-cancer example, and in delineating regions of inflammation in an H&E-stained kidney sample. In an example of a multiplexed ICH sample, brown, red, and blue chromogens were isolated into separate images without crosstalk or interference from the (also blue) hematoxylin counterstain. Cytomics requires both accurate architectural segmentation as well as multiplexed molecular imaging to associate molecular phenotypes with relevant cellular and tissue compartments. Multispectral imaging can assist in both these tasks, and conveys new utility to brightfield-based microscopy approaches. Copyright 2006 International Society for Analytical Cytology.

Status of the Nanoscopium scanning nanoprobe beamline of Synchrotron Soleil

NASA Astrophysics Data System (ADS)

Somogyi, A.; Medjoubi, K.; Kewish, C. M.; Leroux, V.; Ribbens, M.; Baranton, G.; Polack, F.; Samama, J. P.

2013-09-01

The Nanoscopium 155 m-long scanning nanoprobe beamline of Synchrotron Soleil (St Aubin, France) is dedicated to quantitative multi-modal imaging. Dedicated experimental stations, working in consecutive operation mode, will provide coherent scatter imaging and spectro-microscopy techniques in the 5-20 keV energy range for various user communities. Next to fast scanning, cryogenic cooling will reduce the radiation damage of sensitive samples during the measurements. Nanoscopium is in the construction phase, the first user experiments are expected in 2014. The main characteristics of the beamline and an overview of its status are given in this contribution.

Optical properties of metamorphic GaAs/InAlGaAs/InGaAs heterostructures with InAs/InGaAs quantum wells, emitting light in the 1250–1400-nm spectral range

DOE Office of Scientific and Technical Information (OSTI.GOV)

Egorov, A. Yu., E-mail: anton@beam.ioffe.ru; Karachinsky, L. Ya.; Novikov, I. I.

It is demonstrated that metamorphic GaAs/InAlGaAs/InGaAs heterostructures with InAs/InGaAs quantum wells, which emit light in the 1250–1400 nm spectral range, can be fabricated by molecular-beam epitaxy. The structural and optical properties of the heterostructures are studied by X-ray diffraction analysis, transmission electron microscopy, and the photoluminescence method. Comparative analysis of the integrated photoluminescence intensity of the heterostructures and a reference sample confirm the high efficiency of radiative recombination in the heterostructures. It is confirmed by transmission electron microscopy that dislocations do not penetrate into the active region of the metamorphic heterostructures, where the radiative recombination of carriers occurs.

Self-interference fluorescence microscopy with three-phase detection for depth-resolved confocal epi-fluorescence imaging.

PubMed

Braaf, Boy; de Boer, Johannes F

2017-03-20

Three-dimensional confocal fluorescence imaging of in vivo tissues is challenging due to sample motion and limited imaging speeds. In this paper a novel method is therefore presented for scanning confocal epi-fluorescence microscopy with instantaneous depth-sensing based on self-interference fluorescence microscopy (SIFM). A tabletop epi-fluorescence SIFM setup was constructed with an annular phase plate in the emission path to create a spectral self-interference signal that is phase-dependent on the axial position of a fluorescent sample. A Mach-Zehnder interferometer based on a 3 × 3 fiber-coupler was developed for a sensitive phase analysis of the SIFM signal with three photon-counter detectors instead of a spectrometer. The Mach-Zehnder interferometer created three intensity signals that alternately oscillated as a function of the SIFM spectral phase and therefore encoded directly for the axial sample position. Controlled axial translation of fluorescent microsphere layers showed a linear dependence of the SIFM spectral phase with sample depth over axial image ranges of 500 µm and 80 µm (3.9 × Rayleigh range) for 4 × and 10 × microscope objectives respectively. In addition, SIFM was in good agreement with optical coherence tomography depth measurements on a sample with indocyanine green dye filled capillaries placed at multiple depths. High-resolution SIFM imaging applications are demonstrated for fluorescence angiography on a dye-filled capillary blood vessel phantom and for autofluorescence imaging on an ex vivo fly eye.

Multimodal imaging of the disease progression of birdshot chorioretinopathy.

PubMed

Teussink, Michel M; Huis In Het Veld, Paulien I; de Vries, Lieuwe A M; Hoyng, Carel B; Klevering, B Jeroen; Theelen, Thomas

2016-12-01

To study outer retinal deterioration in relation to clinical disease activity in patients with birdshot chorioretinopathy using fundus autofluorescence and spectral-domain optical coherence tomography (OCT). A single-centre retrospective cohort study was carried out on 42 eyes of 21 patients with birdshot disease, using a multimodal imaging approach including fundus autofluorescence, OCT, fluorescein angiography and indocyanine green angiography in combination with a patient chart review. The patients' overall clinical activity of retinal vasculitis during the follow-up period was determined by periods of clinical activity as indicated by fluorescein angiography and associated treatment decisions. Image analysis was performed to examine the spatial correspondence between autofluorescence changes and disruption of the photoreceptor inner segment ellipsoid zone on OCT. Three common types of outer retinal lesions were observed in fovea-centred images of 43% of patients: circular patches of chorioretinal atrophy, ellipsoid zone disruption on OCT, and outer retinal atrophy on autofluorescence and OCT. There was good spatial correspondence between ellipsoid zone disruption and areas of diffuse hyper-autofluorescence outside the fovea. Interestingly, the ellipsoid zone disruption recovered in four out of seven patients upon intensified therapeutic immunosuppression. Most patients only developed peripapillary atrophy and occasional perivascular hypo-autofluorescence. A multimodal imaging approach with autofluorescence imaging and OCT may help to detect ellipsoid zone disruption in the central retina of patients with birdshot disease. Our results suggest that ellipsoid zone disruption may be related to both the activity and duration of retinal vasculitis, and could help to determine therapeutic success in birdshot disease. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A multimodal wave spectrum-based approach for statistical downscaling of local wave climate

USGS Publications Warehouse

Hegermiller, Christie; Antolinez, Jose A A; Rueda, Ana C.; Camus, Paula; Perez, Jorge; Erikson, Li; Barnard, Patrick; Mendez, Fernando J.

2017-01-01

Characterization of wave climate by bulk wave parameters is insufficient for many coastal studies, including those focused on assessing coastal hazards and long-term wave climate influences on coastal evolution. This issue is particularly relevant for studies using statistical downscaling of atmospheric fields to local wave conditions, which are often multimodal in large ocean basins (e.g. the Pacific). Swell may be generated in vastly different wave generation regions, yielding complex wave spectra that are inadequately represented by a single set of bulk wave parameters. Furthermore, the relationship between atmospheric systems and local wave conditions is complicated by variations in arrival time of wave groups from different parts of the basin. Here, we address these two challenges by improving upon the spatiotemporal definition of the atmospheric predictor used in statistical downscaling of local wave climate. The improved methodology separates the local wave spectrum into “wave families,” defined by spectral peaks and discrete generation regions, and relates atmospheric conditions in distant regions of the ocean basin to local wave conditions by incorporating travel times computed from effective energy flux across the ocean basin. When applied to locations with multimodal wave spectra, including Southern California and Trujillo, Peru, the new methodology improves the ability of the statistical model to project significant wave height, peak period, and direction for each wave family, retaining more information from the full wave spectrum. This work is the base of statistical downscaling by weather types, which has recently been applied to coastal flooding and morphodynamic applications.

Hybrid single-source online Fourier transform coherent anti-Stokes Raman scattering/optical coherence tomography.

PubMed

Kamali, Tschackad; Považay, Boris; Kumar, Sunil; Silberberg, Yaron; Hermann, Boris; Werkmeister, René; Drexler, Wolfgang; Unterhuber, Angelika

2014-10-01

We demonstrate a multimodal optical coherence tomography (OCT) and online Fourier transform coherent anti-Stokes Raman scattering (FTCARS) platform using a single sub-12 femtosecond (fs) Ti:sapphire laser enabling simultaneous extraction of structural and chemical ("morphomolecular") information of biological samples. Spectral domain OCT prescreens the specimen providing a fast ultrahigh (4×12  μm axial and transverse) resolution wide field morphologic overview. Additional complementary intrinsic molecular information is obtained by zooming into regions of interest for fast label-free chemical mapping with online FTCARS spectroscopy. Background-free CARS is based on a Michelson interferometer in combination with a highly linear piezo stage, which allows for quick point-to-point extraction of CARS spectra in the fingerprint region in less than 125 ms with a resolution better than 4  cm(-1) without the need for averaging. OCT morphology and CARS spectral maps indicating phosphate and carbonate bond vibrations from human bone samples are extracted to demonstrate the performance of this hybrid imaging platform.

Combined analysis of whole human blood parameters by Raman spectroscopy and spectral-domain low-coherence interferometry

NASA Astrophysics Data System (ADS)

Gnyba, M.; Wróbel, M. S.; Karpienko, K.; Milewska, D.; Jedrzejewska-Szczerska, M.

2015-07-01

In this article the simultaneous investigation of blood parameters by complementary optical methods, Raman spectroscopy and spectral-domain low-coherence interferometry, is presented. Thus, the mutual relationship between chemical and physical properties may be investigated, because low-coherence interferometry measures optical properties of the investigated object, while Raman spectroscopy gives information about its molecular composition. A series of in-vitro measurements were carried out to assess sufficient accuracy for monitoring of blood parameters. A vast number of blood samples with various hematological parameters, collected from different donors, were measured in order to achieve a statistical significance of results and validation of the methods. Preliminary results indicate the benefits in combination of presented complementary methods and form the basis for development of a multimodal system for rapid and accurate optical determination of selected parameters in whole human blood. Future development of optical systems and multivariate calibration models are planned to extend the number of detected blood parameters and provide a robust quantitative multi-component analysis.

Photoswitchable non-fluorescent thermochromic dye-nanoparticle hybrid probes

PubMed Central

Harrington, Walter N.; Haji, Mwafaq R.; Galanzha, Ekaterina I.; Nedosekin, Dmitry A.; Nima, Zeid A.; Watanabe, Fumiya; Ghosh, Anindya; Biris, Alexandru S.; Zharov, Vladimir P.

2016-01-01

Photoswitchable fluorescent proteins with controllable light–dark states and spectral shifts in emission in response to light have led to breakthroughs in the study of cell biology. Nevertheless, conventional photoswitching is not applicable for weakly fluorescent proteins and requires UV light with low depth penetration in bio-tissue. Here we introduce a novel concept of photoswitchable hybrid probes consisting of thermochromic dye and absorbing nanoparticles, in which temperature-sensitive light–dark states and spectral shifts in absorption can be switched through controllable photothermal heating of doped nanoparticles. The proof-of-concept is demonstrated through the use of two different types of temperature-sensitive dyes doped with magnetic nanoparticles and reversibly photoswitched by a near-infrared laser. Photoacoustic imaging revealed the high contrast of these probes, which is sufficient for their visualization in cells and deep tissue. Our results suggest that these new photoswitchable multicolour probes can be used for multimodal cellular diagnostics and potentially for magnetic and photothermal therapy. PMID:27824110

Intensity liquid level sensor based on multimode interference and fiber Bragg grating

NASA Astrophysics Data System (ADS)

Oliveira, Ricardo; Aristilde, Stenio; Osório, Jonas H.; Franco, Marcos A. R.; Bilro, Lúcia; Nogueira, Rogério N.; Cordeiro, Cristiano M. B.

2016-12-01

In this paper an intensity liquid level sensor based on a single-mode—no-core—single-mode (SMS) fiber structure together with a Bragg grating inscribed in the later single mode fiber is proposed. As the no-core fiber is sensitive to the external refractive index, the SMS spectral response will be shifted related to the length of no-core fiber that is immersed in a liquid. By positioning the FBG central wavelength at the spectral region of the SMS edge filter, it is possible to measure the liquid level using the reflected FBG peak power through an intensity-based approach. The sensor is also self-referenced using the peak power of another FBG that is placed before and far from the sensing part. The temperature error analysis was also studied revealing that the sensor can operate in environments where the temperature changes are minimal. The possibility to use a second setup that makes the whole device temperature insensitive is also discussed.

Deriving photometric redshifts using fuzzy archetypes and self-organizing maps - I. Methodology

NASA Astrophysics Data System (ADS)

Speagle, Joshua S.; Eisenstein, Daniel J.

2017-07-01

We propose a method to substantially increase the flexibility and power of template fitting-based photometric redshifts by transforming a large number of galaxy spectral templates into a corresponding collection of 'fuzzy archetypes' using a suitable set of perturbative priors designed to account for empirical variation in dust attenuation and emission-line strengths. To bypass widely separated degeneracies in parameter space (e.g. the redshift-reddening degeneracy), we train self-organizing maps (SOMs) on large 'model catalogues' generated from Monte Carlo sampling of our fuzzy archetypes to cluster the predicted observables in a topologically smooth fashion. Subsequent sampling over the SOM then allows full reconstruction of the relevant probability distribution functions (PDFs). This combined approach enables the multimodal exploration of known variation among galaxy spectral energy distributions with minimal modelling assumptions. We demonstrate the power of this approach to recover full redshift PDFs using discrete Markov chain Monte Carlo sampling methods combined with SOMs constructed from Large Synoptic Survey Telescope ugrizY and Euclid YJH mock photometry.

Doppler Global Velocimetry at NASA Glenn Research Center: System Discussion and Results

NASA Technical Reports Server (NTRS)

Lant, Christian T.

2003-01-01

A ruggedized Doppler Global Velocimetry system has been built and tested at NASA Glenn Research Center. One component of planar velocity measurements of subsonic and supersonic flows from an under-expanded free jet are reported, which agree well with predicted values. An error analysis evaluates geometric and spectral error terms, and characterizes speckle noise in isotropic data. A multimode, fused fiber optic bundle is demonstrated to couple up to 650 mJ/pulse of laser light without burning or fiber ablation, and without evidence of Stimulated Brillouin Scattering or other spectral-broadening problems. Comparisons are made between spinning wheel data using illumination by freespace beam propagation and fiber optic beam delivery. The fiber bundle illumination is found to provide more spatially even and stable illumination than is typically available from pulsed Nd:YAG laser beams. The fiber bundle beam delivery is also a step toward making remote measurements and automatic real-time plume sectioning feasible in wind tunnel environments.

The central role of recognition in auditory perception: a neurobiological model.

PubMed

McLachlan, Neil; Wilson, Sarah

2010-01-01

The model presents neurobiologically plausible accounts of sound recognition (including absolute pitch), neural plasticity involved in pitch, loudness and location information integration, and streaming and auditory recall. It is proposed that a cortical mechanism for sound identification modulates the spectrotemporal response fields of inferior colliculus neurons and regulates the encoding of the echoic trace in the thalamus. Identification involves correlation of sequential spectral slices of the stimulus-driven neural activity with stored representations in association with multimodal memories, verbal lexicons, and contextual information. Identities are then consolidated in auditory short-term memory and bound with attribute information (usually pitch, loudness, and direction) that has been integrated according to the identities' spectral properties. Attention to, or recall of, a particular identity will excite a particular sequence in the identification hierarchies and so lead to modulation of thalamus and inferior colliculus neural spectrotemporal response fields. This operates as an adaptive filter for identities, or their attributes, and explains many puzzling human auditory behaviors, such as the cocktail party effect, selective attention, and continuity illusions.

Tethered SECM endoscopic capsule for the diagnosis of eosinophilic esophagitis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Do, Dukho; Kang, DongKyun; Tabatabaei, Nima; Grant, Catriona N.; Nishioka, Norman S.; Rosenberg, Mireille; Hesterberg, Paul E.; Yuan, Qian; Garber, John J.; Katz, Aubrey J.; Shreffler, Wayne G.; Tearney, Guillermo J.

2017-02-01

Eosinophilic Esophagitis (EoE) is an inflammatory disease caused by inhaled or ingested food allergies, and characterized by the infiltration of eosinophils in the esophagus. The gold standard for diagnosing EoE is to conduct endoscopy and obtain multiple biopsy specimens from different portions of the esophagus; an exam is considered positive if more than 15 eosinophils per high power field (HPF) in any of the biopsies. This method of diagnosis is problematic because endoscopic biopsy is expensive and poorly tolerated and the esophageal eosinophil burden needs to be monitored frequently during the course of the disease. Spectrally encoded confocal microscopy (SECM) is a high-speed confocal microscopy technology that can visualize individual eosinophils in large microscopic images of the human esophagus, equivalent to more than 30,000 HPF. Previously, we have demonstrated that tethered capsule SECM can be conducted in unsedated subjects with diagnosed EoE. However, speckle noise and the relatively low resolution in images obtained with the first capsule prototypes made it challenging to distinguish eosinophils from other cells. In this work, we present a next-generation tethered SECM capsule, which has been modified to significantly improve image quality. First, we substituted the single mode fiber with a dual-clad fiber to reduce speckle noise. A gradient-index multimode fiber was fusion spliced at the tip of the dual-clad fiber to increase the effective numerical aperture of the fiber from 0.09 to 0.15, expanding the beam more rapidly to increase the illumination aperture at the objective. These modifications enabled the new SECM capsule to achieve a lateral resolution of 1.8 µm and an axial resolution of 16.1 µm, which substantially improves the capacity of this probe to visualize cellular features in human tissue. The total size of the SECM capsule remained 6.75 mm in diameter and 31 mm in length. We are now in the process of testing this new SECM capsule in humans. Early results using this new SECM capsule suggest that this technology has the potential to be an effective tool for the diagnosis of EoE.

The STIS MAMA status: Current detector performance

NASA Technical Reports Server (NTRS)

Danks, A. C.; Joseph, C.; Bybee, R.; Argebright, V.; Abraham, J.; Kimble, R.; Woodgate, B.

1992-01-01

The STIS (Space Telescope Imaging Spectrograph) is a second generation Hubble instrument scheduled to fly in 1997. Through a variety of modes, the instrument will provide spectral resolutions from R approximately 50 in the objective spectroscopy mode to 100,000 in the high resolution echelle mode in the wavelength region from 115 to 1000 nm. In the UV the instrument employs two MAMA (Multimode Anode Microchannel plate Arrays) 1024 by 1024 pixel detectors, which provide high DQE (Detective Quantum Efficiency), and good dynamic range and resolution. The current progress and performance of these detectors are reported, illustrating that the technology is mature and that the performance is very close to flight requirements.

Fiber-Optic Linear Displacement Sensor Based On Matched Interference Filters

NASA Astrophysics Data System (ADS)

Fuhr, Peter L.; Feener, Heidi C.; Spillman, William B.

1990-02-01

A fiber optic linear displacement sensor has been developed in which a pair of matched interference filters are used to encode linear position on a broadband optical signal as relative intensity variations. As the filters are displaced, the optical beam illuminates varying amounts of each filter. Determination of the relative intensities at each filter pairs' passband is based on measurements acquired with matching filters and photodetectors. Source power variation induced errors are minimized by basing determination of linear position on signal Visibility. A theoretical prediction of the sensor's performance is developed and compared with experiments performed in the near IR spectral region using large core multimode optical fiber.

Non-linear imaging and characterization of atherosclerotic arterial tissue using combined two photon fluorescence, second-harmonic generation and CARS microscopy

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Matthäus, Christian; Meyer, Tobias; Lattermann, Annika; Dietzek, Benjamin; Brehm, Bernhard R.; Popp, Jürgen; Pavone, Francesco S.

2014-02-01

Atherosclerosis is among the most widespread cardiovascular diseases and one of the leading cause of death in the Western World. Characterization of arterial tissue in atherosclerotic condition is extremely interesting from the diagnostic point of view. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires a morpho-functional approach. Multimodal non-linear microscopy has the potential to bridge this gap by providing morpho-functional information on the examined tissues in a label-free way. Here we employed multiple non-linear microscopy techniques, including CARS, TPF, and SHG to provide intrinsic optical contrast from various tissue components in both arterial wall and atherosclerotic plaques. CARS and TPF microscopy were used to respectively image lipid depositions within plaques and elastin in the arterial wall. Cholesterol deposition in the lumen and collagen in the arterial wall were selectively imaged by SHG microscopy and distinguished by forward-backward SHG ratio. Image pattern analysis allowed characterizing collagen organization in different tissue regions. Different values of fiber mean size, distribution and anisotropy are calculated for lumen and media prospectively allowing for automated classification of atherosclerotic lesions. The presented method represents a promising diagnostic tool for evaluating atherosclerotic tissue and has the potential to find a stable place in clinical setting as well as to be applied in vivo in the near future.