Quantitative imaging of fibrotic and morphological changes in liver of non-alcoholic steatohepatitis (NASH) model mice by second harmonic generation (SHG) and auto-fluorescence (AF) imaging using two-photon excitation microscopy (TPEM).

PubMed

Yamamoto, Shin; Oshima, Yusuke; Saitou, Takashi; Watanabe, Takao; Miyake, Teruki; Yoshida, Osamu; Tokumoto, Yoshio; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi; Imamura, Takeshi

2016-12-01

Non-alcoholic steatohepatitis (NASH) is a common liver disorder caused by fatty liver. Because NASH is associated with fibrotic and morphological changes in liver tissue, a direct imaging technique is required for accurate staging of liver tissue. For this purpose, in this study we took advantage of two label-free optical imaging techniques, second harmonic generation (SHG) and auto-fluorescence (AF), using two-photon excitation microscopy (TPEM). Three-dimensional ex vivo imaging of tissues from NASH model mice, followed by image processing, revealed that SHG and AF are sufficient to quantitatively characterize the hepatic capsule at an early stage and parenchymal morphologies associated with liver disease progression, respectively.

Investigation of Optical Cavity Modes and Ultrafast Carrier Dynamics in Zinc Oxide Rods Using Second-Harmonic Generation and Transient Absorption Pump-Probe Microscopy

NASA Astrophysics Data System (ADS)

Mehl, Brian Peter

The polydispersity intrinsic to nanoscale and microscale semiconductor materials poses a major challenge to using individual objects as building blocks for device applications. The ability to manipulate the shape of ZnO structures is enormous, making it an ideal material for studying shape-dependent phenomena. We have built a nonlinear microscope used to directly image optical cavity modes in ZnO rods using second-harmonic generation. Images of second-harmonic generation in needle-shaped ZnO rods obtained from individual structures show areas of enhanced second-harmonic intensity along the longitudinal axis of the rod that are periodically distributed and symmetrically situated relative to the rod midpoint. The spatial modulation is a direct consequence of the fundamental optical field coupling into standing wave resonator modes of the ZnO structure, leading to an enhanced backscattered second-harmonic condition that cannot be achieved in bulk ZnO. A more complicated second-harmonic image is observed when excitation is below the band gap, which is attributed to whispering gallery modes. Additionally, the nonlinear microscope was combined with transient absorption pump-probe to follow the electron-hole recombination dynamics at different points within individual needle-shaped ZnO rods to characterize spatial differences in dynamical behavior. The results from pump-probe experiments are correlated with spatially resolved ultrafast emission measurements, and scanning electron microscopy provides structural details. Dramatically different electron-hole recombination dynamics are observed in the narrow tips compared to the interior, with the ends exhibiting a greater propensity for electron-hole plasma formation and faster recombination of carriers across the band gap that stem from a physical confinement of the charge carriers. In the interior of the rod, a greater fraction of the electron-hole recombination is trap-mediated and occurs on a significantly longer time scale.

Macromolecular structure of cellulose studied by second-harmonic generation imaging microscopy

NASA Astrophysics Data System (ADS)

Brown, R. Malcom; Millard, Andrew C.; Campagnola, Paul J.

2003-11-01

The macromolecular structure of purified cellulose samples is studied by second-harmonic generation (SHG) imaging microscopy. We show that the SHG contrast in both Valonia and Acetobacter cellulose strongly resembles that of collagen from animal tissues, both in terms of morphology and polarization anisotropy. Polarization analysis shows that microfibrils in each lamella are highly aligned and ordered and change directions by 90° in adjacent lamellae. The angular dependence of the SHG intensity fits well to a cos2 θ distribution, which is characteristic of the electric dipole interaction. Enzymatic degradation of Valonia fibers by cellulase is followed in real time by SHG imaging and results in exponential decay kinetics, showing that SHG imaging microscopy is ideal for monitoring dynamics in biological systems.

Second harmonic generation imaging of the collagen in myocardium for atrial fibrillation diagnosis

NASA Astrophysics Data System (ADS)

Tsai, Ming-Rung; Chiou, Yu-We; Sun, Chi-Kuang

2009-02-01

Myocardial fibrosis, a common sequela of cardiac hypertrophy, has been shown to be associated with arrhythmias in experimental models. Some research has indicated that myocardial fibrosis plays an important role in predisposing patients to atrial fibrillation. Second harmonic generation (SHG) is an optically nonlinear coherent process to image the collagen network. In this presentation, we observe the SHG images of the collagen matrix in atrial myocardium and we analyzed of collagen fibers arrangement by using Fourier-transform analysis. Moreover, comparing the SHG images of the collagen fibers in atrial myocardium between normal sinus rhythm (NSR) and atrial fibrillation (AF), our result indicated that it is possible to realize the relation between myocardial fibrosis and AF.

Investigation of superharmonic sound propagation and imaging in biological tissues in vitro.

PubMed

Ma, Qingyu; Zhang, Dong; Gong, Xiufen; Ma, Yong

2006-04-01

This article presents both theoretical and experimental studies on the superharmonic generation and its imaging in biological tissues. A superharmonic component is defined as a summation of the third-, fourth-, and fifth-order harmonics. A superharmonic signal is produced using an 8-mm-diam, 2.5-MHz planar piston source that is excited by eight-cycle, 2.5-MHz tone bursts. Axial and lateral field distributions of the superharmonic component and the second harmonic are first calculated based on the nonlinear KZK model and then compared with those experimentally determined at two different source pressures of 0.5 and 1 MPa. Results indicate that the amplitude of the superharmonic component can exceed that of the second harmonic, depending on the axial distance and the fundamental pressure amplitude. Also, the 3-dB beamwidth of the superharmonic component is about 23% narrower than that of the second harmonic. Additional experiments are performed in vitro using liver and fatty tissues in transmission mode and produced two-dimensional images using the fundamental, the second harmonic, and the superharmonic signals. Although the clinical applicability of this work still needs to be assessed, these results indicate that the superharmonic image quality is better than that of the other two images.

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.

Determination of three-dimensional molecular orientation of type-I collagen by circularly-polarized second harmonic generation imaging

NASA Astrophysics Data System (ADS)

Zhuo, Guan-Yu; Hung, Wei-Han; Kao, Fu-Jen

2017-04-01

The content of collagen is up to 30% existing in mammals. It supports the main component of connective tissues such as skin, ligament, and cartilage. Among various types of collagen, type-I collagen is of the most abundance and has been broadly studied due to the importance in bioscience. Second harmonic generation (SHG) microscopy is an effective tool used to study the collagen organization without labeling. In this study, we used circular polarization instead of linear polarization to retrieve three-dimensional (3D) molecular orientation of type-I collagen with only two cross polarized SHG images without acquiring an image stack of varying polarization.

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.

Long-term imaging of mouse embryos using adaptive harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Thayil, Anisha; Watanabe, Tomoko; Jesacher, Alexander; Wilson, Tony; Srinivas, Shankar; Booth, Martin

2011-04-01

We present a detailed description of an adaptive harmonic generation (HG) microscope and culture techniques that permit long-term, three-dimensional imaging of mouse embryos. HG signal from both pre- and postimplantation stage (0.5-5.5 day-old) mouse embryos are fully characterized. The second HG images reveal central spindles during cytokinesis whereas third HG images show several features, such as lipid droplets, nucleoli, and plasma membranes. The embryos are found to develop normally during one-day-long discontinuous HG imaging, permitting the observation of several dynamic events, such as morula compaction and blastocyst formation.

Bioinspired second harmonic generation

NASA Astrophysics Data System (ADS)

Sonay, Ali Y.; Pantazis, Periklis

2017-07-01

Second harmonic generation (SHG) is a microscopic technique applicable to a broad spectrum of biological and medical imaging due to its excellent photostability, high signal-to-noise ratio (SNR) and narrow emission profile. Current SHG microscopy techniques rely on two main contrast modalities. These are endogenous SHG generated by tissue structures, which is clinically relevant but cannot be targeted to another location, or SHG nanoprobes, inorganic nanocrystals that can be directed to proteins and cells of interest, but cannot be applied for clinical imaging due to their chemical composition. Here we analyzed SHG signal generated by large-scale peptide assemblies. Our results show the sequence of peptides play an important role on both the morphology and SHG signal of the peptide assemblies. Changing peptide sequence allows confinement of large number of peptides to smaller voxels, generating intense SHG signal. With miniaturization of these peptides and their proper functionalization strategies, such bioinspired nanoparticles would emerge as valuable tools for clinical imaging.

High-resolution frequency domain second harmonic optical coherence tomography

NASA Astrophysics Data System (ADS)

Su, Jianping; Tomov, I. V.; Jiang, Yi; Chen, Zhongping

2007-02-01

We used continuum generated in an 8.5 cm long fiber by a femtosecond Yb fiber laser to improve threefold the axial resolution of frequency domain SH-OCT to 12μm. The acquisition time was shortened by more than two orders of magnitude compared to time domain SH-OCT. The system was applied to image biological tissue of fish scales, pig leg tendon and rabbit eye sclera. Highly organized collagen fibrils can be visualized in the recorded images. Polarization dependence on second harmonic has been used to obtain polarization resolved images.

Towards protein-crystal centering using second-harmonic generation (SHG) microscopy

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

Kissick, David J.; Dettmar, Christopher M.; Becker, Michael

2013-05-01

The potential of second-harmonic generation (SHG) microscopy for automated crystal centering to guide synchrotron X-ray diffraction of protein crystals has been explored. The potential of second-harmonic generation (SHG) microscopy for automated crystal centering to guide synchrotron X-ray diffraction of protein crystals was explored. These studies included (i) comparison of microcrystal positions in cryoloops as determined by SHG imaging and by X-ray diffraction rastering and (ii) X-ray structure determinations of selected proteins to investigate the potential for laser-induced damage from SHG imaging. In studies using β{sub 2} adrenergic receptor membrane-protein crystals prepared in lipidic mesophase, the crystal locations identified by SHGmore » images obtained in transmission mode were found to correlate well with the crystal locations identified by raster scanning using an X-ray minibeam. SHG imaging was found to provide about 2 µm spatial resolution and shorter image-acquisition times. The general insensitivity of SHG images to optical scatter enabled the reliable identification of microcrystals within opaque cryocooled lipidic mesophases that were not identified by conventional bright-field imaging. The potential impact of extended exposure of protein crystals to five times a typical imaging dose from an ultrafast laser source was also assessed. Measurements of myoglobin and thaumatin crystals resulted in no statistically significant differences between structures obtained from diffraction data acquired from exposed and unexposed regions of single crystals. Practical constraints for integrating SHG imaging into an active beamline for routine automated crystal centering are discussed.« less

Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy

PubMed Central

Small, David M.; Jones, Jason S.; Tendler, Irwin I.; Miller, Paul E.; Ghetti, Andre; Nishimura, Nozomi

2017-01-01

Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool. PMID:29359098

Second Harmonic Generation Imaging Analysis of Collagen Arrangement in Human Cornea.

PubMed

Park, Choul Yong; Lee, Jimmy K; Chuck, Roy S

2015-08-01

To describe the horizontal arrangement of human corneal collagen bundles by using second harmonic generation (SHG) imaging. Human corneas were imaged with an inverted two photon excitation fluorescence microscope. The excitation laser (Ti:Sapphire) was tuned to 850 nm. Backscatter signals of SHG were collected through a 425/30-nm bandpass emission filter. Multiple, consecutive, and overlapping image stacks (z-stacks) were acquired to generate three dimensional data sets. ImageJ software was used to analyze the arrangement pattern (irregularity) of collagen bundles at each image plane. Collagen bundles in the corneal lamellae demonstrated a complex layout merging and splitting within a single lamellar plane. The patterns were significantly different in the superficial and limbal cornea when compared with deep and central regions. Collagen bundles were smaller in the superficial layer and larger in deep lamellae. By using SHG imaging, the horizontal arrangement of corneal collagen bundles was elucidated at different depths and focal regions of the human cornea.

Polarization-resolved second-harmonic-generation imaging of photoaged dermal collagen fiber

NASA Astrophysics Data System (ADS)

Yasui, Takeshi; Takahashi, Yu; Araki, Tsutomu

2009-02-01

Polarization-resolved second-harmonic-generation (SHG) microscopy is useful for assessment of collagen fiber orientation in tissues. In this paper, we investigated the relation between wrinkle direction and collagen orientation in ultraviolet-B-exposed (UVB-exposed) skin using polarization-resolved SHG microscopy. A polarization anisotropic image of the SHG light indicated that wrinkle direction in UVB-exposed skin is predominantly parallel to the orientation of dermal collagen fibers whereas no-UVB-exposed skin was dominated by collagen orientation parallel to the meridian line of body. The method proposed has the potential to become a powerful non-invasive tool for assessment of cutaneous photoaging.

3D second harmonic generation imaging tomography by multi-view excitation

PubMed Central

Campbell, Kirby R.; Wen, Bruce; Shelton, Emily M.; Swader, Robert; Cox, Benjamin L.; Eliceiri, Kevin; Campagnola, Paul J.

2018-01-01

Biological tissues have complex 3D collagen fiber architecture that cannot be fully visualized by conventional second harmonic generation (SHG) microscopy due to electric dipole considerations. We have developed a multi-view SHG imaging platform that successfully visualizes all orientations of collagen fibers. This is achieved by rotating tissues relative to the excitation laser plane of incidence, where the complete fibrillar structure is then visualized following registration and reconstruction. We evaluated high frequency and Gaussian weighted fusion reconstruction algorithms, and found the former approach performs better in terms of the resulting resolution. The new approach is a first step toward SHG tomography. PMID:29541654

Parallel transmit beamforming using orthogonal frequency division multiplexing applied to harmonic imaging--a feasibility study.

PubMed

Demi, Libertario; Verweij, Martin D; Van Dongen, Koen W A

2012-11-01

Real-time 2-D or 3-D ultrasound imaging systems are currently used for medical diagnosis. To achieve the required data acquisition rate, these systems rely on parallel beamforming, i.e., a single wide-angled beam is used for transmission and several narrow parallel beams are used for reception. When applied to harmonic imaging, the demand for high-amplitude pressure wave fields, necessary to generate the harmonic components, conflicts with the use of a wide-angled beam in transmission because this results in a large spatial decay of the acoustic pressure. To enhance the amplitude of the harmonics, it is preferable to do the reverse: transmit several narrow parallel beams and use a wide-angled beam in reception. Here, this concept is investigated to determine whether it can be used for harmonic imaging. The method proposed in this paper relies on orthogonal frequency division multiplexing (OFDM), which is used to create distinctive parallel beams in transmission. To test the proposed method, a numerical study has been performed, in which the transmit, receive, and combined beam profiles generated by a linear array have been simulated for the second-harmonic component. Compared with standard parallel beamforming, application of the proposed technique results in a gain of 12 dB for the main beam and in a reduction of the side lobes. Experimental verification in water has also been performed. Measurements obtained with a single-element emitting transducer and a hydrophone receiver confirm the possibility of exciting a practical ultrasound transducer with multiple Gaussian modulated pulses, each having a different center frequency, and the capability to generate distinguishable second-harmonic components.

Development of ultrasound transducer diffractive field theory for nonlinear propagation-based imaging

NASA Astrophysics Data System (ADS)

Kharin, Nikolay A.

2000-04-01

In nonlinear ultrasound imaging the images are formed using the second harmonic energy generated due to the nonlinear nature of finite amplitude propagation. This propagation can be modeled using the KZK wave equation. This paper presents further development of nonlinear diffractive field theory based on the KZK equation and its solution by means of the slowly changing profile method for moderate nonlinearity. The analytical expression for amplitudes and phases of sum frequency wave are obtained in addition to the second harmonic wave. Also, the analytical expression for the relative curvature of the wave fronts of fundamental and second harmonic signals are derived. The media with different nonlinear properties and absorption coefficients were investigated to characterize the diffractive field of the transducer at medical frequencies. All expressions demonstrate good agreement with experimental results. The expressions are novel and provide an easy way for prediction of amplitude and phase structure of nonlinearly distorted field of a transducer. The sum frequency signal technique could be implemented as well as second harmonic technique to improve the quality of biomedical images. The results obtained are of importance for medical diagnostic ultrasound equipment design.

Simultaneous stimulated Raman scattering and higher harmonic generation imaging for liver disease diagnosis without labeling

NASA Astrophysics Data System (ADS)

Lin, Jian; Wang, Zi; Zheng, Wei; Huang, Zhiwei

2014-02-01

Nonlinear optical microscopy (e.g., higher harmonic (second-/third- harmonic) generation (HHG), simulated Raman scattering (SRS)) has high diagnostic sensitivity and chemical specificity, making it a promising tool for label-free tissue and cell imaging. In this work, we report a development of a simultaneous SRS and HHG imaging technique for characterization of liver disease in a bile-duct-ligation rat-modal. HHG visualizes collagens formation and reveals the cell morphologic changes associated with liver fibrosis; whereas SRS identifies the distributions of hepatic fat cells formed in steatosis liver tissue. This work shows that the co-registration of SRS and HHG images can be an effective means for label-free diagnosis and characterization of liver steatosis/fibrosis at the cellular and molecular levels.

Multimodal, multiphoton microscopy and image correlation analysis for characterizing corneal thermal damage

NASA Astrophysics Data System (ADS)

Lo, Wen; Chang, Yu-Lin; Liu, Jia-Shiu; Hseuh, Chiu-Mei; Hovhannisyan, Vladimir; Chen, Shean-Jen; Tan, Hsin-Yuan; Dong, Chen-Yuan

2009-09-01

We used the combination of multiphoton autofluorescence (MAF), forward second-harmonic generation (FWSHG), and backward second-harmonic generation (BWSHG) imaging for the qualitative and quantitative characterization of thermal damage of ex vivo bovine cornea. We attempt to characterize the structural alterations by qualitative MAF, FWSHG, and BWSHG imaging in the temperature range of 37 to 90°C. In addition to measuring the absolute changes in the three types of signals at the stromal surface, we also performed image correlation analysis between FWSHG and BWSHG and demonstrate that with increasing thermal damage, image correlation between FWSHG and BWSHG significantly increases. Our results show that while MAF and BWSHG intensities may be used as preliminary indicators of the extent of corneal thermal damage, the most sensitive measures are provided by the decay in FWSHG intensity and the convergence of FWSHG and BWSHG images.

High-resolution frequency-domain second-harmonic optical coherence tomography

NASA Astrophysics Data System (ADS)

Su, Jianping; Tomov, Ivan V.; Jiang, Yi; Chen, Zhongping

2007-04-01

We used continuum generated in an 8.5 cm long fiber by a femtosecond Yb fiber laser to improve threefold the axial resolution of frequency domain second-harmonic optical coherence tomography (SH-OCT) to 12 μm. The acquisition time was shortened by more than 2 orders of magnitude compared to the time-domain SH-OCT. The system was applied to image biological tissue of fish scales, pig leg tendon, and rabbit eye sclera. Highly organized collagen fibrils can be visualized in the recorded images. Polarization dependence on the SH has been used to obtain polarization resolved images.

Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues.

PubMed Central

Campagnola, Paul J; Millard, Andrew C; Terasaki, Mark; Hoppe, Pamela E; Malone, Christian J; Mohler, William A

2002-01-01

We find that several key endogenous protein structures give rise to intense second-harmonic generation (SHG)-nonabsorptive frequency doubling of an excitation laser line. Second-harmonic imaging microscopy (SHIM) on a laser-scanning system proves, therefore, to be a powerful and unique tool for high-resolution, high-contrast, three-dimensional studies of live cell and tissue architecture. Unlike fluorescence, SHG suffers no inherent photobleaching or toxicity and does not require exogenous labels. Unlike polarization microscopy, SHIM provides intrinsic confocality and deep sectioning in complex tissues. In this study, we demonstrate the clarity of SHIM optical sectioning within unfixed, unstained thick specimens. SHIM and two-photon excited fluorescence (TPEF) were combined in a dual-mode nonlinear microscopy to elucidate the molecular sources of SHG in live cells and tissues. SHG arose not only from coiled-coil complexes within connective tissues and muscle thick filaments, but also from microtubule arrays within interphase and mitotic cells. Both polarization dependence and a local symmetry cancellation effect of SHG allowed the signal from species generating the second harmonic to be decoded, by ratiometric correlation with TPEF, to yield information on local structure below optical resolution. The physical origin of SHG within these tissues is addressed and is attributed to the laser interaction with dipolar protein structures that is enhanced by the intrinsic chirality of the protein helices. PMID:11751336

Bi-harmonic cantilever design for improved measurement sensitivity in tapping-mode atomic force microscopy.

PubMed

Loganathan, Muthukumaran; Bristow, Douglas A

2014-04-01

This paper presents a method and cantilever design for improving the mechanical measurement sensitivity in the atomic force microscopy (AFM) tapping mode. The method uses two harmonics in the drive signal to generate a bi-harmonic tapping trajectory. Mathematical analysis demonstrates that the wide-valley bi-harmonic tapping trajectory is as much as 70% more sensitive to changes in the sample topography than the standard single-harmonic trajectory typically used. Although standard AFM cantilevers can be driven in the bi-harmonic tapping trajectory, they require large forcing at the second harmonic. A design is presented for a bi-harmonic cantilever that has a second resonant mode at twice its first resonant mode, thereby capable of generating bi-harmonic trajectories with small forcing signals. Bi-harmonic cantilevers are fabricated by milling a small cantilever on the interior of a standard cantilever probe using a focused ion beam. Bi-harmonic drive signals are derived for standard cantilevers and bi-harmonic cantilevers. Experimental results demonstrate better than 30% improvement in measurement sensitivity using the bi-harmonic cantilever. Images obtained through bi-harmonic tapping exhibit improved sharpness and surface tracking, especially at high scan speeds and low force fields.

Monitoring the effect of low-level laser therapy in healing process of skin with second harmonic generation imaging techniques

NASA Astrophysics Data System (ADS)

Zhang, Xiaoman; Yu, Biying; Weng, Cuncheng; Li, Hui

2014-11-01

The 632nm wavelength low intensity He-Ne laser was used to irradiated on 15 mice which had skin wound. The dynamic changes and wound healing processes were observed with nonlinear spectral imaging technology. We observed that:(1)The wound healing process was accelerated by the low-level laser therapy(LLLT);(2)The new tissues produced second harmonic generation (SHG) signals. Collagen content and microstructure differed dramatically at different time pointed along the wound healing. Our observation shows that the low intensity He-Ne laser irradiation can accelerate the healing process of skin wound in mice, and SHG imaging technique can be used to observe wound healing process, which is useful for quantitative characterization of wound status during wound healing process.

In-phased second harmonic wave array generation with intra-Talbot-cavity frequency-doubling.

PubMed

Hirosawa, Kenichi; Shohda, Fumio; Yanagisawa, Takayuki; Kannari, Fumihiko

2015-03-23

The Talbot cavity is one promising method to synchronize the phase of a laser array. However, it does not achieve the lowest array mode with the same phase but the highest array mode with the anti-phase between every two adjacent lasers, which is called out-phase locking. Consequently, their far-field images exhibit 2-peak profiles. We propose intra-Talbot-cavity frequency-doubling. By placing a nonlinear crystal in a Talbot cavity, the Talbot cavity generates an out-phased fundamental wave array, which is converted into an in-phase-locked second harmonic wave array at the nonlinear crystal. We demonstrate numerical calculations and experiments on intra-Talbot-cavity frequency-doubling and obtain an in-phase-locked second harmonic wave array for a Nd:YVO₄ array laser.

Invited Review Article: Imaging techniques for harmonic and multiphoton absorption fluorescence microscopy

PubMed Central

Carriles, Ramón; Schafer, Dawn N.; Sheetz, Kraig E.; Field, Jeffrey J.; Cisek, Richard; Barzda, Virginijus; Sylvester, Anne W.; Squier, Jeffrey A.

2009-01-01

We review the current state of multiphoton microscopy. In particular, the requirements and limitations associated with high-speed multiphoton imaging are considered. A description of the different scanning technologies such as line scan, multifoci approaches, multidepth microscopy, and novel detection techniques is given. The main nonlinear optical contrast mechanisms employed in microscopy are reviewed, namely, multiphoton excitation fluorescence, second harmonic generation, and third harmonic generation. Techniques for optimizing these nonlinear mechanisms through a careful measurement of the spatial and temporal characteristics of the focal volume are discussed, and a brief summary of photobleaching effects is provided. Finally, we consider three new applications of multiphoton microscopy: nonlinear imaging in microfluidics as applied to chemical analysis and the use of two-photon absorption and self-phase modulation as contrast mechanisms applied to imaging problems in the medical sciences. PMID:19725639

Quantitative second-harmonic generation imaging to detect osteogenesis imperfecta in human skin samples

NASA Astrophysics Data System (ADS)

Adur, J.; Ferreira, A. E.; D'Souza-Li, L.; Pelegati, V. B.; de Thomaz, A. A.; Almeida, D. B.; Baratti, M. O.; Carvalho, H. F.; Cesar, C. L.

2012-03-01

Osteogenesis Imperfecta (OI) is a genetic disorder that leads to bone fractures due to mutations in the Col1A1 or Col1A2 genes that affect the primary structure of the collagen I chain with the ultimate outcome in collagen I fibrils that are either reduced in quantity or abnormally organized in the whole body. A quick test screening of the patients would largely reduce the sample number to be studied by the time consuming molecular genetics techniques. For this reason an assessment of the human skin collagen structure by Second Harmonic Generation (SHG) can be used as a screening technique to speed up the correlation of genetics/phenotype/OI types understanding. In the present work we have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization of the OI human skin samples comparing with normal control patients. By comparing fibril collagen distribution and spatial organization, we calculated the anisotropy and texture patterns of this structural protein. The analysis of the anisotropy was performed by means of the two-dimensional Discrete Fourier Transform and image pattern analysis with Gray-Level Co-occurrence Matrix (GLCM). From these results, we show that statistically different results are obtained for the normal and disease states of OI.

Biological Effects of Laser Radiation. Volume IV. Optical Second Harmonic Generation in Biological Tissues.

DTIC Science & Technology

1978-10-17

characteristics for optical second- harmonic generation. The collage component of conective tissue may be the principal site for the observed harmonic...Generation in Tissue ; Second Harmonic Generation in Collage; Glutathione, 5MB; Mechanisms; Conversion Efficiency; Significance of order UL AIM UY#m~wmev...sclera, and skin on 694 im. Q-switched ruby laser irradiation. A possible source of this second-harmonic generation was tissue collagen; because of

Time domain simulation of nonlinear acoustic beams generated by rectangular pistons with application to harmonic imaging

NASA Astrophysics Data System (ADS)

Yang, Xinmai; Cleveland, Robin O.

2005-01-01

A time-domain numerical code (the so-called Texas code) that solves the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation has been extended from an axis-symmetric coordinate system to a three-dimensional (3D) Cartesian coordinate system. The code accounts for diffraction (in the parabolic approximation), nonlinearity and absorption and dispersion associated with thermoviscous and relaxation processes. The 3D time domain code was shown to be in agreement with benchmark solutions for circular and rectangular sources, focused and unfocused beams, and linear and nonlinear propagation. The 3D code was used to model the nonlinear propagation of diagnostic ultrasound pulses through tissue. The prediction of the second-harmonic field was sensitive to the choice of frequency-dependent absorption: a frequency squared f2 dependence produced a second-harmonic field which peaked closer to the transducer and had a lower amplitude than that computed for an f1.1 dependence. In comparing spatial maps of the harmonics we found that the second harmonic had dramatically reduced amplitude in the near field and also lower amplitude side lobes in the focal region than the fundamental. These findings were consistent for both uniform and apodized sources and could be contributing factors in the improved imaging reported with clinical scanners using tissue harmonic imaging. .

Time domain simulation of nonlinear acoustic beams generated by rectangular pistons with application to harmonic imaging.

PubMed

Yang, Xinmai; Cleveland, Robin O

2005-01-01

A time-domain numerical code (the so-called Texas code) that solves the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation has been extended from an axis-symmetric coordinate system to a three-dimensional (3D) Cartesian coordinate system. The code accounts for diffraction (in the parabolic approximation), nonlinearity and absorption and dispersion associated with thermoviscous and relaxation processes. The 3D time domain code was shown to be in agreement with benchmark solutions for circular and rectangular sources, focused and unfocused beams, and linear and nonlinear propagation. The 3D code was used to model the nonlinear propagation of diagnostic ultrasound pulses through tissue. The prediction of the second-harmonic field was sensitive to the choice of frequency-dependent absorption: a frequency squared f2 dependence produced a second-harmonic field which peaked closer to the transducer and had a lower amplitude than that computed for an f1.1 dependence. In comparing spatial maps of the harmonics we found that the second harmonic had dramatically reduced amplitude in the near field and also lower amplitude side lobes in the focal region than the fundamental. These findings were consistent for both uniform and apodized sources and could be contributing factors in the improved imaging reported with clinical scanners using tissue harmonic imaging.

Effect of composition and temperature on the second harmonic generation in silver phosphate glasses

NASA Astrophysics Data System (ADS)

Konidakis, I.; Psilodimitrakopoulos, S.; Kosma, K.; Lemonis, A.; Stratakis, E.

2018-01-01

We herein employ nonlinear laser imaging microscopy to explicitly study the dynamics of second harmonic generation (SHG) in silver iodide phosphate glasses. While glasses of this family have gained extensive scientific attention over the years due to their superior conducting properties, considerably less attention has been paid to their unique nonlinear optical characteristics. In the present study, firstly, it is demonstrated that SHG signal intensity is enhanced upon increasing silver content due to the random formation of silver microstructures within the glass network. Secondly, the SHG temperature dynamics were explored near the glass transition temperature (Tg) regime, where significant glass relaxation phenomena occur. It is found that heating towards the Tg improves the SHG efficiency, whereas above Tg, the capacity of glasses to generate second harmonic radiation is drastically suppressed. The novel findings of this work are considered important in terms of the potential employment of these glasses for the realization of advanced photonic applications like optical-switches and wavelength conversion devices.

Membrane potential dynamics of axons in cultured hippocampal neurons probed by second-harmonic-generation imaging

NASA Astrophysics Data System (ADS)

Nuriya, Mutsuo; Yasui, Masato

2010-03-01

The electrical properties of axons critically influence the nature of communication between neurons. However, due to their small size, direct measurement of membrane potential dynamics in intact and complex mammalian axons has been a challenge. Furthermore, quantitative optical measurements of axonal membrane potential dynamics have not been available. To characterize the basic principles of somatic voltage signal propagation in intact axonal arbors, second-harmonic-generation (SHG) imaging is applied to cultured mouse hippocampal neurons. When FM4-64 is applied extracellularly to dissociated neurons, whole axonal arbors are visualized by SHG imaging. Upon action potential generation by somatic current injection, nonattenuating action potentials are recorded in intact axonal arbors. Interestingly, however, both current- and voltage-clamp recordings suggest that nonregenerative subthreshold somatic voltage changes at the soma are poorly conveyed to these axonal sites. These results reveal the nature of membrane potential dynamics of cultured hippocampal neurons, and further show the possibility of SHG imaging in physiological investigations of axons.

Bright high-repetition-rate source of narrowband extreme-ultraviolet harmonics beyond 22 eV

PubMed Central

Wang, He; Xu, Yiming; Ulonska, Stefan; Robinson, Joseph S.; Ranitovic, Predrag; Kaindl, Robert A.

2015-01-01

Novel table-top sources of extreme-ultraviolet light based on high-harmonic generation yield unique insight into the fundamental properties of molecules, nanomaterials or correlated solids, and enable advanced applications in imaging or metrology. Extending high-harmonic generation to high repetition rates portends great experimental benefits, yet efficient extreme-ultraviolet conversion of correspondingly weak driving pulses is challenging. Here, we demonstrate a highly-efficient source of femtosecond extreme-ultraviolet pulses at 50-kHz repetition rate, utilizing the ultraviolet second-harmonic focused tightly into Kr gas. In this cascaded scheme, a photon flux beyond ≈3 × 1013 s−1 is generated at 22.3 eV, with 5 × 10−5 conversion efficiency that surpasses similar harmonics directly driven by the fundamental by two orders-of-magnitude. The enhancement arises from both wavelength scaling of the atomic dipole and improved spatio-temporal phase matching, confirmed by simulations. Spectral isolation of a single 72-meV-wide harmonic renders this bright, 50-kHz extreme-ultraviolet source a powerful tool for ultrafast photoemission, nanoscale imaging and other applications. PMID:26067922

Polarization-resolved second-harmonic generation microscopy as a method to visualize protein-crystal domains

PubMed Central

DeWalt, Emma L.; Begue, Victoria J.; Ronau, Judith A.; Sullivan, Shane Z.; Das, Chittaranjan; Simpson, Garth J.

2013-01-01

Polarization-resolved second-harmonic generation (PR-SHG) microscopy is described and applied to identify the presence of multiple crystallographic domains within protein-crystal conglomerates, which was confirmed by synchrotron X-ray diffraction. Principal component analysis (PCA) of PR-SHG images resulted in principal component 2 (PC2) images with areas of contrasting negative and positive values for conglomerated crystals and PC2 images exhibiting uniformly positive or uniformly negative values for single crystals. Qualitative assessment of PC2 images allowed the identification of domains of different internal ordering within protein-crystal samples as well as differentiation between multi-domain conglomerated crystals and single crystals. PR-SHG assessments of crystalline domains were in good agreement with spatially resolved synchrotron X-ray diffraction measurements. These results have implications for improving the productive throughput of protein structure determination through early identification of multi-domain crystals. PMID:23275165

Harmonic generation with a dual frequency pulse.

PubMed

Keravnou, Christina P; Averkiou, Michalakis A

2014-05-01

Nonlinear imaging was implemented in commercial ultrasound systems over the last 15 years offering major advantages in many clinical applications. In this work, pulsing schemes coupled with a dual frequency pulse are presented. The pulsing schemes considered were pulse inversion, power modulation, and power modulated pulse inversion. The pulse contains a fundamental frequency f and a specified amount of its second harmonic 2f. The advantages and limitations of this method were evaluated with both acoustic measurements of harmonic generation and theoretical simulations based on the KZK equation. The use of two frequencies in a pulse results in the generation of the sum and difference frequency components in addition to the other harmonic components. While with single frequency pulses, only power modulation and power modulated pulse inversion contained odd harmonic components, with the dual frequency pulse, pulse inversion now also contains odd harmonic components.

Ex-vivo multiphoton analysis of rabbit corneal wound healing following photorefractive keratectomy

NASA Astrophysics Data System (ADS)

Wang, Tsung-Jen; Lo, Wen; Dong, Chen-Yuan; Hu, Fung-Rong

2008-02-01

The aim of this study is to assess the application of multiphoton autofluorescence and second harmonic generation (SHG) microscopy for investigating corneal wound healing after high myopic (-10.0D) photorefractive keratectomy (PRK) procedures on the rabbit eyes. The effect of PRK on the morphology and distribution of keratocytes were investigated using multiphoton excited autofluorescence imaging, while the effect of PRK on the arrangement of collagen fibers was monitored by second-harmonic generation imaging. Without histological processing, multiphoton microscopy is able to characterize corneal damage and wound healing from PRK. Our results show that this technique has potential application in the clinical evaluation of corneal damage due to refractive surgery, and may be used to study the unwanted side effects of these procedures.

Application of Fourier transform-second-harmonic generation imaging to the rat cervix.

PubMed

Lau, T Y; Sangha, H K; Chien, E K; McFarlin, B L; Wagoner Johnson, A J; Toussaint, K C

2013-07-01

We present the application of Fourier transform-second-harmonic generation (FT-SHG) imaging to evaluate the arrangement of collagen fibers in five nonpregnant rat cervices. Tissue slices from the mid-cervix and near the external orifice of the cervix were analyzed in both two-dimensions (2D) and three-dimensions (3D). We validate that the cervical microstructure can be quantitatively assessed in three dimensions using FT-SHG imaging and observe collagen fibers oriented both in and out-of-plane in the outermost and the innermost layers, which cannot be observed using 2D FT-SHG analysis alone. This approach has the potential to be a clinically applicable method for measuring progressive changes in collagen organization during cervical remodeling in humans. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Imaging Fibrosis and Separating Collagens using Second Harmonic Generation and Phasor Approach to Fluorescence Lifetime Imaging

PubMed Central

Ranjit, Suman; Dvornikov, Alexander; Stakic, Milka; Hong, Suk-Hyun; Levi, Moshe; Evans, Ronald M.; Gratton, Enrico

2015-01-01

In this paper we have used second harmonic generation (SHG) and phasor approach to auto fluorescence lifetime imaging (FLIM) to obtain fingerprints of different collagens and then used these fingerprints to observe bone marrow fibrosis in the mouse femur. This is a label free approach towards fast automatable detection of fibrosis in tissue samples. FLIM has previously been used as a method of contrast in different tissues and in this paper phasor approach to FLIM is used to separate collagen I from collagen III, the markers of fibrosis, the largest groups of disorders that are often without any effective therapy. Often characterized by an increase in collagen content of the corresponding tissue, the samples are usually visualized by histochemical staining, which is pathologist dependent and cannot be automated. PMID:26293987

A new ultrasonic transducer for improved contrast nonlinear imaging

NASA Astrophysics Data System (ADS)

Bouakaz, Ayache; ten Cate, Folkert; de Jong, Nico

2004-08-01

Second harmonic imaging has provided significant improvement in contrast detection over fundamental imaging. This improvement is a result of a higher contrast-to-tissue ratio (CTR) achievable at the second harmonic frequency. Nevertheless, the differentiation between contrast and tissue at the second harmonic frequency is still in many situations cumbersome and contrast detection remains nowadays as one of the main challenges, especially in the capillaries. The reduced CTR is mainly caused by the generation of second harmonic energy from nonlinear propagation effects in tissue, which hence obscures the echoes from contrast bubbles. In a previous study, we demonstrated theoretically that the CTR increases with the harmonic number. Therefore the purpose of our study was to increase the CTR by selectively looking to the higher harmonic frequencies. In order to be able to receive these high frequency components (third up to the fifth harmonic), a new ultrasonic phased array transducer has been constructed. The main advantage of the new design is its wide frequency bandwidth. The new array transducer contains two different types of elements arranged in an interleaved pattern (odd and even elements). This design enables separate transmission and reception modes. The odd elements operate at 2.8 MHz and 80% bandwidth, whereas the even elements have a centre frequency of 900 kHz with a bandwidth of 50%. The probe is connected to a Vivid 5 system (GE-Vingmed) and proper software is developed for driving. The total bandwidth of such a transducer is estimated to be more than 150% which enables higher harmonic imaging at an adequate sensitivity and signal to noise ratio compared to standard medical array transducers. We describe in this paper the design and fabrication of the array transducer. Moreover its acoustic properties are measured and its performances for nonlinear contrast imaging are evaluated in vitro and in vivo. The preliminary results demonstrate the advantages of such a transducer design for improved contrast detection.

Numerical modeling of Harmonic Imaging and Pulse Inversion fields

NASA Astrophysics Data System (ADS)

Humphrey, Victor F.; Duncan, Tracy M.; Duck, Francis

2003-10-01

Tissue Harmonic Imaging (THI) and Pulse Inversion (PI) Harmonic Imaging exploit the harmonics generated as a result of nonlinear propagation through tissue to improve the performance of imaging systems. A 3D finite difference model, that solves the KZK equation in the frequency domain, is used to investigate the finite amplitude fields produced by rectangular transducers driven with short pulses and their inverses, in water and homogeneous tissue. This enables the characteristic of the fields and the effective PI field to be calculated. The suppression of the fundamental field in PI is monitored, and the suppression of side lobes and a reduction in the effective beamwidth for each field are calculated. In addition, the differences between the pulse and inverse pulse spectra resulting from the use of very short pulses are noted, and the differences in the location of the fundamental and second harmonic spectral peaks observed.

Second-harmonic generation imaging of collagen fibers in myocardium for atrial fibrillation diagnosis

NASA Astrophysics Data System (ADS)

Tsai, Ming-Rung; Chiu, Yu-Wei; Lo, Men Tzung; Sun, Chi-Kuang

2010-03-01

Atrial fibrillation (AF) is the most common irregular heart rhythm and the mortality rate for patients with AF is approximately twice the mortality rate for patients with normal sinus rhythm (NSR). Some research has indicated that myocardial fibrosis plays an important role in predisposing patients to AF. Therefore, realizing the relationship between myocardial collagen fibrosis and AF is significant. Second-harmonic generation (SHG) is an optically nonlinear coherent process to image the collagen network. We perform SHG microscopic imaging of the collagen fibers in the human atrial myocardium. Utilizing the SHG images, we can identify the differences in morphology and the arrangement of collagen fibers between NSR and AF tissues. We also quantify the arrangement of the collagen fibers using Fourier transform images and calculating the values of angle entropy. We indicate that SHG imaging, a nondestructive and reproducible method to analyze the arrangement of collagen fibers, can provide explicit information about the relationship between myocardial fibrosis and AF.

Polarization dependant in vivo second harmonic generation imaging of Caenorhabditis elegans vulval, pharynx, and body wall muscles

NASA Astrophysics Data System (ADS)

Psilodimitrakopoulos, Sotiris; Santos, Susana; Amat-Roldan, Ivan; Mathew, Manoj; Thayil K. N., Anisha; Artigas, David; Loza-Alvarez, Pablo

2008-02-01

Second harmonic generation (SHG) imaging has emerged in recent years as an important laboratory imaging technique since it can provide unique structural information with submicron resolution. It enjoys the benefits of non-invasive interaction establishing this imaging modality as ideal for in vivo investigation of tissue architectures. In this study we present, polarization dependant high resolution SHG images of Caenorhabditis elegans muscles in vivo. We imaged a variety of muscular structures such as body walls, pharynx and vulva. By fitting the experimental data into a cylindrical symmetry spatial model we mapped the corresponding signal distribution of the χ (2) tensor and identified its main axis orientation for different sarcomeres of the earth worm. The cylindrical symmetry was considered to arise from the thick filaments architecture of the inside active volume. Moreover, our theoretical analysis allowed calculating the mean orientation of harmonophores (myosin helical pitch). Ultimately, we recorded and analysed vulvae muscle dynamics, where SHG signal decreased during in vivo contraction.

Measuring the effect of a Western diet on liver tissue architecture by FLIM autofluorescence and harmonic generation microscopy

PubMed Central

Ranjit, Suman; Dvornikov, Alexander; Dobrinskikh, Evgenia; Wang, Xiaoxin; Luo, Yuhuan; Levi, Moshe; Gratton, Enrico

2017-01-01

The phasor approach to auto-fluorescence lifetime imaging was used to identify and characterize a long lifetime species (LLS) (~7.8 ns) in livers of mice fed with a Western diet. The size of the areas containing this LLS species depends on the type of diet and the size distribution shows Western diet has much larger LLS sizes. Combination of third harmonic generation images with FLIM identified the LLS species with fat droplets and the droplet size distribution was estimated. Second harmonic generation microscopy combined with phasor FLIM shows that there is an increase in fibrosis with a Western diet. A new decomposition in three components of the phasor plot shows that a Western diet is correlated with a higher fraction of free NADH, signifying more reducing condition and more glycolytic condition. Multiparametric analysis of phasor distribution shows that from the distribution of phasor points, a Western diet fed versus a low fat diet fed samples of mice livers can be separated. The phasor approach for the analysis of FLIM images of autofluorescence in liver specimens can result in discovery of new fluorescent species and then these new fluorescent species can help assess tissue architecture. Finally integrating FLIM and second and third harmonic analysis provides a measure of the advancement of fibrosis as an effect of diet. PMID:28717559

Symmetry properties of second harmonics generated by antisymmetric Lamb waves

NASA Astrophysics Data System (ADS)

Zhu, Wujun; Xiang, Yanxun; Liu, Chang-Jun; Deng, Mingxi; Xuan, Fu-Zhen

2018-03-01

Symmetry properties of second harmonics generated by antisymmetric primary Lamb waves are systematically studied in this work. In theory, the acoustic field of second harmonic Lamb waves is obtained by using the perturbation approximation and normal modal method, and the energy flux transfer from the primary Lamb waves to second harmonics is mainly explored. Symmetry analyses indicate that either the symmetric or antisymmetric Lamb waves can merely generate the symmetric second harmonics. Finite element simulations are performed on the nonlinear Lamb wave propagation of the antisymmetric A0 mode in the low frequency region. The signals of the second harmonics and the symmetric second harmonic s0 mode are found to be exactly equivalent in the time domain. The relative acoustic nonlinearity parameter A2/A12 oscillates with the propagation distance, and the oscillation amplitude and spatial period are well consistent with the theoretical prediction of the A0-s0 mode pair, which means that only the second harmonic s0 mode is generated by the antisymmetric primary A0 mode. Experiments are further conducted to examine the cumulative generation of symmetric second harmonics for the antisymmetric-symmetric mode pair A3-s6. Results show that A2/A12 increases linearly with the propagation distance, which means that the symmetric second harmonic s6 mode is generated cumulatively by the antisymmetric primary A3 mode. The present investigation systematically corroborates the proposed theory that only symmetric second harmonics can be generated accompanying the propagation of antisymmetric primary Lamb waves in a plate.

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

A pilot study for distinguishing chromophobe renal cell carcinoma and oncocytoma using second harmonic generation imaging and convolutional neural network analysis of collagen fibrillar structure

NASA Astrophysics Data System (ADS)

Judd, Nicolas; Smith, Jason; Jain, Manu; Mukherjee, Sushmita; Icaza, Michael; Gallagher, Ryan; Szeligowski, Richard; Wu, Binlin

2018-02-01

A clear distinction between oncocytoma and chromophobe renal cell carcinoma (chRCC) is critically important for clinical management of patients. But it may often be difficult to distinguish the two entities based on hematoxylin and eosin (H and E) stained sections alone. In this study, second harmonic generation (SHG) signals which are very specific to collagen were used to image collagen fibril structure. We conduct a pilot study to develop a new diagnostic method based on the analysis of collagen associated with kidney tumors using convolutional neural networks (CNNs). CNNs comprise a type of machine learning process well-suited for drawing information out of images. This study examines a CNN model's ability to differentiate between oncocytoma (benign), and chRCC (malignant) kidney tumor images acquired with second harmonic generation (SHG), which is very specific for collagen matrix. To the best of our knowledge, this is the first study that attempts to distinguish the two entities based on their collagen structure. The model developed from this study demonstrated an overall classification accuracy of 68.7% with a specificity of 66.3% and sensitivity of 74.6%. While these results reflect an ability to classify the kidney tumors better than chance, further studies will be carried out to (a) better realize the tumor classification potential of this method with a larger sample size and (b) combining SHG with two-photon excited intrinsic fluorescence signal to achieve better classification.

Characterization of human carotid atherosclerotic tissues imaged by combining multiple multiphoton microscopy techniques

NASA Astrophysics Data System (ADS)

Baria, E.; Cicchi, R.; Nesi, G.; Massi, D.; Pavone, F. S.

2017-07-01

We combined Second Harmonic Generation, Two-Photon Fluorescence and Fluorescence Lifetime Imaging Microscopy for studying human carotid ex vivo tissue sections affected by atherosclerosis, resulting in the discrimination of different arterial regions within the plaques.

Imaging articular cartilage using second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Mansfield, Jessica C.; Winlove, C. Peter; Knapp, Karen; Matcher, Stephen J.

2006-02-01

Sub cellular resolution images of equine articular cartilage have been obtained using both second harmonic generation microscopy (SHGM) and two-photon fluorescence microscopy (TPFM). The SHGM images clearly map the distribution of the collagen II fibers within the extracellular matrix while the TPFM images show the distribution of endogenous two-photon fluorophores in both the cells and the extracellular matrix, highlighting especially the pericellular matrix and bright 2-3μm diameter features within the cells. To investigate the source of TPF in the extracellular matrix experiments have been carried out to see if it may originate from the proteoglycans. Pure solutions of the following proteoglycans hyaluronan, chondroitin sulfate and aggrecan have been imaged, only the aggrecan produced any TPF and here the intensity was not great enough to account for the TPF in the extracellular matrix. Also cartilage samples were subjected to a process to remove proteoglycans and cellular components. After this process the TPF from the samples had decreased by a factor of two, with respect to the SHG intensity.

Non-phase-matched enhancement of second-harmonic generation in multilayer nonlinear structures with internal reflections.

PubMed

Centini, Marco; D'Aguanno, Giuseppe; Sciscione, Letizia; Sibilia, Concita; Bertolotti, Mario; Scalora, Michael; Bloemer, Mark J

2004-08-15

Traditional notions of second-harmonic generation rely on phase matching or quasi phase matching to achieve good conversion efficiencies. We present an entirely new concept for efficient second-harmonic generation that is based on the interference of counterpropagating waves in multilayer structures. Conversion efficiencies are an order of magnitude larger than with phase-matched second-harmonic generation in similar multilayer structures.

Third order harmonic imaging for biological tissues using three phase-coded pulses.

PubMed

Ma, Qingyu; Gong, Xiufen; Zhang, Dong

2006-12-22

Compared to the fundamental and the second harmonic imaging, the third harmonic imaging shows significant improvements in image quality due to the better resolution, but it is degraded by the lower sound pressure and signal-to-noise ratio (SNR). In this study, a phase-coded pulse technique is proposed to selectively enhance the sound pressure of the third harmonic by 9.5 dB whereas the fundamental and the second harmonic components are efficiently suppressed and SNR is also increased by 4.7 dB. Based on the solution of the KZK nonlinear equation, the axial and lateral beam profiles of harmonics radiated from a planar piston transducer were theoretically simulated and experimentally examined. Finally, the third harmonic images using this technique were performed for several biological tissues and compared with the images obtained by the fundamental and the second harmonic imaging. Results demonstrate that the phase-coded pulse technique yields a dramatically cleaner and sharper contrast image.

Nonlinear spectral imaging of human normal skin, basal cell carcinoma and squamous cell carcinoma based on two-photon excited fluorescence and second-harmonic generation

NASA Astrophysics Data System (ADS)

Xiong, S. Y.; Yang, J. G.; Zhuang, J.

2011-10-01

In this work, we use nonlinear spectral imaging based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) for analyzing the morphology of collagen and elastin and their biochemical variations in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin tissue. It was found in this work that there existed apparent differences among BCC, SCC and normal skin in terms of their thickness of the keratin and epithelial layers, their size of elastic fibers, as well as their distribution and spectral characteristics of collagen. These differences can potentially be used to distinguish BCC and SCC from normal skin, and to discriminate between BCC and SCC, as well as to evaluate treatment responses.

Using Second Harmonic Generation Microscopy to Study the Three-Dimensional Structure of Collagen and its Degradation Mechanism

NASA Astrophysics Data System (ADS)

Mega, Yair

Collagen is one of the most abundant proteins found in the human body. Its crystalline structure possesses no centrosymmetry, allowing it to emit second-harmonic waves. Second harmonic generation (SHG) microscopy utilizes the latter quality to produce high-resolution images of collagen rich tissues and therefore become a key research tool in the biomedical field. We developed a new model, intended to be used together with second harmonic generation (SHG) microscopy, to thoroughly investigate collagen-based tissues. We use our SHG model to reveal information in real time from enzymatic biochemical processes. We also present a novel method used to measure quantitatively the direction of the fibers within the tissue, from SHG images. Using this method, we were able to reconstruct an angular map of the orientation of collagen fibers from multiple sections across the entire area of a human cornea. The structure we obtained demonstrates the criss-crossing structure of the human cornea, previously suggested in the literature. In addition, we also report work on a unique step-wise three-photon fluorescence excitation discovered in melanin. This unique fluorescence mechanism was exploited to discriminate melanin on a small-size, low-cost and low laser power setup which was used as a prototype for a handheld device. The latter study is a part of a larger on-going effort in our group to explore new diagnosis methods to be used for early skin cancer screening. Finally, this work demonstrates a spectroscopy-based method to correct for blood vessel thickness effect. The method analyzes spectral shift from a molecular imaging agent and correlate the shifts to the length of the optical path in blood. The correction method described in this work is intended to be implemented on a guided catheter near infrared fluorescence (NIRF) intra-vascular imaging system. In this imaging system, this study's results will used to correct for the radial distance between the imaging tip of the catheter and fluorescing agents chemically bonded to plaques on walls of the arteries.

Second harmonic generation at fatigue cracks by low-frequency Lamb waves: Experimental and numerical studies

NASA Astrophysics Data System (ADS)

Yang, Yi; Ng, Ching-Tai; Kotousov, Andrei; Sohn, Hoon; Lim, Hyung Jin

2018-01-01

This paper presents experimental and theoretical analyses of the second harmonic generation due to non-linear interaction of Lamb waves with a fatigue crack. Three-dimensional (3D) finite element (FE) simulations and experimental studies are carried out to provide physical insight into the mechanism of second harmonic generation. The results demonstrate that the 3D FE simulations can provide a reasonable prediction on the second harmonic generated due to the contact nonlinearity at the fatigue crack. The effect of the wave modes on the second harmonic generation is also investigated in detail. It is found that the magnitude of the second harmonic induced by the interaction of the fundamental symmetric mode (S0) of Lamb wave with the fatigue crack is much higher than that by the fundamental anti-symmetric mode (A0) of Lamb wave. In addition, a series of parametric studies using 3D FE simulations are conducted to investigate the effect of the fatigue crack length to incident wave wavelength ratio, and the influence of the excitation frequency on the second harmonic generation. The outcomes show that the magnitude and directivity pattern of the generated second harmonic depend on the fatigue crack length to incident wave wavelength ratio as well as the ratio of S0 to A0 incident Lamb wave amplitude. In summary, the findings of this study can further advance the use of second harmonic generation in damage detection.

Optical second harmonic generation from V-shaped chromium nanohole arrays

NASA Astrophysics Data System (ADS)

Khoa Quang, Ngo; Miyauchi, Yoshihiro; Mizutani, Goro; Charlton, Martin D.; Chen, Ruiqi; Boden, Stuart; Rutt, Harvey

2014-02-01

We observed rotational anisotropy of optical second harmonic generation (SHG) from an array of V-shaped chromium nanoholes fabricated by electron beam lithography. Phenomenological analysis indicated that the effective nonlinear susceptibility element \\chi _{313}^{(2)} had a characteristic contribution to the observed anisotropic SHG intensity patterns. Here, coordinate 1 is in the direction of the tip of V shapes in the substrate plane, and 3 indicates the direction perpendicular to the sample surface. The SHG intensity for the S-polarized output light was very weak, probably owing to the cancellation effect of the image dipoles generated at the metal-air boundary. The possible origin of the observed nonlinearity is discussed in terms of the susceptibility elements obtained.

Monitoring fibrous scaffold guidance of three-dimensional collagen organisation using minimally-invasive second harmonic generation.

PubMed

Delaine-Smith, Robin M; Green, Nicola H; Matcher, Stephen J; MacNeil, Sheila; Reilly, Gwendolen C

2014-01-01

The biological and mechanical function of connective tissues is largely determined by controlled cellular alignment and therefore it seems appropriate that tissue-engineered constructs should be architecturally similar to the in vivo tissue targeted for repair or replacement. Collagen organisation dictates the tensile properties of most tissues and so monitoring the deposition of cell-secreted collagen as the construct develops is essential for understanding tissue formation. In this study, electrospun fibres with a random or high degree of orientation, mimicking two types of tissue architecture found in the body, were used to culture human fibroblasts for controlling cell alignment. The minimally-invasive technique of second harmonic generation was used with the aim of monitoring and profiling the deposition and organisation of collagen at different construct depths over time while construct mechanical properties were also determined over the culture period. It was seen that scaffold fibre organisation affected cell migration and orientation up to 21 days which in turn had an effect on collagen organisation. Collagen in random fibrous constructs was deposited in alternating configurations at different depths however a high degree of organisation was observed throughout aligned fibrous constructs orientated in the scaffold fibre direction. Three-dimensional second harmonic generation images showed that deposited collagen was more uniformly distributed in random constructs but aligned constructs were more organised and had higher intensities. The tensile properties of all constructs increased with increasing collagen deposition and were ultimately dictated by collagen organisation. This study highlights the importance of scaffold architecture for controlling the development of well-organised tissue engineered constructs and the usefulness of second harmonic generation imaging for monitoring collagen maturation in a minimally invasive manner.

Evaluation of the histological and mechanical features of tendon healing in a rabbit model with the use of second-harmonic-generation imaging and tensile testing.

PubMed

Hase, E; Sato, K; Yonekura, D; Minamikawa, T; Takahashi, M; Yasui, T

2016-11-01

This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing. A total of eight male Japanese white rabbits were used for this study. The flexor digitorum tendons in their right leg were sharply transected, and then were repaired by intratendinous stitching. At four weeks post-operatively, the rabbits were killed and the flexor digitorum tendons in both right and left legs were excised and used as specimens for tendon healing (n = 8) and control (n = 8), respectively. Each specimen was examined by SHG imaging, followed by tensile testing, and the results of the two testing modalities were assessed for correlation. While the SHG light intensity of the healing tendon samples was significantly lower than that of the uninjured tendon samples, 2D Fourier transform SHG images showed a clear difference in collagen fibre structure between the uninjured and the healing samples, and among the healing samples. The mean intensity of the SHG image showed a moderate correlation (R 2 = 0.37) with Young's modulus obtained from the tensile testing. Our results indicate that SHG microscopy may be a potential indicator of tendon healing.Cite this article: E. Hase, K. Sato, D. Yonekura, T. Minamikawa, M. Takahashi, T. Yasui. Evaluation of the histological and mechanical features of tendon healing in a rabbit model with the use of second-harmonic-generation imaging and tensile testing. Bone Joint Res 2016;5:577-585. DOI: 10.1302/2046-3758.511.BJR-2016-0162.R1. © 2016 Yasui et al.

Experimental and numerical investigation of tissue harmonic imaging (THI)

NASA Astrophysics Data System (ADS)

Jing, Yuan; Yang, Xinmai; Cleveland, Robin O.

2003-04-01

In THI the probing ultrasonic pulse has enough amplitude that it undergoes nonlinear distortion and energy shifts from the fundamental frequency of the pulse into its higher harmonics. Images generated from the second harmonic (SH) have superior quality to the images formed from the fundamental frequency. Experiments with a single element focused ultrasound transducer were used to compare a line target embedded in a tissue phantom using either fundamental or SH imaging. SH imaging showed an improvement in both the axial resolution (0.70 mm vs 0.92 mm) and the lateral resolution (1.02 mm vs 2.70 mm) of the target. In addition, the contrast-to-tissue ratio of the target was 2 dB higher with SH imaging. A three-dimensional model of the forward propagation has been developed to simulate the experimental system. The model is based on a time-domain code for solving the KZK equation and accounts for arbitrary spatial variations in all tissue properties. The code was used to determine the impact of a nearfield layer of fat on the fundamental and second harmonic signals. For a 15 mm thick layer the SH side-lobes remained the same but the fundamental side-lobes increased by 2 dB. [Work supported by the NSF through the Center for Subsurface Sensing and Imaging Systems.

Investigation on fibrous collagen modifications during corneal laser welding by second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Matteini, Paolo; Ratto, Fulvio; Rossi, Francesca; Cicchi, Riccardo; Stringari, Chiara; Kapsokalyvas, Dimitrios; Pavone, Francesco S.; Pini, Roberto

2009-02-01

The structural modifications in the collagen lattice of corneal stroma induced by near-infrared laser welding were investigated with second-harmonic generation (SHG) imaging. The corneal laser welding procedure is performed by staining the wound edges with a saturated water solution of Indocyanine Green (ICG) followed by irradiation with a 810 nm diode laser operated in continuous (CWLW: continuous wave laser welding) or pulsed (PLW: pulsed laser welding) mode. Both these procedures can provide closure of corneal wounds by inducing different structural modifications in the extracellular matrix. SHG imaging of native corneal stroma revealed collagen bundles composed of many regularly aligned collagen fibrils. After CWLW the regular lamellar arrangement was lost; collagen bundles appeared densely packed with an increasing disordered arrangement toward the welded cut. The weld was characterized by a loss of details; nevertheless, the observation of the second harmonic signal at this site indicated the lack of collagen denaturation. By contrast, PLW mode produced welding spots at the interface between donor and recipient corneal layers, which were characterized by a severe loss of the SHG signal, suggesting the occurrence of a complete collagen denaturation. SHG imaging appeared to be a powerful tool for visualizing the supramolecular morphological modifications in the collagen matrix after laser welding.

Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

NASA Astrophysics Data System (ADS)

Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M. D.; de Jong, N.; Vos, H. J.

2015-10-01

Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. "superharmonic" imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which `signal' denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

Linking high harmonics from gases and solids.

PubMed

Vampa, G; Hammond, T J; Thiré, N; Schmidt, B E; Légaré, F; McDonald, C R; Brabec, T; Corkum, P B

2015-06-25

When intense light interacts with an atomic gas, recollision between an ionizing electron and its parent ion creates high-order harmonics of the fundamental laser frequency. This sub-cycle effect generates coherent soft X-rays and attosecond pulses, and provides a means to image molecular orbitals. Recently, high harmonics have been generated from bulk crystals, but what mechanism dominates the emission remains uncertain. To resolve this issue, we adapt measurement methods from gas-phase research to solid zinc oxide driven by mid-infrared laser fields of 0.25 volts per ångström. We find that when we alter the generation process with a second-harmonic beam, the modified harmonic spectrum bears the signature of a generalized recollision between an electron and its associated hole. In addition, we find that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology. Future experiments will permit the band structure of a solid to be tomographically reconstructed.

Experimental demonstration of efficient and robust second harmonic generation using the adiabatic temperature gradient method

NASA Astrophysics Data System (ADS)

Dimova, E.; Steflekova, V.; Karatodorov, S.; Kyoseva, E.

2018-03-01

We propose a way of achieving efficient and robust second-harmonic generation. The technique proposed is similar to the adiabatic population transfer in a two-state quantum system with crossing energies. If the phase mismatching changes slowly, e.g., due to a temperature gradient along the crystal, and makes the phase match for second-harmonic generation to occur, then the energy would be converted adiabatically to the second harmonic. As an adiabatic technique, the second-harmonic generation scheme presented is stable to variations in the crystal parameters, as well as in the input light, crystal length, input intensity, wavelength and angle of incidence.

Second and Third Harmonic Generation in Metal-Based Nanostructures

DTIC Science & Technology

2010-01-01

Prudenzano, D. de Ceglia, N. Akozbek, M.J. Bloemer, P. Ashley, and M. Scalora , "Enhanced transmission and second harmonic generation from...Fazio, C. Sibilia, M. J. Bloemer, and M. Scalora , "Second-harmonic generation from metallodielectric multilayer photonic-band-gap structures", Phys...harmonic generation", Phys. Rev. B 38, 7985 (1988). [50] M. A. Vincenti, D. de Ceglia, M. Buncick, N. Akozbek, M. J. Bloemer, and M. Scalora

Extracting morphologies from third harmonic generation images of structurally normal human brain tissue.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2017-06-01

The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering, segmentation and validation, to extract this information challenging. We developed a salient edge-enhancing model of anisotropic diffusion for image filtering, based on higher order statistics. We split the intrinsic 3-phase segmentation problem into two 2-phase segmentation problems, each of which we solved with a dedicated model, active contour weighted by prior extreme. We applied the novel proposed algorithms to THG images of structurally normal ex-vivo human brain tissue, revealing key tissue components-brain cells, microvessels and neuropil, enabling statistical characterization of these components. Comprehensive comparison to manually delineated ground truth validated the proposed algorithms. Quantitative comparison to second harmonic generation/auto-fluorescence images, acquired simultaneously from the same tissue area, confirmed the correctness of the main THG features detected. The software and test datasets are available from the authors. z.zhang@vu.nl. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Second Harmonic Generation Mediated by Aligned Water in Starch Granules.

PubMed

Cisek, Richard; Tokarz, Danielle; Krouglov, Serguei; Steup, Martin; Emes, Michael J; Tetlow, Ian J; Barzda, Virginijus

2014-12-26

The origin of second harmonic generation (SHG) in starch granules was investigated using ab initio quantum mechanical modeling and experimentally examined using polarization-in, polarization-out (PIPO) second harmonic generation microscopy. Ab initio calculations revealed that the largest contribution to the SHG signal from A- and B-type allomorphs of starch originates from the anisotropic organization of hydroxide and hydrogen bonds mediated by aligned water found in the polymers. The hypothesis was experimentally tested by imaging maize starch granules under various hydration and heat treatment conditions that alter the hydrogen bond network. The highest SHG intensity was found in fully hydrated starch granules, and heat treatment diminished the SHG intensity. The PIPO SHG imaging showed that dried starch granules have a much higher nonlinear optical susceptibility component ratio than fully hydrated granules. In contrast, deuterated starch granules showed a smaller susceptibility component ratio demonstrating that SHG is highly sensitive to the organization of the hydroxyl and hydrogen bond network. The polarization SHG imaging results of potato starch granules, representing starch allomorph B, were compared to those of maize starch granules representing allomorph A. The results showed that the amount of aligned water was higher in the maize granules. Nonlinear microscopy of starch granules provides evidence that varying hydration conditions leads to significant changes in the nonlinear susceptibility ratio as well as the SHG intensity, supporting the hypothesis from ab initio calculations that the dominant contribution to SHG is due to the ordered hydroxide and hydrogen bond network.

Efficient second to ninth harmonic generation using megawatt peak power microchip laser.

PubMed

Bhandari, R; Tsuji, N; Suzuki, T; Nishifuji, M; Taira, T

2013-11-18

We report the design and use of a megawatt peak power Nd:YAG/Cr4+:YAG microchip laser for efficient second to ninth harmonic generation. We show that the sub-nanosecond pulse width region, between 100 ps and 1 ns, is ideally suited for efficient wavelength conversion. Using this feature, we report 85% second harmonic generation efficiency using lithium triborate (LBO), 60% fourth harmonic generation efficiency usingß-barium borate, and 44% IR to UV third harmonic generation efficiency using Type I and Type II LBO. Finally, we report the first demonstration of 118 nm VUV generation in xenon gas using a microchip laser.

Resonant second harmonic generation in a gallium nitride two-dimensional photonic crystal on silicon

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

Zeng, Y.; Roland, I.; Checoury, X.

We demonstrate second harmonic generation in a gallium nitride photonic crystal cavity embedded in a two-dimensional free-standing photonic crystal platform on silicon. The photonic crystal nanocavity is optically pumped with a continuous-wave laser at telecom wavelengths in the transparency window of the nitride material. The harmonic generation is evidenced by the spectral range of the emitted signal, the quadratic power dependence vs. input power, and the spectral dependence of second harmonic signal. The harmonic emission pattern is correlated to the harmonic polarization generated by the second-order nonlinear susceptibilities χ{sub zxx}{sup (2)}, χ{sub zyy}{sup (2)} and the electric fields of the fundamentalmore » cavity mode.« less

Self-Action of Second Harmonic Generation and Longitudinal Temperature Gradient in Nonlinear-Optical Crystals

NASA Astrophysics Data System (ADS)

Baranov, A. I.; Konyashkin, A. V.; Ryabushkin, O. A.

2015-09-01

Model of second harmonic generation with thermal self-action was developed. Second harmonic generation temperature phase matching curves were measured and calculated for periodically polled lithium niobate crystal. Both experimental and calculated data show asymmetrical shift of temperature tuning curves with pump power.

Reflection second harmonic generation on a z -cut congruent lithium niobate crystal

NASA Astrophysics Data System (ADS)

Sono, T. J.; Scott, J. G.; Sones, C. L.; Valdivia, C. E.; Mailis, S.; Eason, R. W.; Frey, J. G.; Danos, L.

2006-11-01

Reflection second harmonic generation experiments were performed on z -cut congruent lithium niobate crystals (LiNbO3) to reveal the interfacial layer symmetry as the crystal is rotated around the z axis. To suppress the bulk contribution, the fundamental wavelength was selected to be 532nm , resulting in second harmonic generation at a wavelength within the absorption region of the crystal. The polarity of the direction of the y -axis was determined from second harmonic generation data and used to show that this direction also inverts during domain inversion.

Thermal effects in high-power CW second harmonic generation in Mg-doped stoichiometric lithium tantalate.

PubMed

Tovstonog, Sergey V; Kurimura, Sunao; Suzuki, Ikue; Takeno, Kohei; Moriwaki, Shigenori; Ohmae, Noriaki; Mio, Norikatsu; Katagai, Toshio

2008-07-21

We investigated thermal behaviors of single-pass second-harmonic generation of continuous wave green radiation with high efficiency by quasi-phase matching in periodically poled Mg-doped stoichiometric lithium tantalate (PPMgSLT). Heat generation turned out to be directly related to the green light absorption in the material. Strong relation between an upper limit of the second harmonic power and confocal parameter was found. Single-pass second-harmonic generation of 16.1 W green power was achieved with 17.6% efficiency in Mg:SLT at room temperature.

Comparison of fundamental, second harmonic, and superharmonic imaging: a simulation study.

PubMed

van Neer, Paul L M J; Danilouchkine, Mikhail G; Verweij, Martin D; Demi, Libertario; Voormolen, Marco M; van der Steen, Anton F W; de Jong, Nico

2011-11-01

In medical ultrasound, fundamental imaging (FI) uses the reflected echoes from the same spectral band as that of the emitted pulse. The transmission frequency determines the trade-off between penetration depth and spatial resolution. Tissue harmonic imaging (THI) employs the second harmonic of the emitted frequency band to construct images. Recently, superharmonic imaging (SHI) has been introduced, which uses the third to the fifth (super) harmonics. The harmonic level is determined by two competing phenomena: nonlinear propagation and frequency dependent attenuation. Thus, the transmission frequency yielding the optimal trade-off between the spatial resolution and the penetration depth differs for THI and SHI. This paper quantitatively compares the concepts of fundamental, second harmonic, and superharmonic echocardiography at their optimal transmission frequencies. Forward propagation is modeled using a 3D-KZK implementation and the iterative nonlinear contrast source (INCS) method. Backpropagation is assumed to be linear. Results show that the fundamental lateral beamwidth is the narrowest at focus, while the superharmonic one is narrower outside the focus. The lateral superharmonic roll-off exceeds the fundamental and second harmonic roll-off. Also, the axial resolution of SHI exceeds that of FI and THI. The far-field pulse-echo superharmonic pressure is lower than that of the fundamental and second harmonic. SHI appears suited for echocardiography and is expected to improve its image quality at the cost of a slight reduction in depth-of-field.

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.

Computational segmentation of collagen fibers from second-harmonic generation images of breast cancer

NASA Astrophysics Data System (ADS)

Bredfeldt, Jeremy S.; Liu, Yuming; Pehlke, Carolyn A.; Conklin, Matthew W.; Szulczewski, Joseph M.; Inman, David R.; Keely, Patricia J.; Nowak, Robert D.; Mackie, Thomas R.; Eliceiri, Kevin W.

2014-01-01

Second-harmonic generation (SHG) imaging can help reveal interactions between collagen fibers and cancer cells. Quantitative analysis of SHG images of collagen fibers is challenged by the heterogeneity of collagen structures and low signal-to-noise ratio often found while imaging collagen in tissue. The role of collagen in breast cancer progression can be assessed post acquisition via enhanced computation. To facilitate this, we have implemented and evaluated four algorithms for extracting fiber information, such as number, length, and curvature, from a variety of SHG images of collagen in breast tissue. The image-processing algorithms included a Gaussian filter, SPIRAL-TV filter, Tubeness filter, and curvelet-denoising filter. Fibers are then extracted using an automated tracking algorithm called fiber extraction (FIRE). We evaluated the algorithm performance by comparing length, angle and position of the automatically extracted fibers with those of manually extracted fibers in twenty-five SHG images of breast cancer. We found that the curvelet-denoising filter followed by FIRE, a process we call CT-FIRE, outperforms the other algorithms under investigation. CT-FIRE was then successfully applied to track collagen fiber shape changes over time in an in vivo mouse model for breast cancer.

Visualization of collagen regeneration in mouse dorsal skin using second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Luo, T.; Chen, J. X.; Zhuo, S. M.; Lu, K. C.; Jiang, X. S.; Liu, Q. G.

2009-03-01

The purpose of this study is to highlight a clearer understanding of the process of collagen regeneration during wound healing. By means of second harmonic generation (SHG) microscopy, the changes of collagen arrangement at the wound margin were analyzed at 0, 3, 5, 7, 11 and 13 days post injury. The degree of collagen disorders associated with the healing process was quantitatively obtained using the aspect ratio of polar plot image of collagen azimuthal angles and the healing status of collagen could be estimated by arithmetical mean deviation ( Ra) of the collagen SHG images. Our results suggest that SHG microscopy has potential advances in the collagen studies during wound healing and the arrangement of collagen fibers gradually transformed from disorder to order so as to contract the wound. It is capable of promoting clinical application of the noninvasive imaging tool and the analysis methods of collagen disorder as an effective scar management for prevention and treatment about aberrant healing.

Harmonic magneto-electric response in GaFeO3

NASA Astrophysics Data System (ADS)

Naiya, Amit Kumar; Awasthi, A. M.

2018-04-01

GaFeO3 is a well-known multiferroic material. Like optical second harmonic generation, it also generates radio frequency (RF) second harmonic due to its non-centrosymmetric orthorhombic structure. The harmonic RF response also features a magneto-electric character comparable in prominence to that of the fundamental response. We measured complex parts of the fundamental and the second harmonic over 80 K to 300 K. The second harmonic permittivity and its phase angle change sign at the spin glass transition temperature Tg = 200 K and becomes dispersive above ˜280 K.

Monitoring the interfacial electric field in pure and doped SrTiO3 surfaces by means of phase-resolved optical second harmonic generation

NASA Astrophysics Data System (ADS)

Rubano, Andrea; Mou, Sen; Paparo, Domenico

2018-05-01

Oxides and new functional materials such as oxide-based hetero-structures are very good candidates to achieve the goal of the next generation electronics. One of the main features that rules the electronic behavior of these compounds is the interfacial electric field which confines the charge carriers to a quasi-two-dimensional space region. The sign of the confined charge clearly depends on the electric field direction, which is however a very elusive quantity, as most techniques can only detect its absolute value. Even more valuable would be to access the sign of the interfacial electric field directly during the sample growth, being thus able to optimize the growth conditions directly looking at the feature of interest. For this aim, solid and reliable sensors are needed for monitoring the thin films while grown. Recently optical second harmonic generation has been proposed by us as a tool for non-invasive, non-destructive, real-time, in-situ imaging of oxide epitaxial film growth. The spatial resolution of this technique has been exploited to obtain real-time images of the sample under investigation. Here we propose to exploit another very important physical property of the second harmonic wave: its phase, which is directly coupled with the electric field direction, as shown by our measurements.

Sub-40 fs, 1060-nm Yb-fiber laser enhances penetration depth in nonlinear optical microscopy of human skin

NASA Astrophysics Data System (ADS)

Balu, Mihaela; Saytashev, Ilyas; Hou, Jue; Dantus, Marcos; Tromberg, Bruce J.

2015-12-01

Advancing the practical utility of nonlinear optical microscopy requires continued improvement in imaging depth and contrast. We evaluated second-harmonic generation (SHG) and third-harmonic generation images from ex vivo human skin and showed that a sub-40 fs, 1060-nm Yb-fiber laser can enhance SHG penetration depth by up to 80% compared to a >100 fs, 800 nm Ti:sapphire source. These results demonstrate the potential of fiber-based laser systems to address a key performance limitation related to nonlinear optical microscopy (NLOM) technology while providing a low-barrier-to-access alternative to Ti:sapphire sources that could help accelerate the movement of NLOM into clinical practice.

Second Harmonic Generation of Unpolarized Light

NASA Astrophysics Data System (ADS)

Ding, Changqin; Ulcickas, James R. W.; Deng, Fengyuan; Simpson, Garth J.

2017-11-01

A Mueller tensor mathematical framework was applied for predicting and interpreting the second harmonic generation (SHG) produced with an unpolarized fundamental beam. In deep tissue imaging through SHG and multiphoton fluorescence, partial or complete depolarization of the incident light complicates polarization analysis. The proposed framework has the distinct advantage of seamlessly merging the purely polarized theory based on the Jones or Cartesian susceptibility tensors with a more general Mueller tensor framework capable of handling partial depolarized fundamental and/or SHG produced. The predictions of the model are in excellent agreement with experimental measurements of z -cut quartz and mouse tail tendon obtained with polarized and depolarized incident light. The polarization-dependent SHG produced with unpolarized fundamental allowed determination of collagen fiber orientation in agreement with orthogonal methods based on image analysis. This method has the distinct advantage of being immune to birefringence or depolarization of the fundamental beam for structural analysis of tissues.

Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions

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

Chowdhury, Azhad U.; Ye, Dong Hye; Song, Zhengtian

Second harmonic generation (SHG) was integrated with Raman spectroscopy for the analysis of pharmaceutical materials. Particulate formulations of clopidogrel bisulfate were prepared in two crystal forms (Form I and Form II). Image analysis approaches enable automated identification of particles by bright field imaging, followed by classification by SHG. Quantitative SHG microscopy enabled discrimination of crystal form on a per particle basis with 99.95% confidence in a total measurement time of ~10 ms per particle. Complementary measurements by Raman and synchrotron XRD are in excellent agreement with the classifications made by SHG, with measurement times of ~1 min and several secondsmore » per particle, respectively. Coupling these capabilities with at-line monitoring may enable real-time feedback for reaction monitoring during pharmaceutical production to favor the more bioavailable but metastable Form I with limits of detection in the ppm regime.« less

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

PubMed

Minami, Yasunori; Kudo, Masatoshi

2009-12-31

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

Second harmonic generation microscopy of the living human cornea

NASA Astrophysics Data System (ADS)

Artal, Pablo; Ávila, Francisco; Bueno, Juan

2018-02-01

Second Harmonic Generation (SHG) microscopy provides high-resolution structural imaging of the corneal stroma without the need of labelling techniques. This powerful tool has never been applied to living human eyes so far. Here, we present a new compact SHG microscope specifically developed to image the structural organization of the corneal lamellae in living healthy human volunteers. The research prototype incorporates a long-working distance dry objective that allows non-contact three-dimensional SHG imaging of the cornea. Safety assessment and effectiveness of the system were firstly tested in ex-vivo fresh eyes. The maximum average power of the used illumination laser was 20 mW, more than 10 times below the maximum permissible exposure (according to ANSI Z136.1-2000). The instrument was successfully employed to obtain non-contact and non-invasive SHG of the living human eye within well-established light safety limits. This represents the first recording of in vivo SHG images of the human cornea using a compact multiphoton microscope. This might become an important tool in Ophthalmology for early diagnosis and tracking ocular pathologies.

Quantitative evaluation of skeletal muscle defects in second harmonic generation images.

PubMed

Liu, Wenhua; Raben, Nina; Ralston, Evelyn

2013-02-01

Skeletal muscle pathologies cause irregularities in the normally periodic organization of the myofibrils. Objective grading of muscle morphology is necessary to assess muscle health, compare biopsies, and evaluate treatments and the evolution of disease. To facilitate such quantitation, we have developed a fast, sensitive, automatic imaging analysis software. It detects major and minor morphological changes by combining texture features and Fourier transform (FT) techniques. We apply this tool to second harmonic generation (SHG) images of muscle fibers which visualize the repeating myosin bands. Texture features are then calculated by using a Haralick gray-level cooccurrence matrix in MATLAB. Two scores are retrieved from the texture correlation plot by using FT and curve-fitting methods. The sensitivity of the technique was tested on SHG images of human adult and infant muscle biopsies and of mouse muscle samples. The scores are strongly correlated to muscle fiber condition. We named the software MARS (muscle assessment and rating scores). It is executed automatically and is highly sensitive even to subtle defects. We propose MARS as a powerful and unbiased tool to assess muscle health.

Quantitative evaluation of skeletal muscle defects in second harmonic generation images

NASA Astrophysics Data System (ADS)

Liu, Wenhua; Raben, Nina; Ralston, Evelyn

2013-02-01

Skeletal muscle pathologies cause irregularities in the normally periodic organization of the myofibrils. Objective grading of muscle morphology is necessary to assess muscle health, compare biopsies, and evaluate treatments and the evolution of disease. To facilitate such quantitation, we have developed a fast, sensitive, automatic imaging analysis software. It detects major and minor morphological changes by combining texture features and Fourier transform (FT) techniques. We apply this tool to second harmonic generation (SHG) images of muscle fibers which visualize the repeating myosin bands. Texture features are then calculated by using a Haralick gray-level cooccurrence matrix in MATLAB. Two scores are retrieved from the texture correlation plot by using FT and curve-fitting methods. The sensitivity of the technique was tested on SHG images of human adult and infant muscle biopsies and of mouse muscle samples. The scores are strongly correlated to muscle fiber condition. We named the software MARS (muscle assessment and rating scores). It is executed automatically and is highly sensitive even to subtle defects. We propose MARS as a powerful and unbiased tool to assess muscle health.

Enhanced second-harmonic generation from resonant GaAs gratings.

PubMed

de Ceglia, D; D'Aguanno, G; Mattiucci, N; Vincenti, M A; Scalora, M

2011-03-01

We theoretically study second harmonic generation in nonlinear, GaAs gratings. We find large enhancement of conversion efficiency when the pump field excites the guided mode resonances of the grating. Under these circumstances the spectrum near the pump wavelength displays sharp resonances characterized by dramatic enhancements of local fields and favorable conditions for second-harmonic generation, even in regimes of strong linear absorption at the harmonic wavelength. In particular, in a GaAs grating pumped at 1064 nm, we predict second-harmonic conversion efficiencies approximately 5 orders of magnitude larger than conversion rates achievable in either bulk or etalon structures of the same material.

Imaging Collagen in Scar Tissue: Developments in Second Harmonic Generation Microscopy for Biomedical Applications

PubMed Central

Mostaço-Guidolin, Leila; Rosin, Nicole L.; Hackett, Tillie-Louise

2017-01-01

The ability to respond to injury with tissue repair is a fundamental property of all multicellular organisms. The extracellular matrix (ECM), composed of fibrillar collagens as well as a number of other components is dis-regulated during repair in many organs. In many tissues, scaring results when the balance is lost between ECM synthesis and degradation. Investigating what disrupts this balance and what effect this can have on tissue function remains an active area of research. Recent advances in the imaging of fibrillar collagen using second harmonic generation (SHG) imaging have proven useful in enhancing our understanding of the supramolecular changes that occur during scar formation and disease progression. Here, we review the physical properties of SHG, and the current nonlinear optical microscopy imaging (NLOM) systems that are used for SHG imaging. We provide an extensive review of studies that have used SHG in skin, lung, cardiovascular, tendon and ligaments, and eye tissue to understand alterations in fibrillar collagens in scar tissue. Lastly, we review the current methods of image analysis that are used to extract important information about the role of fibrillar collagens in scar formation. PMID:28809791

Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Sun, Tzu-Lin; Liu, Yuan; Sung, Ming-Chin; Chen, Hsiao-Ching; Yang, Chun-Hui; Hovhannisyan, Vladimir; Lin, Wei-Chou; Jeng, Yung-Ming; Chen, Wei-Liang; Chiou, Ling-Ling; Huang, Guan-Tarn; Kim, Ki-Hean; So, Peter T. C.; Chen, Yang-Fang; Lee, Hsuan-Shu; Dong, Chen-Yuan

2010-05-01

Conventionally, liver fibrosis is diagnosed using histopathological techniques. The traditional method is time-consuming in that the specimen preparation procedure requires sample fixation, slicing, and labeling. Our goal is to apply multiphoton microscopy to efficiently image and quantitatively analyze liver fibrosis specimens bypassing steps required in histological preparation. In this work, the combined imaging modality of multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) was used for the qualitative imaging of liver fibrosis of different METAVIR grades under label-free, ex vivo conditions. We found that while MAF is effective in identifying cellular architecture in the liver specimens, it is the spectrally distinct SHG signal that allows the characterization of the extent of fibrosis. We found that qualitative SHG imaging can be used for the effective identification of the associated features of liver fibrosis specimens graded METAVIR 0 to 4. In addition, we attempted to associate quantitative SHG signal to the different METAVIR grades and found that an objective determination of the extent of disease progression can be made. Our approach demonstrates the potential of using multiphoton imaging in rapid classification of ex vivo liver fibrosis in the clinical setting and investigation of liver fibrosis-associated physiopathology in animal models in vivo.

Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy.

PubMed

Sun, Tzu-Lin; Liu, Yuan; Sung, Ming-Chin; Chen, Hsiao-Ching; Yang, Chun-Hui; Hovhannisyan, Vladimir; Lin, Wei-Chou; Jeng, Yung-Ming; Chen, Wei-Liang; Chiou, Ling-Ling; Huang, Guan-Tarn; Kim, Ki-Hean; So, Peter T C; Chen, Yang-Fang; Lee, Hsuan-Shu; Dong, Chen-Yuan

2010-01-01

Conventionally, liver fibrosis is diagnosed using histopathological techniques. The traditional method is time-consuming in that the specimen preparation procedure requires sample fixation, slicing, and labeling. Our goal is to apply multiphoton microscopy to efficiently image and quantitatively analyze liver fibrosis specimens bypassing steps required in histological preparation. In this work, the combined imaging modality of multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) was used for the qualitative imaging of liver fibrosis of different METAVIR grades under label-free, ex vivo conditions. We found that while MAF is effective in identifying cellular architecture in the liver specimens, it is the spectrally distinct SHG signal that allows the characterization of the extent of fibrosis. We found that qualitative SHG imaging can be used for the effective identification of the associated features of liver fibrosis specimens graded METAVIR 0 to 4. In addition, we attempted to associate quantitative SHG signal to the different METAVIR grades and found that an objective determination of the extent of disease progression can be made. Our approach demonstrates the potential of using multiphoton imaging in rapid classification of ex vivo liver fibrosis in the clinical setting and investigation of liver fibrosis-associated physiopathology in animal models in vivo.

Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

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

Peruzzini, D.; Viti, J.; Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam

2015-10-28

Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. “superharmonic” imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performedmore » to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which ‘signal’ denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.« less

Studies in nonlinear optics and functional magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Dai, Tehui

There are two parts in this thesis. The first part will involve a study in the anomalous dispersion phase matched second-harmonic generation, and the second part will be a study in functional magnetic resonance imaging (fMRI) and a biophysical model of the human muscle. In part I, we report on a series of tricyanovinylaniline chromophores for use as dopants in poled poly(methyl methacrylate) waveguides for anomalous-dispersion phase- matched second-harmonic generation. Second-harmonic generation measurements as a function of mode index confirmed anomalous dispersion phase-matching efficiencies as large as 245%/Wcm2 over a propagation length of ~35 μm. The waveguide coupling technique limited the interaction length. The photostability of the chromophores was measured directly and found to agree qualitatively with second-harmonic measurements over time and was found to be improved over previously reported materials. In part II, we designed a system that could record joint force and surface electromyography (EMG) simultaneously with fMRI data. I-Egh quality force and EMG data were obtained at the same time that excellent fMRI brain images were achieved. Using this system we determined the relationship between the fMRI-measured brain activation and the handgrip force, and between the fMRI-measured brain activation and the EMG of finger flexor muscles. We found that in the whole brain and in the majority of motor function-related cortical fields, the degree of muscle activation is directly proportional to the amplitude of the brain signal determined by the fMRI measurement. The similarity in the relationship between muscle output and fMRI signal in a number of brain areas suggests that multiple cortical fields are involved in controlling muscle force. The factors that may contribute to the fMRI signals are discussed. A biophysical twitch force model was developed to predict force response under electrical stimulation. Comparison between experimental and modeled force profiles, peak forces, and force duration shows excellent agreement between the model and the experimental data. It is concluded that the present model allows us to reproduce the main features of muscle activation under stimulation.

A novel clinical multimodal multiphoton tomograph for AF, SHG, CARS imaging, and FLIM

NASA Astrophysics Data System (ADS)

Weinigel, Martin; Breunig, Hans Georg; König, Karsten

2014-02-01

We report on a flexible nonlinear medical tomograph with multiple miniaturized detectors for simultaneous acquisition of two-photon autofluorescence (AF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) images. The simultaneous visualization of the distribution of endogenous fluorophores NAD(P)H, melanin and elastin, SHG-active collagen and as well as non-fluorescent lipids within human skin in vivo is possible. Furthermore, fluorescence lifetime images (FLIM) can be generated using time-correlated single photon counting.

Role of phase matching in pulsed second-harmonic generation: Walk-off and phase-locked twin pulses in negative-index media

NASA Astrophysics Data System (ADS)

Roppo, Vito; Centini, Marco; Sibilia, Concita; Bertolotti, Mario; de Ceglia, Domenico; Scalora, Michael; Akozbek, Neset; Bloemer, Mark J.; Haus, Joseph W.; Kosareva, Olga G.; Kandidov, Valery P.

2007-09-01

The present investigation is concerned with the study of pulsed second-harmonic generation under conditions of phase and group velocity mismatch, and generally low conversion efficiencies and pump intensities. In positive-index, nonmetallic materials, we generally find qualitative agreement with previous reports regarding the presence of a double-peaked second harmonic signal, which comprises a pulse that walks off and propagates at the nominal group velocity one expects at the second-harmonic frequency, and a second pulse that is “captured” and propagates under the pump pulse. We find that the origin of the double-peaked structure resides in a phase-locking mechanism that characterizes not only second-harmonic generation, but also χ(3) processes and third-harmonic generation. The phase-locking mechanism that we describe occurs for arbitrarily small pump intensities, and so it is not a soliton effect, which usually relies on a threshold mechanism, although multicolor solitons display similar phase locking characteristics. Thus, in second harmonic generation a phase-matched component is always generated, even under conditions of material phase mismatch: This component is anomalous, because the material does not allow energy exchange between the pump and the second-harmonic beam. On the other hand, if the material is phase matched, phase locking and phase matching are indistinguishable, and the conversion process becomes efficient. We also report a similar phase-locking phenomenon in negative index materials. A spectral analysis of the pump and the generated signals reveals that the phase-locking phenomenon causes the forward moving, phase-locked second-harmonic pulse to experience the same negative index as the pump pulse, even though the index of refraction at the second-harmonic frequency is positive. Our analysis further shows that the reflected second-harmonic pulse generated at the interface and the forward-moving, phase-locked pulse appear to be part of the same pulse initially generated at the surface, part of which is immediately back-reflected, while the rest becomes trapped and dragged along by the pump pulse. These pulses thus constitute twin pulses generated at the interface, having the same negative wave vector, but propagating in opposite directions. Almost any break of the longitudinal symmetry, even an exceedingly small χ(2) discontinuity, releases the trapped pulse which then propagates in the backward direction. These dynamics are indicative of very rich and intricate interactions that characterize ultrashort pulse propagation phenomena.

Role of phase matching in pulsed second-harmonic generation: Walk-off and phase-locked twin pulses in negative-index media

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

Roppo, Vito; Centini, Marco; Sibilia, Concita

The present investigation is concerned with the study of pulsed second-harmonic generation under conditions of phase and group velocity mismatch, and generally low conversion efficiencies and pump intensities. In positive-index, nonmetallic materials, we generally find qualitative agreement with previous reports regarding the presence of a double-peaked second harmonic signal, which comprises a pulse that walks off and propagates at the nominal group velocity one expects at the second-harmonic frequency, and a second pulse that is 'captured' and propagates under the pump pulse. We find that the origin of the double-peaked structure resides in a phase-locking mechanism that characterizes not onlymore » second-harmonic generation, but also {chi}{sup (3)} processes and third-harmonic generation. The phase-locking mechanism that we describe occurs for arbitrarily small pump intensities, and so it is not a soliton effect, which usually relies on a threshold mechanism, although multicolor solitons display similar phase locking characteristics. Thus, in second harmonic generation a phase-matched component is always generated, even under conditions of material phase mismatch: This component is anomalous, because the material does not allow energy exchange between the pump and the second-harmonic beam. On the other hand, if the material is phase matched, phase locking and phase matching are indistinguishable, and the conversion process becomes efficient. We also report a similar phase-locking phenomenon in negative index materials. A spectral analysis of the pump and the generated signals reveals that the phase-locking phenomenon causes the forward moving, phase-locked second-harmonic pulse to experience the same negative index as the pump pulse, even though the index of refraction at the second-harmonic frequency is positive. Our analysis further shows that the reflected second-harmonic pulse generated at the interface and the forward-moving, phase-locked pulse appear to be part of the same pulse initially generated at the surface, part of which is immediately back-reflected, while the rest becomes trapped and dragged along by the pump pulse. These pulses thus constitute twin pulses generated at the interface, having the same negative wave vector, but propagating in opposite directions. Almost any break of the longitudinal symmetry, even an exceedingly small {chi}{sup (2)} discontinuity, releases the trapped pulse which then propagates in the backward direction. These dynamics are indicative of very rich and intricate interactions that characterize ultrashort pulse propagation phenomena.« less

New Details of the Human Corneal Limbus Revealed With Second Harmonic Generation Imaging.

PubMed

Park, Choul Yong; Lee, Jimmy K; Zhang, Cheng; Chuck, Roy S

2015-09-01

To report novel findings of the human corneal limbus by using second harmonic generation (SHG) imaging. Corneal limbus was imaged by using an inverted two-photon excitation fluorescence microscope. Laser (Ti:Sapphire) was tuned at 850 nm for two-photon excitation. Backscatter signals of SHG and autofluorescence (AF) were collected through a 425/30-nm emission filter and a 525/45-emission filter, respectively. Multiple, consecutive, and overlapping image stacks (z-stack) were acquired for the corneal limbal area. Two novel collagen structures were revealed by SHG imaging at the limbus: an anterior limbal cribriform layer and presumed anchoring fibers. Anterior limbal cribriform layer is an intertwined reticular collagen architecture just beneath the limbal epithelial niche and is located between the peripheral cornea and Tenon's/scleral tissue. Autofluorescence imaging revealed high vascularity in this structure. Central to the anterior limbal cribriform layer, radial strands of collagen were found to connect the peripheral cornea to the limbus. These presumed anchoring fibers have both collagen and elastin and were found more extensively in the superficial layers than deep layer and were absent in very deep limbus near Schlemm's canal. By using SHG imaging, new details of the collagen architecture of human corneal limbal area were elucidated. High resolution images with volumetric analysis revealed two novel collagen structures.

Research of second harmonic generation images based on texture analysis

NASA Astrophysics Data System (ADS)

Liu, Yao; Li, Yan; Gong, Haiming; Zhu, Xiaoqin; Huang, Zufang; Chen, Guannan

2014-09-01

Texture analysis plays a crucial role in identifying objects or regions of interest in an image. It has been applied to a variety of medical image processing, ranging from the detection of disease and the segmentation of specific anatomical structures, to differentiation between healthy and pathological tissues. Second harmonic generation (SHG) microscopy as a potential noninvasive tool for imaging biological tissues has been widely used in medicine, with reduced phototoxicity and photobleaching. In this paper, we clarified the principles of texture analysis including statistical, transform, structural and model-based methods and gave examples of its applications, reviewing studies of the technique. Moreover, we tried to apply texture analysis to the SHG images for the differentiation of human skin scar tissues. Texture analysis method based on local binary pattern (LBP) and wavelet transform was used to extract texture features of SHG images from collagen in normal and abnormal scars, and then the scar SHG images were classified into normal or abnormal ones. Compared with other texture analysis methods with respect to the receiver operating characteristic analysis, LBP combined with wavelet transform was demonstrated to achieve higher accuracy. It can provide a new way for clinical diagnosis of scar types. At last, future development of texture analysis in SHG images were discussed.

Quantitative analysis on collagen of dermatofibrosarcoma protuberans skin by second harmonic generation microscopy.

PubMed

Wu, Shulian; Huang, Yudian; Li, Hui; Wang, Yunxia; Zhang, Xiaoman

2015-01-01

Dermatofibrosarcoma protuberans (DFSP) is a skin cancer usually mistaken as other benign tumors. Abnormal DFSP resection results in tumor recurrence. Quantitative characterization of collagen alteration on the skin tumor is essential for developing a diagnostic technique. In this study, second harmonic generation (SHG) microscopy was performed to obtain images of the human DFSP skin and normal skin. Subsequently, structure and texture analysis methods were applied to determine the differences in skin texture characteristics between the two skin types, and the link between collagen alteration and tumor was established. Results suggest that combining SHG microscopy and texture analysis methods is a feasible and effective method to describe the characteristics of skin tumor like DFSP. © Wiley Periodicals, Inc.

Intercalating dyes for enhanced contrast in second-harmonic generation imaging of protein crystals

PubMed Central

Newman, Justin A.; Scarborough, Nicole M.; Pogranichniy, Nicholas R.; Shrestha, Rashmi K.; Closser, Richard G.; Das, Chittaranjan; Simpson, Garth J.

2015-01-01

The second-harmonic generation (SHG) activity of protein crystals was found to be enhanced by up to ∼1000-fold by the intercalation of SHG phores within the crystal lattice. Unlike the intercalation of fluorophores, the SHG phores produced no significant background SHG from solvated dye or from dye intercalated into amorphous aggregates. The polarization-dependent SHG is consistent with the chromophores adopting the symmetry of the crystal lattice. In addition, the degree of enhancement for different symmetries of dyes is consistent with theoretical predictions based on the molecular nonlinear optical response. Kinetics studies indicate that intercalation arises over a timeframe of several minutes in lysozyme, with detectable enhancements within seconds. These results provide a potential means to increase the overall diversity of protein crystals and crystal sizes amenable to characterization by SHG microscopy. PMID:26143918

Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies.

PubMed

Sun, Wanxin; Chang, Shi; Tai, Dean C S; Tan, Nancy; Xiao, Guangfa; Tang, Huihuan; Yu, Hanry

2008-01-01

Liver fibrosis is associated with an abnormal increase in an extracellular matrix in chronic liver diseases. Quantitative characterization of fibrillar collagen in intact tissue is essential for both fibrosis studies and clinical applications. Commonly used methods, histological staining followed by either semiquantitative or computerized image analysis, have limited sensitivity, accuracy, and operator-dependent variations. The fibrillar collagen in sinusoids of normal livers could be observed through second-harmonic generation (SHG) microscopy. The two-photon excited fluorescence (TPEF) images, recorded simultaneously with SHG, clearly revealed the hepatocyte morphology. We have systematically optimized the parameters for the quantitative SHG/TPEF imaging of liver tissue and developed fully automated image analysis algorithms to extract the information of collagen changes and cell necrosis. Subtle changes in the distribution and amount of collagen and cell morphology are quantitatively characterized in SHG/TPEF images. By comparing to traditional staining, such as Masson's trichrome and Sirius red, SHG/TPEF is a sensitive quantitative tool for automated collagen characterization in liver tissue. Our system allows for enhanced detection and quantification of sinusoidal collagen fibers in fibrosis research and clinical diagnostics.

Module for multiphoton high-resolution hyperspectral imaging and spectroscopy

NASA Astrophysics Data System (ADS)

Zeytunyan, Aram; Baldacchini, Tommaso; Zadoyan, Ruben

2018-02-01

We developed a module for dual-output, dual-wavelength lasers that facilitates multiphoton imaging and spectroscopy experiments and enables hyperspectral imaging with spectral resolution up to 5 cm-1. High spectral resolution is achieved by employing spectral focusing. Specifically, two sets of grating pairs are used to control the chirps in each laser beam. In contrast with the approach that uses fixed-length glass rods, grating pairs allow matching the spectral resolution and the linewidths of the Raman lines of interest. To demonstrate the performance of the module, we report the results of spectral focusing CARS and SRS microscopy experiments for various test samples and Raman shifts. The developed module can be used for a variety of multimodal imaging and spectroscopy applications, such as single- and multi-color two-photon fluorescence, second harmonic generation, third harmonic generation, pump-probe, transient absorption, and others.

Dynamics of short pulses and phase matched second harmonic generation in negative index materials.

PubMed

Scalora, Michael; D'Aguanno, Giuseppe; Bloemer, Mark; Centini, Marco; de Ceglia, Domenico; Mattiucci, Nadia; Kivshar, Yuri S

2006-05-29

We study pulsed second harmonic generation in metamaterials under conditions of significant absorption. Tuning the pump in the negative index range, a second harmonic signal is generated in the positive index region, such that the respective indices of refraction have the same magnitudes but opposite signs. This insures that a forward-propagating pump is exactly phase matched to the backward-propagating second harmonic signal. Using peak intensities of ~500 MW/cm(2), assuming chi((2))~80pm/V, we predict conversion efficiencies of 12% and 0.2% for attenuation lengths of 50 and 5microm, respectively.

CARS molecular fingerprinting using a sub-nanosecond supercontinuum light source

NASA Astrophysics Data System (ADS)

Kano, Hideaki; Akiyama, Toshihiro; Inoko, Akihito; Kobayashi, Tsubasa; Leproux, Philippe; Couderc, Vincent; Kaji, Yuichi; Oshika, Tetsuro

2018-02-01

We have visualized living cells and tissues using an ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS) microspectroscopic system by using a sub-nanosecond supercontinuum (SC) light source. Owing to the ultrabroadband spectral profile of the SC, we can generate multiplex CARS signals in the spectral range of 500-3800 cm-1, which covers the whole molecular fingerprint region, as well as the C-H and O-H stretching regions. Through the combination of the ultrabroadband multiplex CARS method with second harmonic generation (SHG) and third harmonic generation (THG) processes, we have successfully performed selective imaging of ciliary rootlet-composing Rootletin filaments in rat retina.

Spin current and second harmonic generation in non-collinear magnetic systems: the hydrodynamic model

NASA Astrophysics Data System (ADS)

Karashtin, E. A.; Fraerman, A. A.

2018-04-01

We report a theoretical study of the second harmonic generation in a noncollinearly magnetized conductive medium with equilibrium spin current. The hydrodynamic model is used to unravel the mechanism of a novel effect of the double frequency signal generation that is attributed to the spin current. According to our calculations, this second harmonic response appears due to the ‘non-adiabatic’ spin polarization of the conduction electrons induced by the oscillations in the non-uniform magnetization forced by the electric field of the electromagnetic wave. Together with the linear velocity response this leads to the generation of the double frequency spin current. This spin current is converted to the electric current via the inverse spin Hall effect, and the double-frequency electric current emits the second harmonic radiation. Possible experiment for detection of the new second harmonic effect is proposed.

Role of antenna modes and field enhancement in second harmonic generation from dipole nanoantennas.

PubMed

de Ceglia, Domenico; Vincenti, Maria Antonietta; De Angelis, Costantino; Locatelli, Andrea; Haus, Joseph W; Scalora, Michael

2015-01-26

We study optical second harmonic generation from metallic dipole antennas with narrow gaps. Enhancement of the fundamental-frequency field in the gap region plays a marginal role on conversion efficiency. In the symmetric configuration, i.e., with the gap located at the center of the antenna axis, reducing gap size induces a significant red-shift of the maximum conversion efficiency peak. Either enhancement or inhibition of second-harmonic emission may be observed as gap size is decreased, depending on the antenna mode excited at the harmonic frequency. The second-harmonic signal is extremely sensitive to the asymmetry introduced by gap's displacements with respect to the antenna center. In this situation, second-harmonic light can couple to all the available antenna modes. We perform a multipolar analysis that allows engineering the far-field SH emission and find that the interaction with quasi-odd-symmetry modes generates radiation patterns with a strong dipolar component.

Physics of tissue harmonic imaging by ultrasound

NASA Astrophysics Data System (ADS)

Jing, Yuan

Tissue Harmonic Imaging (THI) is an imaging modality that is currently deployed on diagnostic ultrasound scanners. In THI the amplitude of the ultrasonic pulse that is used to probe the tissue is large enough that the pulse undergoes nonlinear distortion as it propagates into the tissue. One result of the distortion is that as the pulse propagates energy is shifted from the fundamental frequency of the source pulse into its higher harmonics. These harmonics will scatter off objects in the tissue and images formed from the scattered higher harmonics are considered to have superior quality to the images formed from the fundamental frequency. Processes that have been suggested as possibly responsible for the improved imaging in THI include: (1) reduced sensitivity to reverberation, (2) reduced sensitivity to aberration, and (3) reduction in side lobes. By using a combination of controlled experiments and numerical simulations, these three reasons have been investigated. A single element transducer and a clinical ultrasound scanner with a phased array transducer were used to image a commercial tissue-mimicking phantom with calibrated targets. The higher image quality achieved with THI was quantified in terms of spatial resolution and "clutter" signals. A three-dimensional model of the forward propagation of nonlinear sound beams in media with arbitrary spatial properties (a generalized KZK equation) was developed. A time-domain code for solving the KZK equation was validated with measurements of the acoustic field generated by the single element transducer and the phased array transducer. The code was used to investigate the impact of aberration using tissue-like media with three-dimensional variations in all acoustic properties. The three-dimensional maps of tissue properties were derived from the datasets available through the Visible Female project. The experiments and simulations demonstrated that second harmonic imaging (1) suffers less clutter associated with reverberation; (2) is not immune to aberration effects and (3) suffers less clutter due to reduced side-lobe levels. The results indicate that side lobe suppression is the most significant reason for the improvement of second harmonic imaging.

Prediction of Metastasis Using Second Harmonic Generation

DTIC Science & Technology

2016-07-01

extracellular matrix through which metastasizing cells must travel. We and others have demonstrated that tumor collagen structure, as measured with the...algorithm using separate training and validation sets, etc. Keywords: metastasis, overtreatment, extracellular matrix , collagen , second harmonic...optical process called second harmonic generation (SHG), influences tumor metastasis. This suggests that collagen structure may provide prognostic

Periodically poled potassium niobate for second-harmonic generation at 463 nm.

PubMed

Meyn, J P; Klein, M E; Woll, D; Wallenstein, R; Rytz, D

1999-08-15

We report on the fabrication and characterization of quasi-phase-matched potassium niobate crystals for second-harmonic generation. Periodic 30-mum -pitch antiparallel ferroelectric domains are fabricated by means of poling in an electrical field. Both birefrigence and periodic phase shift of the generated second harmonic contribute to phase matching when the d(31) nonlinear optical tensor element is used. 3.8 mW of second-harmonic radiation at 463 nm is generated by frequency doubling of the output of master-oscillator power-amplifier diode laser in a 5-mm-long crystal. The measured effective nonlinear coefficient is 3.7pm/V. The measured spectral acceptance bandwidth of 0.25 nm corresponds to the theoretical value.

Enhancement and inhibition of second-harmonic generation and absorption in a negative index cavity.

PubMed

de Ceglia, Domenico; D'Orazio, Antonella; De Sario, Marco; Petruzzelli, Vincenzo; Prudenzano, Francesco; Centini, Marco; Cappeddu, Mirko G; Bloemer, Mark J; Scalora, Michael

2007-02-01

We study second-harmonic generation in a negative-index material cavity. The transmission spectrum shows a bandgap between the electric and magnetic plasma frequencies. The nonlinear process is made efficient by local phase-matching conditions between a forward-propagating pump and a backward-propagating second-harmonic signal. By simultaneously exciting the cavity with counterpropagating pulses, and by varying their relative phase difference, one is able to enhance or inhibit linear absorption and the second-harmonic conversion efficiency.

Comparison of Cornea Module and DermaInspect for noninvasive imaging of ocular surface pathologies

NASA Astrophysics Data System (ADS)

Steven, Philipp; Müller, Maya; Koop, Norbert; Rose, Christian; Hüttmann, Gereon

2009-11-01

Minimally invasive imaging of ocular surface pathologies aims at securing clinical diagnosis without actual tissue probing. For this matter, confocal microscopy (Cornea Module) is in daily use in ophthalmic practice. Multiphoton microscopy is a new optical technique that enables high-resolution imaging and functional analysis of living tissues based on tissue autofluorescence. This study was set up to compare the potential of a multiphoton microscope (DermaInspect) to the Cornea Module. Ocular surface pathologies such as pterygia, papillomae, and nevi were investigated in vivo using the Cornea Module and imaged immediately after excision by DermaInspect. Two excitation wavelengths, fluorescence lifetime imaging and second-harmonic generation (SHG), were used to discriminate different tissue structures. Images were compared with the histopathological assessment of the samples. At wavelengths of 730 nm, multiphoton microscopy exclusively revealed cellular structures. Collagen fibrils were specifically demonstrated by second-harmonic generation. Measurements of fluorescent lifetimes enabled the highly specific detection of goblet cells, erythrocytes, and nevus-cell clusters. At the settings used, DermaInspect reaches higher resolutions than the Cornea Module and obtains additional structural information. The parallel detection of multiphoton excited autofluorescence and confocal imaging could expand the possibilities of minimally invasive investigation of the ocular surface toward functional analysis at higher resolutions.

Analysis of human knee osteoarthritic cartilage using polarization sensitive second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Kumar, Rajesh; Grønhaug, Kirsten M.; Romijn, Elisabeth I.; Drogset, Jon O.; Lilledahl, Magnus B.

2014-05-01

Osteoarthritis is one of the most prevalent joint diseases in the world. Although the cause of osteoarthritis is not exactly clear, the disease results in a degradation of the quality of the articular cartilage including collagen and other extracellular matrix components. We have investigated alterations in the structure of collagen fibers in the cartilage tissue of the human knee using mulitphoton microscopy. Due to inherent high nonlinear susceptibility, ordered collagen fibers present in the cartilage tissue matrix produces strong second harmonic generation (SHG) signals. Significant morphological differences are found in different Osteoarthritic grades of cartilage by SHG microscopy. Based on the polarization analysis of the SHG signal, we find that a few locations of hyaline cartilage (mainly type II collagen) is being replaced by fibrocartilage (mainly type I cartilage), in agreement with earlier literature. To locate the different types and quantify the alteration in the structure of collagen fiber, we employ polarization-SHG microscopic analysis, also referred to as _-tensor imaging. The image analysis of p-SHG image obtained by excitation polarization measurements would represent different tissue constituents with different numerical values at pixel level resolution.

Quantitative analysis of biological tissues using Fourier transform-second-harmonic generation imaging

NASA Astrophysics Data System (ADS)

Ambekar Ramachandra Rao, Raghu; Mehta, Monal R.; Toussaint, Kimani C., Jr.

2010-02-01

We demonstrate the use of Fourier transform-second-harmonic generation (FT-SHG) imaging of collagen fibers as a means of performing quantitative analysis of obtained images of selected spatial regions in porcine trachea, ear, and cornea. Two quantitative markers, preferred orientation and maximum spatial frequency are proposed for differentiating structural information between various spatial regions of interest in the specimens. The ear shows consistent maximum spatial frequency and orientation as also observed in its real-space image. However, there are observable changes in the orientation and minimum feature size of fibers in the trachea indicating a more random organization. Finally, the analysis is applied to a 3D image stack of the cornea. It is shown that the standard deviation of the orientation is sensitive to the randomness in fiber orientation. Regions with variations in the maximum spatial frequency, but with relatively constant orientation, suggest that maximum spatial frequency is useful as an independent quantitative marker. We emphasize that FT-SHG is a simple, yet powerful, tool for extracting information from images that is not obvious in real space. This technique can be used as a quantitative biomarker to assess the structure of collagen fibers that may change due to damage from disease or physical injury.

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.

Deep-subwavelength waveguiding via inhomogeneous second-harmonic generation.

PubMed

Roppo, Vito; Vincenti, Maria Antonietta; de Ceglia, Domenico; Scalora, Michael

2012-08-01

We theoretically investigate second-harmonic generation in extremely narrow, subwavelength semiconductor and dielectric waveguides. We discuss a guiding mechanism characterized by the inhibition of diffraction and the suppression of cutoff limits in the context of a light trapping phenomenon that sets in under conditions of general phase and group velocity mismatch between the fundamental and the generated harmonic.

The role of ferroelectric domain structure in second harmonic generation in random quadratic media.

PubMed

Roppo, Vito; Wang, W; Kalinowski, K; Kong, Y; Cojocaru, C; Trull, J; Vilaseca, R; Scalora, M; Krolikowski, W; Kivshar, Yu

2010-03-01

We study theoretically and numerically the second harmonic generation in a nonlinear crystal with random distribution of ferroelectric domains. We show that the specific features of disordered domain structure greatly affect the emission pattern of the generated harmonics. This phenomena can be used to characterize the degree of disorder in nonlinear photonic structures.

Ophthalmic imaging using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Teng, Shu-Wen; Peng, Ju-Li; Lin, Huei-Hsing; Wu, Hai-Yin; Lo, Wen; Sun, Yen; Lin, Wei-Chou; Lin, Sung-Jan; Jee, Shiou-Hwa; Tan, Hsin-Yuan; Dong, Chen-Yuan

2005-04-01

This purpose of this study is to demonstrate the feasibility of using multiphoton microscopy in ophthalmologic imaging. Without the introduction of extrinsic fluorescence molecules, multiphoton induced autofluorescence and second harmonic generation signals can be used to obtain useful structural information of normal and diseased corneas. Our work can potentially lead to the in vivo application of multiphoton microscopy in investigating corneal physiology and pathologies.

Spontaneous Polarization in Bio-organic Materials Studied by Scanning Pyroelectric Microscopy (SPEM) and Second Harmonic Generation Microscopy (SHGM)

NASA Astrophysics Data System (ADS)

Putzeys, T.; Wübbenhorst, M.; van der Veen, M. A.

2015-06-01

Bio-organic materials such as bones, teeth, and tendon generally show nonlinear optical (Masters and So in Handbook of Biomedical Nonlinear Optical Microscopy, 2008), pyro- and piezoelectric (Fukada and Yasuda in J Phys Soc Jpn 12:1158, 1957) properties, implying a permanent polarization, the presence of which can be rationalized by describing the growth of the sample and the creation of a polar axis according to Markov's theory of stochastic processes (Hulliger in Biophys J 84:3501, 2003; Batagiannis et al. in Curr Opin Solid State Mater Sci 17:107, 2010). Two proven, versatile techniques for probing spontaneous polarization distributions in solids are scanning pyroelectric microscopy (SPEM) and second harmonic generation microscopy (SHGM). The combination of pyroelectric scanning with SHG-microscopy in a single experimental setup leading to complementary pyroelectric and nonlinear optical data is demonstrated, providing us with a more complete image of the polarization in organic materials. Crystals consisting of a known polar and hyperpolarizable material, CNS (4-chloro-4-nitrostilbene) are used as a reference sample, to verify the functionality of the setup, with both SPEM and SHGM images revealing the same polarization domain information. In contrast, feline and human nails exhibit a pyroelectric response, but a second harmonic response is absent for both keratin containing materials, implying that there may be symmetry-allowed SHG, but with very inefficient second harmonophores. This new approach to polarity detection provides additional information on the polar and hyperpolar nature in a variety of (bio) materials.

Dual-pulse frequency compounded superharmonic imaging.

PubMed

van Neer, Paul L M J; Danilouchkine, Mikhail G; Matte, Guillaume M; van der Steen, Anton F W; de Jong, Nico

2011-11-01

Tissue second-harmonic imaging is currently the default mode in commercial diagnostic ultrasound systems. A new modality, superharmonic imaging (SHI), combines the third through fifth harmonics originating from nonlinear wave propagation through tissue. SHI could further improve the resolution and quality of echographic images. The superharmonics have gaps between the harmonics because the transducer has a limited bandwidth of about 70% to 80%. This causes ghost reflection artifacts in the superharmonic echo image. In this work, a new dual-pulse frequency compounding (DPFC) method to eliminate these artifacts is introduced. In the DPFC SHI method, each trace is constructed by summing two firings with slightly different center frequencies. The feasibility of the method was established using a single-element transducer. Its acoustic field was modeled in KZK simulations and compared with the corresponding measurements obtained with a hydrophone apparatus. Subsequently, the method was implemented on and optimized for a setup consisting of an interleaved phased-array transducer (44 elements at 1 MHz and 44 elements at 3.7 MHz, optimized for echocardiography) and a programmable ultrasound system. DPFC SHI effectively suppresses the ghost reflection artifacts associated with imaging using multiple harmonics. Moreover, compared with the single-pulse third harmonic, DPFC SHI improved the axial resolution by 3.1 and 1.6 times at the -6-dB and -20-dB levels, respectively. Hence, DPFC offers the possibility of generating harmonic images of a higher quality at a cost of a moderate frame rate reduction.

Polarization-resolved second-harmonic generation imaging for liver fibrosis assessment without labeling

NASA Astrophysics Data System (ADS)

Lin, Jian; Pan, Shiying; Zheng, Wei; Huang, Zhiwei

2013-10-01

We apply the polarization-resolved second-harmonic generation (PR-SHG) microscopy to investigate the changes of collagen typings (type I vs type III) and collagen fibril orientations of liver tissue in bile-duct-ligation (BDL) rat models. The PR-SHG results show that the second-order susceptibility tensor ratios (χ31/χ15 and χ33/χ15) of collagen fibers increase with liver fibrotic progression after BDL surgery, reflecting an increase of the type III collagen component with the severity of liver fibrosis; and the square root of the collagen type III to type I ratio linearly correlates (R2 = 0.98) with histopathological scores. Furthermore, the collagen fibril orientations become more random with liver fibrosis transformation as compared to normal liver tissue. This work demonstrates that PR-SHG microscopy has the potential for label-free diagnosis and characterization of liver fibrosis based on quantitative analysis of collagen typings and fibril orientations.

Polarization-Modulated Second Harmonic Generation Microscopy in Collagen

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

Stoller, P C

Collagen is a key structural protein in the body; several pathological conditions lead to changes in collagen. Among imaging modalities that can be used in vivo, second harmonic generation (SHG) microscopy has a key advantage: it provides {approx}1 {micro}m resolution information about collagen structure as a function of depth. A new technique--polarization-modulated SHG--is presented: it permits simultaneous measurement of collagen orientation, of a lower bound on the magnitude of the second order nonlinear susceptibility tensor, and of the ratio of the two independent elements in this tensor. It is applied to characterizing SHG in collagen and to determining effects ofmore » biologically relevant changes in collagen structure. The magnitude of the second harmonic signal in two dimensional images varies with position even in structurally homogeneous tissue; this phenomenon is due to interference between second harmonic light generated by neighboring fibrils, which are randomly oriented parallel or anti-parallel to each other. Studies in which focal spot size was varied indicated that regions where fibrils are co-oriented are less than {approx}1.5 {micro}m in diameter. A quartz reference was used to determine the spot size as well as a lower limit (d{sub xxx} > 0.3 pm/V) for the magnitude of the second order nonlinear susceptibility. The ratio of the two independent tensor elements ranged between d{sub XYY}/d{sub XXX} = 0.60 and 0.75. SHG magnitude alone was not useful for identifying structural anomalies in collagenous tissue. Instead, changes in the polarization dependence of SHG were used to analyze biologically relevant perturbations in collagen structure. Changes in polarization dependence were observed in dehydrated samples, but not in highly crosslinked samples, despite significant alterations in packing structure. Complete thermal denaturation and collagenase digestion produced samples with no detectable SHG signal. Collagen orientation was measured in thin samples of several different tissues in transmission mode as well as at different depths (up to 200 {micro}m) in thick samples in reflection mode; birefringence had no effect on the measurement. These studies showed that SHG microscopy was capable of detecting pathophysiological changes in collagen structure, suggesting that this technique has potential clinical applications.« less

Harmonic generation in magnetized quantum plasma

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

Kumar, Punit; Singh, Abhisek Kumar; Singh, Shiv

2016-05-06

A study of second harmonic generation by propagation of a linearly polarized electromagnetic wave through homogeneous high density quantum plasma in the presence of transverse magnetic field. The nonlinear current density and dispersion relations for the fundamental and second harmonic frequencies have been obtained using the recently developed quantum hydrodynamic (QHD) model. The effect of quantum Bohm potential, Fermi pressure and the electron spin have been taken into account. The second harmonic is found to be less dispersed than the first.

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.

Quantifying collagen orientation in breast tissue biopsies using SLIM (Conference Presentation)

NASA Astrophysics Data System (ADS)

Majeed, Hassaan; Okoro, Chukwuemeka; Balla, Andre; Toussaint, Kimani C.; Popescu, Gabriel

2017-02-01

Breast cancer is a major public health problem worldwide, being the most common type of cancer among women according to the World Health Organization (WHO). The WHO has further stressed the importance of an early determination of the disease course through prognostic markers. Recent studies have shown that the alignment of collagen fibers in tumor adjacent stroma correlate with poorer health outcomes in patients. Such studies have typically been carried out using Second-Harmonic Generation (SHG) microscopy. SHG images are very useful for quantifying collagen fiber orientation due their specificity to non-centrosymmetric structures in tissue, leading to high contrast in collagen rich areas. However, the imaging throughput in SHG microscopy is limited by its point scanning geometry. In this work, we show that SLIM, a wide-field high-throughput QPI technique, can be used to obtain the same information on collagen fiber orientation as is obtainable through SHG microscopy. We imaged a tissue microarray containing both benign and malignant cores using both SHG microscopy and SLIM. The cellular (non-collagenous) structures in the SLIM images were next segmented out using an algorithm developed in-house. Using the previously published Fourier Transform Second Harmonic Generation (FT-SHG) tool, the fiber orientations in SHG and segmented SLIM images were then quantified. The resulting histograms of fiber orientation angles showed that both SHG and SLIM generate similar measurements of collagen fiber orientation. The SLIM modality, however, can generate these results at much higher throughput due to its wide-field, whole-slide scanning capabilities.

Analysis and measurement of the modulation transfer function of harmonic shear wave induced phase encoding imaging.

PubMed

McAleavey, Stephen A

2014-05-01

Shear wave induced phase encoding (SWIPE) imaging generates ultrasound backscatter images of tissue-like elastic materials by using traveling shear waves to encode the lateral position of the scatters in the phase of the received echo. In contrast to conventional ultrasound B-scan imaging, SWIPE offers the potential advantages of image formation without beam focusing or steering from a single transducer element, lateral resolution independent of aperture size, and the potential to achieve relatively high lateral resolution with low frequency ultrasound. Here a Fourier series description of the phase modulated echo signal is developed, demonstrating that echo harmonics at multiples of the shear wave frequency reveal target k-space data at identical multiples of the shear wavenumber. Modulation transfer functions of SWIPE imaging systems are calculated for maximum shear wave acceleration and maximum shear constraints, and compared with a conventionally focused aperture. The relative signal-to-noise ratio of the SWIPE method versus a conventionally focused aperture is found through these calculations. Reconstructions of wire targets in a gelatin phantom using 1 and 3.5 MHz ultrasound and a cylindrical shear wave source are presented, generated from the fundamental and second harmonic of the shear wave modulation frequency, demonstrating weak dependence of lateral resolution with ultrasound frequency.

Surface plasma wave assisted second harmonic generation of laser over a metal film

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

Chauhan, Santosh; Parashar, J., E-mail: j.p.parashar@gmail.com

2015-01-15

Second harmonic generation of laser mode converted surface plasma wave (SPW) over a corrugated metal film is studied. The laser, impinged on the metal film, under attenuated total reflection configuration, excites SPW over the metal–vacuum interface. The excited SPW extends over a much wider surface area than the laser spot cross-section. It exerts a second harmonic ponderomotive force on metal electrons, imparting them velocity that beats with the surface ripple to produce a nonlinear current, driving resonant second harmonic surface plasma wave.

Kolakoski sequence as an element to radiate giant forward and backward second harmonic signals

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

Parvini, T. S.; Tehranchi, M. M., E-mail: m-hamidi@sbu.ac.ir, E-mail: teranchi@sbu.ac.ir; Laser and Plasma Research Institute, Shahid Beheshti University, Tehran

2015-11-14

We propose a novel type of aperiodic one-dimensional photonic crystal structures which can be used for generating giant forward and backward second harmonic signals. The studied structure is formed by stacking together the air and nonlinear layers according to the Kolakoski self-generation scheme in which each nonlinear layer contains a pair of antiparallel 180° poled LiNbO{sub 3} crystal layers. For different generation stages of the structure, conversion efficiencies of forward and backward second harmonic waves have been calculated by nonlinear transfer matrix method. Numerical simulations show that conversion efficiencies in the Kolakoski-based multilayer are larger than the perfect ones formore » at least one order of magnitude. Especially for 33rd and 39th generation stages, forward second harmonic wave are 42 and 19 times larger, respectively. In this paper, we validate the strong fundamental field enhancement and localization within Kolakoski-based multilayer due to periodicity breaking which consequently leads to very strong radiation of backward and forward second harmonic signals. Following the applications of analogous aperiodic structures, we expect that Kolakosi-based multilayer can play a role in optical parametric devices such as multicolor second harmonic generators with high efficiency.« less

Efficient second harmonic generation by para-nitroaniline embedded in electro-spun polymeric nanofibres

NASA Astrophysics Data System (ADS)

Gonçalves, Hugo; Saavedra, Inês; Ferreira, Rute AS; Lopes, PE; de Matos Gomes, Etelvina; Belsley, Michael

2018-03-01

Intense well polarized second harmonic light was generated by poly(methyl methacrylate) nanofibres with embedded para-nitroaniline nanocrystals. Subwavelength diameter fibres were electro-spun using a 1:2 weight ratio of chromophore to polymer. Analysis of the generated second harmonic light indicates that the para-nitroaniline molecules, which nominally crystalize in the centrosymmetric space group, were organized into noncentrosymmetric structures leading to a second order susceptibility dominated by a single tensor element. Under the best deposition conditions, the nanofibrers display an effective nonlinear optical susceptibility approximately two orders of magnitude greater than that of potassium dihydrogen phosphate. Generalizing this approach to a broad range of organic molecules with strong individual molecular second order nonlinear responses, but which nominally form centrosymmetric organic crystals, could open a new pathway for the fabrication of efficient sub-micron sized second harmonic light generators.

Simultaneous quadruple modal nonlinear optical imaging for gastric diseases diagnosis and characterization

NASA Astrophysics Data System (ADS)

Wang, Zi; Zheng, Wei; Lin, Jian; Huang, Zhiwei

2015-03-01

We report the development of a unique simultaneous quadruple-modal nonlinear optical microscopy (i.e., stimulated Raman scattering (SRS), second-harmonic generation (SHG), two-photon excitation fluorescence (TPEF), and third-harmonic generation (THG)) platform for characterization of the gastric diseases (i.e., gastritis, intestinal metaplasia (IM), intestinal type adenocarcinoma). SRS highlights the goblet cells found in IM. SHG images the distribution of collagen in lamina propria. Collagen is found to aggregate for intestinal type adenocarcinoma. TPEF reveals the cell morphology and can reflect the damage inside glands caused by the diseases. THG visualizes the nuclei with high spatial resolution, which facilitates the identification of neutrophils that are usually used as a feature of inflammation. This work shows that the co-registration of quadruple-modal images can be an effective means for diagnosis and characterization of gastric diseases at the cellular and molecular levels.

NONLINEAR OPTICS PHENOMENA: Second harmonic generation from DF laser radiation in ZnGeP2

NASA Astrophysics Data System (ADS)

Andreev, Yu M.; Velikanov, S. D.; Yerutin, A. S.; Zapol'skiĭ, A. F.; Konkin, D. V.; Mishkin, S. N.; Smirnov, S. V.; Frolov, Yu N.; Shchurov, V. V.

1992-11-01

We have succeeded in generating the second harmonic of the radiation from a DF laser for the first time, using single crystals of ZnGeP2. For crystals with lengths of 10.1 and 13.6 mm, the overall external efficiencies of the entire oscillator system were 4 and 6.2%. The internal efficiencies of second-harmonic generation in the crystals were 7.6 and 11.8%, respectively.

Kerr-like behaviour of second harmonic generation in the far-off resonant regime

NASA Astrophysics Data System (ADS)

Peřinová, Vlasta; Lukš, Antonín; Křepelka, Jaromír; Leoński, Wiesław; Peřina, Jan

2018-05-01

We separate the Kerr-like behaviour of the second-harmonic generation in the far-off resonant regime from the oscillations caused by the time-dependence of the interaction energy. To this purpose, we consider the approximation obtained from the exact dynamics by the method of small rotations. The Floquet-type decomposition of the approximate dynamics comprises the Kerr-like dynamics and oscillations of the same order of magnitude as those assumed for the exact dynamics of the second-harmonic generation. We have found that a superposition of two states of concentrated quantum phase arises in the fundamental mode in the second-harmonic generation in the far-off resonant limit at a later time than a superposition of two coherent states in the corresponding Kerr medium and the difference is larger for higher initial coherent amplitudes. The quantum phase fluctuation is higher for the same initial coherent amplitudes in the fundamental mode in the second-harmonic generation in the far-off resonant limit than in the corresponding Kerr medium and the difference is larger for higher initial coherent amplitudes.

Computer model for harmonic ultrasound imaging.

PubMed

Li, Y; Zagzebski, J A

2000-01-01

Harmonic ultrasound imaging has received great attention from ultrasound scanner manufacturers and researchers. In this paper, we present a computer model that can generate realistic harmonic images. In this model, the incident ultrasound is modeled after the "KZK" equation, and the echo signal is modeled using linear propagation theory because the echo signal is much weaker than the incident pulse. Both time domain and frequency domain numerical solutions to the "KZK" equation were studied. Realistic harmonic images of spherical lesion phantoms were generated for scans by a circular transducer. This model can be a very useful tool for studying the harmonic buildup and dissipation processes in a nonlinear medium, and it can be used to investigate a wide variety of topics related to B-mode harmonic imaging.

Computer model for harmonic ultrasound imaging.

PubMed

Li, Y; Zagzebski, J A

2000-01-01

Harmonic ultrasound imaging has received great attention from ultrasound scanner manufacturers and researchers. Here, the authors present a computer model that can generate realistic harmonic images. In this model, the incident ultrasound is modeled after the "KZK" equation, and the echo signal is modeled using linear propagation theory because the echo signal is much weaker than the incident pulse. Both time domain and frequency domain numerical solutions to the "KZK" equation were studied. Realistic harmonic images of spherical lesion phantoms were generated for scans by a circular transducer. This model can be a very useful tool for studying the harmonic buildup and dissipation processes in a nonlinear medium, and it can be used to investigate a wide variety of topics related to B-mode harmonic imaging.

Quantification of collagen fiber organization in biological tissues at cellular and molecular scales using second-harmonic generation imaging

NASA Astrophysics Data System (ADS)

Ambekar Ramachandra Rao, Raghu

Collagen is the most abundant structural protein found in the human body, and is responsible for providing structure and function to tissues. Collagen molecules organize naturally into structures called fibers on the scale of the wavelength of light and lack inversion symmetry, thus allowing for the process of second harmonic generation (SHG) when exposed to intense incident light. We have developed two quantitative techniques: Fourier transform-second-harmonic generation (FT-SHG) imaging and generalized chi2 second-harmonic generation (chi2-SHG) imaging. In order to show that FT-SHG imaging can be used as a valuable diagnostic tool for real-world biological problems, we first investigate collagenase-induced injury in horse tendons. Clear differences in collagen fiber organization between normal and injured tendon are quantified. In particular, we observe that the regularly oriented organization of collagen fibers in normal tendons is disrupted in injured tendons leading to a more random organization. We also observe that FT-SHG microscopy is more sensitive in assessing tendon injury compared to the conventional polarized light microscopy. The second study includes quantifying collagen fibers in cortical bone using FT-SHG imaging and comparing it with scanning electron microscopy (SEM). Further, as an example study, we show how FT-SHG imaging could be used to quantify changes in bone structure as a function of age. Some initial work and future directions for extending FT-SHG to 3D are also discussed. The second technique, chi2-SHG imaging, takes advantage of the coherent nature of SHG and utilizes polarization to extract the second-order susceptibility (d elements) which provides information on molecular organization, i.e., it provides access to sub-diffractional changes "optically". We use chi2-SHG in combination with FT-SHG imaging to investigate a couple of biological problems. First, we quantify differences in collagen fiber organization between cornea and sclera of the eye in order to investigate their properties of transparency and opacity, respectively. We find from chi2-SHG imaging that there is no statistical difference in the values of d elements between cornea and sclera, indicating that the underlying collagen structure generating SHG from the two is similar at the level of detection of SHG microscopy. However, the difference lies in the spatial organization of these collagen fibers as observed from FT-SHG imaging. We find that cornea contains lamellae with patches of ordered and uniform diameter collagen fibers with axial order, which could be the reason for its transparent behavior. Conversely, there are no lamellae in sclera (i.e., no axial order), and fibers are thicker, denser, have inconsistent diameters, and possess relatively inhomogeneous orientations, leading to its opaque nature. We also utilized the two techniques to assess differences in stromal collagen fibers for several human breast tissue conditions: normal, hyperplasia, dysplasia, and malignant. Using FT-SHG imaging, we note differences between malignant and other pathological conditions through the metric A.I. ratio. Using generalized chi2-SHG imaging, we observe structural changes in collagen at the molecular scale, and a particular d element showed a more sensitive differentiation between breast tissue conditions, except between hyperplasia and normal/dysplasia. We also find that the trigonal symmetry (3m) is a more appropriate model to describe collagen fibers in malignant tissues as opposed to the conventionally used hexagonal symmetry (C6). Furthermore, the percentage of abnormal collagen fibers could potentially be used as a metric for differentiating breast tissue conditions. We also introduce a technique for extending chi2-SHG to fibers with curvature which is useful for generating chi2-image maps (in terms of d elements) instead of the conventional SHG intensity images. The spatial variations in d elements will provide additional information. For example, in breast cancer tissues, it may help in observing how fibers change from normal to malignant spatially, especially around region of cancerous cells. Finally, we discuss some of the interesting immediate and later future work of quantitative SHG imaging we aim to carry out in our lab. (Abstract shortened by UMI.)

Analysis of second-harmonic-generation microscopy in a mouse model of ovarian carcinoma

NASA Astrophysics Data System (ADS)

Watson, Jennifer M.; Rice, Photini F.; Marion, Samuel L.; Brewer, Molly A.; Davis, John R.; Rodriguez, Jeffrey J.; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

2012-07-01

Second-harmonic-generation (SHG) imaging of mouse ovaries ex vivo was used to detect collagen structure changes accompanying ovarian cancer development. Dosing with 4-vinylcyclohexene diepoxide and 7,12-dimethylbenz[a]anthracene resulted in histologically confirmed cases of normal, benign abnormality, dysplasia, and carcinoma. Parameters for each SHG image were calculated using the Fourier transform matrix and gray-level co-occurrence matrix (GLCM). Cancer versus normal and cancer versus all other diagnoses showed the greatest separation using the parameters derived from power in the highest-frequency region and GLCM energy. Mixed effects models showed that these parameters were significantly different between cancer and normal (P<0.008). Images were classified with a support vector machine, using 25% of the data for training and 75% for testing. Utilizing all images with signal greater than the noise level, cancer versus not-cancer specimens were classified with 81.2% sensitivity and 80.0% specificity, and cancer versus normal specimens were classified with 77.8% sensitivity and 79.3% specificity. Utilizing only images with greater than of 75% of the field of view containing signal improved sensitivity and specificity for cancer versus normal to 81.5% and 81.1%. These results suggest that using SHG to visualize collagen structure in ovaries could help with early cancer detection.

Coherence-domain imaging with harmonic holography

NASA Astrophysics Data System (ADS)

Pu, Ye; Psaltis, Demetri

2017-08-01

Observing the fast dynamics of specific molecules or targets in three-dimensional (3D) space and time inside a crowded and complex environment, such as living cells or tissues, remain one of the grand open challenges in modern science. Harmonic holography tackle this challenge by combining the 3D imaging capability of holography with the ultrafast, coherent optical contrast offered by second-harmonic radiating imaging probes (SHRIMPs). Similar to fluorescence, the second-harmonic signal emitted from SHRIMPs provides a color contrast against the uninterested background scattering, which can be efficiently suppressed by an optical filter. We review the latest developments in SHRIMPs and harmonic holography and discuss their further applications in fluidics and biofluidics.

Second-harmonic generation of practical Bessel beams

NASA Astrophysics Data System (ADS)

Huang, Jin H.; Ding, Desheng; Hsu, Yin-Sung

2009-11-01

A fast Gaussian expansion approach is used to investigate fundamental and second-harmonic generation in practical Bessel beams of finite aperture. The analysis is based on the integral solutions of the KZK equation under the quasilinear approximation. The influence of the medium's attenuation on the beam profile is considered. Analysis results show that the absorption parameter has a significant effect on the far-field beam profile of the second harmonic. Under certain circumstances, the second harmonic of a practical Bessel beam still has the main properties of an ideal Bessel beam of infinite aperture when it propagates within its depth of field.

Mode matching in multiresonant plasmonic nanoantennas for enhanced second harmonic generation

NASA Astrophysics Data System (ADS)

Celebrano, Michele; Wu, Xiaofei; Baselli, Milena; Großmann, Swen; Biagioni, Paolo; Locatelli, Andrea; de Angelis, Costantino; Cerullo, Giulio; Osellame, Roberto; Hecht, Bert; Duò, Lamberto; Ciccacci, Franco; Finazzi, Marco

2015-05-01

Boosting nonlinear frequency conversion in extremely confined volumes remains a challenge in nano-optics research, but can enable applications in nanomedicine, photocatalysis and background-free biosensing. To obtain brighter nonlinear nanoscale sources, approaches that enhance the electromagnetic field intensity and counter the lack of phase matching in nanoplasmonic systems are often employed. However, the high degree of symmetry in the crystalline structure of plasmonic materials (metals in particular) and in nanoantenna designs strongly quenches second harmonic generation. Here, we describe doubly-resonant single-crystalline gold nanostructures with no axial symmetry displaying spatial mode overlap at both the excitation and second harmonic wavelengths. The combination of these features allows the attainment of a nonlinear coefficient for second harmonic generation of ˜5 × 10-10 W-1, enabling a second harmonic photon yield higher than 3 × 106 photons per second. Theoretical estimations point toward the use of our nonlinear plasmonic nanoantennas as efficient platforms for label-free molecular sensing.

Epi-detected quadruple-modal nonlinear optical microscopy for label-free imaging of the tooth

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

Wang, Zi; Zheng, Wei; Huang, Zhiwei, E-mail: biehzw@nus.edu.sg

2015-01-19

We present an epi-detected quadruple-modal nonlinear optical microscopic imaging technique (i.e., coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), third-harmonic generation (THG), and two-photon excited fluorescence (TPEF)) based on a picosecond (ps) laser-pumped optical parametric oscillator system for label-free imaging of the tooth. We demonstrate that high contrast ps-CARS images covering both the fingerprint (500–1800 cm{sup −1}) and high-wavenumber (2500–3800 cm{sup −1}) regions can be acquired to uncover the distributions of mineral and organic biomaterials in the tooth, while high quality TPEF, SHG, and THG images of the tooth can also be acquired under ps laser excitation without damaging the samples. Themore » quadruple-modal nonlinear microscopic images (CARS/SHG/THG/TPEF) acquired provide better understanding of morphological structures and biochemical/biomolecular distributions in the dentin, enamel, and the dentin-enamel junction of the tooth without labeling, facilitating optical diagnosis and characterization of the tooth in dentistry.« less

Investigation of Second- and Third-Harmonic Generation in Few-Layer Gallium Selenide by Multiphoton Microscopy

PubMed Central

Karvonen, Lasse; Säynätjoki, Antti; Mehravar, Soroush; Rodriguez, Raul D.; Hartmann, Susanne; Zahn, Dietrich R. T.; Honkanen, Seppo; Norwood, Robert A.; Peyghambarian, N.; Kieu, Khanh; Lipsanen, Harri; Riikonen, Juha

2015-01-01

Gallium selenide (GaSe) is a layered semiconductor and a well-known nonlinear optical crystal. The discovery of graphene has created a new vast research field focusing on two-dimensional materials. We report on the nonlinear optical properties of few-layer GaSe using multiphoton microscopy. Both second- and third-harmonic generation from few-layer GaSe flakes were observed. Unexpectedly, even the peak at the wavelength of 390 nm, corresponding to the fourth-harmonic generation or the sum frequency generation from third-harmonic generation and pump light, was detected during the spectral measurements in thin GaSe flakes. PMID:25989113

Fiber bundle based endomicroscopy prototype with two collection channels for simultaneous coherent anti-Stokes Raman scattering and second harmonic generation imaging

NASA Astrophysics Data System (ADS)

Liu, Zhengfan; Satira, Zachary A.; Wang, Xi; Xu, Xiaoyun; Chen, Xu; Wong, Kelvin; Chen, Shufen; Xin, Jianguo; Wong, Stephen T. C.

2014-02-01

Label-free multiphoton imaging is promising for replacing biopsy and could offer new strategies for intraoperative or surgical applications. Coherent anti-Stokes Raman scattering (CARS) imaging could provide lipid-band contrast, and second harmonic generation (SHG) imaging is useful for imaging collagen, tendon and muscle fibers. A combination of these two imaging modalities could provide rich information and this combination has been studied by researchers to investigate diseases through microscopy imaging. The combination of these two imaging modalities in endomicroscopy imaging has been rarely investigated. In this research, a fiber bundle consisted of one excitation fiber and 18 collection fibers was developed in our endomicroscopy prototype. The 18 collection fibers were divided into two collection channels with 9 fibers in each channel. These two channels could be used together as one channel for effective signal collection or used separately for simplifying detection part of the system. Differences of collection pattern of these two channels were investigated. Collection difference of central excitation fiber and surrounding 18 fibers was also investigated, which reveals the potential ability of this system to measure forward to backward (F/B) ratio in SHG imaging. CARS imaging of mouse adipocyte and SHG imaging of mouse tail tendon were performed to demonstrate the CARS and SHG tissue imaging performance of this system. Simultaneous CARS and SHG imaging ability of this system was demonstrated by mouse tail imaging. This fiber bundle based endomicroscopy imaging prototype, offers a promising platform for constructing efficient fiber-based CARS and SHG multimodal endomicroscopes for label free intraoperative imaging applications.

Current-driven second-harmonic domain wall resonance in ferromagnetic metal/nonmagnetic metal bilayers: A field-free method for spin Hall angle measurements

NASA Astrophysics Data System (ADS)

Hajiali, M. R.; Hamdi, M.; Roozmeh, S. E.; Mohseni, S. M.

2017-10-01

We study the ac current-driven domain wall motion in bilayer ferromagnetic metal (FM)/nonmagnetic metal (NM) nanowires. The solution of the modified Landau-Lifshitz-Gilbert equation including all the spin transfer torques is used to describe motion of the domain wall in the presence of the spin Hall effect. We show that the domain wall center has a second-harmonic frequency response in addition to the known first-harmonic excitation. In contrast to the experimentally observed second-harmonic response in harmonic Hall measurements of spin-orbit torque in magnetic thin films, this second-harmonic response directly originates from spin-orbit torque driven domain wall dynamics. Based on the spin current generated by domain wall dynamics, the longitudinal spin motive force generated voltage across the length of the nanowire is determined. The second-harmonic response introduces additionally a practical field-free and all-electrical method to probe the effective spin Hall angle for FM/NM bilayer structures that could be applied in experiments. Our results also demonstrate the capability of utilizing FM/NM bilayer structures in domain wall based spin-torque signal generators and resonators.

Clinical coherent anti-Stokes Raman scattering and multiphoton tomography of human skin with a femtosecond laser and photonic crystal fiber

NASA Astrophysics Data System (ADS)

Breunig, Hans Georg; Weinigel, Martin; Bückle, Rainer; Kellner-Höfer, Marcel; Lademann, Jürgen; Darvin, Maxim E.; Sterry, Wolfram; König, Karsten

2013-02-01

We report on in vivo coherent anti-Stokes Raman scattering spectroscopy (CARS), two-photon fluorescence and second-harmonic-generation imaging on human skin with a novel multimodal clinical CARS/multiphoton tomograph. CARS imaging is realized by a combination of femtosecond pulses with broadband continuum pulses generated by a photonic crystal fiber. The images reveal the microscopic distribution of (i) non-fluorescent lipids, (ii) endogenous fluorophores and (iii) the collagen network inside the human skin in vivo with subcellular resolution. Examples of healthy as well as cancer-affected skin are presented.

Optical harmonic generator

DOEpatents

Summers, M.A.; Eimerl, D.; Boyd, R.D.

1982-06-10

A pair of uniaxial birefringent crystal elements are fixed together to form a serially arranged, integral assembly which, alternatively, provides either a linearly or elliptically polarized second-harmonic output wave or a linearly polarized third-harmonic output wave. The extraordinary or e directions of the crystal elements are oriented in the integral assembly to be in quadrature (90/sup 0/). For a second-harmonic generation in the Type-II-Type-II angle tuned case, the input fundamental wave has equal amplitude o and e components. For a third-harmonic generation, the input fundamental wave has o and e components whose amplitudes are in a ratio of 2:1 (o:e reference first crystal). In the typical case of a linearly polarized input fundamental wave this can be accomplished by simply rotating the crystal assembly about the input beam direction by 10/sup 0/. For both second and third harmonic generation input precise phase-matching is achieved by tilting the crystal assembly about its two sensitive axeses (o).

Optical harmonic generator

DOEpatents

Summers, Mark A.; Eimerl, David; Boyd, Robert D.

1985-01-01

A pair of uniaxial birefringent crystal elements are fixed together to form a serially arranged, integral assembly which, alternatively, provides either a linearly or elliptically polarized second-harmonic output wave or a linearly polarized third-harmonic output wave. The "extraordinary" or "e" directions of the crystal elements are oriented in the integral assembly to be in quadrature (90.degree.). For a second-harmonic generation in the Type-II-Type-II angle tuned case, the input fundamental wave has equal amplitude "o" and "e" components. For a third-harmonic generation, the input fundamental wave has "o" and "e" components whose amplitudes are in a ratio of 2:1 ("o":"e" reference first crystal). In the typical case of a linearly polarized input fundamental wave this can be accomplished by simply rotating the crystal assembly about the input beam direction by 10.degree.. For both second and third harmonic generation input precise phase-matching is achieved by tilting the crystal assembly about its two sensitive axes ("o").

Second harmonic generation by self-focusing of intense hollow Gaussian laser beam in collisionless plasma

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

Purohit, Gunjan, E-mail: gunjan75@gmail.com; Rawat, Priyanka; Gauniyal, Rakhi

2016-01-15

The effect of self focused hollow Gaussian laser beam (HGLB) (carrying null intensity in center) on the excitation of electron plasma wave (EPW) and second harmonic generation (SHG) has been investigated in collisionless plasma, where relativistic-ponderomotive and only relativistic nonlinearities are operative. The relativistic change of electron mass and the modification of the background electron density due to ponderomotive nonlinearity lead to self-focusing of HGLB in plasma. Paraxial ray theory has been used to derive coupled equations for the self focusing of HGLB in plasma, generation of EPW, and second harmonic. These coupled equations are solved analytically and numerically tomore » study the laser intensity in the plasma, electric field associated with the excited EPW, and the power of SHG. Second harmonic emission is generated due to nonlinear coupling between incident HGLB and EPW satisfying the proper phase matching conditions. The results show that the effect of including the ponderomotive nonlinearity is significant on the generation of EPW and second harmonic. The electric field associated with EPW and the power of SHG are found to be highly sensitive to the order of the hollow Gaussian beam.« less

Second-harmonic generation using tailored whispering gallery modes

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

Dumeige, Yannick; Feron, Patrice

It has been shown that whispering gallery modes can be used to obtain a combination of modal and geometrical quasi-phase-matching in second-harmonic generation. This could be achieved in isotropic, nonferroelectric, strongly dispersive and highly nonlinear materials such as III-V semiconductors. Unfortunately the poor overlap between the second-harmonic field and second order nonlinear polarization limits the conversion efficiency. In this paper we show that by engineering the refractive index it is possible to increase field overlap and to enhance effective second order nonlinear polarization of semiconductor microdisks.

3D texture analysis for classification of second harmonic generation images of human ovarian cancer

NASA Astrophysics Data System (ADS)

Wen, Bruce; Campbell, Kirby R.; Tilbury, Karissa; Nadiarnykh, Oleg; Brewer, Molly A.; Patankar, Manish; Singh, Vikas; Eliceiri, Kevin. W.; Campagnola, Paul J.

2016-10-01

Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class. By applying k-nearest neighbor classification using these learned models, we achieved 83-91% accuracies for the six classes. The 3D method outperformed the analogous 2D classification on the same tissues, where we suggest this is due the increased information content. This classification based on ECM structural changes will complement conventional classification based on genetic profiles and can serve as an additional biomarker. Moreover, the texture analysis algorithm is quite general, as it does not rely on single morphological metrics such as fiber alignment, length, and width but their combined convolution with a customizable basis set.

Kinetic Modeling of Accelerated Stability Testing Enabled by Second Harmonic Generation Microscopy.

PubMed

Song, Zhengtian; Sarkar, Sreya; Vogt, Andrew D; Danzer, Gerald D; Smith, Casey J; Gualtieri, Ellen J; Simpson, Garth J

2018-04-03

The low limits of detection afforded by second harmonic generation (SHG) microscopy coupled with image analysis algorithms enabled quantitative modeling of the temperature-dependent crystallization of active pharmaceutical ingredients (APIs) within amorphous solid dispersions (ASDs). ASDs, in which an API is maintained in an amorphous state within a polymer matrix, are finding increasing use to address solubility limitations of small-molecule APIs. Extensive stability testing is typically performed for ASD characterization, the time frame for which is often dictated by the earliest detectable onset of crystal formation. Here a study of accelerated stability testing on ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, has been conducted. Under the condition for accelerated stability testing at 50 °C/75%RH and 40 °C/75%RH, ritonavir crystallization kinetics from amorphous solid dispersions were monitored by SHG microscopy. SHG microscopy coupled by image analysis yielded limits of detection for ritonavir crystals as low as 10 ppm, which is about 2 orders of magnitude lower than other methods currently available for crystallinity detection in ASDs. The four decade dynamic range of SHG microscopy enabled quantitative modeling with an established (JMAK) kinetic model. From the SHG images, nucleation and crystal growth rates were independently determined.

In vivo multiphoton and second harmonic generation microscopy of epithelial carcinogenesis

NASA Astrophysics Data System (ADS)

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

2006-02-01

Multiphoton microscopy and second harmonic generation microscopy were used to image epithelial changes in a hamster model for oral malignant transformation. In vivo imaging was performed to characterize morphometric alterations in normal and precancerous regions. Morphometric measurements such as cell nucleus area and epithelial thicknesses obtained from MPM-SHGM were in excellent agreement with histology obtained after in vivo imaging. MPM-SHGM was highly sensitive to spectroscopic and architectural alterations throughout carcinogenesis, showing statistically significant changes in morphology. MPM revealed hyperkeratosis, nuclear enlargement/crowding in dysplasia, and immune cell infiltration. SHGM revealed alterations in submucosal architecture, with a decrease in SHG density evident during early stages of precancer. By combining MPM with SHGM, the basement membrane could be identified in normal, hyperplasia, and dysplasia samples and in some cases of early invasion. The combined technique of MPM-SHGM has the potential to serve as an adjunct to biopsy for assessing precancerous changes and will be investigated further for that purpose. Additionally, the method can provide spatiotemporal assessment of early neoplastic changes in order to elucidate the stages of transformation in vivo and could be used to assess therapeutic efficacy of agents being tested for the treatment of epithelial precancers/cancer.

Second harmonic generation imaging as a potential tool for staging pregnancy and predicting preterm birth

NASA Astrophysics Data System (ADS)

Akins, Meredith L.; Luby-Phelps, Katherine; Mahendroo, Mala

2010-03-01

We use second harmonic generation (SHG) microscopy to assess changes in collagen structure of murine cervix during cervical remodeling of normal pregnancy and in a preterm birth model. Visual inspection of SHG images revealed substantial changes in collagen morphology throughout normal gestation. SHG images collected in both the forward and backward directions were analyzed quantitatively for changes in overall mean intensity, forward to backward intensity ratio, collagen fiber size, and porosity. Changes in mean SHG intensity and intensity ratio take place in early pregnancy, suggesting that submicroscopic changes in collagen fibril size and arrangement occur before macroscopic changes become evident. Fiber size progressively increased from early to late pregnancy, while pores between collagen fibers became larger and farther apart. Analysis of collagen features in premature cervical remodeling show that changes in collagen structure are dissimilar from normal remodeling. The ability to quantify multiple morphological features of collagen that characterize normal cervical remodeling and distinguish abnormal remodeling in preterm birth models supports future studies aimed at development of SHG endoscopic devices for clinical assessment of collagen changes during pregnancy in women and for predicting risk of preterm labor which occurs in 12.5% of all pregnancies.

In vivo observation of age-related structural changes of dermal collagen in human facial skin using collagen-sensitive second harmonic generation microscope equipped with 1250-nm mode-locked Cr:Forsterite laser

NASA Astrophysics Data System (ADS)

Yasui, Takeshi; Yonetsu, Makoto; Tanaka, Ryosuke; Tanaka, Yuji; Fukushima, Shu-ichiro; Yamashita, Toyonobu; Ogura, Yuki; Hirao, Tetsuji; Murota, Hiroyuki; Araki, Tsutomu

2013-03-01

In vivo visualization of human skin aging is demonstrated using a Cr:Forsterite (Cr:F) laser-based, collagen-sensitive second harmonic generation (SHG) microscope. The deep penetration into human skin, as well as the specific sensitivity to collagen molecules, achieved by this microscope enables us to clearly visualize age-related structural changes of collagen fiber in the reticular dermis. Here we investigated intrinsic aging and/or photoaging in the male facial skin. Young subjects show dense distributions of thin collagen fibers, whereas elderly subjects show coarse distributions of thick collagen fibers. Furthermore, a comparison of SHG images between young and elderly subjects with and without a recent life history of excessive sun exposure show that a combination of photoaging with intrinsic aging significantly accelerates skin aging. We also perform image analysis based on two-dimensional Fourier transformation of the SHG images and extracted an aging parameter for human skin. The in vivo collagen-sensitive SHG microscope will be a powerful tool in fields such as cosmeceutical sciences and anti-aging dermatology.

Inhibition of linear absorption in opaque materials using phase-locked harmonic generation.

PubMed

Centini, Marco; Roppo, Vito; Fazio, Eugenio; Pettazzi, Federico; Sibilia, Concita; Haus, Joseph W; Foreman, John V; Akozbek, Neset; Bloemer, Mark J; Scalora, Michael

2008-09-12

We theoretically predict and experimentally demonstrate inhibition of linear absorption for phase and group velocity mismatched second- and third-harmonic generation in strongly absorbing materials, GaAs, in particular, at frequencies above the absorption edge. A 100-fs pump pulse tuned to 1300 nm generates 650 and 435 nm second- and third-harmonic pulses that propagate across a 450-microm-thick GaAs substrate without being absorbed. We attribute this to a phase-locking mechanism that causes the pump to trap the harmonics and to impress on them its dispersive properties.

Second harmonic generation: Effects of the multiple reflections of the fundamental and the second harmonic waves on the Maker fringes

NASA Astrophysics Data System (ADS)

Tellier, Gildas; Boisrobert, Christian

2007-11-01

The Maker fringes technique is commonly used for the determination of nonlinear optical coefficients. In this article, we present a new formulation of Maker fringes in parallel-surface samples, using boundary conditions taking into account the anisotropy of the crystal, the refractive-index dispersion, and the reflections of the fundamental and the second harmonic waves inside the material. Complete expressions for the generated second harmonic intensity are given for birefringent crystals for the case of no pump depletion. A comparison between theory and experimental results is made, showing the accuracy of our theoretical expressions.

Effects of electromagnetic fields on the nonlinear optical properties of asymmetric double quantum well under intense laser field

NASA Astrophysics Data System (ADS)

Yesilgul, U.; Sari, H.; Ungan, F.; Martínez-Orozco, J. C.; Restrepo, R. L.; Mora-Ramos, M. E.; Duque, C. A.; Sökmen, I.

2017-03-01

In this study, the effects of electric and magnetic fields on the optical rectification and second and third harmonic generation in asymmetric double quantum well under the intense non-resonant laser field is theoretically investigated. We calculate the optical rectification and second and third harmonic generation within the compact density-matrix approach. The theoretical findings show that the influence of electric, magnetic, and intense laser fields leads to significant changes in the coefficients of nonlinear optical rectification, second and third harmonic generation.

Frequency doubling in poled polymers using anomalous dispersion phase-matching

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

Kowalczyk, T.C.; Singer, K.D.; Cahill, P.A.

1995-10-01

The authors report on a second harmonic generation in a poled polymer waveguide using anomalous dispersion phase-matching. Blue light ({lambda} = 407 nm) was produced by phase-matching the lowest order fundamental and harmonic modes over a distance of 32 {micro}m. The experimental conversion efficiency was {eta} = 1.2 {times} 10{sup {minus}4}, in agreement with theory. Additionally, they discuss a method of enhancing the conversion efficiency for second harmonic generation using anomalous dispersion phase-matching to optimize Cerenkov second harmonic generation. The modeling shows that a combination of phase-matching techniques creates larger conversion efficiencies and reduces critical fabrication requirements of the individualmore » phase-matching techniques.« less

Continuum generation in ultra high numerical aperture fiber with application to multiphoton microscopy

NASA Astrophysics Data System (ADS)

Sayler, Nicholas

Nonlinear microscopy benefits from broadband laser sources, enabling efficient excitation of an array of fluorophores, for example. This work demonstrates broadening of a narrow band input pulse (6 nm to 40 nm) centered at 1040 nm with excellent shot-to-shot stability. In a preliminary demonstration, multiphoton imaging with pulses from the fiber is performed. In particular second harmonic imaging of corn starch is performed.

Imaging Prostate Cancer Microenvironment by Collagen Hybridization

DTIC Science & Technology

2013-10-01

There is an emerging concept of using non-cellular solid state compartment as a source for therapeutic targets and for selective imaging of micro ... using second harmonic generation and two-photon micros - copy. J. Biomed. Opt. 14, 044013. Bioconjugate Chemistry Communication dx.doi.org/10.1021...Chiu WC, Lai CC, Liou GG, Li HC, Chou MY: Production of multivalent protein binders using a self- trimerizing collagen-like peptide scaffold. FASEB J

Polarization-modulated second harmonic generation ellipsometric microscopy at video rate.

PubMed

DeWalt, Emma L; Sullivan, Shane Z; Schmitt, Paul D; Muir, Ryan D; Simpson, Garth J

2014-08-19

Fast 8 MHz polarization modulation coupled with analytical modeling, fast beam-scanning, and synchronous digitization (SD) have enabled simultaneous nonlinear optical Stokes ellipsometry (NOSE) and polarized laser transmittance imaging with image acquisition rates up to video rate. In contrast to polarimetry, in which the polarization state of the exiting beam is recorded, NOSE enables recovery of the complex-valued Jones tensor of the sample that describes all polarization-dependent observables of the measurement. Every video-rate scan produces a set of 30 images (10 for each detector with three detectors operating in parallel), each of which corresponds to a different polarization-dependent result. Linear fitting of this image set contracts it down to a set of five parameters for each detector in second harmonic generation (SHG) and three parameters for the transmittance of the incident beam. These parameters can in turn be used to recover the Jones tensor elements of the sample. Following validation of the approach using z-cut quartz, NOSE microscopy was performed for microcrystals of both naproxen and glucose isomerase. When weighted by the measurement time, NOSE microscopy was found to provide a substantial (>7 decades) improvement in the signal-to-noise ratio relative to our previous measurements based on the rotation of optical elements and a 3-fold improvement relative to previous single-point NOSE approaches.

Second harmonic detection in the electrochemical strain microscopy of Ag-ion conducting glass

DOE PAGES

Yang, Sangmo; Okatan, Mahmut Baris; Paranthaman, Mariappan Parans; ...

2014-11-14

The first and second harmonic electromechanical responses and their cross-correlation in Ag-ion conducting glass were investigated using band-excitation electrochemical strain microscopy (ESM). Consecutive ESM images with increasing magnitudes of the applied AC voltage allowed observation of not only reversible surface displacement but also irreversible silver nanoparticle formation above a certain threshold voltage. The second harmonic ESM response was anticorrelated with the first harmonic response in many local regions. Furthermore, the nucleation sites of silver nanoparticles were closely related to the anti-correlated regions, specifically, with low second harmonic and high first harmonic ESM responses. The possible origins of the second harmonicmore » ESM response are discussed.« less

Third harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Squier, Jeffrey A.; Muller, Michiel; Brakenhoff, G. J.; Wilson, Kent R.

1998-10-01

Third harmonic generation microscopy is used to make dynamical images of living systems for the first time. A 100 fs excitation pulse at 1.2 æm results in a 400 nm signal which is generated directly within the specimen. Chara plant rhizoids have been imaged, showing dynamic plant activity, and non-fading image characteristics even with continuous viewing, indicating prolonged viability under these THG-imaging conditions.

Complete spatial and temporal locking in phase-mismatched second-harmonic generation.

PubMed

Fazio, Eugenio; Pettazzi, Federico; Centini, Marco; Chauvet, Mathieu; Belardini, Alessandro; Alonzo, Massimo; Sibilia, Concita; Bertolotti, Mario; Scalora, Micheal

2009-03-02

We experimentally demonstrate simultaneous phase and group velocity locking of fundamental and generated second harmonic pulses in Lithium Niobate, under conditions of material phase mismatch. In phase-mismatched, pulsed second harmonic generation in addition to a reflected signal two forward-propagating pulses are also generated at the interface between a linear and a second order nonlinear material: the first pulse results from the solution of the homogeneous wave equation, and propagates at the group velocity expected from material dispersion; the second pulse is the solution of the inhomogeneous wave equation, is phase-locked and trapped by the pump pulse, and follows the pump trajectory. At normal incidence, the normal and phase locked pulses simply trail each other. At oblique incidence, the consequences can be quite dramatic. The homogeneous pulse refracts as predicted by material dispersion and Snell's law, yielding at least two spatially separate second harmonic spots at the medium's exit. We thus report the first experimental results showing that, at oblique incidence, fundamental and phase-locked second harmonic pulses travel with the same group velocity and follow the same trajectory. This is direct evidence that, at least up to first order, the effective dispersion of the phase-locked pulse is similar to the dispersion of the pump pulse.

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.

Second harmonic generation in a molecular magnetic chain

NASA Astrophysics Data System (ADS)

Cavigli, L.; Sessoli, R.; Gurioli, M.; Bogani, L.

2006-05-01

A setup for the determination of all the components of the second harmonic generation tensor in molecular materials is presented. It allows overcoming depletion problems, which one can expect to be common in molecular systems. A preliminary characterization of the nonlinear properties of the single chain magnet CoPhOMe is carried out. We observe a high second harmonic signal, comparable to that of urea, and show that the bulk contributions are dominant over the surface ones.

Effect of skew angle on second harmonic guided wave measurement in composite plates

NASA Astrophysics Data System (ADS)

Cho, Hwanjeong; Choi, Sungho; Lissenden, Cliff J.

2017-02-01

Waves propagating in anisotropic media are subject to skewing effects due to the media having directional wave speed dependence, which is characterized by slowness curves. Likewise, the generation of second harmonics is sensitive to micro-scale damage that is generally not detectable from linear features of ultrasonic waves. Here, the effect of skew angle on second harmonic guided wave measurement in a transversely isotropic lamina and a quasi-isotropic laminate are numerically studied. The strain energy density function for a nonlinear transversely isotropic material is formulated in terms of the Green-Lagrange strain invariants. The guided wave mode pairs for cumulative second harmonic generation in the plate are selected in accordance with the internal resonance criteria - i.e., phase matching and non-zero power flux. Moreover, the skew angle dispersion curves for the mode pairs are obtained from the semi-analytical finite element method using the derivative of the slowness curve. The skew angles of the primary and secondary wave modes are calculated and wave propagation simulations are carried out using COMSOL. Numerical simulations revealed that the effect of skew angle mismatch can be significant for second harmonic generation in anisotropic media. The importance of skew angle matching on cumulative second harmonic generation is emphasized and the accompanying issue of the selection of internally resonant mode pairs for both a unidirectional transversely isotropic lamina and a quasi-isotropic laminate is demonstrated.

Investigation of second harmonic generation and multispectral imaging as new contrast mechanisms in scanning laser optical tomography

NASA Astrophysics Data System (ADS)

Nolte, Lena; Antonopoulos, Georgios C.; Heisterkamp, Alexander; Ripken, Tammo; Meyer, Heiko

2018-02-01

Scanning laser optical tomography (SLOT) is a 3D imaging technique, based on the principle of computed tomography to visualize samples up to magnitude of several centimeters. Intrinsic contrast mechanisms as absorption, scattering and autofluorescence provide information about the 3D architecture and composition of the sample. Another valuable intrinsic contrast mechanism is second harmonic generation (SHG), which is generated in noncentrosymmetric materials and commonly used to image collagen in biological samples. The angular dependence of the SHG signal, however, produces artifacts in reconstructed optical tomography datasets (OPT, SLOT). Thus, successful use of this intrinsic contrast mechanism is impaired. We investigate these artifacts by simulation and experiment and propose an elimination procedure that enables successful reconstruction of SHG-SLOT data. Nevertheless, in many cases specific labeling of certain structures is necessary to make them visible. Using multiple dyes in one sample can lead to crosstalk between the different channels and reduce contrast of the images. Also autofluorescence of the sample itself can account for that. By using multispectral imaging in combination with spectral unmixing techniques, this loss can be compensated. Therefore either a spectrally resolved detection path, or spectrally resolved excitation is required. Therefore we integrated a white supercontinuum light source in our SLOT-setup that enables a spectral selection of the excitation beam and extended the detection path to a four channel setup. This enables the detection of three fluorescence channels and one absorption channel in parallel, and increases the contrast in the reconstructed 3D images significantly.

Nonlinear focusing of ultrasonic waves by an axisymmetric diffraction grating embedded in water

NASA Astrophysics Data System (ADS)

Jiménez, N.; Romero-García, V.; Picó, R.; Garcia-Raffi, L. M.; Staliunas, K.

2015-11-01

We report the nonlinear focusing of ultrasonic waves by an axisymmetric diffraction grating immersed in water. In the linear regime, the system presents high focal gain (32 dB), with a narrow beam-width and intense side lobes as it is common in focusing by Fresnel-like lenses. Activating the nonlinearity of the host medium by using high amplitude incident waves, the focusing properties of the lens dramatically change. Theoretical predictions show that the focal gain of the system extraordinary increases in the strongly nonlinear regime (Mach number of 6.1 × 10-4). Particularly, the harmonic generation is locally activated at the focal spot, and the second harmonic beam is characterized by strongly reduced side-lobes and an excellent beam profile as experiments show in agreement with theory. The results can motivate applications in medical therapy or second harmonic imaging.

Synchronous-digitization for Video Rate Polarization Modulated Beam Scanning Second Harmonic Generation Microscopy.

PubMed

Sullivan, Shane Z; DeWalt, Emma L; Schmitt, Paul D; Muir, Ryan M; Simpson, Garth J

2015-03-09

Fast beam-scanning non-linear optical microscopy, coupled with fast (8 MHz) polarization modulation and analytical modeling have enabled simultaneous nonlinear optical Stokes ellipsometry (NOSE) and linear Stokes ellipsometry imaging at video rate (15 Hz). NOSE enables recovery of the complex-valued Jones tensor that describes the polarization-dependent observables, in contrast to polarimetry, in which the polarization stated of the exciting beam is recorded. Each data acquisition consists of 30 images (10 for each detector, with three detectors operating in parallel), each of which corresponds to polarization-dependent results. Processing of this image set by linear fitting contracts down each set of 10 images to a set of 5 parameters for each detector in second harmonic generation (SHG) and three parameters for the transmittance of the fundamental laser beam. Using these parameters, it is possible to recover the Jones tensor elements of the sample at video rate. Video rate imaging is enabled by performing synchronous digitization (SD), in which a PCIe digital oscilloscope card is synchronized to the laser (the laser is the master clock.) Fast polarization modulation was achieved by modulating an electro-optic modulator synchronously with the laser and digitizer, with a simple sine-wave at 1/10th the period of the laser, producing a repeating pattern of 10 polarization states. This approach was validated using Z-cut quartz, and NOSE microscopy was performed for micro-crystals of naproxen.

Synchronous-digitization for video rate polarization modulated beam scanning second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Sullivan, Shane Z.; DeWalt, Emma L.; Schmitt, Paul D.; Muir, Ryan D.; Simpson, Garth J.

2015-03-01

Fast beam-scanning non-linear optical microscopy, coupled with fast (8 MHz) polarization modulation and analytical modeling have enabled simultaneous nonlinear optical Stokes ellipsometry (NOSE) and linear Stokes ellipsometry imaging at video rate (15 Hz). NOSE enables recovery of the complex-valued Jones tensor that describes the polarization-dependent observables, in contrast to polarimetry, in which the polarization stated of the exciting beam is recorded. Each data acquisition consists of 30 images (10 for each detector, with three detectors operating in parallel), each of which corresponds to polarization-dependent results. Processing of this image set by linear fitting contracts down each set of 10 images to a set of 5 parameters for each detector in second harmonic generation (SHG) and three parameters for the transmittance of the fundamental laser beam. Using these parameters, it is possible to recover the Jones tensor elements of the sample at video rate. Video rate imaging is enabled by performing synchronous digitization (SD), in which a PCIe digital oscilloscope card is synchronized to the laser (the laser is the master clock.) Fast polarization modulation was achieved by modulating an electro-optic modulator synchronously with the laser and digitizer, with a simple sine-wave at 1/10th the period of the laser, producing a repeating pattern of 10 polarization states. This approach was validated using Z-cut quartz, and NOSE microscopy was performed for micro-crystals of naproxen.

Nonresonant Local Fields Enhance Second-Harmonic Generation from Metal Nanoislands with Dielectric Cover

NASA Astrophysics Data System (ADS)

Chervinskii, Semyon; Koskinen, Kalle; Scherbak, Sergey; Kauranen, Martti; Lipovskii, Andrey

2018-03-01

We study second-harmonic generation from gold nanoislands covered with amorphous titanium oxide (TiO2 ) films. As the TiO2 thickness increases, the plasmon resonance of the nanoislands shifts away from the second-harmonic wavelength of 532 nm, diminishing the resonant enhancement of the process at this wavelength. Nevertheless, the second-harmonic signal is enhanced by up to a factor of 45 with increasing TiO2 thickness. This unexpected effect arises from the scaling of local fields at the fundamental wavelength of 1064 nm—which is at the far tail of the resonance—due to a change in the dielectric environment of the nanoislands.

Comparison of mechanisms involved in image enhancement of Tissue Harmonic Imaging

NASA Astrophysics Data System (ADS)

Cleveland, Robin O.; Jing, Yuan

2006-05-01

Processes that have been suggested as responsible for the improved imaging in Tissue Harmonic Imaging (THI) include: 1) reduced sensitivity to reverberation, 2) reduced sensitivity to aberration, and 3) reduction in the amplitude of diffraction side lobes. A three-dimensional model of the forward propagation of nonlinear sound beams in media with arbitrary spatial properties (a generalized KZK equation) was developed and solved using a time-domain code. The numerical simulations were validated through experiments with tissue mimicking phantoms. The impact of aberration from tissue-like media was determined through simulations using three-dimensional maps of tissue properties derived from datasets available through the Visible Female Project. The experiments and simulations demonstrated that second harmonic imaging suffers less clutter from reverberation and side-lobes but is not immune to aberration effects. The results indicate that side lobe suppression is the most significant reason for the improvement of second harmonic imaging.

Character of skin on photo-thermal response and its regeneration process using second-harmonic generation microscopy.

PubMed

Wu, Shu-lian; Li, Hui; Zhang, Xiao-man; Chen, Wei R; Wang, Yun-Xia

2014-01-01

Quantitative characterization of skin collagen on photo-thermal response and its regeneration process is an important but difficult task. In this study, morphology and spectrum characteristics of collagen during photo-thermal response and its light-induced remodeling process were obtained by second-harmonic generation microscope in vivo. The texture feature of collagen orientation index and fractal dimension was extracted by image processing. The aim of this study is to detect the information hidden in skin texture during the process of photo-thermal response and its regeneration. The quantitative relations between injured collagen and texture feature were established for further analysis of the injured characteristics. Our results show that it is feasible to determine the main impacts of phototherapy on the skin. It is important to understand the process of collagen remodeling after photo-thermal injuries from texture feature.

Two-harmonic complex spectral-domain optical coherence tomography using achromatic sinusoidal phase modulation

NASA Astrophysics Data System (ADS)

Lu, Sheng-Hua; Huang, Siang-Ru; Chou, Che-Chung

2018-03-01

We resolve the complex conjugate ambiguity in spectral-domain optical coherence tomography (SD-OCT) by using achromatic two-harmonic method. Unlike previous researches, the optical phase of the fiber interferometer is modulated by an achromatic phase shifter based on an optical delay line. The achromatic phase modulation leads to a wavelength-independent scaling coefficient for the two harmonics. Dividing the mean absolute value of the first harmonic by that of the second harmonic in a B-scan interferogram directly gives the scaling coefficient. It greatly simplifies the determination of the magnitude ratio between the two harmonics without the need of third harmonic and cumbersome iterative calculations. The inverse fast Fourier transform of the complex-valued interferogram constructed with the scaling coefficient, first and second harmonics yields a full-range OCT image. Experimental results confirm the effectiveness of the proposed achromatic two-harmonic technique for suppressing the mirror artifacts in SD-OCT images.

Second-harmonic generation in shear wave beams with different polarizations

NASA Astrophysics Data System (ADS)

Spratt, Kyle S.; Ilinskii, Yurii A.; Zabolotskaya, Evgenia A.; Hamilton, Mark F.

2015-10-01

A coupled pair of nonlinear parabolic equations was derived by Zabolotskaya [1] that model the transverse components of the particle motion in a collimated shear wave beam propagating in an isotropic elastic solid. Like the KZK equation, the parabolic equation for shear wave beams accounts consistently for the leading order effects of diffraction, viscosity and nonlinearity. The nonlinearity includes a cubic nonlinear term that is equivalent to that present in plane shear waves, as well as a quadratic nonlinear term that is unique to diffracting beams. The work by Wochner et al. [2] considered shear wave beams with translational polarizations (linear, circular and elliptical), wherein second-order nonlinear effects vanish and the leading order nonlinear effect is third-harmonic generation by the cubic nonlinearity. The purpose of the current work is to investigate the quadratic nonlinear term present in the parabolic equation for shear wave beams by considering second-harmonic generation in Gaussian beams as a second-order nonlinear effect using standard perturbation theory. In order for second-order nonlinear effects to be present, a broader class of source polarizations must be considered that includes not only the familiar translational polarizations, but also polarizations accounting for stretching, shearing and rotation of the source plane. It is found that the polarization of the second harmonic generated by the quadratic nonlinearity is not necessarily the same as the polarization of the source-frequency beam, and we are able to derive a general analytic solution for second-harmonic generation from a Gaussian source condition that gives explicitly the relationship between the polarization of the source-frequency beam and the polarization of the second harmonic.

Precise, motion-free polarization control in Second Harmonic Generation microscopy using a liquid crystal modulator in the infinity space.

PubMed

Lien, Chi-Hsiang; Tilbury, Karissa; Chen, Shean-Jen; Campagnola, Paul J

2013-01-01

Second Harmonic Generation (SHG) microscopy coupled with polarization analysis has great potential for use in tissue characterization, as molecular and supramolecular structural details can be extracted. Such measurements are difficult to perform quickly and accurately. Here we present a new method that uses a liquid crystal modulator (LCM) located in the infinity space of a SHG laser scanning microscope that allows the generation of any desired linear or circular polarization state. As the device contains no moving parts, polarization can be rotated accurately and faster than by manual or motorized control. The performance in terms of polarization purity was validated using Stokes vector polarimetry, and found to have minimal residual polarization ellipticity. SHG polarization imaging characteristics were validated against well-characterized specimens having cylindrical and/or linear symmetries. The LCM has a small footprint and can be implemented easily in any standard microscope and is cost effective relative to other technologies.

Precise, motion-free polarization control in Second Harmonic Generation microscopy using a liquid crystal modulator in the infinity space

PubMed Central

Lien, Chi-Hsiang; Tilbury, Karissa; Chen, Shean-Jen; Campagnola, Paul J.

2013-01-01

Second Harmonic Generation (SHG) microscopy coupled with polarization analysis has great potential for use in tissue characterization, as molecular and supramolecular structural details can be extracted. Such measurements are difficult to perform quickly and accurately. Here we present a new method that uses a liquid crystal modulator (LCM) located in the infinity space of a SHG laser scanning microscope that allows the generation of any desired linear or circular polarization state. As the device contains no moving parts, polarization can be rotated accurately and faster than by manual or motorized control. The performance in terms of polarization purity was validated using Stokes vector polarimetry, and found to have minimal residual polarization ellipticity. SHG polarization imaging characteristics were validated against well-characterized specimens having cylindrical and/or linear symmetries. The LCM has a small footprint and can be implemented easily in any standard microscope and is cost effective relative to other technologies. PMID:24156059

Strong second harmonic generation in two-dimensional ferroelectric IV-monochalcogenides

NASA Astrophysics Data System (ADS)

Panday, Suman Raj; Fregoso, Benjamin M.

2017-11-01

The two-dimensional ferroelectrics GeS, GeSe, SnS and SnSe are expected to have large spontaneous in-plane electric polarization and enhanced shift-current response. Using density functional methods, we show that these materials also exhibit the largest effective second harmonic generation reported so far. It can reach magnitudes up to 10~nm~V-1 which is about an order of magnitude larger than that of prototypical GaAs. To rationalize this result we model the optical response with a simple one-dimensional two-band model along the spontaneous polarization direction. Within this model the second-harmonic generation tensor is proportional to the shift-current response tensor. The large shift current and second harmonic responses of GeS, GeSe, SnS and SnSe make them promising non-linear materials for optoelectronic applications.

Large enhancement of interface second-harmonic generation near the zero-n(-) gap of a negative-index Bragg grating.

PubMed

D'Aguanno, Giuseppe; Mattiucci, Nadia; Bloemer, Mark J; Scalora, Michael

2006-03-01

We predict a large enhancement of interface second-harmonic generation near the zero-n(-) gap of a Bragg grating made of alternating layers of negative- and positive-index materials. Field localization and coherent oscillations of the nonlinear dipoles located at the structure's interfaces conspire to yield conversion efficiencies at least an order of magnitude greater than those achievable in the same length of nonlinear, phase-matched bulk material. These findings thus point to a new class of second-harmonic-generation devices made of standard centrosymmetric materials.

Second harmonic generation in photonic crystal cavities in (111)-oriented GaAs

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

Buckley, Sonia, E-mail: bucklesm@stanford.edu; Radulaski, Marina; Vučković, Jelena

2013-11-18

We demonstrate second harmonic generation at telecommunications wavelengths in photonic crystal cavities in (111)-oriented GaAs. We fabricate 30 photonic crystal structures in both (111)- and (100)-oriented GaAs and observe an increase in generated second harmonic power in the (111) orientation, with the mean power increased by a factor of 3, although there is a large scatter in the measured values. We discuss possible reasons for this increase, in particular, the reduced two photon absorption for transverse electric modes in (111) orientation, as well as a potential increase due to improved mode overlap.

Exploring infrared neural stimulation with multimodal nonlinear imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Adams, Wilson R.; Mahadevan-Jansen, Anita

2017-02-01

Infrared neural stimulation (INS) provides optical control of neural excitability using near to mid-infrared (mid-IR) light, which allows for spatially selective, artifact-free excitation without the introduction of exogenous agents or genetic modification. Although neural excitability is mediated by a transient temperature increase due to water absorption of IR energy, the molecular nature of IR excitability in neural tissue remains unknown. Current research suggests that transient changes in local tissue temperature give rise to a myriad of cellular responses that have been individually attributed to IR mediated excitability. To further elucidate the underlying biophysical mechanisms, we have begun work towards employing a novel multimodal nonlinear imaging platform to probe the molecular underpinnings of INS. Our imaging system performs coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG) and thermal imaging into a single platform that allows for unprecedented co-registration of thermal and biochemical information in real-time. Here, we present our work leveraging CARS and SRS in acute thalamocortical brain slice preparations. We observe the evolution of lipid and protein-specific Raman bands during INS and electrically evoked activity in real-time. Combined with two-photon fluorescence and second harmonic generation, we offer insight to cellular metabolism and membrane dynamics during INS. Thermal imaging allows for the coregistration of acquired biochemical information with temperature information. Our work previews the versatility and capabilities of coherent Raman imaging combined with multiphoton imaging to observe biophysical phenomena for neuroscience applications.

Cumulative phase delay imaging for contrast-enhanced ultrasound tomography

NASA Astrophysics Data System (ADS)

Demi, Libertario; van Sloun, Ruud J. G.; Wijkstra, Hessel; Mischi, Massimo

2015-11-01

Standard dynamic-contrast enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrast-agent (UCA) concentration based on the amplitude of the nonlinear (harmonic) components generated during ultrasound (US) propagation through UCAs. However, harmonic components generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio reduction, and resulting in possible misclassification of tissue and misinterpretation of UCA concentration. Furthermore, no contrast-specific modality exists for DCE-US tomography; in particular speed-of-sound changes due to UCAs are well within those caused by different tissue types. Recently, a new marker for UCAs has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, tomographic US images based on CPD are for the first time presented and compared to speed-of-sound US tomography. Results show the applicability of this marker for contrast specific US imaging, with cumulative phase delay imaging (CPDI) showing superior capabilities in detecting and localizing UCA, as compared to speed-of-sound US tomography. Cavities (filled with UCA) which were down to 1 mm in diameter were clearly detectable. Moreover, CPDI is free of the above mentioned nonlinear artifacts. These results open important possibilities to DCE-US tomography, with potential applications to breast imaging for cancer localization.

Cumulative phase delay imaging for contrast-enhanced ultrasound tomography.

PubMed

Demi, Libertario; van Sloun, Ruud J G; Wijkstra, Hessel; Mischi, Massimo

2015-11-07

Standard dynamic-contrast enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrast-agent (UCA) concentration based on the amplitude of the nonlinear (harmonic) components generated during ultrasound (US) propagation through UCAs. However, harmonic components generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio reduction, and resulting in possible misclassification of tissue and misinterpretation of UCA concentration. Furthermore, no contrast-specific modality exists for DCE-US tomography; in particular speed-of-sound changes due to UCAs are well within those caused by different tissue types. Recently, a new marker for UCAs has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, tomographic US images based on CPD are for the first time presented and compared to speed-of-sound US tomography. Results show the applicability of this marker for contrast specific US imaging, with cumulative phase delay imaging (CPDI) showing superior capabilities in detecting and localizing UCA, as compared to speed-of-sound US tomography. Cavities (filled with UCA) which were down to 1 mm in diameter were clearly detectable. Moreover, CPDI is free of the above mentioned nonlinear artifacts. These results open important possibilities to DCE-US tomography, with potential applications to breast imaging for cancer localization.

Determination of collagen fibril size via absolute measurements of second-harmonic generation signals

NASA Astrophysics Data System (ADS)

Bancelin, Stéphane; Aimé, Carole; Gusachenko, Ivan; Kowalczuk, Laura; Latour, Gaël; Coradin, Thibaud; Schanne-Klein, Marie-Claire

2014-09-01

The quantification of collagen fibril size is a major issue for the investigation of pathological disorders associated with structural defects of the extracellular matrix. Second-harmonic generation microscopy is a powerful technique to characterize the macromolecular organization of collagen in unstained biological tissues. Nevertheless, due to the complex coherent building of this nonlinear optical signal, it has never been used to measure fibril diameter so far. Here we report absolute measurements of second-harmonic signals from isolated fibrils down to 30 nm diameter, via implementation of correlative second-harmonic-electron microscopy. Moreover, using analytical and numerical calculations, we demonstrate that the high sensitivity of this technique originates from the parallel alignment of collagen triple helices within fibrils and the subsequent constructive interferences of second-harmonic radiations. Finally, we use these absolute measurements as a calibration for ex vivo quantification of fibril diameter in the Descemet’s membrane of a diabetic rat cornea.

Second harmonic generation in gallium phosphide photonic crystal nanocavities with ultralow continuous wave pump power.

PubMed

Rivoire, Kelley; Lin, Ziliang; Hatami, Fariba; Masselink, W Ted; Vucković, Jelena

2009-12-07

We demonstrate second harmonic generation in photonic crystal nanocavities fabricated in the semiconductor gallium phosphide. We observe second harmonic radiation at 750 nm with input powers of only nanowatts coupled to the cavity and conversion effciency P(out)/P(2)(in,coupled)=430%/W. The large electronic band gap of GaP minimizes absorption loss, allowing effcient conversion. Our results are promising for integrated, low-power light sources and on-chip reduction of input power in other nonlinear processes.

Phase-matched second- and third-harmonic generation in plasmas with density ripple

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

Dahiya, Deepak; Sajal, Vivek; Sharma, A. K.

The generation of second and third harmonics by the interaction of an ultrashort laser pulse with underdense plasma having a density ripple is studied at intensities I{lambda}{sup 2}=10{sup 16}-10{sup 19} W cm{sup -2} {mu}m{sup 2} using fully relativistic two-dimensional particle-in-cell simulations with high spectral resolution. A theoretical model is developed for second- and third-harmonic conversion efficiencies. When the laser is plane polarized in the simulation plane even and odd harmonics are excited in the same polarization as the laser polarization. The highest efficiency of generation of a specific harmonic occurs when the ripple wave vector value k{sub q} satisfies phase-matchingmore » conditions. The efficiency of phase-matched harmonic generation is an order of magnitude higher than the one without phase matching. The efficiency increases rapidly in weak and moderate relativistic regime and tends to saturate in strong relativistic regime. At moderately relativistic intensities and low plasma densities, the simulation and recent experimental results are fairly reproduced by an analytical theory.« less

Nonlinear viscous higher harmonics generation due to incident and reflecting internal wave beam collision

NASA Astrophysics Data System (ADS)

Aksu, Anil A.

2017-09-01

In this paper, we have considered the non-linear effects arising due to the collision of incident and reflected internal wave beams. It has already been shown analytically [Tabaei et al., "Nonlinear effects in reflecting and colliding internal wave beams," J. Fluid Mech. 526, 217-243 (2005)] and numerically [Rodenborn et al., "Harmonic generation by reflecting internal waves," Phys. Fluids 23, 026601 (2011)] that the internal wave beam collision generates the higher harmonics and mean flow in a linear stratification. In this paper, similar to previous analytical work, small amplitude wave theory is employed; however, it is formulated from energetics perspective which allows considering internal wave beams as the product of slowly varying amplitude and fast complex exponential. As a result, the mean energy propagation equation for the second harmonic wave is obtained. Finally, a similar dependence on the angle of incidence is obtained for the non-linear energy transfer to the second harmonic with previous analyses. A possible physical mechanism for this angle dependence on the second harmonic generation is also discussed here. In addition to previous studies, the viscous effects are also included in the mean energy propagation equation for the incident, the reflecting, and the second harmonic waves. Moreover, even though the mean flow obtained here is only confined to the interaction region, it is also affected by viscosity via the decay in the incident and the reflecting internal wave beams. Furthermore, a framework for the non-linear harmonic generation in non-linear stratification is also proposed here.

Image storage in coumarin-based copolymer thin films by photoinduced dimerization.

PubMed

Gindre, Denis; Iliopoulos, Konstantinos; Krupka, Oksana; Champigny, Emilie; Morille, Yohann; Sallé, Marc

2013-11-15

We report a technique to encode grayscale digital images in thin films composed of copolymers containing coumarins. A nonlinear microscopy setup was implemented and two nonlinear optical processes were used to store and read information. A third-order process (two-photon absorption) was used to photoinduce a controlled dimer-to-monomer ratio within a defined tiny volume in the material, which corresponds to each recorded bit of data. Moreover, a second-order process (second-harmonic generation) was used to read the stored information, which has been found to be highly dependent upon the monomer-to-dimer ratio.

Optical bistability and second-harmonic generation in thin film coupled cavity photonic crystal structures

NASA Astrophysics Data System (ADS)

Diao, Liyong

This thesis deals with design, fabrication and modeling of bistable and multi-stable switching dynamics and second-harmonic generation in two groups of thin film coupled cavity photonic crystal structures. The first component studies optical bistability and multistability in such structures. Optical bistability and multistability are modelled by a nonlinear transfer matrix method. The second component is focused on the modelling and experimental measurement of second-harmonic generation in such structures. It is found that coupled cavity structures can reduce the threshold and index change for bistable operation, but single cavity structures can do the same. However, there is a clear advantage in using coupled cavity structures for multistability in that the threshold for multistability can be reduced. Second-harmonic generation is enhanced by field localization due to the resonant effect at the fundamental wavelength in single and coupled cavity structures by simulated and measured results. The work in this thesis makes three significant contributions. First, in the successful fabrication of thin film coupled cavity structures, the simulated linear transmissions of such structures match those of the fabricated structures almost exactly. Second, the newly defined figure of merit at the maximum transmission point on the bistable curve can be used to compare the material damage tolerance to any other Kerr effect nonlinear gate. Third, the simulated second-harmonic generation agrees excellently with experimental results. More generally optical thin film fabrication has commercial applications in many industry sections, such as electronics, opto-electronics, optical coating, solar cell and MEMS.

Quasi-phase-matched second-harmonic generation of 532 nm radiation in 25 degrees -rotated, x-cut, near-stoichiometric, lithium tantalate fabricated by vapor transport equilibration.

PubMed

Hum, D S; Route, R K; Fejer, M M

2007-04-15

Quasi-phase-matched second-harmonic generation of 532 nm radiation in 25 degrees -rotated, x-cut, near-stoichiometric lithium tantalate has been performed. Using a face-normal topology for frequency conversion applications allows scalable surface area to avoid surface and volume damage in high-power interactions. First-order, quasi-phase-matched second-harmonic generation was achieved using near-stoichiometric lithium tantalate fabricated by vapor transport equilibration. These crystals supported 1 J of 1064 nm radiation and generated 21 mJ of 532 nm radiation from a 7 ns, Q-switched Nd:YAG laser within a factor of 4.2 of expectation.

Qualitative and quantitative effects of harmonic echocardiographic imaging on endocardial edge definition and side-lobe artifacts

NASA Technical Reports Server (NTRS)

Rubin, D. N.; Yazbek, N.; Garcia, M. J.; Stewart, W. J.; Thomas, J. D.

2000-01-01

Harmonic imaging is a new ultrasonographic technique that is designed to improve image quality by exploiting the spontaneous generation of higher frequencies as ultrasound propagates through tissue. We studied 51 difficult-to-image patients with blinded side-by-side cineloop evaluation of endocardial border definition by harmonic versus fundamental imaging. In addition, quantitative intensities from cavity versus wall were compared for harmonic versus fundamental imaging. Harmonic imaging improved left ventricular endocardial border delineation over fundamental imaging (superior: harmonic = 71.1%, fundamental = 18.7%; similar: 10.2%; P <.001). Quantitative analysis of 100 wall/cavity combinations demonstrated brighter wall segments and more strikingly darker cavities during harmonic imaging (cavity intensity on a 0 to 255 scale: fundamental = 15.6 +/- 8.6; harmonic = 6.0 +/- 5.3; P <.0001), which led to enhanced contrast between the wall and cavity (1.89 versus 1.19, P <.0001). Harmonic imaging reduces side-lobe artifacts, resulting in a darker cavity and brighter walls, thereby improving image contrast and endocardial delineation.

Texture analysis applied to second harmonic generation image data for disease classification and development of a multi-view second harmonic generation imaging platform

NASA Astrophysics Data System (ADS)

Wen, Lianggong

Many diseases, e.g. ovarian cancer, breast cancer and pulmonary fibrosis, are commonly associated with drastic alterations in surrounding connective tissue, and changes in the extracellular matrix (ECM) are associated with the vast majority of cellular processes in disease progression and carcinogenesis: cell differentiation, proliferation, biosynthetic ability, polarity, and motility. We use second harmonic generation (SHG) microscopy for imaging the ECM because it is a non-invasive, non-linear laser scanning technique with high sensitivity and specificity for visualizing fibrillar collagen. In this thesis, we are interested in developing imaging techniques to understand how the ECM, especially the collagen architecture, is remodeled in diseases. To quantitate remodeling, we implement a 3D texture analysis to delineate the collagen fibrillar morphology observed in SHG microscopy images of human normal and high grade malignant ovarian tissues. In the learning stage, a dictionary of "textons"---frequently occurring texture features that are identified by measuring the image response to a filter bank of various shapes, sizes, and orientations---is created. By calculating a representative model based on the texton distribution for each tissue type using a training set of respective mages, we then perform classification between normal and high grade malignant ovarian tissues classification based on the area under receiver operating characteristic curves (true positives versus false positives). The local analysis algorithm is a more general method to probe rapidly changing fibrillar morphologies than global analyses such as FFT. It is also more versatile than other texture approaches as the filter bank can be highly tailored to specific applications (e.g., different disease states) by creating customized libraries based on common image features. Further, we describe the development of a multi-view 3D SHG imaging platform. Unlike fluorescence microscopy, SHG excites intrinsic characteristics of collagen, bypassing the need for additional primary and secondary imaging labels. However, single view image collection from endogenous SHG contrast of collagen molecules is not "a true 3D technique", because collagen fibers oriented along the plane of the lasers used to excite them are invisible to the excitation The loss of information means that researchers cannot resolve the 3D structure of the ECM using this technique. We are developing a new, multi-view approach that involves rotation of agarose embedded sample in FEP tubing, so that the excitation beam path travels to from multiple angles, to reveal new insight in understanding the 3D collagen structure and its role in normal and diseased tissue.

Measurement of absorption spectrum of deuterium oxide (D{sub 2}O) and its application to signal enhancement in multiphoton microscopy at the 1700-nm window

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

Wang, Yuxin; Wen, Wenhui; Wang, Kai

2016-01-11

1700-nm window has been demonstrated to be a promising excitation window for deep-tissue multiphoton microscopy (MPM). Long working-distance water immersion objective lenses are typically used for deep-tissue imaging. However, absorption due to immersion water at 1700 nm is still high and leads to dramatic decrease in signals. In this paper, we demonstrate measurement of absorption spectrum of deuterium oxide (D{sub 2}O) from 1200 nm to 2600 nm, covering the three low water-absorption windows potentially applicable for deep-tissue imaging (1300 nm, 1700 nm, and 2200 nm). We apply this measured result to signal enhancement in MPM at the 1700-nm window. Compared with water immersion, D{sub 2}O immersionmore » enhances signal levels in second-harmonic generation imaging, 3-photon fluorescence imaging, and third-harmonic generation imaging by 8.1, 24.8, and 24.7 times with 1662-nm excitation, in good agreement with theoretical calculation based on our absorption measurement. This suggests D{sub 2}O a promising immersion medium for deep-tissue imaging.« less

Large enhancement of second harmonic generation from transition-metal dichalcogenide monolayer on grating near bound states in the continuum.

PubMed

Wang, Tiecheng; Zhang, Shihao

2018-01-08

Second harmonic generation from the two-layer structure where a transition-metal dichalcogenide monolayer is put on a one-dimensional grating has been studied. This grating supports bound states in the continuum which have no leakage lying within the continuum of radiation modes, we can enhance the second harmonic generation from the transition-metal dichalcogenide monolayer by more than four orders of magnitude based on the critical field enhancement near the bound states in the continuum. In order to complete this calculation, the scattering matrix theory has been extended to include the nonlinear effect and the scattering matrix of a two-dimensional material including nonlinear terms; furthermore, two methods to observe the bound states in the continuum are considered, where one is tuning the thickness of the grating and the other is changing the incident angle of the electromagnetic wave. We have also discussed various modulation of the second harmonic generation enhancement by adjusting the azimuthal angle of the transition-metal dichalcogenide monolayer.

Direct observation of trapped charges under field-plate in p-GaN gate AlGaN/GaN high electron mobility transistors by electric field-induced optical second-harmonic generation

NASA Astrophysics Data System (ADS)

Katsuno, Takashi; Manaka, Takaaki; Soejima, Narumasa; Iwamoto, Mitsumasa

2017-02-01

Trapped charges underneath the field-plate (FP) in a p-gallium nitride (GaN) gate AlGaN/ GaN high electron mobility transistor device were visualized by using electric field-induced optical second-harmonic generation imaging. Second-harmonic (SH) signals in the off-state of the device with FP indicated that the electric field decreased at the p-GaN gate edge and concentrated at the FP edge. Nevertheless, SH signals originating from trapped charges were slightly observed at the p-GaN gate edge and were not observed at the FP edge in the on-state. Compared with the device without FP, reduction of trapped charges at the p-GaN gate edge of the device with FP is attributed to attenuation of the electric field with the aid of the FP. Negligible trapped charges at the FP edge is owing to lower trap density of the SiO2/AlGaN interface at the FP edge compared with that of the SiO2/p-GaN sidewall interface at the p-GaN gate edge and attenuated electric field by the thickness of the SiO2 passivation layer on the AlGaN surface.

Dual CARS and SHG image acquisition scheme that combines single central fiber and multimode fiber bundle to collect and differentiate backward and forward generated photons

PubMed Central

Weng, Sheng; Chen, Xu; Xu, Xiaoyun; Wong, Kelvin K.; Wong, Stephen T. C.

2016-01-01

In coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) imaging, backward and forward generated photons exhibit different image patterns and thus capture salient intrinsic information of tissues from different perspectives. However, they are often mixed in collection using traditional image acquisition methods and thus are hard to interpret. We developed a multimodal scheme using a single central fiber and multimode fiber bundle to simultaneously collect and differentiate images formed by these two types of photons and evaluated the scheme in an endomicroscopy prototype. The ratio of these photons collected was calculated for the characterization of tissue regions with strong or weak epi-photon generation while different image patterns of these photons at different tissue depths were revealed. This scheme provides a new approach to extract and integrate information captured by backward and forward generated photons in dual CARS/SHG imaging synergistically for biomedical applications. PMID:27375938

Functional imaging of skeletal muscle fiber in different physiological states by second harmonic generation

NASA Astrophysics Data System (ADS)

Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Tesi, C.; Piroddi, N.; Poggesi, C.; Castiglioni, C.; Milani, A.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

2007-07-01

The intrinsically ordered arrays of proteins in skeletal muscle allows imaging of this tissue by Second Harmonic Generation (SHG). Biochemical and colocalization studies have gathered an increasing wealth of clues for the attribution of the molecular origin of the muscle SHG signal to the motor protein myosin. Thus, SHG represents a potentially very powerful tool in the investigation of structural dynamics occurring in muscle during active production of force. A full characterization of the polarization-dependence of the SHG signal represents a very selective information on the orientation of the emitting proteins and their dynamics during contraction, provided that different physiological states of muscle (relaxed, rigor and active) exhibit distinct patterns of SHG polarization dependence. Here polarization data are obtained from single frog muscle fibers at rest and during isometric contraction and interpreted, by means of a model, in terms of an average orientation of the SHG emitters which are structured with a cylindrical symmetry about the fiber axis. Optimizing the setup for accurate polarization measurements with SHG, we developed a line scan imaging method allowing measurement of SHG polarization curves in different physiological states. We demonstrate that muscle fiber displays a measurable variation of the orientation of SHG emitters with the transition from rest to isometric contraction.

Second harmonic generation microscopy differentiates collagen type I and type III in COPD

NASA Astrophysics Data System (ADS)

Suzuki, Masaru; Kayra, Damian; Elliott, W. Mark; Hogg, James C.; Abraham, Thomas

2012-03-01

The structural remodeling of extracellular matrix proteins in peripheral lung region is an important feature in chronic obstructive pulmonary disease (COPD). Multiphoton microscopy is capable of inducing specific second harmonic generation (SHG) signal from non-centrosymmetric structural proteins such as fibrillar collagens. In this study, SHG microscopy was used to examine structural remodeling of the fibrillar collagens in human lungs undergoing emphysematous destruction (n=2). The SHG signals originating from these diseased lung thin sections from base to apex (n=16) were captured simultaneously in both forward and backward directions. We found that the SHG images detected in the forward direction showed well-developed and well-structured thick collagen fibers while the SHG images detected in the backward direction showed striking different morphological features which included the diffused pattern of forward detected structures plus other forms of collagen structures. Comparison of these images with the wellestablished immunohistochemical staining indicated that the structures detected in the forward direction are primarily the thick collagen type I fibers and the structures identified in the backward direction are diffusive structures of forward detected collagen type I plus collagen type III. In conclusion, we here demonstrate the feasibility of SHG microscopy in differentiating fibrillar collagen subtypes and understanding their remodeling in diseased lung tissues.

In situ quantitative evaluation of osteoblastic collagen synthesis under cyclic strain by using second-harmonic-generation microscope

NASA Astrophysics Data System (ADS)

Matsubara, Oki; Hase, Eiji; Minamikawa, Takeo; Yasui, Takeshi; Sato, Katsuya

2016-03-01

Osteoblast-produced collagen matrix in bone is influenced by the mechanical stimulus from their surroundings. However, it has been still unclear how mechanical stimulus affects collagen production by osteoblasts. Therefore, it is strongly required to investigate the characteristics of osteoblastic bone regenerative tissue engineering. Recently, second-harmonic-generation (SHG) microscope has attracted attention for in situ visualization of collagen fiber because of less invasiveness, unstaining and no fixation, as well as high spatial resolution and 3D imaging. Using SHG microscopy, one can track the temporal dynamics of collagen fiber during the cultured period of the sample. We applied cyclic stretch strain to osteoblasts (MC3T3-E1) by using originally developed cell stretching device. The stimulation time was set to 5min or 3hours with same strain 5% and same frequency 0.5Hz. Cells were seeded onto the PDMS (polydimethylsiloxane) rubber chamber at a density of 50,000 cells/cm2 and cultured in α-MEM with 10% FBS, 1% P/S, 1% Ascorbic acid, 0.2% hydrocortisone and 2% β-Glycerophosphate. SHG imaging was carried out every 7 days. As a result, we confirmed from SHG image that the collagen production was enhanced by the cyclic stretch strain, stretch stimulation time and stretch application term.

Multiphoton spectroscopy of human skin in vivo

NASA Astrophysics Data System (ADS)

Breunig, Hans G.; Weinigel, Martin; König, Karsten

2012-03-01

In vivo multiphoton-intensity images and emission spectra of human skin are reported. Optical sections from different depths of the epidermis and dermis have been measured with near-infrared laser-pulse excitation. While the intensity images reveal information on the morphology, the spectra show emission characteristics of main endogenous skin fluorophores like keratin, NAD(P)H, melanin, elastin and collagen as well as of second harmonic generation induced by the excitation-light interaction with the dermal collagen network.

Determination of the spectral dependence of reduced scattering and quantitative second-harmonic generation imaging for detection of fibrillary changes in ovarian cancer

NASA Astrophysics Data System (ADS)

Campbell, Kirby R.; Tilbury, Karissa B.; Campagnola, Paul J.

2015-03-01

Here, we examine ovarian cancer extracellular matrix (ECM) modification by measuring the wavelength dependence of optical scattering measurements and quantitative second-harmonic generation (SHG) imaging metrics in the range of 800-1100 nm in order to determine fibrillary changes in ex vivo normal ovary, type I, and type II ovarian cancer. Mass fractals of the collagen fiber structure is analyzed based on a power law correlation function using spectral dependence measurements of the reduced scattering coefficient μs' where the mass fractal dimension is related to the power. Values of μs' are measured using independent methods of determining the values of μs and g by on-axis attenuation measurements using the Beer-Lambert Law and by fitting the angular distribution of scattering to the Henyey-Greenstein phase function, respectively. Quantitativespectral SHG imaging on the same tissues determines FSHG/BSHG creation ratios related to size and harmonophore distributions. Both techniques probe fibril packing order, but the optical scattering probes structures of sizes from about 50-2000 nm where SHG imaging - although only able to resolve individual fibers - builds contrast from the assembly of fibrils. Our findings suggest that type I ovarian tumor structure has the most ordered collagen fibers followed by normal ovary then type II tumors showing the least order.

Ultrashort pulse chirp measurement via transverse second-harmonic generation in strontium barium niobate crystal

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

Trull, J.; Wang, B.; Parra, A.

2015-06-01

Pulse compression in dispersive strontium barium niobate crystal with a random size and distribution of the anti-parallel orientated nonlinear domains is observed via transverse second harmonic generation. The dependence of the transverse width of the second harmonic trace along the propagation direction allows for the determination of the initial chirp and duration of pulses in the femtosecond regime. This technique permits a real-time analysis of the pulse evolution and facilitates fast in-situ correction of pulse chirp acquired in the propagation through an optical system.

Real-time and sub-wavelength ultrafast coherent diffraction imaging in the extreme ultraviolet.

PubMed

Zürch, M; Rothhardt, J; Hädrich, S; Demmler, S; Krebs, M; Limpert, J; Tünnermann, A; Guggenmos, A; Kleineberg, U; Spielmann, C

2014-12-08

Coherent Diffraction Imaging is a technique to study matter with nanometer-scale spatial resolution based on coherent illumination of the sample with hard X-ray, soft X-ray or extreme ultraviolet light delivered from synchrotrons or more recently X-ray Free-Electron Lasers. This robust technique simultaneously allows quantitative amplitude and phase contrast imaging. Laser-driven high harmonic generation XUV-sources allow table-top realizations. However, the low conversion efficiency of lab-based sources imposes either a large scale laser system or long exposure times, preventing many applications. Here we present a lensless imaging experiment combining a high numerical aperture (NA = 0.8) setup with a high average power fibre laser driven high harmonic source. The high flux and narrow-band harmonic line at 33.2 nm enables either sub-wavelength spatial resolution close to the Abbe limit (Δr = 0.8λ) for long exposure time, or sub-70 nm imaging in less than one second. The unprecedented high spatial resolution, compactness of the setup together with the real-time capability paves the way for a plethora of applications in fundamental and life sciences.

Harmonic generation and parametric decay in the ion cyclotron frequency range

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

Skiff, F.N.; Wong, K.L.; Ono, M.

1984-06-01

Harmonic generation and parametric decay are examined in a toroidal ACT-I plasma using electrostatic plate antennas. The harmonic generation, which is consistent with sheath rectification, is sufficiently strong that the nonlinearly generated harmonic modes themselves decay parametrically. Resonant and nonresonant parametric decay of the second harmonic are observed and compared with uniform pump theory. Resonant decay of lower hybrid waves into lower hybrid waves and slow ion cyclotron waves is seen for the first time. Surprisingly, the decay processes are nonlinearly saturated, indicating absolute instability.

Quasi-phase-matching and second-harmonic generation enhancement in a semiconductor microresonator array using slow-light effects

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

Dumeige, Yannick

We theoretically analyze the second-harmonic generation process in a sequence of unidirectionnaly coupled doubly resonant whispering gallery mode semiconductor resonators. By using a convenient design, it is possible to coherently sum the second-harmonic fields generated inside each resonator. We show that resonator coupling allows the bandwidth of the phase-matching curve to be increased with respect to single-resonator configurations simultaneously taking advantage of the resonant feature of the resonators. This quasi-phase-matching technique could be applied to obtain small-footprint nonlinear devices with large bandwidth and limited nonlinear losses. The results are discussed in the framework of the slow-light-effect enhancement of second-order opticalmore » nonlinearities.« less

Pulse compression of harmonic chirp signals using the fractional fourier transform.

PubMed

Arif, M; Cowell, D M J; Freear, S

2010-06-01

In ultrasound harmonic imaging with chirp-coded excitation, a harmonic matched filter (HMF) is typically used on the received signal to perform pulse compression of the second harmonic component (SHC) to recover signal axial resolution. Designing the HMF for the compression of the SHC is a problematic issue because it requires optimal window selection. In the compressed second harmonic signal, the sidelobe level may increase and the mainlobe width (MLW) widen under a mismatched condition, resulting in loss of axial resolution. We propose the use of the fractional Fourier transform (FrFT) as an alternative tool to perform compression of the chirp-coded SHC generated as a result of the nonlinear propagation of an ultrasound signal. Two methods are used to experimentally assess the performance benefits of the FrFT technique over the HMF techniques. The first method uses chirp excitation with central frequency of 2.25 MHz and bandwidth of 1 MHz. The second method uses chirp excitation with pulse inversion to increase the bandwidth to 2 MHz. In this study, experiments were performed in a water tank with a single-element transducer mounted coaxially with a hydrophone in a pitch-catch configuration. Results are presented that indicate that the FrFT can perform pulse compression of the second harmonic chirp component, with a 14% reduction in the MLW of the compressed signal when compared with the HMF. Also, the FrFT provides at least 23% reduction in the MLW of the compressed signal when compared with the harmonic mismatched filter (HMMF). The FrFT maintains comparable peak and integrated sidelobe levels when compared with the HMF and HMMF techniques. Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Range side lobe inversion for chirp-encoded dual-band tissue harmonic imaging.

PubMed

Shen, Che-Chou; Peng, Jun-Kai; Wu, Chi

2014-02-01

Dual-band (DB) harmonic imaging is performed by transmitting and receiving at both fundamental band (f0) and second-harmonic band (2f0). In our previous work, particular chirp excitation has been developed to increase the signal- to-noise ratio in DB harmonic imaging. However, spectral overlap between the second-order DB harmonic signals results in range side lobes in the pulse compression. In this study, a novel range side lobe inversion (RSI) method is developed to alleviate the level of range side lobes from spectral overlap. The method is implemented by firing an auxiliary chirp to change the polarity of the range side lobes so that the range side lobes can be suppressed in the combination of the original chirp and the auxiliary chirp. Hydrophone measurements show that the RSI method reduces the range side lobe level (RSLL) and thus increases the quality of pulse compression in DB harmonic imaging. With the signal bandwidth of 60%, the RSLL decreases from -23 dB to -36 dB and the corresponding compression quality improves from 78% to 94%. B-mode images also indicate that the magnitude of range side lobe is suppressed by 7 dB when the RSI method is applied.

Efficient second-harmonic imaging of collagen in histological slides using Bessel beam excitation

NASA Astrophysics Data System (ADS)

Vuillemin, Nelly; Mahou, Pierre; Débarre, Delphine; Gacoin, Thierry; Tharaux, Pierre-Louis; Schanne-Klein, Marie-Claire; Supatto, Willy; Beaurepaire, Emmanuel

2016-07-01

Second-harmonic generation (SHG) is the most specific label-free indicator of collagen accumulation in widespread pathologies such as fibrosis, and SHG-based measurements hold important potential for biomedical analyses. However, efficient collagen SHG scoring in histological slides is hampered by the limited depth-of-field of usual nonlinear microscopes relying on focused Gaussian beam excitation. In this work we analyze theoretically and experimentally the use of Bessel beam excitation to address this issue. Focused Bessel beams can provide an axially extended excitation volume for nonlinear microscopy while preserving lateral resolution. We show that shaping the focal volume has consequences on signal level and scattering directionality in the case of coherent signals (such as SHG) which significantly differ from the case of incoherent signals (two-photon excited fluorescence, 2PEF). We demonstrate extended-depth SHG-2PEF imaging of fibrotic mouse kidney histological slides. Finally, we show that Bessel beam excitation combined with spatial filtering of the harmonic light in wave vector space can be used to probe collagen accumulation more efficiently than the usual Gaussian excitation scheme. These results open the way to SHG-based histological diagnoses.

Efficient second-harmonic imaging of collagen in histological slides using Bessel beam excitation

PubMed Central

Vuillemin, Nelly; Mahou, Pierre; Débarre, Delphine; Gacoin, Thierry; Tharaux, Pierre-Louis; Schanne-Klein, Marie-Claire; Supatto, Willy; Beaurepaire, Emmanuel

2016-01-01

Second-harmonic generation (SHG) is the most specific label-free indicator of collagen accumulation in widespread pathologies such as fibrosis, and SHG-based measurements hold important potential for biomedical analyses. However, efficient collagen SHG scoring in histological slides is hampered by the limited depth-of-field of usual nonlinear microscopes relying on focused Gaussian beam excitation. In this work we analyze theoretically and experimentally the use of Bessel beam excitation to address this issue. Focused Bessel beams can provide an axially extended excitation volume for nonlinear microscopy while preserving lateral resolution. We show that shaping the focal volume has consequences on signal level and scattering directionality in the case of coherent signals (such as SHG) which significantly differ from the case of incoherent signals (two-photon excited fluorescence, 2PEF). We demonstrate extended-depth SHG-2PEF imaging of fibrotic mouse kidney histological slides. Finally, we show that Bessel beam excitation combined with spatial filtering of the harmonic light in wave vector space can be used to probe collagen accumulation more efficiently than the usual Gaussian excitation scheme. These results open the way to SHG-based histological diagnoses. PMID:27435390

Frequency-doubled microwave waveforms generation using a dual-polarization quadrature phase shift keying modulator driven by a single frequency radio frequency signal

NASA Astrophysics Data System (ADS)

Zhu, Zihang; Zhao, Shanghong; Li, Xuan; Qu, Kun; Lin, Tao

2018-01-01

A photonic approach to generate frequency-doubled microwave waveforms using an integrated dual-polarization quadrature phase shift keying (DP-QPSK) modulator driven by a sinusoidal radio frequency (RF) signal is proposed. By adjusting the dc bias points of the DP-QPSK modulator, the obtained second-order and six-order harmonics are in phase while the fourth-order harmonics are complementary when the orthogonal polarized outputs of the modulator are photodetected. After properly setting the modulation indices of the modulator, the amplitude of the second-order harmonic is 9 times of that of the six-order harmonic, indicating a frequency-doubled triangular waveform is generated. If a broadband 90° microwave phase shifter is attached after the photodetector (PD) to introduce a 90° phase shift, a frequency-doubled square waveform can be obtained after adjusting the amplitude of the second-order harmonic 3 times of that of the six-order harmonic. The proposal is first theoretically analyzed and then validated by simulation. Simulation results show that a 10 GHz triangular and square waveform sequences are successfully generated from a 5 GHz sinusoidal RF drive signal.

Studying the effect of photodynamic therapy (PDT) to enhance healing of femur fractures using polarimetric second-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Golaraei, Ahmad; Raja, Vaishnavi; Akens, Margarete K.; Wilson, Brian C.; Barzda, Virginijus

2017-07-01

Linear polarization-in, polarization-out second-harmonic generation microscopy was used to study the effect of Photodynamic therapy treatment on enhancing the healing of femur fracture by investigating the ultrastructure of collagen as a major component of bone matrix.

Two-pass-internal second-harmonic generation using a prism coupler.

NASA Technical Reports Server (NTRS)

Gonzalez, D. G.; Nieh, S. T. K.; Steier, W. H.

1973-01-01

A dispersive quartz prism is used to couple the total second harmonic generated in both directions by an internal cavity frequency doubler. The study shows that the dispersion of air and mirror reflection phase shifts can be compensated for by a slight nonphase match condition in the doubler.

Centroid stabilization in alignment of FOA corner cube: designing of a matched filter

NASA Astrophysics Data System (ADS)

Awwal, Abdul; Wilhelmsen, Karl; Roberts, Randy; Leach, Richard; Miller Kamm, Victoria; Ngo, Tony; Lowe-Webb, Roger

2015-02-01

The current automation of image-based alignment of NIF high energy laser beams is providing the capability of executing multiple target shots per day. An important aspect of performing multiple shots in a day is to reduce additional time spent aligning specific beams due to perturbations in those beam images. One such alignment is beam centration through the second and third harmonic generating crystals in the final optics assembly (FOA), which employs two retro-reflecting corner cubes to represent the beam center. The FOA houses the frequency conversion crystals for third harmonic generation as the beams enters the target chamber. Beam-to-beam variations and systematic beam changes over time in the FOA corner-cube images can lead to a reduction in accuracy as well as increased convergence durations for the template based centroid detector. This work presents a systematic approach of maintaining FOA corner cube centroid templates so that stable position estimation is applied thereby leading to fast convergence of alignment control loops. In the matched filtering approach, a template is designed based on most recent images taken in the last 60 days. The results show that new filter reduces the divergence of the position estimation of FOA images.

Surface diffusion of Sb on Ge(111) investigated by second harmonic microscopy

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

Schultz, K.A.

Surface diffusion of Sb on Ge(111) has been measured with the newly-developed technique of second harmonic microscopy. In this method, concentration profiles at submonolayer coverage are imaged directly by second harmonic generation with 5 [mu]m spatial resolution. A Boltzmann-Matano analysis of the concentration profiles yields the coverage dependence of the diffusivity D without parameterization. Experiments were performed at roughly 70% of the bulk melting temperature T[sub m]. In the coverage range of 0 < [theta] < 0.6, the activation energy E[sub diff] remains constant at 47.5 [+-] 1.5 kcal/mol. The corresponding pre-exponential factor decreases from 8.7 [times] 10[sup 3[+-]0.4] tomore » 1.6 [times] 10[sup 2[+-]0.4] cm[sup 2]/sec. The results are explained in terms of a new vacancy model for surface diffusion at high-temperatures. The model accounts semiquantitatively for the large values of E[sub diff] and D[sub o], and suggest that these quantities may be manipulated by bulk doping levels and photon illumination of the surface.« less

Nonlinear Lamb waves for fatigue damage identification in FRP-reinforced steel plates.

PubMed

Wang, Yikuan; Guan, Ruiqi; Lu, Ye

2017-09-01

A nonlinear Lamb-wave-based method for fatigue crack detection in steel plates with and without carbon fibre reinforcement polymer (CFRP) reinforcement is presented in this study. Both numerical simulation and experimental evaluation were performed for Lamb wave propagation and its interaction with a fatigue crack on these two steel plate types. With the generation of the second harmonic, the damage-induced wave nonlinearities were identified by surface-bonded piezoelectric sensors. Numerical simulation revealed that the damage-induced wave component at the second harmonic was slightly affected by the existence of CFRP laminate, although the total wave energy was decreased because of wave leakage into the CFRP laminate. Due to unavoidable nonlinearity from the experimental environments, it was impractical to directly extract the time-of-flight of the second harmonic for locating the crack. To this end, the correlation coefficient of benchmark and signal with damage at double frequency in the time domain was calculated, based on which an imaging method was introduced to locate the fatigue crack in steel plates with and without CFRP laminates. Copyright © 2017 Elsevier B.V. All rights reserved.

Fully automated muscle quality assessment by Gabor filtering of second harmonic generation images

NASA Astrophysics Data System (ADS)

Paesen, Rik; Smolders, Sophie; Vega, José Manolo de Hoyos; Eijnde, Bert O.; Hansen, Dominique; Ameloot, Marcel

2016-02-01

Although structural changes on the sarcomere level of skeletal muscle are known to occur due to various pathologies, rigorous studies of the reduced sarcomere quality remain scarce. This can possibly be explained by the lack of an objective tool for analyzing and comparing sarcomere images across biological conditions. Recent developments in second harmonic generation (SHG) microscopy and increasing insight into the interpretation of sarcomere SHG intensity profiles have made SHG microscopy a valuable tool to study microstructural properties of sarcomeres. Typically, sarcomere integrity is analyzed by fitting a set of manually selected, one-dimensional SHG intensity profiles with a supramolecular SHG model. To circumvent this tedious manual selection step, we developed a fully automated image analysis procedure to map the sarcomere disorder for the entire image at once. The algorithm relies on a single-frequency wavelet-based Gabor approach and includes a newly developed normalization procedure allowing for unambiguous data interpretation. The method was validated by showing the correlation between the sarcomere disorder, quantified by the M-band size obtained from manually selected profiles, and the normalized Gabor value ranging from 0 to 1 for decreasing disorder. Finally, to elucidate the applicability of our newly developed protocol, Gabor analysis was used to study the effect of experimental autoimmune encephalomyelitis on the sarcomere regularity. We believe that the technique developed in this work holds great promise for high-throughput, unbiased, and automated image analysis to study sarcomere integrity by SHG microscopy.

Quantification of collagen distributions in rat hyaline and fibro cartilages based on second harmonic generation imaging

NASA Astrophysics Data System (ADS)

Zhu, Xiaoqin; Liao, Chenxi; Wang, Zhenyu; Zhuo, Shuangmu; Liu, Wenge; Chen, Jianxin

2016-10-01

Hyaline cartilage is a semitransparent tissue composed of proteoglycan and thicker type II collagen fibers, while fibro cartilage large bundles of type I collagen besides other territorial matrix and chondrocytes. It is reported that the meniscus (fibro cartilage) has a greater capacity to regenerate and close a wound compared to articular cartilage (hyaline cartilage). And fibro cartilage often replaces the type II collagen-rich hyaline following trauma, leading to scar tissue that is composed of rigid type I collagen. The visualization and quantification of the collagen fibrillar meshwork is important for understanding the role of fibril reorganization during the healing process and how different types of cartilage contribute to wound closure. In this study, second harmonic generation (SHG) microscope was applied to image the articular and meniscus cartilage, and textural analysis were developed to quantify the collagen distribution. High-resolution images were achieved based on the SHG signal from collagen within fresh specimens, and detailed observations of tissue morphology and microstructural distribution were obtained without shrinkage or distortion. Textural analysis of SHG images was performed to confirm that collagen in fibrocartilage showed significantly coarser compared to collagen in hyaline cartilage (p < 0.01). Our results show that each type of cartilage has different structural features, which may significantly contribute to pathology when damaged. Our findings demonstrate that SHG microscopy holds potential as a clinically relevant diagnostic tool for imaging degenerative tissues or assessing wound repair following cartilage injury.

The analysis of harmonic generation coefficients in the ablative Rayleigh-Taylor instability

NASA Astrophysics Data System (ADS)

Lu, Yan; Fan, Zhengfeng; Lu, Xinpei; Ye, Wenhua; Zou, Changlin; Zhang, Ziyun; Zhang, Wen

2017-10-01

In this research, we use the numerical simulation method to investigate the generation coefficients of the first three harmonics and the zeroth harmonic in the Ablative Rayleigh-Taylor Instability. It is shown that the interface shifts to the low temperature side during the ablation process. In consideration of the third-order perturbation theory, the first three harmonic amplitudes of the weakly nonlinear regime are calculated and then the harmonic generation coefficients are obtained by curve fitting. The simulation results show that the harmonic generation coefficients changed with time and wavelength. Using the higher-order perturbation theory, we find that more and more harmonics are generated in the later weakly nonlinear stage, which is caused by the negative feedback of the later higher harmonics. Furthermore, extending the third-order theory to the fifth-order theory, we find that the second and the third harmonics coefficients linearly depend on the wavelength, while the feedback coefficients are almost constant. Further analysis also shows that when the fifth-order theory is considered, the normalized effective amplitudes of second and third harmonics can reach about 25%-40%, which are only 15%-25% in the frame of the previous third-order theory. Therefore, the third order perturbation theory is needed to be modified by the higher-order theory when ηL reaches about 20% of the perturbation wavelength.

Multiple layer optical memory system using second-harmonic-generation readout

DOEpatents

Boyd, Gary T.; Shen, Yuen-Ron

1989-01-01

A novel optical read and write information storage system is described which comprises a radiation source such as a laser for writing and illumination, the radiation source being capable of radiating a preselected first frequency; a storage medium including at least one layer of material for receiving radiation from the radiation source and capable of being surface modified in response to said radiation source when operated in a writing mode and capable of generating a pattern of radiation of the second harmonic of the preselected frequency when illuminated by the radiation source at the preselected frequency corresponding to the surface modifications on the storage medium; and a detector to receive the pattern of second harmonic frequency generated.

Three-Dimensional Geometry of Collagenous Tissues by Second Harmonic Polarimetry.

PubMed

Reiser, Karen; Stoller, Patrick; Knoesen, André

2017-06-01

Collagen is a biological macromolecule capable of second harmonic generation, allowing label-free detection in tissues; in addition, molecular orientation can be determined from the polarization dependence of the second harmonic signal. Previously we reported that in-plane orientation of collagen fibrils could be determined by modulating the polarization angle of the laser during scanning. We have now extended this method so that out-of-plane orientation angles can be determined at the same time, allowing visualization of the 3-dimensional structure of collagenous tissues. This approach offers advantages compared with other methods for determining out-of-plane orientation. First, the orientation angles are directly calculated from the polarimetry data obtained in a single scan, while other reported methods require data from multiple scans, use of iterative optimization methods, application of fitting algorithms, or extensive post-optical processing. Second, our method does not require highly specialized instrumentation, and thus can be adapted for use in almost any nonlinear optical microscopy setup. It is suitable for both basic and clinical applications. We present three-dimensional images of structurally complex collagenous tissues that illustrate the power of such 3-dimensional analyses to reveal the architecture of biological structures.

Three-Dimensional Geometry of Collagenous Tissues by Second Harmonic Polarimetry

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

Reiser, Karen; Stoller, Patrick; Knoesen, André

Collagen is a biological macromolecule capable of second harmonic generation, allowing label-free detection in tissues; in addition, molecular orientation can be determined from the polarization dependence of the second harmonic signal. Previously we reported that in-plane orientation of collagen fibrils could be determined by modulating the polarization angle of the laser during scanning. We have now extended this method so that out-of-plane orientation angles can be determined at the same time, allowing visualization of the 3-dimensional structure of collagenous tissues. This approach offers advantages compared with other methods for determining out-of-plane orientation. First, the orientation angles are directly calculated frommore » the polarimetry data obtained in a single scan, while other reported methods require data from multiple scans, use of iterative optimization methods, application of fitting algorithms, or extensive post-optical processing. Second, our method does not require highly specialized instrumentation, and thus can be adapted for use in almost any nonlinear optical microscopy setup. It is suitable for both basic and clinical applications. We present three-dimensional images of structurally complex collagenous tissues that illustrate the power of such 3-dimensional analyses to reveal the architecture of biological structures.« less

Three-Dimensional Geometry of Collagenous Tissues by Second Harmonic Polarimetry

DOE PAGES

Reiser, Karen; Stoller, Patrick; Knoesen, André

2017-06-01

Collagen is a biological macromolecule capable of second harmonic generation, allowing label-free detection in tissues; in addition, molecular orientation can be determined from the polarization dependence of the second harmonic signal. Previously we reported that in-plane orientation of collagen fibrils could be determined by modulating the polarization angle of the laser during scanning. We have now extended this method so that out-of-plane orientation angles can be determined at the same time, allowing visualization of the 3-dimensional structure of collagenous tissues. This approach offers advantages compared with other methods for determining out-of-plane orientation. First, the orientation angles are directly calculated frommore » the polarimetry data obtained in a single scan, while other reported methods require data from multiple scans, use of iterative optimization methods, application of fitting algorithms, or extensive post-optical processing. Second, our method does not require highly specialized instrumentation, and thus can be adapted for use in almost any nonlinear optical microscopy setup. It is suitable for both basic and clinical applications. We present three-dimensional images of structurally complex collagenous tissues that illustrate the power of such 3-dimensional analyses to reveal the architecture of biological structures.« less

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.

Implementation of parallel transmit beamforming using orthogonal frequency division multiplexing--achievable resolution and interbeam interference.

PubMed

Demi, Libertario; Viti, Jacopo; Kusters, Lieneke; Guidi, Francesco; Tortoli, Piero; Mischi, Massimo

2013-11-01

The speed of sound in the human body limits the achievable data acquisition rate of pulsed ultrasound scanners. To overcome this limitation, parallel beamforming techniques are used in ultrasound 2-D and 3-D imaging systems. Different parallel beamforming approaches have been proposed. They may be grouped into two major categories: parallel beamforming in reception and parallel beamforming in transmission. The first category is not optimal for harmonic imaging; the second category may be more easily applied to harmonic imaging. However, inter-beam interference represents an issue. To overcome these shortcomings and exploit the benefit of combining harmonic imaging and high data acquisition rate, a new approach has been recently presented which relies on orthogonal frequency division multiplexing (OFDM) to perform parallel beamforming in transmission. In this paper, parallel transmit beamforming using OFDM is implemented for the first time on an ultrasound scanner. An advanced open platform for ultrasound research is used to investigate the axial resolution and interbeam interference achievable with parallel transmit beamforming using OFDM. Both fundamental and second-harmonic imaging modalities have been considered. Results show that, for fundamental imaging, axial resolution in the order of 2 mm can be achieved in combination with interbeam interference in the order of -30 dB. For second-harmonic imaging, axial resolution in the order of 1 mm can be achieved in combination with interbeam interference in the order of -35 dB.

Probing Graphene χ((2)) Using a Gold Photon Sieve.

PubMed

Lobet, Michaël; Sarrazin, Michaël; Cecchet, Francesca; Reckinger, Nicolas; Vlad, Alexandru; Colomer, Jean-François; Lis, Dan

2016-01-13

Nonlinear second harmonic optical activity of graphene covering a gold photon sieve was determined for different polarizations. The photon sieve consists of a subwavelength gold nanohole array placed on glass. It combines the benefits of efficient light trapping and surface plasmon propagation to unravel different elements of graphene second-order susceptibility χ((2)). Those elements efficiently contribute to second harmonic generation. In fact, the graphene-coated photon sieve produces a second harmonic intensity at least two orders of magnitude higher compared with a bare, flat gold layer and an order of magnitude coming from the plasmonic effect of the photon sieve; the remaining enhancement arises from the graphene layer itself. The measured second harmonic generation yield, supplemented by semianalytical computations, provides an original method to constrain the graphene χ((2)) elements. The values obtained are |d31 + d33| ≤ 8.1 × 10(3) pm(2)/V and |d15| ≤ 1.4 × 10(6) pm(2)/V for a second harmonic signal at 780 nm. This original method can be applied to any kind of 2D materials covering such a plasmonic structure.

Simultaneous negative refraction and focusing of fundamental frequency and second-harmonic fields by two-dimensional photonic crystals

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

Zhang, Jun; College of Physics and Electronic Engineering, Henan Normal University, 453007 Xinxiang, Henan; Zhang, Xiangdong, E-mail: zhangxd@bit.edu.cn

2015-09-28

Simultaneous negative refraction for both the fundamental frequency (FF) and second-harmonic (SH) fields in two-dimensional nonlinear photonic crystals have been found through both the physical analysis and exact numerical simulation. By combining such a property with the phase-matching condition and strong second-order susceptibility, we have designed a SH lens to realize focusing for both the FF and SH fields at the same time. Good-quality non-near field images for both FF and SH fields have been observed. The physical mechanism for such SH focusing phenomena has been disclosed, which is different from the backward SH generation as has been pointed outmore » in the previous investigations. In addition, the effect of absorption losses on the phenomena has also been discussed. Thus, potential applications of these phenomena to biphotonic microscopy technique are anticipated.« less

A robust collagen scoring method for human liver fibrosis by second harmonic microscopy.

PubMed

Guilbert, Thomas; Odin, Christophe; Le Grand, Yann; Gailhouste, Luc; Turlin, Bruno; Ezan, Frédérick; Désille, Yoann; Baffet, Georges; Guyader, Dominique

2010-12-06

Second Harmonic Generation (SHG) microscopy offers the opportunity to image collagen of type I without staining. We recently showed that a simple scoring method, based on SHG images of histological human liver biopsies, correlates well with the Metavir assessment of fibrosis level (Gailhouste et al., J. Hepatol., 2010). In this article, we present a detailed study of this new scoring method with two different objective lenses. By using measurements of the objectives point spread functions and of the photomultiplier gain, and a simple model of the SHG intensity, we show that our scoring method, applied to human liver biopsies, is robust to the objective's numerical aperture (NA) for low NA, the choice of the reference sample and laser power, and the spatial sampling rate. The simplicity and robustness of our collagen scoring method may open new opportunities in the quantification of collagen content in different organs, which is of main importance in providing diagnostic information and evaluation of therapeutic efficiency.

Fast epi-detected broadband multiplex CARS and SHG imaging of mouse skull cells

PubMed Central

Capitaine, Erwan; Moussa, Nawel Ould; Louot, Christophe; Bardet, Sylvia M.; Kano, Hideaki; Duponchel, Ludovic; Lévêque, Philippe; Couderc, Vincent; Leproux, Philippe

2017-01-01

We present a bimodal imaging system able to obtain epi-detected mutiplex coherent anti-Stokes Raman scattering (M-CARS) and second harmonic generation (SHG) signals coming from biological samples. We studied a fragment of mouse parietal bone and could detect broadband anti-Stokes and SHG responses originating from bone cells and collagen respectively. In addition we compared two post-processing methods to retrieve the imaginary part of the third-order nonlinear susceptibility related to the spontaneous Raman scattering. PMID:29359100

Quantification of liver fibrosis via second harmonic imaging of the Glisson's capsule from liver surface.

PubMed

Xu, Shuoyu; Kang, Chiang Huen; Gou, Xiaoli; Peng, Qiwen; Yan, Jie; Zhuo, Shuangmu; Cheng, Chee Leong; He, Yuting; Kang, Yuzhan; Xia, Wuzheng; So, Peter T C; Welsch, Roy; Rajapakse, Jagath C; Yu, Hanry

2016-04-01

Liver surface is covered by a collagenous layer called the Glisson's capsule. The structure of the Glisson's capsule is barely seen in the biopsy samples for histology assessment, thus the changes of the collagen network from the Glisson's capsule during the liver disease progression are not well studied. In this report, we investigated whether non-linear optical imaging of the Glisson's capsule at liver surface would yield sufficient information to allow quantitative staging of liver fibrosis. In contrast to conventional tissue sections whereby tissues are cut perpendicular to the liver surface and interior information from the liver biopsy samples were used, we have established a capsule index based on significant parameters extracted from the second harmonic generation (SHG) microscopy images of capsule collagen from anterior surface of rat livers. Thioacetamide (TAA) induced liver fibrosis animal models was used in this study. The capsule index is capable of differentiating different fibrosis stages, with area under receiver operating characteristics curve (AUC) up to 0.91, making it possible to quantitatively stage liver fibrosis via liver surface imaging potentially with endomicroscopy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of structural modification on second harmonic generation in collagen

NASA Astrophysics Data System (ADS)

Stoller, Patrick C.; Reiser, Karen M.; Celliers, Peter M.; Rubenchik, Alexander M.

2003-07-01

The effects of structural perturbation on second harmonic generation in collagen were investigated. Type I collagen fascicles obtained from rat tails were structurally modified by increasing nonenzymatic cross-linking, by thermal denaturation, by collagenase digestion, or by dehydration. Changes in polarization dependence were observed in the dehydrated samples. Surprisingly, no changes in polarization dependence were observed in highly crosslinked samples, despite significant alterations in packing structure. Complete thermal denaturation and collagenase digestion produced samples with no detectable second harmonic signal. Prior to loss of signal, no change in polarization dependence was observed in partially heated or digested collagen.

Application of mid-infrared pulses for quasi-phase-matching of high-order harmonics in silver plasma.

PubMed

Ganeev, Rashid A; Husakou, Anton; Suzuki, Masayuki; Kuroda, Hiroto

2016-02-22

We demonstrate the quasi-phase-matching of a group of harmonics generated in Ag multi-jet plasma using tunable pulses in the region of 1160 - 1540 nm and their second harmonic emission. The numerical treatment of this effect includes microscopic description of the harmonic generation, propagation of the pump pulse, and the propagation of the generated harmonics. We obtained more than 30-fold growth of harmonics at the conditions of quasi-phase-matching in the region of 35 nm using eight-jet plasma compared with the case of imperforated plasma.

Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis

DTIC Science & Technology

2014-09-01

Harmonic Generation to Image the Extracellular Matrix During Tumor Progression. Invited Perspective Intravital Manuscript Submitted. Sullivan K...harmonic generation (the SHG “F/B ratio”) in thick intact tissue, with a single image scan. This will be necessary for us to pursue our goal of...quantifying matrix changes dynamically, in intact tumor models. The first method determines F/B by generating a series of backscattered images using a series

Efficient forward second-harmonic generation from planar archimedean nanospirals

DOE PAGES

Davidson, II, Roderick B.; Ziegler, Jed I.; Vargas, Guillermo; ...

2015-05-01

Here, the enhanced electric field at plasmonic resonances in nanoscale antennas can lead to efficient harmonic generation, especially when the plasmonic geometry is asymmetric on either inter-particle or intra-particle levels. The planar Archimedean nanospiral offers a unique geometrical asymmetry for second-harmonic generation (SHG) because the SHG results neither from arranging centrosymmetric nanoparticles in asymmetric groupings, nor from non-centrosymmetric nanoparticles that retain a local axis of symmetry. Here, we report forward SHG from planar arrays of Archimedean nanospirals using 15 fs pulses from a Ti:sapphire oscillator tuned to 800 nm wavelength.

Optical second harmonic generation from Pt nanowires with boomerang-like cross-sectional shapes

NASA Astrophysics Data System (ADS)

Ogata, Yoichi; Anh Tuan, Nguyen; Miyauchi, Yoshihiro; Mizutani, Goro

2011-08-01

We have fabricated Pt nanowires with boomerang-like cross-sectional shapes on the MgO(110) faceted template and observed their optical second-harmonic generation (SHG) response. In the TEM images the Pt nanowires on the MgO substrate had macroscopic C2v symmetry, however, their structure had microscopic imperfections. In the SHG response, as a function of the sample rotation angle around the substrate normal, we found contributions from the nonlinear susceptibility elements χ113, χ223, χ311, χ322, and χ333 originating from the broken symmetry in the 3; [110] direction of the MgO substrate. The indices 1 and 2 denote the [001] and [11¯0] directions, respectively. Under C2v symmetry no SHG is expected in the s-in/s-out polarization configuration, however, a finite SHG was observed in this polarization configuration. We suggest that the SHG in the forbidden configuration might originate from the imperfections in the nanowire structure.

Atom-Dependent Edge-Enhanced Second-Harmonic Generation on MoS2 Monolayers.

PubMed

Lin, Kuang-I; Ho, Yen-Hung; Liu, Shu-Bai; Ciou, Jian-Jhih; Huang, Bo-Ting; Chen, Christopher; Chang, Han-Ching; Tu, Chien-Liang; Chen, Chang-Hsiao

2018-02-14

Edge morphology and lattice orientation of single-crystal molybdenum disulfide (MoS 2 ) monolayers, a transition metal dichalcogenide (TMD), possessing a triangular shape with different edges grown by chemical vapor deposition are characterized by atomic force microscopy and transmission electron microscopy. Multiphoton laser scanning microscopy is utilized to study one-dimensional atomic edges of MoS 2 monolayers with localized midgap electronic states, which result in greatly enhanced optical second-harmonic generation (SHG). Microscopic S-zigzag edge and S-Mo Klein edge (bare Mo atoms protruding from a S-zigzag edge) terminations and the edge-atom dependent resonance energies can therefore be deduced based on SHG images. Theoretical calculations based on density functional theory clearly explain the lower energy of the S-zigzag edge states compared to the corresponding S-Mo Klein edge states. Characterization of the atomic-scale variation of edge-enhanced SHG is a step forward in this full-optical and high-yield technique of atomic-layer TMDs.

Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure

PubMed Central

Chen, Xiyi; Nadiarynkh, Oleg; Plotnikov, Sergey; Campagnola, Paul J

2013-01-01

Second-harmonic generation (SHG) microscopy has emerged as a powerful modality for imaging fibrillar collagen in a diverse range of tissues. Because of its underlying physical origin, it is highly sensitive to the collagen fibril/fiber structure, and, importantly, to changes that occur in diseases such as cancer, fibrosis and connective tissue disorders. We discuss how SHG can be used to obtain more structural information on the assembly of collagen in tissues than is possible by other microscopy techniques. We first provide an overview of the state of the art and the physical background of SHG microscopy, and then describe the optical modifications that need to be made to a laser-scanning microscope to enable the measurements. Crucial aspects for biomedical applications are the capabilities and limitations of the different experimental configurations. We estimate that the setup and calibration of the SHG instrument from its component parts will require 2–4 weeks, depending on the level of the user’s experience. PMID:22402635

Second harmonic generation of q-Gaussian laser beam in preformed collisional plasma channel with nonlinear absorption

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

Gupta, Naveen, E-mail: naveens222@rediffmail.com; Singh, Arvinder, E-mail: arvinder6@lycos.com; Singh, Navpreet, E-mail: navpreet.nit@gmail.com

2015-11-15

This paper presents a scheme for second harmonic generation of an intense q-Gaussian laser beam in a preformed parabolic plasma channel, where collisional nonlinearity is operative with nonlinear absorption. Due to nonuniform irradiance of intensity along the wavefront of the laser beam, nonuniform Ohmic heating of plasma electrons takes place. Due to this nonuniform heating of plasma, the laser beam gets self-focused and produces strong density gradients in the transverse direction. The generated density gradients excite an electron plasma wave at pump frequency that interacts with the pump beam to produce its second harmonics. The formulation is based on amore » numerical solution of the nonlinear Schrodinger wave equation in WKB approximation followed by moment theory approach. A second order nonlinear differential equation governing the propagation dynamics of the laser beam with distance of propagation has been obtained and is solved numerically by Runge Kutta fourth order technique. The effect of nonlinear absorption on self-focusing of the laser beam and conversion efficiency of its second harmonics has been investigated.« less

Enhancing resolution and contrast in second-harmonic generation microscopy using an advanced maximum likelihood estimation restoration method

NASA Astrophysics Data System (ADS)

Sivaguru, Mayandi; Kabir, Mohammad M.; Gartia, Manas Ranjan; Biggs, David S. C.; Sivaguru, Barghav S.; Sivaguru, Vignesh A.; Berent, Zachary T.; Wagoner Johnson, Amy J.; Fried, Glenn A.; Liu, Gang Logan; Sadayappan, Sakthivel; Toussaint, Kimani C.

2017-02-01

Second-harmonic generation (SHG) microscopy is a label-free imaging technique to study collagenous materials in extracellular matrix environment with high resolution and contrast. However, like many other microscopy techniques, the actual spatial resolution achievable by SHG microscopy is reduced by out-of-focus blur and optical aberrations that degrade particularly the amplitude of the detectable higher spatial frequencies. Being a two-photon scattering process, it is challenging to define a point spread function (PSF) for the SHG imaging modality. As a result, in comparison with other two-photon imaging systems like two-photon fluorescence, it is difficult to apply any PSF-engineering techniques to enhance the experimental spatial resolution closer to the diffraction limit. Here, we present a method to improve the spatial resolution in SHG microscopy using an advanced maximum likelihood estimation (AdvMLE) algorithm to recover the otherwise degraded higher spatial frequencies in an SHG image. Through adaptation and iteration, the AdvMLE algorithm calculates an improved PSF for an SHG image and enhances the spatial resolution by decreasing the full-width-at-halfmaximum (FWHM) by 20%. Similar results are consistently observed for biological tissues with varying SHG sources, such as gold nanoparticles and collagen in porcine feet tendons. By obtaining an experimental transverse spatial resolution of 400 nm, we show that the AdvMLE algorithm brings the practical spatial resolution closer to the theoretical diffraction limit. Our approach is suitable for adaptation in micro-nano CT and MRI imaging, which has the potential to impact diagnosis and treatment of human diseases.

Label-free imaging of brain and brain tumor specimens with combined two-photon excited fluorescence and second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Jiang, Liwei; Wang, Xingfu; Wu, Zanyi; Du, Huiping; Wang, Shu; Li, Lianhuang; Fang, Na; Lin, Peihua; Chen, Jianxin; Kang, Dezhi; Zhuo, Shuangmu

2017-10-01

Label-free imaging techniques are gaining acceptance within the medical imaging field, including brain imaging, because they have the potential to be applied to intraoperative in situ identifications of pathological conditions. In this paper, we describe the use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopy in combination for the label-free detection of brain and brain tumor specimens; gliomas. Two independently detecting channels were chosen to subsequently collect TPEF/SHG signals from the specimen to increase TPEF/SHG image contrasts. Our results indicate that the combined TPEF/SHG microscopic techniques can provide similar rat brain structural information and produce a similar resolution like conventional H&E staining in neuropathology; including meninges, cerebral cortex, white-matter structure corpus callosum, choroid plexus, hippocampus, striatum, and cerebellar cortex. It can simultaneously detect infiltrating human brain tumor cells, the extracellular matrix collagen fiber of connective stroma within brain vessels and collagen depostion in tumor microenvironments. The nuclear-to-cytoplasmic ratio and collagen content can be extracted as quantitative indicators for differentiating brain gliomas from healthy brain tissues. With the development of two-photon fiberscopes and microendoscope probes and their clinical applications, the combined TPEF and SHG microcopy may become an important multimodal, nonlinear optical imaging approach for real-time intraoperative histological diagnostics of residual brain tumors. These occur in various brain regions during ongoing surgeries through the method of simultaneously identifying tumor cells, and the change of tumor microenvironments, without the need for the removal biopsies and without the need for tissue labelling or fluorescent markers.

Magneto-thermal-acoustic differential-frequency imaging of magnetic nanoparticle with magnetic spatial localization: a theoretical prediction

NASA Astrophysics Data System (ADS)

Piao, Daqing

2017-02-01

The magneto-thermo-acoustic effect that we predicted in 2013 refers to the generation of acoustic-pressure wave from magnetic nanoparticle (MNP) when thermally mediated under an alternating magnetic field (AMF) at a pulsed or frequency-chirped application. Several independent experimental studies have since validated magneto-thermoacoustic effect, and a latest report has discovered acoustic-wave generation from MNP at the second-harmonic frequency of the AMF when operating continuously. We propose that applying two AMFs with differing frequencies to MNP will produce acoustic-pressure wave at the summation and difference of the two frequencies, in addition to the two second-harmonic frequencies. Analysis of the specific absorption dynamics of the MNP when exposed to two AMFs of differing frequencies has shown some interesting patterns of acoustic-intensity at the multiple frequency components. The ratio of the acoustic-intensity at the summation-frequency over that of the difference-frequency is determined by the frequency-ratio of the two AMFs, but remains independent of the AMF strengths. The ratio of the acoustic-intensity at the summation- or difference-frequency over that at each of the two second-harmonic frequencies is determined by both the frequency-ratio and the field-strength-ratio of the two AMFs. The results indicate a potential strategy for localization of the source of a continuous-wave magneto-thermalacoustic signal by examining the frequency spectrum of full-field non-differentiating acoustic detection, with the field-strength ratio changed continuously at a fixed frequency-ratio. The practicalities and challenges of this magnetic spatial localization approach for magneto-thermo-acoustic imaging using a simple envisioned set of two AMFs arranged in parallel to each other are discussed.

Layer-Dependent Third-Harmonic Generation in Graphene

NASA Astrophysics Data System (ADS)

Yang, Hao; Guan, Honghua; Dadap, Jerry; Osgood, Richard; Richard Osgood Team

Graphene has become a subject of intense interest and study because of its remarkable 2D electronic properties. Multilayer graphene also offers an array of properties that are also of interest for optical physics and devices. Despite its second-order-nonlinear optical response is intrinsically weak, third-order nonlinear optical effects in graphene are symmetry-allowed thus leading to studies of several third-order process in few-layer graphene. In this work, we report third-harmonic generation in multilayer graphene mounted on fused silica and with thicknesses which approach the bulk continuum. THG signals show cubic power dependence with respect to the intensity of fundamental beam. Third-harmonic generation spectroscopy enables a good fit using linear optical detection, which shows strong contrast for different layer number graphene. The maximum THG efficiency appears at layer number around 30. Two models are used for describing this layer dependent phenomenon and shows absorption plays a key role in THG of multilayer graphene. This work also provides a new imaging technology for graphene detection and identification with better contrast and resolution. U.S. Department of Energy under Contract No. DE-FG 02-04-ER-46157.

Organization of astaxanthin within oil bodies of Haematococcus pluvialis studied with polarization-dependent harmonic generation microscopy.

PubMed

Tokarz, Danielle; Cisek, Richard; El-Ansari, Omar; Espie, George S; Fekl, Ulrich; Barzda, Virginijus

2014-01-01

Nonlinear optical microscopy was used to image the localization of astaxanthin accumulation in the green alga, Haematococcus pluvialis. Polarization-in, polarization-out (PIPO) second harmonic generation (SHG) and third harmonic generation (THG) microscopy was applied to study the crystalline organization of astaxanthin molecules in light-stressed H. pluvialis in vivo. Since astaxanthin readily forms H- and J-aggregates in aqueous solutions, PIPO THG studies of astaxanthin aggregates contained in red aplanospores were compared to PIPO THG of in vitro self-assembled H- and J-aggregates of astaxanthin. The PIPO THG data clearly showed an isotropic organization of astaxanthin in red aplanospores of H. pluvialis. This is in contrast to the highly anisotropic organization of astaxanthin in synthetic H- and J-aggregates, which showed to be uniaxial. Since carotenoids in vitro preferentially form H- and J-aggregates, but in vivo form a randomly organized structure, this implies that astaxanthin undergoes a different way of packing in biological organisms, which is either due to the unique physical environment of the alga or is controlled enzymatically.

Organization of Astaxanthin within Oil Bodies of Haematococcus pluvialis Studied with Polarization-Dependent Harmonic Generation Microscopy

PubMed Central

Tokarz, Danielle; Cisek, Richard; El-Ansari, Omar; Espie, George S.; Fekl, Ulrich; Barzda, Virginijus

2014-01-01

Nonlinear optical microscopy was used to image the localization of astaxanthin accumulation in the green alga, Haematococcus pluvialis. Polarization-in, polarization-out (PIPO) second harmonic generation (SHG) and third harmonic generation (THG) microscopy was applied to study the crystalline organization of astaxanthin molecules in light-stressed H. pluvialis in vivo. Since astaxanthin readily forms H- and J-aggregates in aqueous solutions, PIPO THG studies of astaxanthin aggregates contained in red aplanospores were compared to PIPO THG of in vitro self-assembled H- and J-aggregates of astaxanthin. The PIPO THG data clearly showed an isotropic organization of astaxanthin in red aplanospores of H. pluvialis. This is in contrast to the highly anisotropic organization of astaxanthin in synthetic H- and J-aggregates, which showed to be uniaxial. Since carotenoids in vitro preferentially form H- and J-aggregates, but in vivo form a randomly organized structure, this implies that astaxanthin undergoes a different way of packing in biological organisms, which is either due to the unique physical environment of the alga or is controlled enzymatically. PMID:25215522

Molecular imaging of melanin distribution in vivo and quantitative differential diagnosis of human pigmented lesions using label-free harmonic generation biopsy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, Chi-Kuang; Wei, Ming-Liang; Su, Yu-Hsiang; Weng, Wei-Hung; Liao, Yi-Hua

2017-02-01

Harmonic generation microscopy is a noninvasive repetitive imaging technique that provides real-time 3D microscopic images of human skin with a sub-femtoliter resolution and high penetration down to the reticular dermis. In this talk, we show that with a strong resonance effect, the third-harmonic-generation (THG) modality provides enhanced contrast on melanin and allows not only differential diagnosis of various pigmented skin lesions but also quantitative imaging for longterm tracking. This unique capability makes THG microscopy the only label-free technique capable of identifying the active melanocytes in human skin and to image their different dendriticity patterns. In this talk, we will review our recent efforts to in vivo image melanin distribution and quantitatively diagnose pigmented skin lesions using label-free harmonic generation biopsy. This talk will first cover the spectroscopic study on the melanin enhanced THG effect in human cells and the calibration strategy inside human skin for quantitative imaging. We will then review our recent clinical trials including: differential diagnosis capability study on pigmented skin tumors; as well as quantitative virtual biopsy study on pre- and post- treatment evaluation on melasma and solar lentigo. Our study indicates the unmatched capability of harmonic generation microscopy to perform virtual biopsy for noninvasive histopathological diagnosis of various pigmented skin tumors, as well as its unsurpassed capability to noninvasively reveal the pathological origin of different hyperpigmentary diseases on human face as well as to monitor the efficacy of laser depigmentation treatments. This work is sponsored by National Health Research Institutes.

Improved Efficiency Type II Second Harmonic Generation

NASA Technical Reports Server (NTRS)

Barnes, Norman P.; Walsh, Brian M.; Reichle, Donald J., Jr.

2009-01-01

Second harmonic efficiency is limited by lateral and temporal separation of the ordinary and extraordinary components of the fundamental. A mode locked dual beam laser demonstrated these effects and a novel method to minimize them.

Energy exchange properties during second-harmonic generation in finite one-dimensional photonic band-gap structures with deep gratings.

PubMed

D'Aguanno, Giuseppe; Centini, Marco; Scalora, Michael; Sibilia, Concita; Bertolotti, Mario; Bloemer, Mark J; Bowden, Charles M

2003-01-01

We study second-harmonic generation in finite, one-dimensional, photonic band-gap structures with large index contrast in the regime of pump depletion and global phase-matching conditions. We report a number of surprising results: above a certain input intensity, field dynamics resemble a multiwave mixing process, where backward and forward components compete for the available energy; the pump field is mostly reflected, revealing a type of optical limiting behavior; and second-harmonic generation becomes balanced in both directions, showing unusual saturation effects with increasing pump intensity. This dynamics was unexpected, and it is bound to influence the way one goes about thinking and designing nonlinear frequency conversion devices in a practical way.

Efficient 2(nd) and 4(th) harmonic generation of a single-frequency, continuous-wave fiber amplifier.

PubMed

Sudmeyer, Thomas; Imai, Yutaka; Masuda, Hisashi; Eguchi, Naoya; Saito, Masaki; Kubota, Shigeo

2008-02-04

We demonstrate efficient cavity-enhanced second and fourth harmonic generation of an air-cooled, continuous-wave (cw), single-frequency 1064 nm fiber-amplifier system. The second harmonic generator achieves up to 88% total external conversion efficiency, generating more than 20-W power at 532 nm wavelength in a diffraction-limited beam (M(2) < 1.05). The nonlinear medium is a critically phase-matched, 20-mm long, anti-reflection (AR) coated LBO crystal operated at 25 degrees C. The fourth harmonic generator is based on an AR-coated, Czochralski-grown beta-BaB(2)O(4) (BBO) crystal optimized for low loss and high damage threshold. Up to 12.2 W of 266-nm deep-UV (DUV) output is obtained using a 6-mm long critically phase-matched BBO operated at 40 degrees C. This power level is more than two times higher than previously reported for cw 266-nm generation. The total external conversion efficiency from the fundamental at 1064 nm to the fourth harmonic at 266 nm is >50%.

20 MHz/40 MHz dual element transducers for high frequency harmonic imaging.

PubMed

Kim, Hyung Ham; Cannata, Jonathan M; Liu, Ruibin; Chang, Jin Ho; Silverman, Ronald H; Shung, K Kirk

2008-12-01

Concentric annular type dual element transducers for second harmonic imaging at 20 MHz / 40 MHz were designed and fabricated to improve spatial resolution and depth of penetration for ophthalmic imaging applications. The outer ring element was designed to transmit the 20 MHz signal and the inner circular element was designed to receive the 40 MHz second harmonic signal. Lithium niobate (LiNbO(3)), with its low dielectric constant, was used as the piezoelectric material to achieve good electrical impedance matching. Double matching layers and conductive backing were used and optimized by KLM modeling to achieve high sensitivity and wide bandwidth for harmonic imaging and superior time-domain characteristics. Prototype transducers were fabricated and evaluated quantitatively and clinically. The average measured center frequency for the transmit ring element was 21 MHz and the one-way --3 dB bandwidth was greater than 50%. The 40 MHz receive element functioned at 31 MHz center frequency with acceptable bandwidth to receive attenuated and frequency downshifted harmonic signal. The lateral beam profile for the 20 MHz ring elements at the focus matched the Field II simulated results well, and the effect of outer ring diameter was also examined. Images of a posterior segment of an excised pig eye and a choroidal nevus of human eye were obtained both for single element and dual element transducers and compared to demonstrate the advantages of dual element harmonic imaging.

Simultaneously phase-matched second- and third-harmonic generation from 1.55 microm radiation in annealed proton-exchanged periodically poled lithium niobate waveguides.

PubMed

Marangoni, M; Lobino, M; Ramponi, R

2006-09-15

Third-harmonic generation (THG) in the cw regime from C-band radiation was achieved in annealed proton-exchanged periodically poled lithium niobate (PPLN) waveguides. By suitable design of fabrication parameters and operating conditions, quasi-phase-matching (QPM) is obtained simultaneously for the second-harmonic generation process (omega-->2omega, first-order QPM) and for the sum-frequency-generation process (omega+2omega-->3omega, third-order QPM), which provides the third harmonic of the pump field. The high overlap between the field profiles of the interacting modes--TM00 at omega and TM10 at 2omega and 3omega--results in what is believed to be the highest ever reported normalized conversion efficiency for THG from telecommunication wavelengths, equal to 0.72%W(-2) cm(-4).

A theoretical investigation of chirp insonification of ultrasound contrast agents.

PubMed

Barlow, Euan; Mulholland, Anthony J; Gachagan, Anthony; Nordon, Alison

2011-08-01

A theoretical investigation of second harmonic imaging of an Ultrasound Contrast Agent (UCA) under chirp insonification is considered. By solving the UCA's dynamical equation analytically, the effect that the chirp signal parameters and the UCA shell parameters have on the amplitude of the second harmonic frequency are examined. This allows optimal parameter values to be identified which maximise the UCA's second harmonic response. A relationship is found for the chirp parameters which ensures that a signal can be designed to resonate a UCA for a given set of shell parameters. It is also shown that the shell thickness, shell viscosity and shell elasticity parameter should be as small as realistically possible in order to maximise the second harmonic amplitude. Keller-Herring, Second Harmonic, Chirp, Ultrasound Contrast Agent. Copyright © 2011 Elsevier B.V. All rights reserved.

Generation of coherent terahertz radiation in ultrafast laser-gas interactionsa)

NASA Astrophysics Data System (ADS)

Kim, Ki-Yong

2009-05-01

The generation of intense terahertz radiation in ultrafast laser-gas interactions is studied on a basis of transient electron current model. When an ultrashort pulse laser's fundamental and its second harmonic fields are mixed to ionize a gas, a nonvanishing, directional photoelectron current can be produced, which simultaneously emits terahertz radiation in the far field. Here, the generation mechanism is examined with an analytic derivation and numerical simulations, in which tunneling ionization and subsequent electron motion in the combined laser field play a key role. In the simulations, three types of laser-gas interactions are considered: (i) mixing the fundamental and its second harmonic fields, (ii) mixing nonharmonic, two-color fields, and (iii) focusing single-color, few-cycle pulses. In these interactions, terahertz generation and other nonlinear effects driven by the transient current are investigated. In particular, anticorrelation between terahertz and second (or third) harmonic generation is observed and analyzed.

Second harmonic generation in resonant optical structures

DOEpatents

Eichenfield, Matt; Moore, Jeremy; Friedmann, Thomas A.; Olsson, Roy H.; Wiwi, Michael; Padilla, Camille; Douglas, James Kenneth; Hattar, Khalid Mikhiel

2018-01-09

An optical second-harmonic generator (or spontaneous parametric down-converter) includes a microresonator formed of a nonlinear optical medium. The microresonator supports at least two modes that can be phase matched at different frequencies so that light can be converted between them: A first resonant mode having substantially radial polarization and a second resonant mode having substantially vertical polarization. The first and second modes have the same radial order. The thickness of the nonlinear medium is less than one-half the pump wavelength within the medium.

Field localization and enhancement of phase-locked second- and third-order harmonic generation in absorbing semiconductor cavities

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

Roppo, V.; Charles M. Bowden Research Facility, US Army RDECOM, Redstone Arsenal, Alabama 35803; Cojocaru, C.

We predict and experimentally observe the enhancement by three orders of magnitude of phase mismatched second and third harmonic generation in a GaAs cavity at 650 and 433 nm, respectively, well above the absorption edge. Phase locking between the pump and the harmonics changes the effective dispersion of the medium and inhibits absorption. Despite hostile conditions the harmonics resonate inside the cavity and become amplified leading to relatively large conversion efficiencies. Field localization thus plays a pivotal role despite the presence of absorption, and ushers in a new class of semiconductor-based devices in the visible and uv ranges.

Second harmonic generation imaging - a new method for unraveling molecular information of starch.

PubMed

Zhuo, Zong-Yan; Liao, Chien-Sheng; Huang, Chen-Han; Yu, Jiun-Yann; Tzeng, Yu-Yi; Lo, Wen; Dong, Chen-Yuan; Chui, Hsiang-Chen; Huang, Yu-Chan; Lai, Hsi-Mei; Chu, Shi-Wei

2010-07-01

We present a new method, second harmonic generation (SHG) imaging for the study of starch structure. SHG imaging can provide the structural organization and molecular orientation information of bio-tissues without centrosymmetry. In recent years, SHG has proven its capability in the study of crystallized bio-molecules such as collagen and myosin. Starch, the most important food source and a promising future energy candidate, has, for a decade, been shown to exhibit strong SHG response. By comparing SHG intensity from different starch species, we first identified that the SHG-active molecule is amylopectin, which accounts for the crystallinity in starch granules. With the aid of SHG polarization anisotropy, we extracted the complete χ((2)) tensor of amylopectin, which reflects the underlying molecular details. Through χ((2)) tensor analysis, three-dimensional orientation and packing symmetry of amylopectin are determined. The helical angle of the double-helix in amylopectin is also deduced from the tensor, and the value corresponds well to previous X-ray studies, further verifying amylopectin as SHG source. It is noteworthy that the nm-sized structure of amylopectin inside a starch granule can be determined by this far-field optical method with 1-μm excitation wavelength. Since SHG is a relatively new tool for plant research, a detailed understanding of SHG in starch structure will be useful for future high-resolution imaging and quantitative analyses for food/energy applications. Copyright © 2010 Elsevier Inc. All rights reserved.

Conversion of the optical orbital angular momentum in a plasmon-assisted second-harmonic generation

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

Wang, Yongmei; Wei, Dunzhao; Zhu, Yunzhi

We experimentally demonstrate the plasmon-assisted second-harmonic generation of an optical orbital angular momentum (OAM) beam. Because of the shape resonance, the plasmons in a periodic array of rectangular metal holes greatly enhance the nonlinear optical conversion of an OAM state. The OAM conservation (i.e., 2l{sub 1} = l{sub 2} with l{sub 1} and l{sub 2} being the OAM numbers of the fundamental and second-harmonic waves, respectively) holds well under our experimental configuration. Our results provide a potential way to realize nonlinear optical manipulation of an OAM mode in a nano-photonic device.

High-power continuous-wave tunable 544- and 272-nm beams based on a diode-oscillator fiber-amplifier for calcium spectroscopy

NASA Astrophysics Data System (ADS)

Ko, Kwang-Hoon; Kim, Yonghee; Park, Hyunmin; Cha, Yong-Ho; Kim, Taek-Soo; Lee, Lim; Lim, Gwon; Han, Jaemin; Ko, Kwang-Hee; Jeong, Do-Young

2015-08-01

Continuous-wave single-frequency tunable 544- and 272-nm beams have been demonstrated by the second- and fourth-harmonic conversions of a 1088-nm fundamental beam from a diode-oscillator fiber-amplifier. The single-pass second-harmonic generation with a MgO-doped periodically poled stoichiometric LiTaO3 crystal and the external-cavity frequency-doubling technique with a bulk BBO crystal were employed to achieve an approximately 6-W 544-nm beam and a 1.5-W 272-nm beam, respectively. We characterized the second- and fourth-harmonic generations and discussed their applications to calcium spectroscopy.

Growth and characterization of crystals for IR detectors and second harmonic gereration devices

NASA Technical Reports Server (NTRS)

Lal, Ravi B.; Batra, Ashok K.; Rao, Sistla M.; Bhatia, S. S.; Chunduru, Kunar P.; Paulson, Ron; Moorkherji, Tripty K.

1989-01-01

Two types of materials, L-arginine phosphate (LAP) and doped triglycine sulfate (TGS), are examined for their growth characteristics and relevant properties for second harmonic generation and IR detector applications, respectively.

Effect of Precipitation Morphology on the Second Harmonic Generation of Ultrasonic Wave During Tempering in P92 Steel

NASA Astrophysics Data System (ADS)

Sahu, Minati Kumari; Swaminathan, J.; Bandyopadhyay, Nil Ratan; Sagar, Sarmistha Palit

2017-10-01

This paper reports the generation of second harmonic of ultrasound wave and the variation of its amplitude with the precipitation morphology in P92 steel. P92 steel samples were normalized at 1075 °C and tempered in a range of 715-835 °C at a step of 30 °C to study the effect of nucleation and growth of precipitates on the amplitude of second harmonic of ultrasound wave. It has been observed that the non linear ultrasonic (NLU) parameter which is defined as the ratio of the amplitude of second harmonic to the square of the amplitude of the transmitted signal frequency increases with the nucleation and growth of precipitates. Whereas when the growth of precipitate is restricted and fine secondary precipitates start to nucleate, it decreases. The maximum of NLU parameter corresponds to the optimum tempering temperature for the studied material.

A novel intravital multi-harmonic generation microscope for early diagnosis of oral cancer

NASA Astrophysics Data System (ADS)

Cheng, Yu-Hsiang; Lin, Chih-Feng; Shih, Ting-Fang; Sun, Chi-Kuang

2013-03-01

Oral cancer is one of the most frequently diagnosed human cancers and leading causes of cancer death all over the world, but the prognosis and overall survival rate are still poor because of delay in diagnosis and lack of early intervention. The failure of early diagnosis is due to insufficiency of proper diagnostic and screening tools and most patients are reluctant to undergo biopsy. Optical virtual biopsy techniques, for imaging cells and tissues at microscopic details capable of differentiating benign from malignant lesions non-invasively, are thus highly desirable. A novel multi-harmonic generation microscope, excited by a 1260 nm Cr:forsterite laser, with second and third harmonic signals demonstrating collagen fiber distribution and cell morphology in a sub-micron resolution, was developed for clinical use. To achieve invivo observation inside the human oral cavity, a small objective probe with a suction capability was carefully designed for patients' comfort and stability. By remotely changing its focus point, the same objective can image the mucosa surface with a low magnification, illuminated by side light-emitting diodes, with a charge-coupled device (CCD) for site location selection before the harmonic generation biopsy was applied. Furthermore, the slow galvanometer mirror and the fast resonant mirror provide a 30 fps frame rate for high-speed real-time observation and the z-motor of this system is triggered at the same rate to provide fast 3D scanning, again ensuring patients' comfort. Focusing on the special cytological and morphological changes of the oral epithelial cells, our preliminary result disclosed excellent consistency with traditional histopathology studies.

In-situ second harmonic generation by cancer cell targeting ZnO nanocrystals to effect photodynamic action in subcellular space.

PubMed

Gu, Bobo; Pliss, Artem; Kuzmin, Andrey N; Baev, Alexander; Ohulchanskyy, Tymish Y; Damasco, Jossana A; Yong, Ken-Tye; Wen, Shuangchun; Prasad, Paras N

2016-10-01

This paper introduces the concept of in-situ upconversion of deep penetrating near infrared light via second harmonic generation from ZnO nanocrystals delivered into cells to effect photo activated therapies, such as photodynamic therapy, which usually require activation by visible light with limited penetration through biological tissues. We demonstrated this concept by subcellular activation of a photodynamic therapy drug, Chlorin e6, excited within its strong absorption Soret band by the second harmonic (SH) light, generated at 409 nm by ZnO nanocrystals, which were targeted to cancer cells and internalized through the folate-receptor mediated endocytosis. By a combination of theoretical modeling and experimental measurements, we show that SH light, generated in-situ by ZnO nanocrystals significantly contributes to activation of photosensitizer, leading to cell death through both apoptotic and necrotic pathways initiated in the cytoplasm. This targeted photodynamic action was studied using label-free Coherent Anti-Stokes Raman Scattering imaging of the treated cells to monitor changes in the distribution of native cellular proteins and lipids. We found that initiation of photodynamic therapy with upconverted light led to global reduction in the intracellular concentration of macromolecules, likely due to suppression of proteins and lipids synthesis, which could be considered as a real-time indicator of cellular damage from photodynamic treatment. In prospective applications this in-situ photon upconversion could be further extended using ZnO nanocrystals surface functionalized with a specific organelle targeting group, provided a powerful approach to identify and consequently maximize a cellular response to phototherapy, selectively initiated in a specific cellular organelle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical multiphoton and CARS microscopy

NASA Astrophysics Data System (ADS)

Breunig, H. G.; Weinigel, M.; Darvin, M. E.; Lademann, J.; König, K.

2012-03-01

We report on clinical CARS imaging of human skin in vivo with the certified hybrid multiphoton tomograph CARSDermaInspect. The CARS-DermaInspect provides simultaneous imaging of non-fluorescent intradermal lipid and water as well as imaging of two-photon excited fluorescence from intrinsic molecules. Two different excitation schemes for CARS imaging have been realized: In the first setup, a combination of fs oscillator and optical parametric oscillator provided fs-CARS pump and Stokes pulses, respectively. In the second setup a fs oscillator was combined with a photonic crystal fiber which provided a broadband spectrum. A spectral range out of the broadband-spectrum was selected and used for CARS excitation in combination with the residual fs-oscillator output. In both setups, in addition to CARS, single-beam excitation was used for imaging of two-photon excited fluorescence and second harmonic generation signals. Both CARS-excitation systems were successfully used for imaging of lipids inside the skin in vivo.

Bernstein wave aided laser third harmonic generation in a plasma

NASA Astrophysics Data System (ADS)

Tyagi, Yachna; Tripathi, Deepak; Kumar, Ashok

2016-09-01

The process of Bernstein wave aided resonant third harmonic generation of laser in a magnetized plasma is investigated. The extra-ordinary mode (X-mode) laser of frequency ω 0 and wave number k → 0 , travelling across the magnetic field in a plasma, exerts a second harmonic ponderomotive force on the electrons imparting them an oscillatory velocity v → 2 ω0 , 2 k → 0 . This velocity beats with the density perturbation due to the Bernstein wave to produce a density perturbation at cyclotron frequency shifted second harmonic. The density perturbation couples with the oscillatory velocity v → ω0 , k → 0 of X-mode of the laser to produce the cyclotron frequency shifted third harmonic current density leading to harmonic radiation. The phase matching condition for the up shifted frequency is satisfied when the Bernstein wave is nearly counter-propagating to the laser. As the transverse wave number of the Bernstein wave is large, it is effective in the phase matched third harmonic generation, when the laser frequency is not too far from the upper hybrid frequency.

Evidence of multipolar response of Bacteriorhodopsin by noncollinear second harmonic generation.

PubMed

Bovino, F A; Larciprete, M C; Sibilia, C; Váró, G; Gergely, C

2012-06-18

Noncollinear second harmonic generation from a Bacteriorhodopsin (BR) oriented multilayer film was systematically investigated by varying the polarization state of both fundamental beams. Both experimental results and theoretical simulations, show that the resulting polarization mapping is an useful tool to put in evidence the optical chirality of the investigated film as well as the corresponding multipolar contributions to the nonlinear.

Optical tomography of human skin with subcellular spatial and picosecond time resolution using intense near infrared femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Koenig, Karsten; Wollina, Uwe; Riemann, Iris; Peukert, Christiane; Halbhuber, Karl-Juergen; Konrad, Helga; Fischer, Peter; Fuenfstueck, Veronika; Fischer, Tobias W.; Elsner, Peter

2002-06-01

We describe the novel high resolution imaging tool DermaInspect 100 for non-invasive diagnosis of dermatological disorders based on multiphoton autofluorescence imaging (MAI)and second harmonic generation. Femtosecond laser pulses in the spectral range of 750 nm to 850 nm have been used to image in vitro and in vivo human skin with subcellular spatial and picosecond temporal resolution. The non-linear induced autofluorescence originates mainly from naturally endogenous fluorophores/protein structures like NAD(P)H, flavins, keratin, collagen, elastin, porphyrins and melanin. Second harmonic generation was observed in the stratum corneum and in the dermis. The system with a wavelength-tunable compact 80 MHz Ti:sapphire laser, a scan module with galvo scan mirrors, piezoelectric objective positioner, fast photon detector and time-resolved single photon counting unit was used to perform optical sectioning and 3D autofluorescence lifetime imaging (t-mapping). In addition, a modified femtosecond laser scanning microscope was involved in autofluorescence measurements. Tissues of patients with psoriasis, nevi, dermatitis, basalioma and melanoma have been investigated. Individual cells and skin structures could be clearly visualized. Intracellular components and connective tissue structures could be further characterized by tuning the excitation wavelength in the range of 750 nm to 850 nm and by calculation of mean fluorescence lifetimes per pixel and of particular regions of interest. The novel non-invasive imaging system provides 4D (x,y,z,t) optical biopsies with subcellular resolution and offers the possibility to introduce a further optical diagnostic method in dermatology.

Second-harmonic generation from a thin spherical layer and No-generation conditions

NASA Astrophysics Data System (ADS)

Kapshai, V. N.; Shamyna, A. A.

2017-09-01

In the Rayleigh-Gans-Debye approximation, we solve the problem of second-harmonic generation by an elliptically polarized electromagnetic wave incident on the surface of a spherical particle that is coated by an optically nonlinear layer and is placed in a dielectric. The formulas obtained characterize the spatial distribution of the electric field of the second harmonic in the far-field zone. The most general form of the second-order dielectric susceptibility tensor is considered, which contains four independent components, with three of them being nonchiral and one, chiral. Consistency and inconsistencies between the obtained solution and formulas from works of other authors are found. We analyze the directivity patterns that characterize the spatial distribution of the generated radiation for the nonchiral layer and their dependences on the anisotropy and ellipticity coefficients of the incident wave. It is found that, with increasing radius of the nonlinear layer, the generated radiation becomes more directional. Combinations of parameters for which no radiation is generated are revealed. Based on this, we propose methods for experimental determination of the anisotropy coefficients.

Nonlinear Metasurface for Simultaneous Control of Spin and Orbital Angular Momentum in Second Harmonic Generation.

PubMed

Li, Guixin; Wu, Lin; Li, King F; Chen, Shumei; Schlickriede, Christian; Xu, Zhengji; Huang, Siya; Li, Wendi; Liu, Yanjun; Pun, Edwin Y B; Zentgraf, Thomas; Cheah, Kok W; Luo, Yu; Zhang, Shuang

2017-12-13

The spin and orbital angular momentum (SAM and OAM) of light is providing a new gateway toward high capacity and robust optical communications. While the generation of light with angular momentum is well studied in linear optics, its further integration into nonlinear optical devices will open new avenues for increasing the capacity of optical communications through additional information channels at new frequencies. However, it has been challenging to manipulate the both SAM and OAM of nonlinear signals in harmonic generation processes with conventional nonlinear materials. Here, we report the generation of spin-controlled OAM of light in harmonic generations by using ultrathin photonic metasurfaces. The spin manipulation of OAM mode of harmonic waves is experimentally verified by using second harmonic generation (SHG) from gold meta-atom with 3-fold rotational symmetry. By introducing nonlinear phase singularity into the metasurface devices, we successfully generate and measure the topological charges of spin-controlled OAM mode of SHG through an on-chip metasurface interferometer. The nonlinear photonic metasurface proposed in this work not only opens new avenues for manipulating the OAM of nonlinear optical signals but also benefits the understanding of the nonlinear spin-orbit interaction of light in nanoscale devices.

Analysis of Even Harmonics Generation in an Isolated Electric Power System

NASA Astrophysics Data System (ADS)

Kanao, Norikazu; Hayashi, Yasuhiro; Matsuki, Junya

Harmonics bred from loads are mainly odd order because the current waveform has half-wave symmetry. Since the even harmonics are negligibly small, those are not generally measured in electric power systems. However, even harmonics were measured at a 500/275/154kV substation in Hokuriku Electric Power Company after removal of a transmission line fault. The even harmonics caused malfunctions of protective digital relays because the relays used 4th harmonics at the input filter as automatic supervisory signal. This paper describes the mechanism of generation of the even harmonics by comparing measured waveforms with ATP-EMTP simulation results. As a result of analysis, it is cleared that even harmonics are generated by three causes. The first cause is a magnetizing current of transformers due to flux deviation by DC component of a fault current. The second one is due to harmonic conversion of a synchronous machine which generates even harmonics when direct current component or even harmonic current flow into the machine. The third one is that increase of harmonic impedance due to an isolated power system produces harmonic voltages. The design of the input filter of protective digital relays should consider even harmonics generation in an isolated power system.

Quantitative characterization of collagen in the fibrotic capsule surrounding implanted polymeric microparticles through second harmonic generation imaging

DOE PAGES

Akilbekova, Dana; Bratlie, Kaitlin M.; Abraham, Thomas

2015-06-30

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variationmore » in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively.« less

Quantitative Characterization of Collagen in the Fibrotic Capsule Surrounding Implanted Polymeric Microparticles through Second Harmonic Generation Imaging.

PubMed

Akilbekova, Dana; Bratlie, Kaitlin M

2015-01-01

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variation in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively.

Quantitative Characterization of Collagen in the Fibrotic Capsule Surrounding Implanted Polymeric Microparticles through Second Harmonic Generation Imaging

PubMed Central

Akilbekova, Dana; Bratlie, Kaitlin M.

2015-01-01

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variation in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively. PMID:26125551

Quantitative characterization of collagen in the fibrotic capsule surrounding implanted polymeric microparticles through second harmonic generation imaging

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

Akilbekova, Dana; Bratlie, Kaitlin M.; Abraham, Thomas

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variationmore » in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively.« less

Efficient nonlinear optical conversion of 1.319-micron laser radiation

NASA Astrophysics Data System (ADS)

Byer, Robert L.; Eckardt, Robert C.

1993-01-01

The accomplishments of this program are in the development and application of periodically poled nonlinear optical materials for nonlinear frequency-conversion. We have demonstrated the use of periodically poled lithium niobate (PPLN) as a bulk material for external resonant cavity second-harmonic generation with continuous-wave (cw) output power of 1.7 W. Work that is following this investigation is showing that planar waveguides of PPLN may well be the most satisfactory method of generation of 10's of mW of the 659-nm harmonic of the 1.32-micrometer Nd:YAG laser. We encountered major obstacles obtaining multilayer dielectric coatings necessary to pursue our proposed design of monolithic bulk optical harmonic generators. Additional alternative approaches such as discrete component resonant second harmonic generation employing single domain and periodically poled bulk crystals and monolithic single domain resonators formed by total internal reflection remain under investigation.

Observation of photorefractive simultons in lithium niobate.

PubMed

Fazio, Eugenio; Belardini, Alessandro; Alonzo, Massimo; Centini, Marco; Chauvet, Mathieu; Devaux, Fabrice; Scalora, Michael

2010-04-12

Spatial and temporal locking of fundamental and second harmonic pulses was realized by means of photorefractive nonlinearity and highly mismatched harmonic generation. Due to the presence of both phase-locked and unlocked second harmonic pulses, a twin simultonic state was observed. Simultonic filamentation occurring at high pumping rates allowed us to determine a relation between the simulton's waist and its intensity.

High resolution subsurface imaging using resonance-enhanced detection in 2nd-harmonic KPFM.

PubMed

Cadena, Maria Jose; Reifenberger, Ronald G; Raman, Arvind

2018-06-28

Second harmonic Kelvin probe force microscopy is a robust mechanism for subsurface imaging at the nanoscale. Here we exploit resonance-enhanced detection as a way to boost the subsurface contrast with higher force sensitivity using lower bias voltages, in comparison to the traditional off-resonance case. In this mode, the second harmonic signal of the electrostatic force is acquired at one of the eigenmode frequencies of the microcantilever. As a result, high-resolution subsurface images are obtained in a variety of nanocomposites. To further understand the subsurface imaging detection upon electrostatic forces, we use a finite element model that approximates the geometry of the probe and sample. This allows the investigation of the contrast mechanism, the depth sensitivity and lateral resolution depending on tip-sample properties. © 2018 IOP Publishing Ltd.

Tailored semiconductors for high-harmonic optoelectronics

NASA Astrophysics Data System (ADS)

Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu.; Villeneuve, D. M.; Ropers, Claus; Corkum, P. B.

2017-07-01

The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes.

Nonlinear Optical Characterization of Membrane Protein Microcrystals and Nanocrystals.

PubMed

Newman, Justin A; Simpson, Garth J

2016-01-01

Nonlinear optical methods such as second harmonic generation (SHG) and two-photon excited UV fluorescence (TPE-UVF) imaging are promising approaches to address bottlenecks in the membrane protein structure determination pipeline. The general principles of SHG and TPE-UVF are discussed here along with instrument design considerations. Comparisons to conventional methods in high throughput crystallization condition screening and crystal quality assessment prior to X-ray diffraction are also discussed.

Assessing local stromal alterations in human ovarian cancer subtypes via second harmonic generation microscopy and analysis

NASA Astrophysics Data System (ADS)

Campbell, Kirby R.; Campagnola, Paul J.

2017-11-01

The collagen architecture in all human ovarian cancers is substantially remodeled, where these alterations are manifested in different fiber widths, fiber patterns, and fibril size and packing. Second harmonic generation (SHG) microscopy has differentiated normal tissues from high-grade serous (HGS) tumors with high accuracy; however, the classification between low-grade serous, endometrioid, and benign tumors was less successful. We postulate this is due to known higher genetic variation in these tissues relative to HGS tumors, which are genetically similar, and this results in more heterogeneous collagen remodeling in the respective matrix. Here, we examine fiber widths and SHG emission intensity and directionality locally within images (e.g., 10×10 microns) and show that normal tissues and HGS tumors are more uniform in fiber properties as well as in fibril size and packing than the other tissues. Moreover, these distributions are in good agreement with phase matching considerations relating SHG emission directionality and intensity. The findings show that in addition to average collagen assembly properties the intrinsic heterogeneity must also be considered as another aspect of characterization. These local analyses showed differences not shown in pure intensity-based image analyses and may provide further insight into disease etiology of the different tumor subtypes.

Study of skeletal muscle cross-bridge population dynamics by second harmonic generation

NASA Astrophysics Data System (ADS)

Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Tesi, C.; Pirrodi, N.; Poggesi, C.; Castiglioni, C.; Milani, A.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

2007-02-01

The high degree of structural order in skeletal muscle allows imaging of this tissue by Second Harmonic Generation (SHG). Biochemical and colocalization studies have gathered an increasing wealth of clues for the attribution of the molecular origin of the muscle SHG signal to the motor protein myosin. Thus, SHG represents a potentially very powerful tool in the investigation of structural dynamics occurring in muscle during active production of force and/or shortening. A full characterization of the polarization-dependence of the SHG signal represents a very selective information on the orientation of the emitting proteins and their dynamics during contraction, provided that different physiological states of muscle (relaxed, rigor and active) exhibit distinct patterns of SHG polarization dependence. Here polarization data are obtained from single frog muscle fibers at rest and during isometric contraction and interpreted, by means of a model, in terms of an average orientation of the SHG emitters which are structured with a cylindrical symmetry about the fiber axis. The setup is optimized for accurate polarization measurements with SHG, combined with a line scan imaging method allowing acquisition of SHG polarization curves in different physiological states. We demonstrate that muscle fiber displays a measurable variation of the orientation of SHG emitters with the transition from rest to isometric contraction.

Collagenous extracellular matrix of cartilage submitted to mechanical forces studied by second harmonic generation microscopy.

PubMed

Werkmeister, Elisabeth; de Isla, Natalia; Netter, Patrick; Stoltz, Jean-François; Dumas, Dominique

2010-01-01

Osteoarthritis is a degenerative pathology leading to degradation of the extracellular matrix (ECM). Similar effects can be visualized when applying mechanical or biochemical constraints on cartilaginous tissue. Here, we characterized modification of the ECM appearing under mechanical compression and/or biochemical action (hypoxia environment, nitric oxide and collagenase action). In recent decades, multiphoton microscopy has proved its interest for observing living, thick and opaque biological tissues. Thus, the main components of the cartilaginous ECM can be observed without fluorescent labeling. In particular, the collagen network emits strong second harmonic generation (SHG) signal which could be collected at half of the excitation wavelength. Combining autofluorescence and SHG signal detection enables to obtain complementary structural information. Here, we proved that multiphoton microscopy represents an appropriate tool for ex vitro cartilage imaging. First, we showed that SHG signal specifically comes from collagen (collagenase digestion). Further, we verified that the use of an appropriate band-pass filter enables to reject the autofluorescence from the ECM. Once this specificity was shown, we followed modification of the cartilage ECM submitted to mechanical or biochemical constraints (compression, enzymatic digestion). By performing textural analysis of SHG images (Haralick's method), we showed the restructuration of the collagen network according to constraints.

Simultaneous determination of the second-harmonic generation emission directionality and reduced scattering coefficient from three-dimensional imaging of thick tissues

PubMed Central

Hall, Gunnsteinn; Eliceiri, Kevin W.

2013-01-01

Abstract. Second-harmonic generation (SHG) microscopy has intrinsic contrast for imaging fibrillar collagen and has shown great promise for disease characterization and diagnostics. In addition to morphology, additional information is achievable as the initially emitted SHG radiation directionality is related to subresolution fibril size and distribution. We show that by two parameter fittings, both the emission pattern (FSHG/BSHG)creation and the reduced scattering coefficient μs′, can be obtained from the best fits between three-dimensional experimental data and Monte Carlo simulations. The improved simulation framework accounts for collection apertures for the detected forward and backward components. We apply the new simulation framework to mouse tail tendon for validation and show that the spectral slope of μs′ obtained is similar to that from bulk optical measurements and that the (FSHG/BSHG)creation values are also similar to previous results. Additionally, we find that the SHG emission becomes increasingly forward directed at longer wavelengths, which is consistent with decreased dispersion in refractive index between the laser and SHG wavelengths. As both the spectral slope of μs′ and (FSHG/BSHG)creation have been linked to the underlying tissue structure, simultaneously obtaining these parameters on a microscope platform from the same tissue provides a powerful method for tissue characterization. PMID:24220726

Superharmonic imaging with chirp coded excitation: filtering spectrally overlapped harmonics.

PubMed

Harput, Sevan; McLaughlan, James; Cowell, David M J; Freear, Steven

2014-11-01

Superharmonic imaging improves the spatial resolution by using the higher order harmonics generated in tissue. The superharmonic component is formed by combining the third, fourth, and fifth harmonics, which have low energy content and therefore poor SNR. This study uses coded excitation to increase the excitation energy. The SNR improvement is achieved on the receiver side by performing pulse compression with harmonic matched filters. The use of coded signals also introduces new filtering capabilities that are not possible with pulsed excitation. This is especially important when using wideband signals. For narrowband signals, the spectral boundaries of the harmonics are clearly separated and thus easy to filter; however, the available imaging bandwidth is underused. Wideband excitation is preferable for harmonic imaging applications to preserve axial resolution, but it generates spectrally overlapping harmonics that are not possible to filter in time and frequency domains. After pulse compression, this overlap increases the range side lobes, which appear as imaging artifacts and reduce the Bmode image quality. In this study, the isolation of higher order harmonics was achieved in another domain by using the fan chirp transform (FChT). To show the effect of excitation bandwidth in superharmonic imaging, measurements were performed by using linear frequency modulated chirp excitation with varying bandwidths of 10% to 50%. Superharmonic imaging was performed on a wire phantom using a wideband chirp excitation. Results were presented with and without applying the FChT filtering technique by comparing the spatial resolution and side lobe levels. Wideband excitation signals achieved a better resolution as expected, however range side lobes as high as -23 dB were observed for the superharmonic component of chirp excitation with 50% fractional bandwidth. The proposed filtering technique achieved >50 dB range side lobe suppression and improved the image quality without affecting the axial resolution.

Collagen morphology and texture analysis: from statistics to classification

PubMed Central

Mostaço-Guidolin, Leila B.; Ko, Alex C.-T.; Wang, Fei; Xiang, Bo; Hewko, Mark; Tian, Ganghong; Major, Arkady; Shiomi, Masashi; Sowa, Michael G.

2013-01-01

In this study we present an image analysis methodology capable of quantifying morphological changes in tissue collagen fibril organization caused by pathological conditions. Texture analysis based on first-order statistics (FOS) and second-order statistics such as gray level co-occurrence matrix (GLCM) was explored to extract second-harmonic generation (SHG) image features that are associated with the structural and biochemical changes of tissue collagen networks. Based on these extracted quantitative parameters, multi-group classification of SHG images was performed. With combined FOS and GLCM texture values, we achieved reliable classification of SHG collagen images acquired from atherosclerosis arteries with >90% accuracy, sensitivity and specificity. The proposed methodology can be applied to a wide range of conditions involving collagen re-modeling, such as in skin disorders, different types of fibrosis and muscular-skeletal diseases affecting ligaments and cartilage. PMID:23846580

Phenomenological modeling of nonlinear holograms based on metallic geometric metasurfaces.

PubMed

Ye, Weimin; Li, Xin; Liu, Juan; Zhang, Shuang

2016-10-31

Benefiting from efficient local phase and amplitude control at the subwavelength scale, metasurfaces offer a new platform for computer generated holography with high spatial resolution. Three-dimensional and high efficient holograms have been realized by metasurfaces constituted by subwavelength meta-atoms with spatially varying geometries or orientations. Metasurfaces have been recently extended to the nonlinear optical regime to generate holographic images in harmonic generation waves. Thus far, there has been no vector field simulation of nonlinear metasurface holograms because of the tremendous computational challenge in numerically calculating the collective nonlinear responses of the large number of different subwavelength meta-atoms in a hologram. Here, we propose a general phenomenological method to model nonlinear metasurface holograms based on the assumption that every meta-atom could be described by a localized nonlinear polarizability tensor. Applied to geometric nonlinear metasurfaces, we numerically model the holographic images formed by the second-harmonic waves of different spins. We show that, in contrast to the metasurface holograms operating in the linear optical regime, the wavelength of incident fundamental light should be slightly detuned from the fundamental resonant wavelength to optimize the efficiency and quality of nonlinear holographic images. The proposed modeling provides a general method to simulate nonlinear optical devices based on metallic metasurfaces.

20 MHz/40 MHz Dual Element Transducers for High Frequency Harmonic Imaging

PubMed Central

Kim, Hyung Ham; Cannata, Jonathan M.; Liu, Ruibin; Chang, Jin Ho; Silverman, Ronald H.; Shung, K. Kirk

2009-01-01

Concentric annular type dual element transducers for second harmonic imaging at 20 MHz / 40 MHz were designed and fabricated to improve spatial resolution and depth of penetration for ophthalmic imaging applications. The outer ring element was designed to transmit the 20 MHz signal and the inner circular element was designed to receive the 40 MHz second harmonic signal. Lithium niobate (LiNbO3), with its low dielectric constant, was used as the piezoelectric material to achieve good electrical impedance matching. Double matching layers and conductive backing were used and optimized by KLM modeling to achieve high sensitivity and wide bandwidth for harmonic imaging and superior time-domain characteristics. Prototype transducers were fabricated and evaluated quantitatively and clinically. The average measured center frequency for the transmit ring element was 21 MHz and the one-way –3 dB bandwidth was greater than 50%. The 40 MHz receive element functioned at 31 MHz center frequency with acceptable bandwidth to receive attenuated and frequency downshifted harmonic signal. The lateral beam profile for the 20 MHz ring elements at the focus matched the Field II simulated results well, and the effect of outer ring diameter was also examined. Images of a posterior segment of an excised pig eye and a choroidal nevus of human eye were obtained both for single element and dual element transducers and compared to demonstrate the advantages of dual element harmonic imaging. PMID:19126492

Second-harmonic generation in single crystals of 2-(N,N-dimethylamino)-5-nitroacetanilide (DAN) at 1.3 micron

NASA Astrophysics Data System (ADS)

Kolinsky, P. V.; Chad, R. J.; Jones, R. J.; Hall, S. R.; Norman, P. A.

1987-07-01

Measurements are reported on efficiency phase-matched second-harmonic generation in a single crystal of the organic material 2-(N,N-dimethylamino)-5-nitroacetanilide at the technologically important communications wavelength of 1.3 micron. Using 0.5 mJ pulses, a conversion efficiency of 18 percent has been achieved for a sample 2 mm thick.

Optical second-harmonic-generation probe of two-dimensional ferroelectricity.

PubMed

Aktsipetrov, O A; Misuryaev, T V; Murzina, T V; Blinov, L M; Fridkin, V M; Palto, S P

2000-03-15

Optical second-harmonic generation (SHG) is used as a noninvasive probe of two-dimensional (2D) ferroelectricity in Langmuir-Blodgett (LB) films of the copolymer vinylidene fluoride with trifluoroethylene. The surface 2D ferroelectric-paraelectric phase transition in the topmost layer of the LB films and a thickness-independent (almost 2D) transition in the bulk of these films are observed in temperature studies of SHG.

Second-harmonic generation in AlGaAs microdisks in the telecom range.

PubMed

Mariani, S; Andronico, A; Lemaître, A; Favero, I; Ducci, S; Leo, G

2014-05-15

We report on second-harmonic generation in whispering-gallery-mode AlGaAs microcavities suspended on a GaAs pedestal. Frequency doubling of a 1.58 μm pump is observed with 7×10(-4)   W(-1) conversion efficiency. This device can be integrated in a monolithic photonic chip for classical and quantum applications in the telecom band.

Thermal characteristics of second harmonic generation by phase matched calorimetry.

PubMed

Lim, Hwan Hong; Kurimura, Sunao; Noguchi, Keisuke; Shoji, Ichiro

2014-07-28

We analyze a solution of the heat equation for second harmonic generation (SHG) with a focused Gaussian beam and simulate the temperature rise in SHG materials as a function of the second harmonic power and the focusing conditions. We also propose a quantitative value of the heat removal performance of SHG devices, referred to as the effective heat capacity Cα in phase matched calorimetry. We demonstrate the inverse relation between Cα and the focusing parameter ξ, and propose the universal quantity of the product of Cα and ξ for characterizing the thermal property of SHG devices. Finally, we discuss the strategy to manage thermal dephasing in SHG using the results from simulations.

Tumor tissue characterization using polarization-sensitive second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Tokarz, Danielle; Cisek, Richard; Golaraei, Ahmad; Krouglov, Serguei; Navab, Roya; Niu, Carolyn; Sakashita, Shingo; Yasufuku, Kazuhiro; Tsao, Ming-Sound; Asa, Sylvia L.; Barzda, Virginijus; Wilson, Brian C.

2015-06-01

Changes in the ultrastructure of collagen in various tumor and non-tumor human tissues including lung, pancreas and thyroid were investigated ex vivo by a polarization-sensitive second harmonic generation (SHG) microscopy technique referred to as polarization-in, polarization-out (PIPO) SHG. This involves measuring the orientation of the linear polarization of outgoing SHG as a function of the linear polarization orientation of incident laser radiation. From the PIPO SHG data, the second-order nonlinear optical susceptibility tensor component ratio, χ(2) ZZZ'/χ(2) ZXX', for each pixel of the SHG image was obtained and presented as color-coded maps. Further, the orientation of collagen fibers in the tissue was deduced. Since the χ(2) ZZZ'/χ(2) ZXX' values represent the organization of collagen in the tissue, theses maps revealed areas of altered collagen structure (not simply concentration) within tissue sections. Statistically-significant differences in χ(2) ZZZ'/χ(2) ZXX' were found between tumor and non-tumor tissues, which varied from organ to organ. Hence, PIPO SHG microscopy could potentially be used to aid pathologists in diagnosing cancer. Additionally, PIPO SHG microscopy could aid in characterizing the structure of collagen in other collagen-related biological processes such as wound repair.

PREFACE: Ultrafast biophotonics Ultrafast biophotonics

NASA Astrophysics Data System (ADS)

Gu, Min; Reid, Derryck; Ben-Yakar, Adela

2010-08-01

The use of light to explore biology can be traced to the first observations of tissue made with early microscopes in the mid-seventeenth century, and has today evolved into the discipline which we now know as biophotonics. This field encompasses a diverse range of activities, each of which shares the common theme of exploiting the interaction of light with biological material. With the rapid advancement of ultrafast optical technologies over the last few decades, ultrafast lasers have increasingly found applications in biophotonics, to the extent that the distinctive new field of ultrafast biophotonics has now emerged, where robust turnkey ultrafast laser systems are facilitating cutting-edge studies in the life sciences to take place in everyday laboratories. The broad spectral bandwidths, precision timing resolution, low coherence and high peak powers of ultrafast optical pulses provide unique opportunities for imaging and manipulating biological systems. Time-resolved studies of bio-molecular dynamics exploit the short pulse durations from such lasers, while other applications such as optical coherence tomography benefit from the broad optical bandwidths possible by using super-continuum generation and additionally allowing for high speed imaging with speeds as high as 47 000 scans per second. Continuing progress in laser-system technology is accelerating the adoption of ultrafast techniques across the life sciences, both in research laboratories and in clinical applications, such as laser-assisted in situ keratomileusis (LASIK) eye surgery. Revolutionizing the field of optical microscopy, two-photon excitation fluorescence (TPEF) microscopy has enabled higher spatial resolution with improved depth penetration into biological specimens. Advantages of this nonlinear optical process include: reduced photo-interactions, allowing for extensive imaging time periods; simultaneously exciting multiple fluorescent molecules with only one excitation wavelength; and reduced chromatic aberration effects. These extensive advantages have led to further exploration of nonlinear processes including second-harmonic generation (SHG) microscopy and third-harmonic generation (THG) microscopy. Second-harmonic generation has provided biologists with an extremely powerful tool for generating contrast in biological imaging, with the additional benefit of non-invasive three-dimensional imaging. The recent popularity of THG microscopy is largely due to the fact that three-dimensional imaging is achievable without the need for any labels, but rather relying on the intrinsic properties of the biological specimen itself. This optical nonlinear technique has attracted much attention recently from the biological community due to its non-invasive capabilities. Users of ultrafast lasers in the biological and medical fields are becoming a fast-growing community, employing pulse-shaping microscopy, resolution-enhancing microscopy techniques, linear and nonlinear micro-spectroscopy, functional deep-tissue imaging, optical coherence tomography, nonlinear fluorescence microscopy, molecular imaging and control, harmonic microscopy and femtosecond lifetime imaging, for cutting-edge research concerning the interaction of light with biological dynamics. The adaptability of ultrafast lasers to interact with a large array of materials through nonlinear excitation has enabled precise control of laser fluence allowing for highly localized material interactions, permitting micro-structured fabricated surfaces. The resultant multi-dimensional fabricated micro-structures are capable of replicating and/or manipulating microenvironments for controlled cell biology. In this special issue of Journal of Optics readers have a chance to view a collection of new contributions to the growing research field of ultrafast biophotonics. They are presented with recent advances in ultrafast technology applied to biological and medical investigations, where topics include advances in the visualization and identification of photo-reaction dynamics of biological functions under relevant physiological conditions, theoretically proposed imaging designs for obtaining super-resolved optical sectioned images in single exposures and fabricated micro-structured surfaces for biological micro-environments. We hope the collection will stimulate innovative new research in this growing field by showcasing new techniques for the visualization and manipulation of complex biological systems using linear and and nonlinear optical processes. Professor Min Gu would like to acknowledge Dr Betty Kouskousis for her contribution and support towards this editorial.

Investigation about relationships between the symmetries of ferroelectric crystal Ca0.28Ba0.72Nb2O6 and second-harmonic patterns

NASA Astrophysics Data System (ADS)

Xu, Tianxiang; Yu, Haohai; Zhang, Huaijin; Wang, Jiyang

2015-08-01

The broadband quasi-phase matching (QPM) process in a uniaxial ferroelectric crystal Ca0.28Ba0.72Nb2O6 (CBN-28) was demonstrated with the second-harmonic wavelength range from 450 nm to 650 nm, and the relationship between the symmetries of CBN-28 and the second-harmonic patterns was experimentally and theoretically investigated based on the random anti-parallel domains in the crystal and QPM conditions. The dependences of frequency-doubled patterns on the wavelength and anisotropy of the nonlinear crystal were also studied, and the frequency-doubled photons were found to be trapped on circles. By analyzing the light-matter interacting Hamiltonians, the trapping force for second-harmonic photons was found to be centripetal and tunable by the fundamental lasers, and the variation tendencies of the rotational velocity of second-harmonic generation photons could also be predicated. The results indicate that the CBN-28 ferroelectric crystal is a promising nonlinear optical material for the generation of broadband frequency-doubled waves, and the analysis on centripetal force based on the interaction Hamiltonians may provide a novel recognition for the investigation of QPM process to be further studied.

High-fidelity large area nano-patterning of silicon with femtosecond light sheet

NASA Astrophysics Data System (ADS)

Sidhu, Mehra S.; Munjal, Pooja; Singh, Kamal P.

2018-01-01

We employ a femtosecond light sheet generated by a cylindrical lens to rapidly produce high-fidelity nano-structures over large area on silicon surface. The Fourier analysis of electron microscopy images of the laser-induced surface structures reveals sharp peaks indicating good homogeneity. We observed an emergence of second-order spatial periodicity on increasing the scan speed. Our reliable approach may rapidly nano-pattern curved solid surfaces and tiny objects for diverse potential applications in optical devices, structural coloring, plasmonic substrates and in high-harmonic generation.

Optimization of a phased-array transducer for multiple harmonic imaging in medical applications: frequency and topology.

PubMed

Matte, Guillaume M; Van Neer, Paul L M J; Danilouchkine, Mike G; Huijssen, Jacob; Verweij, Martin D; de Jong, Nico

2011-03-01

Second-harmonic imaging is currently one of the standards in commercial echographic systems for diagnosis, because of its high spatial resolution and low sensitivity to clutter and near-field artifacts. The use of nonlinear phenomena mirrors is a great set of solutions to improve echographic image resolution. To further enhance the resolution and image quality, the combination of the 3rd to 5th harmonics--dubbed the superharmonics--could be used. However, this requires a bandwidth exceeding that of conventional transducers. A promising solution features a phased-array design with interleaved low- and high-frequency elements for transmission and reception, respectively. Because the amplitude of the backscattered higher harmonics at the transducer surface is relatively low, it is highly desirable to increase the sensitivity in reception. Therefore, we investigated the optimization of the number of elements in the receiving aperture as well as their arrangement (topology). A variety of configurations was considered, including one transmit element for each receive element (1/2) up to one transmit for 7 receive elements (1/8). The topologies are assessed based on the ratio of the harmonic peak pressures in the main and grating lobes. Further, the higher harmonic level is maximized by optimization of the center frequency of the transmitted pulse. The achievable SNR for a specific application is a compromise between the frequency-dependent attenuation and nonlinearity at a required penetration depth. To calculate the SNR of the complete imaging chain, we use an approach analogous to the sonar equation used in underwater acoustics. The generated harmonic pressure fields caused by nonlinear wave propagation were modeled with the iterative nonlinear contrast source (INCS) method, the KZK, or the Burger's equation. The optimal topology for superharmonic imaging was an interleaved design with 1 transmit element per 6 receive elements. It improves the SNR by ~5 dB compared with the interleaved (1/2) design reported in literature. The optimal transmit frequency for superharmonic echocardiography was found to be 1.0 to 1.2 MHz. For superharmonic abdominal imaging this frequency was found to be 1.7 to 1.9 MHz. For 2nd-harmonic echocardiography, the optimal transmit frequency of 1.8 MHz reported in the literature was corroborated with our simulation results.

Nonlinear spectral imaging of biological tissues

NASA Astrophysics Data System (ADS)

Palero, J. A.

2007-07-01

The work presented in this thesis demonstrates live high resolution 3D imaging of tissue in its native state and environment. The nonlinear interaction between focussed femtosecond light pulses and the biological tissue results in the emission of natural autofluorescence and second-harmonic signal. Because biological intrinsic emission is generally very weak and extends from the ultraviolet to the visible spectral range, a broad-spectral range and high sensitivity 3D spectral imaging system is developed. Imaging the spectral characteristics of the biological intrinsic emission reveals the structure and biochemistry of the cells and extra-cellular components. By using different methods in visualizing the spectral images, discrimination between different tissue structures is achieved without the use of any stain or fluorescent label. For instance, RGB real color spectral images of the intrinsic emission of mouse skin tissues show blue cells, green hair follicles, and purple collagen fibers. The color signature of each tissue component is directly related to its characteristic emission spectrum. The results of this study show that skin tissue nonlinear intrinsic emission is mainly due to the autofluorescence of reduced nicotinamide adenine dinucleotide (phosphate), flavins, keratin, melanin, phospholipids, elastin and collagen and nonlinear Raman scattering and second-harmonic generation in Type I collagen. In vivo time-lapse spectral imaging is implemented to study metabolic changes in epidermal cells in tissues. Optical scattering in tissues, a key factor in determining the maximum achievable imaging depth, is also investigated in this work.

Evaluation of the optical axis tilt of zinc oxide films via noncollinear second harmonic generation

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

Bovino, F. A.; Larciprete, M. C.; Belardini, A.

2009-06-22

We investigated noncollinear second harmonic generation form zinc oxide films, grown on glass substrates by dual ion beam sputtering technique. At a fixed incidence angle, the generated signal is investigated by scanning the polarization state of both fundamental beams. We show that the map of the generated signal as a function of polarization states of both pump beams, together with the analytical curves, allows to retrieve the orientation of the optical axis and eventually, its angular tilt, with respect to the surface normal.

Theoretical study on second-harmonic generation of focused vortex beams

NASA Astrophysics Data System (ADS)

Tang, Daolong; Wang, Jing; Ma, Jingui; Zhou, Bingjie; Yuan, Peng; Xie, Guoqiang; Zhu, Heyuan; Qian, Liejia

2018-03-01

Second-harmonic generation (SHG) provides a promising route for generating vortex beams of both short wavelength and large topological charge. Here we theoretically investigate the efficiency optimization and beam characteristics of focused vortex-beam SHG. Owing to the increasing beam divergence, vortex beams have distinct features in SHG optimization compared with a Gaussian beam. We show that, under the noncritical phase-matching condition, the Boyd and Kleinman prediction of the optimal focusing parameter for Gaussian-beam SHG remains valid for vortex-beam SHG. However, under the critical phase-matching condition, which is sensitive to the beam divergence, the Boyd and Kleinman prediction is no longer valid. In contrast, the optimal focusing parameter for maximizing the SHG efficiency strongly depends on the vortex order. We also investigate the effects of focusing and phase-matching conditions on the second-harmonic beam characteristics.

A High Power Frequency Doubled Fiber Laser

NASA Technical Reports Server (NTRS)

Thompson, Robert J.; Tu, Meirong; Aveline, Dave; Lundblad, Nathan; Maleki, Lute

2003-01-01

This viewgraph presentation reports on the development of a high power 780 nm laser suitable for space applications of laser cooling. A possible solution is to use frequency doubling of high power 1560 nm telecom lasers. The presentation shows a diagram of the frequency conversion, and a graph of the second harmonic generation in one crystal, and the use of the cascading crystals. Graphs show the second harmonic power as a function of distance between crystals, second harmonic power vs. pump power, tunability of laser systems.

Bismuth ferrite dielectric nanoparticles excited at telecom wavelengths as multicolor sources by second, third, and fourth harmonic generation.

PubMed

Riporto, Jérémy; Demierre, Alexis; Kilin, Vasyl; Balciunas, Tadas; Schmidt, Cédric; Campargue, Gabriel; Urbain, Mathias; Baltuska, Andrius; Le Dantec, Ronan; Wolf, Jean-Pierre; Mugnier, Yannick; Bonacina, Luigi

2018-05-03

We demonstrate the simultaneous generation of second, third, and fourth harmonics from a single dielectric bismuth ferrite nanoparticle excited using a telecom fiber laser at 1560 nm. We first characterize the signals associated with different nonlinear orders in terms of spectrum, excitation intensity dependence, and relative signal strengths. Successively, on the basis of the polarization-resolved emission curves of the three harmonics, we discuss the interplay of susceptibility tensor components at different orders and show how polarization can be used as an optical handle to control the relative frequency conversion properties.

Extreme Ultraviolet Fractional Orbital Angular Momentum Beams from High Harmonic Generation

PubMed Central

Turpin, Alex; Rego, Laura; Picón, Antonio; San Román, Julio; Hernández-García, Carlos

2017-01-01

We investigate theoretically the generation of extreme-ultraviolet (EUV) beams carrying fractional orbital angular momentum. To this end, we drive high-order harmonic generation with infrared conical refraction (CR) beams. We show that the high-order harmonic beams emitted in the EUV/soft x-ray regime preserve the characteristic signatures of the driving beam, namely ringlike transverse intensity profile and CR-like polarization distribution. As a result, through orbital and spin angular momentum conservation, harmonic beams are emitted with fractional orbital angular momentum, and they can be synthesized into structured attosecond helical beams –or “structured attosecond light springs”– with rotating linear polarization along the azimuth. Our proposal overcomes the state of the art limitations for the generation of light beams far from the visible domain carrying non-integer orbital angular momentum and could be applied in fields such as diffraction imaging, EUV lithography, particle trapping, and super-resolution imaging. PMID:28281655

Self-Phase-Matched Second-Harmonic and White-Light Generation in a Biaxial Zinc Tungstate Single Crystal

PubMed Central

Osewski, Pawel; Belardini, Alessandro; Petronijevic, Emilija; Centini, Marco; Leahu, Grigore; Diduszko, Ryszard; Pawlak, Dorota A.; Sibilia, Concita

2017-01-01

Second-order nonlinear optical materials are used to generate new frequencies by exploiting second-harmonic generation (SHG), a phenomenon where a nonlinear material generates light at double the optical frequency of the input beam. Maximum SHG is achieved when the pump and the generated waves are in phase, for example through birefringence in uniaxial crystals. However, applying these materials usually requires a complicated cutting procedure to yield a crystal with a particular orientation. Here we demonstrate the first example of phase matching under the normal incidence of SHG in a biaxial monoclinic single crystal of zinc tungstate. The crystal was grown by the micro-pulling-down method with the (102) plane perpendicular to the growth direction. Additionally, at the same time white light was generated as a result of stimulated Raman scattering and multiphoton luminescence induced by higher-order effects such as three-photon luminescence enhanced by cascaded third-harmonic generation. The annealed crystal offers SHG intensities approximately four times larger than the as grown one; optimized growth and annealing conditions may lead to much higher SHG intensities. PMID:28338074

Self-Phase-Matched Second-Harmonic and White-Light Generation in a Biaxial Zinc Tungstate Single Crystal

NASA Astrophysics Data System (ADS)

Osewski, Pawel; Belardini, Alessandro; Petronijevic, Emilija; Centini, Marco; Leahu, Grigore; Diduszko, Ryszard; Pawlak, Dorota A.; Sibilia, Concita

2017-03-01

Second-order nonlinear optical materials are used to generate new frequencies by exploiting second-harmonic generation (SHG), a phenomenon where a nonlinear material generates light at double the optical frequency of the input beam. Maximum SHG is achieved when the pump and the generated waves are in phase, for example through birefringence in uniaxial crystals. However, applying these materials usually requires a complicated cutting procedure to yield a crystal with a particular orientation. Here we demonstrate the first example of phase matching under the normal incidence of SHG in a biaxial monoclinic single crystal of zinc tungstate. The crystal was grown by the micro-pulling-down method with the (102) plane perpendicular to the growth direction. Additionally, at the same time white light was generated as a result of stimulated Raman scattering and multiphoton luminescence induced by higher-order effects such as three-photon luminescence enhanced by cascaded third-harmonic generation. The annealed crystal offers SHG intensities approximately four times larger than the as grown one; optimized growth and annealing conditions may lead to much higher SHG intensities.

Nonlinear optical effects on the surface of acridine yellow-doped lead-tin fluorophosphate glass

NASA Technical Reports Server (NTRS)

He, K. X.; Bryant, William; Venkateswarlu, Putcha

1991-01-01

The second- and third-order nonlinear optical properties of acridine yellow-doped lead-tin fluorophosphate (LTF) glass have been directly studied by measurement of surface enhanced second harmonic generation and third harmonic generation. The three photon excitation fluorescence is also observed. Based on these results, the large nonlinearities of the acridine LTF system which is a new nonlinear optical material are experimentally demonstrated.

Harmonics Generation by Surface Plasmon Polaritons on Single Nanowires.

PubMed

de Hoogh, Anouk; Opheij, Aron; Wulf, Matthias; Rotenberg, Nir; Kuipers, L

2016-08-17

We present experimental observations of visible wavelength second- and third-harmonic generation on single plasmonic nanowires of variable widths. We identify that near-infrared surface plasmon polaritons, which are guided along the nanowire, act as the source of the harmonics generation. We discuss the underlying mechanism of this nonlinear process, using a combination of spatially resolved measurements and numerical simulations to show that the visible harmonics are generated via a combination of both local and propagating plasmonic modes. Our results provide the first demonstration of nanoscale nonlinear optics with guided, propagating plasmonic modes on a lithographically defined chip, opening up new routes toward integrated optical circuits for information processing.

Influence of mode-beating pulse on laser-induced plasma

NASA Astrophysics Data System (ADS)

Nishihara, M.; Freund, J. B.; Glumac, N. G.; Elliott, G. S.

2018-04-01

This paper addresses the influence of mode-beating pulse on laser-induced plasma. The second harmonic of a Nd:YAG laser, operated either with the single mode or multimode, was used for non-resonant optical breakdown, and subsequent plasma development was visualized using a streak imaging system. The single mode lasing leads to a stable breakdown location and smooth envelopment of the plasma boundary, while the multimode lasing, with the dominant mode-beating frequency of 500-800 MHz, leads to fluctuations in the breakdown location, a globally modulated plasma surface, and growth of local microstructures at the plasma boundary. The distribution of the local inhomogeneity was measured from the elastic scattering signals on the streak image. The distance between the local structures agreed with the expected wavelength of hydrodynamic instability development due to the interference between the surface excited wave and transmitted wave. A numerical simulation, however, indicates that the local microstructure could also be directly generated at the peaks of the higher harmonic components if the multimode pulse contains up to the eighth harmonic of the fundamental cavity mode.

High-harmonic generation in amorphous solids

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

You, Yong Sing; Yin, Yanchun; Wu, Yi

High-harmonic generation in isolated atoms and molecules has been widely utilized in extreme ultraviolet photonics and attosecond pulse metrology. Recently, high-harmonic generation has been observed in solids, which could lead to important applications such as all-optical methods to image valance charge density and reconstruct electronic band structures, as well as compact extreme ultraviolet light sources. So far these studies are confined to crystalline solids; therefore, decoupling the respective roles of long-range periodicity and high density has been challenging. Here we report the observation of high-harmonic generation from amorphous fused silica. We also decouple the role of long-range periodicity by comparingmore » harmonics generated from fused silica and crystalline quartz, which contain the same atomic constituents but differ in long-range periodicity. These results advance current understanding of the strong-field processes leading to high-harmonic generation in solids with implications for the development of robust and compact extreme ultraviolet light sources.« less

High-harmonic generation in amorphous solids

DOE PAGES

You, Yong Sing; Yin, Yanchun; Wu, Yi; ...

2017-09-28

High-harmonic generation in isolated atoms and molecules has been widely utilized in extreme ultraviolet photonics and attosecond pulse metrology. Recently, high-harmonic generation has been observed in solids, which could lead to important applications such as all-optical methods to image valance charge density and reconstruct electronic band structures, as well as compact extreme ultraviolet light sources. So far these studies are confined to crystalline solids; therefore, decoupling the respective roles of long-range periodicity and high density has been challenging. Here we report the observation of high-harmonic generation from amorphous fused silica. We also decouple the role of long-range periodicity by comparingmore » harmonics generated from fused silica and crystalline quartz, which contain the same atomic constituents but differ in long-range periodicity. These results advance current understanding of the strong-field processes leading to high-harmonic generation in solids with implications for the development of robust and compact extreme ultraviolet light sources.« less

Human sperm steer with second harmonics of the flagellar beat.

PubMed

Saggiorato, Guglielmo; Alvarez, Luis; Jikeli, Jan F; Kaupp, U Benjamin; Gompper, Gerhard; Elgeti, Jens

2017-11-10

Sperm are propelled by bending waves traveling along their flagellum. For steering in gradients of sensory cues, sperm adjust the flagellar waveform. Symmetric and asymmetric waveforms result in straight and curved swimming paths, respectively. Two mechanisms causing spatially asymmetric waveforms have been proposed: an average flagellar curvature and buckling. We image flagella of human sperm tethered with the head to a surface. The waveform is characterized by a fundamental beat frequency and its second harmonic. The superposition of harmonics breaks the beat symmetry temporally rather than spatially. As a result, sperm rotate around the tethering point. The rotation velocity is determined by the second-harmonic amplitude and phase. Stimulation with the female sex hormone progesterone enhances the second-harmonic contribution and, thereby, modulates sperm rotation. Higher beat frequency components exist in other flagellated cells; therefore, this steering mechanism might be widespread and could inspire the design of synthetic microswimmers.

Second-harmonic generation and fluorescence lifetime imaging microscopy through a rodent mammary imaging window

NASA Astrophysics Data System (ADS)

Young, Pamela A.; Nazir, Muhammad; Szulczewski, Michael J.; Keely, Patricia J.; Eliceiri, Kevin W.

2012-03-01

Tumor-Associated Collagen Signatures (TACS) have been identified that manifest in specific ways during breast tumor progression and that correspond to patient outcome. There are also compelling metabolic changes associated with carcinoma invasion and progression. We have characterized the difference in the autofluorescent properties of metabolic co-factors, NADH and FAD, between normal and carcinoma breast cell lines. Also, we have shown in vitro that increased collagen density alters metabolic genes which are associated with glycolysis and leads to a more invasive phenotype. Establishing the relationship between collagen density, cellular metabolism, and metastasis in physiologically relevant cancer models is crucial for developing cancer therapies. To study cellular metabolism with respect to collagen density in vivo, we use multiphoton fluorescence excitation microscopy (MPM) in conjunction with a rodent mammary imaging window implanted in defined mouse cancer models. These models are ideal for the study of collagen changes in vivo, allowing determination of corresponding metabolic changes in breast cancer invasion and progression. To measure cellular metabolism, we collect fluorescence lifetime (FLIM) signatures of NADH and FAD, which are known to change based on the microenvironment of the cells. Additionally, MPM systems are capable of collecting second harmonic generation (SHG) signals which are a nonlinear optical property of collagen. Therefore, MPM, SHG, and FLIM are powerful tools with great potential for characterizing key features of breast carcinoma in vivo. Below we present the current efforts of our collaborative group to develop intravital approaches based on these imaging techniques to look at defined mouse mammary models.

Examination of a demyelinated fiber by action-potential-encoded second harmonic generation

NASA Astrophysics Data System (ADS)

Chen, Xin-guang; Luo, Zhi-hui; Yang, Hong-qin; Huang, Yi-mei; Xie, Shu-sen

2012-03-01

Axonal demyelination is a common phenomenon in the nervous system in human. Conventional measured approaches such as surface recording electrode and diffusion tensor imaging, are hard to fast and accurately determine the demyelinated status of a fiber. In this study, we first presented a mathematical model of nerve fiber demyelination, and it was combined with second harmonic generation(SHG) technique to study the characteristics of action-potential-encoded SHG and analyze the sensitivity of SHG signals responded to membrane potential. And then, we used this approach to fast examine the injured myelin sheaths resulted from demyelination. Each myelin sheath of a fiber was examined simultaneously by this approach. The results showed that fiber demyelination led to observable attenuation of action potential amplitude. The delay of action potential conduction would be markedly observed when the fiber demyelination was more than 80%. Furthermore, the normal and injured myelin sheaths of a myelinated fiber could be distinguished via the changes of SHG signals, which revealed the possibility of SHG technique in the examination of a demyelinated fiber. Our study shows that this approach may have potential application values in clinic.

High-contrast imaging of mycobacterium tuberculosis using third-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Kim, Bo Ram; Lee, Eungjang; Park, Seung-Han

2015-07-01

Nonlinear optical microcopy has become an important tool in investigating biomaterials due to its various advantages such as label-free imaging capabilities. In particular, it has been shown that third-harmonic generation (THG) signals can be produced at interfaces between an aqueous medium (e.g. cytoplasm, interstitial fluid) and a mineralized lipidic surface. In this work, we have demonstrated that label-free high-contrast THG images of the mycobacterium tuberculosis can be obtained using THG microscopy.

Observation of tendon repair in animal model using second-harmonic-generation microscopy

NASA Astrophysics Data System (ADS)

Hase, Eiji; Minamikawa, Takeo; Sato, Katsuya; Takahashi, Mitsuhiko; Yasui, Takashi

2016-03-01

Tendon rupture is a trauma difficult to recover the condition before injury. In previous researches, tensile test and staining method have been widely used to elucidate the mechanism of the repair process from the viewpoints of the mechanical property and the histological findings. However, since both methods are destructive and invasive, it is difficult to obtain both of them for the same sample. If both the mechanical property and the histological findings can be obtained from the same sample, one may obtain new findings regarding mechanisms of tendon repairing process. In this paper, we used second-harmonic-generation (SHG) microscopy, showing high selectivity and good image contrast to collagen molecules as well as high spatial resolution, optical three-dimensional sectioning, deep penetration, and without additional staining. Since SHG light intensity sensitively reflects the structural maturity of collagen molecule and its aggregates, it will be a good indicator for the repairing degree of the ruptured tendon. From comparison of SHG images between the 4-weeks-repaired tendon and the sound tendon in the animal model, we confirmed that SHG light intensity of the repaired tendon was significantly lower than that of the sound tendon, indicating that the collagen structure in the repaired tendon is still immature. Furthermore, we performed both SHG imaging and the tensile test for the same sample, and confirmed a correlation between them. This result shows a potential of SHG light for an indicator of the histological and mechanical recovery of the ruptured tendon.

Development of high repetition rate nitric oxide planar laser induced fluorescence imaging

NASA Astrophysics Data System (ADS)

Jiang, Naibo

This thesis has documented the development of a MHz repitition rate pulse burst laser system. Second harmonic and third harmonic efficiencies are improved by adding a Phase Conjugate Mirror to the system. Some high energy fundamental, second harmonic, and third harmonic burst sequences consisting of 1--12 pulses separated in time by between 4 and 12 microseconds are now routinely obtained. The reported burst envelopes are quite uniform. We have also demonstrated the ability to generate ultra-high frequency sequences of broadly wavelength tunable, high intensity laser pulses using a home built injection seeded Optical Parametric Oscillator (OPO), pumped by the second and third harmonic output of the pulse burst laser. Typical OPO output burst sequences consist of 6--10 pulses, separated in time by between 6 and 10 microseconds. With third harmonic pumping of the OPO system, we studied four conditions, two-crystal Singly Resonant OPO (SRO) cavity, three-crystal OPO cavity, single pass two-crystal Doubly Resonant OPO (DRO) cavity and double pass two-crystal OPO cavity. The double pass two-crystal OPO cavity gives the best operation in burst mode. For single pass OPO, the average total OPO conversion efficiency is approximately 25%. For double pass OPO, the average total OPO conversion efficiency is approximately 35%. As a preliminary work, we studied 532nm pumping of a single crystal OPO cavity. With single pulse pumping, the conversion efficiency can reach 30%. For both 355nm and 532nm pumping OPO, we have demonstrated injection seeding. The OPO output light linewidth is significantly narrowed. Some preliminary etalon traces are also reported. By mixing the OPO signal output at 622nm with residual third harmonic at 355nm, we obtained 226nm burst sequences with average pulse energy of ˜0.2 mJ. Injection seeding of the OPO increases the energy achieved by a factor of ˜2. 226nm burst sequences with reasonably uniform burst envelopes are reported. Using the system we have obtained, for the first time by any known optical method, Planar Laser Induced Fluorescence (PLIF) image sequences at ultrahigh (≥100kHz) frame rates, in particular NO PLIF image sequences, have been obtained in a Mach 2 jet. We also studied the possibility of utilizing a 250 kHz pulsed Nd:YVO 4 laser as the master oscillator. 10-pulse-10-mus spacing burst sequences with reasonably uniform burst envelope have been obtained. The total energy of the burst sequence is ˜2.5J.

Automatic computation and solution of generalized harmonic balance equations

NASA Astrophysics Data System (ADS)

Peyton Jones, J. C.; Yaser, K. S. A.; Stevenson, J.

2018-02-01

Generalized methods are presented for generating and solving the harmonic balance equations for a broad class of nonlinear differential or difference equations and for a general set of harmonics chosen by the user. In particular, a new algorithm for automatically generating the Jacobian of the balance equations enables efficient solution of these equations using continuation methods. Efficient numeric validation techniques are also presented, and the combined algorithm is applied to the analysis of dc, fundamental, second and third harmonic response of a nonlinear automotive damper.

Taking a deep look: modern microscopy technologies to optimize the design and functionality of biocompatible scaffolds for tissue engineering in regenerative medicine

PubMed Central

Vielreicher, M.; Schürmann, S.; Detsch, R.; Schmidt, M. A.; Buttgereit, A.; Boccaccini, A.; Friedrich, O.

2013-01-01

This review focuses on modern nonlinear optical microscopy (NLOM) methods that are increasingly being used in the field of tissue engineering (TE) to image tissue non-invasively and without labelling in depths unreached by conventional microscopy techniques. With NLOM techniques, biomaterial matrices, cultured cells and their produced extracellular matrix may be visualized with high resolution. After introducing classical imaging methodologies such as µCT, MRI, optical coherence tomography, electron microscopy and conventional microscopy two-photon fluorescence (2-PF) and second harmonic generation (SHG) imaging are described in detail (principle, power, limitations) together with their most widely used TE applications. Besides our own cell encapsulation, cell printing and collagen scaffolding systems and their NLOM imaging the most current research articles will be reviewed. These cover imaging of autofluorescence and fluorescence-labelled tissue and biomaterial structures, SHG-based quantitative morphometry of collagen I and other proteins, imaging of vascularization and online monitoring techniques in TE. Finally, some insight is given into state-of-the-art three-photon-based imaging methods (e.g. coherent anti-Stokes Raman scattering, third harmonic generation). This review provides an overview of the powerful and constantly evolving field of multiphoton microscopy, which is a powerful and indispensable tool for the development of artificial tissues in regenerative medicine and which is likely to gain importance also as a means for general diagnostic medical imaging. PMID:23864499

Nonlinear dynamics of nanoscale systems

NASA Astrophysics Data System (ADS)

Hodas, Nathan Oken

This work builds theoretical tools to better understand nanoscale systems, and it ex- plores experimental techniques to probe nanoscale dynamics using nonlinear optical microscopy. In both the theory and experiment, this work harnesses nonlinearity to explore new boundaries in the ongoing attempts to understand the amazing world that is much smaller than we can see. In particular, the first part of this work proves the upper-bounds on the number and quality of oscillations when the sys- tem in question is homogeneously driven and has discrete states, a common way of describing nanoscale motors and chemical systems, although it has application to networked systems in general. The consequences of this limit are explored in the context of chemical clocks and limit cycles. This leads to the analysis of sponta- neous oscillations in GFPmut2, where we postulate that the oscillations must be due to coordinated rearrangement of the beta-barrel. Next, we utilize nonlinear optics to probe the constituent structures of zebrafish muscle. By comparing experimental observations with computational models, we show how second harmonic generation differs from fluorescence for confocal imaging. We use the wavelength dependence of the second harmonic generation conversion efficiency to extract information about the microscopic organization of muscle fibers, using the coherent nature of second ix harmonic generation as an analytical probe. Finally, existing experiments have used a related technique, sum-frequency generation, to directly probe the dynamics of free OH bonds at the water-vapor boundary. Using molecular dynamic simulations of the water surface and by designating surface-sensitive free OH bonds on the water surface, many aspects of the sum-frequency generation measurements were calcu- lated and compared with those inferred from experiment. The method utilizes results available from independent IR and Raman experiments to obtain some of the needed quantities, rather than calculating them ab initio. The results provide insight into the microscopic dynamics at the air-water interface and have useful application in the field of on-water catalysis.

A deep learning approach to estimate chemically-treated collagenous tissue nonlinear anisotropic stress-strain responses from microscopy images.

PubMed

Liang, Liang; Liu, Minliang; Sun, Wei

2017-11-01

Biological collagenous tissues comprised of networks of collagen fibers are suitable for a broad spectrum of medical applications owing to their attractive mechanical properties. In this study, we developed a noninvasive approach to estimate collagenous tissue elastic properties directly from microscopy images using Machine Learning (ML) techniques. Glutaraldehyde-treated bovine pericardium (GLBP) tissue, widely used in the fabrication of bioprosthetic heart valves and vascular patches, was chosen to develop a representative application. A Deep Learning model was designed and trained to process second harmonic generation (SHG) images of collagen networks in GLBP tissue samples, and directly predict the tissue elastic mechanical properties. The trained model is capable of identifying the overall tissue stiffness with a classification accuracy of 84%, and predicting the nonlinear anisotropic stress-strain curves with average regression errors of 0.021 and 0.031. Thus, this study demonstrates the feasibility and great potential of using the Deep Learning approach for fast and noninvasive assessment of collagenous tissue elastic properties from microstructural images. In this study, we developed, to our best knowledge, the first Deep Learning-based approach to estimate the elastic properties of collagenous tissues directly from noninvasive second harmonic generation images. The success of this study holds promise for the use of Machine Learning techniques to noninvasively and efficiently estimate the mechanical properties of many structure-based biological materials, and it also enables many potential applications such as serving as a quality control tool to select tissue for the manufacturing of medical devices (e.g. bioprosthetic heart valves). Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Second harmonic generation imaging of skeletal muscle tissue and myofibrils

NASA Astrophysics Data System (ADS)

Campagnola, Paul J.; Mohler, William H.; Plotnikov, Sergey; Millard, Andrew C.

2006-02-01

Second Harmonic Generation (SHG) imaging microscopy is used to examine the morphology and structural properties of intact muscle tissue. Using biochemical and optical analysis, we characterize the molecular structure underlying SHG from the complex muscle sarcomere. We find that SHG from isolated myofibrils is abolished by extraction of myosin, but is unaffected by removal or addition of actin filaments. We thus determined that the SHG emission arises from domains of the sarcomere containing thick filaments. By fitting the SHG polarization anisotropy to theoretical response curves, we find an orientation for the harmonophore that corresponds well to the pitch angle of the myosin rod α-helix with respect to the thick filament axis. Taken together, these data indicate that myosin rod domains are the key structures giving rise to SHG from striated muscle. Using SHG imaging microscopy, we have also examined the effect of optical clearing with glycerol to achieve greater penetration into specimens of skeletal muscle tissue. We find that treatment with 50% glycerol results in a 2.5 fold increase in achievable SHG imaging depth. Fast Fourier Transform (FFT) analysis shows quantitatively that the periodicity of the sarcomere structure is unaltered by the clearing process. Also, comparison of the SHG angular polarization dependence shows no change in the supramolecular organization of acto-myosin complexes. We suggest that the primary mechanism of optical clearing in muscle with glycerol treatment results from the reduction of cytoplasmic protein concentration and concomitant decrease in the secondary inner filter effect on the SHG signal. The pronounced lack of dependence of glycerol concentration on the imaging depth indicates that refractive index matching plays only a minor role in the optical clearing of muscle.

Quantitative fibrosis parameters highly predict esophageal-gastro varices in primary biliary cirrhosis.

PubMed

Wu, Q-M; Zhao, X-Y; You, H

2016-01-01

Esophageal-gastro Varices (EGV) may develop in any histological stages of primary biliary cirrhosis (PBC). We aim to establish and validate quantitative fibrosis (qFibrosis) parameters in portal, septal and fibrillar areas as ideal predictors of EGV in PBC patients. PBC patients with liver biopsy, esophagogastroscopy and Second Harmonic Generation (SHG)/Two-photon Excited Fluorescence (TPEF) microscopy images were retrospectively enrolled in this study. qFibrosis parameters in portal, septal and fibrillar areas were acquired by computer-assisted SHG/TPEF imaging system. Independent predictor was identified using multivariate logistic regression analysis. PBC patients with liver biopsy, esophagogastroscopy and Second Harmonic Generation (SHG)/Two-photon Excited Fluorescence (TPEF) microscopy images were retrospectively enrolled in this study. qFibrosis parameters in portal, septal and fibrillar areas were acquired by computer-assisted SHG/TPEF imaging system. Independent predictor was identified using multivariate logistic regression analysis. Among the forty-nine PBC patients with qFibrosis images, twenty-nine PBC patients with both esophagogastroscopy data and qFibrosis data were selected out for EGV prognosis analysis and 44.8% (13/29) of them had EGV. The qFibrosis parameters of collagen percentage and number of crosslink in fibrillar area, short/long/thin strings number and length/width of the strings in septa area were associated with EGV (p < 0.05). Multivariate logistic analysis showed that the collagen percentage in fibrillar area ≥ 3.6% was an independent factor to predict EGV (odds ratio 6.9; 95% confidence interval 1.6-27.4). The area under receiver operating characteristic (ROC), diagnostic sensitivity and specificity was 0.9, 100% and 75% respectively. Collagen percentage in Collagen percentage in the fibrillar area as an independent predictor can highly predict EGV in PBC patients.

Nanoscale imaging with table-top coherent extreme ultraviolet source based on high harmonic generation

NASA Astrophysics Data System (ADS)

Ba Dinh, Khuong; Le, Hoang Vu; Hannaford, Peter; Van Dao, Lap

2017-08-01

A table-top coherent diffractive imaging experiment on a sample with biological-like characteristics using a focused narrow-bandwidth high harmonic source around 30 nm is performed. An approach involving a beam stop and a new reconstruction algorithm to enhance the quality of reconstructed the image is described.

High second-harmonic generation of antiferromagnetic/ionic-crystal composite medium with negative refraction

NASA Astrophysics Data System (ADS)

Song, Yu-Ling; Ta, Jin-Xing; Wang, Xuan-Zhang

2012-03-01

Second harmonic generation (SHG) from a short-period structure composed of alternating antiferromagnetic (AF) and ionic-crystal layers is investigated, where the generated harmonic waves are situated in the far-infrared range and attributed to the magnetically nonlinear interaction in AF layers. The presence of a kind of appropriate ionic-crystal layers in the structure can support negative refraction for the pumping wave and positive refraction for the SH wave, so the SHG is greatly amplified in the vicinity of each AF resonant frequency. For the composite structure FeF2/TlBr, we found that the SH output is about 8 times higher than that of the FeF2 bulk in the same frequency range.

Soft X-Ray Second Harmonic Generation as an Interfacial Probe

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

Lam, R. K.; Raj, S. L.; Pascal, T. A.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (~284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from themore » first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.« less

Soft X-Ray Second Harmonic Generation as an Interfacial Probe

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

Lam, R. K.; Raj, S. L.; Pascal, T. A.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (~284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from themore » first atomic layer at the open surface. Here, this technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.« less

Thermal dephasing in second-harmonic generation of an amplified copper-vapor laser beam in beta barium borate.

PubMed

Prakash, Om; Dixit, Sudhir Kumar; Bhatnagar, Rajiva

2005-03-20

The conversion efficiency in second-harmonic generation of an amplified beam in a master-oscillator power amplifier copper-vapor laser (CVL) is lower than that of the oscillator beam alone. This lower efficiency is often vaguely attributed to wave-front degradation in the amplifier. We investigate the role of wave-front degradation and thermal dephasing in the second-harmonic generation of a CVL from a beta-barium borate crystal. Choosing two beams with constant intrapulse divergence, one from a generalized diffraction filtered resonator master oscillator alone and other obtained by amplifying oscillator by use of a power amplifier, we show that at low flux levels the decrease in efficiency is due to wave-front degradation. At a fundamental power above the critical power for thermal dephasing, the decrease is due to increased UV absorption and consequent thermal dephasing. Thermal dephasing is higher for the beam with the lower coherence width.

Soft X-Ray Second Harmonic Generation as an Interfacial Probe

DOE PAGES

Lam, R. K.; Raj, S. L.; Pascal, T. A.; ...

2018-01-08

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (~284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from themore » first atomic layer at the open surface. Here, this technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.« less

Soft X-Ray Second Harmonic Generation as an Interfacial Probe

NASA Astrophysics Data System (ADS)

Lam, R. K.; Raj, S. L.; Pascal, T. A.; Pemmaraju, C. D.; Foglia, L.; Simoncig, A.; Fabris, N.; Miotti, P.; Hull, C. J.; Rizzuto, A. M.; Smith, J. W.; Mincigrucci, R.; Masciovecchio, C.; Gessini, A.; Allaria, E.; De Ninno, G.; Diviacco, B.; Roussel, E.; Spampinati, S.; Penco, G.; Di Mitri, S.; Trovò, M.; Danailov, M.; Christensen, S. T.; Sokaras, D.; Weng, T.-C.; Coreno, M.; Poletto, L.; Drisdell, W. S.; Prendergast, D.; Giannessi, L.; Principi, E.; Nordlund, D.; Saykally, R. J.; Schwartz, C. P.

2018-01-01

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (˜284 eV ) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

Guided-wave phase-matched second-harmonic generation in KTiOPO4 waveguide produced by swift heavy-ion irradiation

NASA Astrophysics Data System (ADS)

Cheng, Yazhou; Jia, Yuechen; Akhmadaliev, Shavkat; Zhou, Shengqiang; Chen, Feng

2014-11-01

We report on the guided-wave second-harmonic generation in a KTiOPO4 nonlinear optical waveguide fabricated by a 17 MeV O5+ ion irradiation at a fluence of 1.5×1015 ions/cm2. The waveguide guides light along both TE and TM polarizations, which is suitable for phase-matching frequency doubling. Second harmonics of green light at a wavelength of 532 nm have been generated through the KTiOPO4 waveguide platform under an optical pump of fundamental wave at 1064 nm in both continuous-wave and pulsed regimes, reaching optical conversion efficiencies of 5.36%/W and 11.5%, respectively. The propagation losses have been determined to be ˜3.1 and ˜5.7 dB/cm for the TE and TM polarizations at a wavelength of 632.8 nm, respectively.

Nonlinear ultrasonic imaging with X wave

NASA Astrophysics Data System (ADS)

Du, Hongwei; Lu, Wei; Feng, Huanqing

2009-10-01

X wave has a large depth of field and may have important application in ultrasonic imaging to provide high frame rate (HFR). However, the HFR system suffers from lower spatial resolution. In this paper, a study of nonlinear imaging with X wave is presented to improve the resolution. A theoretical description of realizable nonlinear X wave is reported. The nonlinear field is simulated by solving the KZK nonlinear wave equation with a time-domain difference method. The results show that the second harmonic field of X wave has narrower mainlobe and lower sidelobes than the fundamental field. In order to evaluate the imaging effect with X wave, an imaging model involving numerical calculation of the KZK equation, Rayleigh-Sommerfeld integral, band-pass filtering and envelope detection is constructed to obtain 2D fundamental and second harmonic images of scatters in tissue-like medium. The results indicate that if X wave is used, the harmonic image has higher spatial resolution throughout the entire imaging region than the fundamental image, but higher sidelobes occur as compared to conventional focus imaging. A HFR imaging method with higher spatial resolution is thus feasible provided an apodization method is used to suppress sidelobes.

Second-order nonlinear optical microscopy of spider silk

NASA Astrophysics Data System (ADS)

Zhao, Yue; Hien, Khuat Thi Thu; Mizutani, Goro; Rutt, Harvey N.

2017-06-01

Asymmetric β-sheet protein structures in spider silk should induce nonlinear optical interaction such as second harmonic generation (SHG) which is experimentally observed for a radial line and dragline spider silk using an imaging femtosecond laser SHG microscope. By comparing different spider silks, we found that the SHG signal correlates with the existence of the protein β-sheets. Measurements of the polarization dependence of SHG from the dragline indicated that the β-sheet has a nonlinear response depending on the direction of the incident electric field. We propose a model of what orientation the β-sheet takes in spider silk.

Investigation about relationships between the symmetries of ferroelectric crystal Ca{sub 0.28}Ba{sub 0.72}Nb{sub 2}O{sub 6} and second-harmonic patterns

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

Xu, Tianxiang; Yu, Haohai, E-mail: haohaiyu@sdu.edu.cn; Zhang, Huaijin, E-mail: huaijinzhang@sdu.edu.cn

2015-08-07

The broadband quasi-phase matching (QPM) process in a uniaxial ferroelectric crystal Ca{sub 0.28}Ba{sub 0.72}Nb{sub 2}O{sub 6} (CBN-28) was demonstrated with the second-harmonic wavelength range from 450 nm to 650 nm, and the relationship between the symmetries of CBN-28 and the second-harmonic patterns was experimentally and theoretically investigated based on the random anti-parallel domains in the crystal and QPM conditions. The dependences of frequency-doubled patterns on the wavelength and anisotropy of the nonlinear crystal were also studied, and the frequency-doubled photons were found to be trapped on circles. By analyzing the light-matter interacting Hamiltonians, the trapping force for second-harmonic photons was found tomore » be centripetal and tunable by the fundamental lasers, and the variation tendencies of the rotational velocity of second-harmonic generation photons could also be predicated. The results indicate that the CBN-28 ferroelectric crystal is a promising nonlinear optical material for the generation of broadband frequency-doubled waves, and the analysis on centripetal force based on the interaction Hamiltonians may provide a novel recognition for the investigation of QPM process to be further studied.« less

Biophotonic endoscopy: a review of clinical research techniques for optical imaging and sensing of early gastrointestinal cancer

PubMed Central

Coda, Sergio; Siersema, Peter D.; Stamp, Gordon W. H.; Thillainayagam, Andrew V.

2015-01-01

Detection, characterization, and staging constitute the fundamental elements in the endoscopic diagnosis of gastrointestinal diseases, but histology still remains the diagnostic gold standard. New developments in endoscopic techniques may challenge histopathology in the near future. An ideal endoscopic technique should combine a wide-field, “red flag” screening technique with an optical contrast or microscopy method for characterization and staging, all simultaneously available during the procedure. In theory, biophotonic advances have the potential to unite these elements to allow in vivo “optical biopsy.” These techniques may ultimately offer the potential to increase the rates of detection of high risk lesions and the ability to target biopsies and resections, and so reduce the need for biopsy, costs, and uncertainty for patients. However, their utility and sensitivity in clinical practice must be evaluated against those of conventional histopathology. This review describes some of the most recent applications of biophotonics in endoscopic optical imaging and metrology, along with their fundamental principles and the clinical experience that has been acquired in their deployment as tools for the endoscopist. Particular emphasis has been placed on translational label-free optical techniques, such as fluorescence spectroscopy, fluorescence lifetime imaging microscopy (FLIM), two-photon and multi-photon microscopy, second harmonic generation (SHG) and third harmonic generation (THG) imaging, optical coherence tomography (OCT), diffuse reflectance, Raman spectroscopy, and molecular imaging. PMID:26528489

Symmetry in circularly polarized molecular high-order harmonic generation with intense bicircular laser pulses

NASA Astrophysics Data System (ADS)

Yuan, Kai-Jun; Bandrauk, André D.

2018-02-01

We present symmetry effects of laser fields and molecular geometries in circularly polarized high-order harmonic generation by bichromatic counter-rotating circularly polarized laser pulses. Simulations are performed on oriented molecules by numerically solving time-dependent Schrödinger equations. We discuss how electron recollision trajectories by the orthogonal laser field polarizations influence the harmonic polarization by using a time-frequency analysis of harmonics. It is found that orientation-dependent asymmetric ionization in linear molecules due to Coulomb potentials gives rise to a dependence of the polarization on the harmonic frequency. Effects of Coriolis forces are also presented on harmonic generation. Electron recollision trajectories illustrate the effects of the relative symmetry of the field and the molecule, thus paving a method for circularly polarized attosecond pulse generation and molecular orbital imaging in more complex systems.

Ultrafast Plasmonic Control of Second Harmonic Generation

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

Davidson, Roderick B.; Yanchenko, Anna; Ziegler, Jed I.

Efficient frequency conversion techniques are crucial to the development of plasmonic metasurfaces for information processing and signal modulation. In principle, nanoscale electric-field confinement in nonlinear materials enables higher harmonic conversion efficiencies per unit volume than those attainable in bulk materials. Here we demonstrate efficient second-harmonic generation (SHG) in a serrated nanogap plasmonic geometry that generates steep electric field gradients on a dielectric metasurface. An ultrafast control pulse is used to control plasmon-induced electric fields in a thin-film material with inversion symmetry that, without plasmonic enhancement, does not exhibit an even-order nonlinear optical response. The temporal evolution of the plasmonic near-fieldmore » is characterized with ~100 as resolution using a novel nonlinear interferometric technique. The serrated nanogap is a unique platform in which to investigate optically controlled, plasmonically enhanced harmonic generation in dielectric materials on an ultrafast time scale. Lastly, this metamaterial geometry can also be readily extended to all-optical control of other nonlinear phenomena, such as four-wave mixing and sum- and difference-frequency generation, in a wide variety of dielectric materials.« less

Ultrafast Plasmonic Control of Second Harmonic Generation

DOE PAGES

Davidson, Roderick B.; Yanchenko, Anna; Ziegler, Jed I.; ...

2016-06-01

Efficient frequency conversion techniques are crucial to the development of plasmonic metasurfaces for information processing and signal modulation. In principle, nanoscale electric-field confinement in nonlinear materials enables higher harmonic conversion efficiencies per unit volume than those attainable in bulk materials. Here we demonstrate efficient second-harmonic generation (SHG) in a serrated nanogap plasmonic geometry that generates steep electric field gradients on a dielectric metasurface. An ultrafast control pulse is used to control plasmon-induced electric fields in a thin-film material with inversion symmetry that, without plasmonic enhancement, does not exhibit an even-order nonlinear optical response. The temporal evolution of the plasmonic near-fieldmore » is characterized with ~100 as resolution using a novel nonlinear interferometric technique. The serrated nanogap is a unique platform in which to investigate optically controlled, plasmonically enhanced harmonic generation in dielectric materials on an ultrafast time scale. Lastly, this metamaterial geometry can also be readily extended to all-optical control of other nonlinear phenomena, such as four-wave mixing and sum- and difference-frequency generation, in a wide variety of dielectric materials.« less

Temperature dependence of acoustic harmonics generated by nonlinear ultrasound beam propagation in ex vivo tissue and tissue-mimicking phantoms.

PubMed

Maraghechi, Borna; Kolios, Michael C; Tavakkoli, Jahan

2015-01-01

Hyperthermia is a cancer treatment technique that could be delivered as a stand-alone modality or in conjunction with chemotherapy or radiation therapy. Noninvasive and real-time temperature monitoring of the heated tissue improves the efficacy and safety of the treatment. A temperature-sensitive acoustic parameter is required for ultrasound-based thermometry. In this paper the amplitude and the energy of the acoustic harmonics of the ultrasound backscattered signal are proposed as suitable parameters for noninvasive ultrasound thermometry. A commercial high frequency ultrasound imaging system was used to generate and detect acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues. The pressure amplitude and the energy content of the backscattered fundamental frequency (p1 and E1), the second (p2 and E2) and the third (p3 and E3) harmonics were detected in pulse-echo mode. Temperature was increased from 26° to 46 °C uniformly through both samples. The amplitude and the energy content of the harmonics and their ratio were measured and analysed as a function of temperature. The average p1, p2 and p3 increased by 69%, 100% and 283%, respectively as the temperature was elevated from 26° to 46 °C in tissue samples. In the same experiment the average E1, E2 and E3 increased by 163%, 281% and 2257%, respectively. A similar trend was observed in tissue-mimicking gel phantoms. The findings suggest that the harmonics generated due to nonlinear ultrasound beam propagation are highly sensitive to temperature and could potentially be used for noninvasive ultrasound tissue thermometry.

Efficient high-harmonic generation from a stable and compact ultrafast Yb-fiber laser producing 100 μJ, 350 fs pulses based on bendable photonic crystal fiber

NASA Astrophysics Data System (ADS)

Feehan, James S.; Price, Jonathan H. V.; Butcher, Thomas J.; Brocklesby, William S.; Frey, Jeremy G.; Richardson, David J.

2017-01-01

The development of an Yb3+-fiber-based chirped-pulse amplification system and the performance in the generation of extreme ultraviolet (EUV) radiation by high-harmonic generation is reported. The fiber laser produced 100 μJ, 350 fs output pulses with diffraction-limited beam quality at a repetition rate of 16.7 kHz. The system used commercial single-mode, polarization maintaining fiber technology. This included a 40 μm core, easily packaged, bendable final amplifier fiber in order to enable a compact system, to reduce cost, and provide reliable and environmentally stable long-term performance. The system enabled the generation of 0.4 μW of EUV at wavelengths between 27 and 80 nm with a peak at 45 nm using xenon gas. The EUV flux of 1011 photons per second for a driving field power of 1.67 W represents state-of-the-art generation efficiency for single-fiber amplifier CPA systems, corresponding to a maximum calculated energy conversion efficiency of 2.4 × 10-7 from the infrared to the EUV. The potential for high average power operation at increased repetition rates and further suggested technical improvements are discussed. Future applications could include coherent diffractive imaging in the EUV, and high-harmonic spectroscopy.

Tailored semiconductors for high-harmonic optoelectronics.

PubMed

Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu; Villeneuve, D M; Ropers, Claus; Corkum, P B

2017-07-21

The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Multi-Orbital contributions in High Harmonic Generation

NASA Astrophysics Data System (ADS)

Guehr, Markus

2009-05-01

The high harmonic spectrum generated from atoms or molecules in a strong laser field contains information about the electronic structure of the generation medium. In the high harmonic generation (HHG) process, a free electron wave packet tunnel-ionizes from the molecular orbital in a strong laser field. After being accelerated by the laser electric field, the free electron wave packet coherently recombines to the orbital from which is was initially ionized, thereby emitting the harmonic spectrum. Interferences between the free electron wave packet and the molecular orbital will shape the spectrum in a characteristic way. These interferences have been used to tomographically image the highest occupied molecular orbital (HOMO) of N2 [1]. Molecular electronic states energetically below the HOMO should contribute to laser-driven high harmonic generation (HHG), but this behavior has not been observed previously. We have observed evidence of HHG from multiple orbitals in aligned N2 [2]. The tunneling ionization (and therefore the harmonic generation) is most efficient if the orbital has a large extension in the direction of the harmonic generation polarization. The HOMO with its σg symmetry therefore dominates the harmonic spectrum if the molecular axis is parallel to the harmonic generation polarization, the lower bound πu HOMO-1 dominates in the perpendicular case. The HOMO contributions appear as a regular plateau with a cutoff in the HHG spectrum. In contrast, the HOMO-1 signal is strongly peaked in the cutoff region. We explain this by semi-classical simulations of the recombination process that show constructive interferences between the HOMO-1 and the recombining wave packet in the cutoff region. The ability to monitor several orbitals opens the route to imaging coherent superpositions of electronic orbitals. [1] J. Itatani et al., Nature 432, 867 (2004)[2] B. K. McFarland, J. P. Farrell, P. H. Bucksbaum and M. Gühr, Science 322, 1232 (2008)

Instruments for Optical Spectroscopy and Imaging of Correlated Spin-Orbit Phases

DTIC Science & Technology

2014-10-20

2014. "A Spatially Resolved Optical Second Harmonic Generation (SHG) Study of the Perovskite Iridate Sr2IrO4 with Bulk Sensitivity". (oral) 6...The scattering plane ( light blue) is defined by the incident (red arrow) and radiated (dark blue arrow) beams. S(P)-polarization denotes an...5d transition metal oxides, with particular emphasis on the iridate family. In a conventional SHG-RA experiment, light of frequency  is impinged

Detecting Subtle Plasma Membrane Perturbation in Living Cells Using Second Harmonic Generation Imaging

PubMed Central

Moen, Erick K.; Ibey, Bennett L.; Beier, Hope T.

2014-01-01

The requirement of center asymmetry for the creation of second harmonic generation (SHG) signals makes it an attractive technique for visualizing changes in interfacial layers such as the plasma membrane of biological cells. In this article, we explore the use of lipophilic SHG probes to detect minute perturbations in the plasma membrane. Three candidate probes, Di-4-ANEPPDHQ (Di-4), FM4-64, and all-trans-retinol, were evaluated for SHG effectiveness in Jurkat cells. Di-4 proved superior with both strong SHG signal and limited bleaching artifacts. To test whether rapid changes in membrane symmetry could be detected using SHG, we exposed cells to nanosecond-pulsed electric fields, which are believed to cause formation of nanopores in the plasma membrane. Upon nanosecond-pulsed electric fields exposure, we observed an instantaneous drop of ∼50% in SHG signal from the anodic pole of the cell. When compared to the simultaneously acquired fluorescence signals, it appears that the signal change was not due to the probe diffusing out of the membrane or changes in membrane potential or fluidity. We hypothesize that this loss in SHG signal is due to disruption in the interfacial nature of the membrane. The results show that SHG imaging has great potential as a tool for measuring rapid and subtle plasma membrane disturbance in living cells. PMID:24853757

Detecting subtle plasma membrane perturbation in living cells using second harmonic generation imaging.

PubMed

Moen, Erick K; Ibey, Bennett L; Beier, Hope T

2014-05-20

The requirement of center asymmetry for the creation of second harmonic generation (SHG) signals makes it an attractive technique for visualizing changes in interfacial layers such as the plasma membrane of biological cells. In this article, we explore the use of lipophilic SHG probes to detect minute perturbations in the plasma membrane. Three candidate probes, Di-4-ANEPPDHQ (Di-4), FM4-64, and all-trans-retinol, were evaluated for SHG effectiveness in Jurkat cells. Di-4 proved superior with both strong SHG signal and limited bleaching artifacts. To test whether rapid changes in membrane symmetry could be detected using SHG, we exposed cells to nanosecond-pulsed electric fields, which are believed to cause formation of nanopores in the plasma membrane. Upon nanosecond-pulsed electric fields exposure, we observed an instantaneous drop of ~50% in SHG signal from the anodic pole of the cell. When compared to the simultaneously acquired fluorescence signals, it appears that the signal change was not due to the probe diffusing out of the membrane or changes in membrane potential or fluidity. We hypothesize that this loss in SHG signal is due to disruption in the interfacial nature of the membrane. The results show that SHG imaging has great potential as a tool for measuring rapid and subtle plasma membrane disturbance in living cells. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Discrete retardance second harmonic generation ellipsometry.

PubMed

Dehen, Christopher J; Everly, R Michael; Plocinik, Ryan M; Hedderich, Hartmut G; Simpson, Garth J

2007-01-01

A new instrument was constructed to perform discrete retardance nonlinear optical ellipsometry (DR-NOE). The focus of the design was to perform second harmonic generation NOE while maximizing sample and application flexibility and minimizing data acquisition time. The discrete retardance configuration results in relatively simple computational algorithms for performing nonlinear optical ellipsometric analysis. NOE analysis of a disperse red 19 monolayer yielded results that were consistent with previously reported values for the same surface system, but with significantly reduced acquisition times.

Pulse-modulated second harmonic imaging microscope quantitatively demonstrates marked increase of collagen in tumor after chemotherapy

NASA Astrophysics Data System (ADS)

Raja, Anju M.; Xu, Shuoyu; Sun, Wanxin; Zhou, Jianbiao; Tai, Dean C. S.; Chen, Chien-Shing; Rajapakse, Jagath C.; So, Peter T. C.; Yu, Hanry

2010-09-01

Pulse-modulated second harmonic imaging microscopes (PM-SHIMs) exhibit improved signal-to-noise ratio (SNR) over conventional SHIMs on sensitive imaging and quantification of weak collagen signals inside tissues. We quantify the spatial distribution of sparse collagen inside a xenograft model of human acute myeloid leukemia (AML) tumor specimens treated with a new drug against receptor tyrosine kinase (ABT-869), and observe a significant increase in collagen area percentage, collagen fiber length, fiber width, and fiber number after chemotherapy. This finding reveals new insights into tumor responses to chemotherapy and suggests caution in developing new drugs and therapeutic regimens against cancers.

Effect of aberration on the acoustic field in tissue harmonic imaging (THI)

NASA Astrophysics Data System (ADS)

Jing, Yuan; Cleveland, Robin

2003-10-01

A numerical simulation was used to study the impact of an aberrating layer on the generation of the fundamental and second-harmonic (SH) field in a tissue harmonic imaging scenario. The simulation used a three-dimensional time-domain code for solving the KZK equation and accounted for arbitrary spatial variations in all acoustic properties. The aberration effect was modeled by assuming that the tissue consisted of two layers where the interface has a spatial variation C that acted like an effective phase screen. Initial experiments were carried out with sinusoidal-shaped interfaces. The sinusoidal interface produced grating lobes which were at least 6 dB larger for the fundamental signal than the SH. The energy outside of the main lobe was found to increase linearly as the amplitude of the interface variation increased. The location of the grating lobes was affected by the spatial period on the interface variation. The inhomogeneous nature of tissue was modeled with an interface with a random spatial variation. With the random interface the average sidelobe level for the fundamental was -30 dB whereas the SH had an average sidelobe level of -36 dB. [Work supported by the NSF through the Center for Subsurface Sensing and Imaging Systems.

a Fascinating Two-Photon Process: Magnetically Induced Quadrupole Second Harmonic Genaration

NASA Astrophysics Data System (ADS)

Matsuoka, Masahiro

1990-10-01

After a short prologue, recalling the memory of the first meeting with Professor Bloembergen, the author reviews a topic of a second harmonic generation in centrosymmetric medium, that is, magnetically induced quadrupole SHG. A pictorial description of the process is presented together with a few suggestions for future experiment.

Theoretical Analysis About Quantum Noise Squeezing of Optical Fields From an Intracavity Frequency-Doubled Laser

NASA Technical Reports Server (NTRS)

Zhang, Kuanshou; Xie, Changde; Peng, Kunchi

1996-01-01

The dependence of the quantum fluctuation of the output fundamental and second-harmonic waves upon cavity configuration has been numerically calculated for the intracavity frequency-doubled laser. The results might provide a direct reference for the design of squeezing system through the second-harmonic-generation.

Plasmonic enhancement of second-harmonic generation of dielectric layer embedded in metal-dielectric-metal structure

NASA Astrophysics Data System (ADS)

Kang, Byungjun; Imakita, Kenji; Fujii, Minoru; Hayashi, Shinji

2018-03-01

The enhancement of second-harmonic generation from a dielectric layer embedded in a metal-dielectric-metal structure upon excitation of surface plasmon polaritons is demonstrated experimentally. The metal-dielectric-metal structure consisting of a Gex(SiO2)1-x layer sandwiched by two Ag layers was prepared, and the surface plasmon polaritons were excited in an attenuated total reflection geometry. The measured attenuated total reflection spectra exhibited two reflection dips corresponding to the excitation of two different surface plasmon polariton modes. Strong second-harmonic signals were observed under the excitation of these surface plasmon polariton modes. The results demonstrate that the second-harmonic intensity of the Gex(SiO2)1-x layer is highly enhanced relative to that of the single layer deposited on a substrate. Under the excitation of one of the two surface plasmon polariton modes, the estimated enhancement factor falls in a range between 39.9 and 171, while under the excitation of the other surface plasmon polariton mode, it falls in a range between 3.96 and 84.6.

Signal improvement in multiphoton microscopy by reflection with simple mirrors near the sample

NASA Astrophysics Data System (ADS)

Rehberg, Markus; Krombach, Fritz; Pohl, Ulrich; Dietzel, Steffen

2010-03-01

In conventional fluorescence or confocal microscopy, emitted light is generated not only in the focal plane but also above and below. The situation is different in multiphoton-induced fluorescence and multiphoton-induced higher harmonic generation. Here, restriction of signal generation to a single focal point permits that all emitted photons can contribute to image formation if collected, regardless of their path through the specimen. Often, the intensity of the emitted light is rather low in biological specimens. We present a method to significantly increase the fraction of photons collected by an epi (backward) detector by placing a simple mirror, an aluminum-coated coverslip, directly under the sample. Samples investigated include fluorescent test slides, collagen gels, and thin-layered, intact mouse skeletal muscles. Quantitative analysis revealed an intensity increase of second- and third-harmonic generated signal in skeletal muscle of nine- and sevenfold respectively, and of fluorescent signal in test slides of up to twofold. Our approach thus allows significant signal improvement also for situations were a forward detection is impossible, e.g., due to the anatomy of animals in intravital microscopy.

Comparison of simulated and measured nonlinear ultrasound fields

NASA Astrophysics Data System (ADS)

Du, Yigang; Jensen, Henrik; Jensen, Jørgen Arendt

2011-03-01

In this paper results from a non-linear AS (angular spectrum) based ultrasound simulation program are compared to water-tank measurements. A circular concave transducer with a diameter of 1 inch (25.4 mm) is used as the emitting source. The measured pulses are first compared with the linear simulation program Field II, which will be used to generate the source for the AS simulation. The generated non-linear ultrasound field is measured by a hydrophone in the focal plane. The second harmonic component from the measurement is compared with the AS simulation, which is used to calculate both fundamental and second harmonic fields. The focused piston transducer with a center frequency of 5 MHz is excited by a waveform generator emitting a 6-cycle sine wave. The hydrophone is mounted in the focal plane 118 mm from the transducer. The point spread functions at the focal depth from Field II and measurements are illustrated. The FWHM (full width at half maximum) values are 1.96 mm for the measurement and 1.84 mm for the Field II simulation. The fundamental and second harmonic components of the experimental results are plotted compared with the AS simulations. The RMS (root mean square) errors of the AS simulations are 7.19% and 10.3% compared with the fundamental and second harmonic components of the measurements.

Observations of z-dependent microbunching harmonic intensities using COTR in a SASE FEL.

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

Lumpkin, A. H.; Biedron, S. G.; Dejus, R. J.

The nonlinear generation of harmonics in a self-amplified spontaneous emission (SASE) free-electron laser (FEL) continues to be of interest. Complementary to such studies is the search for information on the electron beam microbunching harmonic components, which are revealed by coherent optical transition radiation (COTR) experiments. An initial z-dependent set of data has been obtained with the fundamental at 530 nm and the second harmonic at 265 nm. The latter data were collected after every other undulator in a nine-undulator string. These results are compared to estimates based on GINGER and an analytical model for nonlinear harmonic generation.

Second Harmonic Generation Confocal Microscopy of Collagen Type I from Rat Tendon Cryosections

PubMed Central

Theodossiou, Theodossis A.; Thrasivoulou, Christopher; Ekwobi, Chidi; Becker, David L.

2006-01-01

We performed second harmonic generation (SHG) imaging of collagen in rat-tendon cryosections, using femtosecond laser scanning confocal microscopy, both in backscattering and transmission geometries. SHG transmission images of collagen fibers were spatially resolved due to a coherent, directional SHG component. This effect was enhanced with the use of an index-matching fluid (ni = 1.52). The average SHG intensity oscillated with wavelength in the backscattered geometry (isotropic SHG component), whereas the spectral profile was consistent with quasi-phase-matching conditions in transmission geometry (forward propagating, coherent SHG component) around 440 nm (λp = 880 nm). Collagen type I from bovine Achilles tendon was imaged for SHG in the backscattered geometry and its first-order effective nonlinear coefficient was determined (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\vert}d_{{\\mathrm{eff}}}{\\vert}\\approx 0.085({\\pm}0.025){\\times}10^{-12}{\\mathrm{mV}}^{-1}\\end{equation*}\\end{document}) by comparison to samples of inorganic materials with known effective nonlinear coefficients (LiNbO3 and LiIO3). The SHG spectral response of collagen type I from bovine Achilles tendon matched that of the rat-tendon cryosections in backscattered geometry. Collagen types I, II, and VI powders (nonfibrous) did not show any detectable SHG, indicating a lack of noncentrosymmetric crystalline structure at the molecular level. The various stages of collagen thermal denaturation were investigated in rat-tendon cryosections using SHG and bright-field imaging. Thermal denaturation resulted in the gradual destruction of the SHG signal. PMID:17130233

Distinguishing human normal or cancerous esophagus tissue ex vivo using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Liu, N. R.; Chen, G. N.; Wu, S. S.; Chen, R.

2014-02-01

Application of multiphoton microscopy (MPM) to clinical cancer research has greatly developed over the last few years. In this paper, we mainly focus on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) for investigating esophageal cancer. We chiefly discuss the SHG/TPEF image and spectral characteristics of normal and cancerous esophagus submucosa with the combined multi-channel imaging mode and Lambda mode of a multiphoton microscope (LSM 510 META). Great differences can be detected, such as collagen content and morphology, glandular-shaped cancer cells, TPEF/SHG intensity ratio, and so on, which demonstrate that the multiphoton imaging technique has the potential ability for minimally-invasive early cancer diagnosis.

Cardiovascular Imaging Using Two-Photon Microscopy

PubMed Central

Scherschel, John A.; Rubart, Michael

2008-01-01

Two-photon excitation microscopy has become the standard technique for high resolution deep tissue and intravital imaging. It provides intrinsic three-dimensional resolution in combination with increased penetration depth compared to single-photon confocal microscopy. This article will describe the basic physical principles of two-photon excitation and will review its multiple applications to cardiovascular imaging, including second harmonic generation and fluorescence laser scanning microscopy. In particular, the capability and limitations of multiphoton microscopy to assess functional heterogeneity on a cellular scale deep within intact, Langendorff-perfused hearts are demonstrated. It will also discuss the use of two-photon excitation-induced release of caged compounds for the study of intracellular calcium signaling and intercellular dye transfer. PMID:18986603

Three-dimensional imaging of sulfides in silicate rocks at submicron resolution with multiphoton microscopy.

PubMed

Bénard, Antoine; Palle, Sabine; Doucet, Luc Serge; Ionov, Dmitri A

2011-12-01

We report the first application of multiphoton microscopy (MPM) to generate three-dimensional (3D) images of natural minerals (micron-sized sulfides) in thick (∼120 μm) rock sections. First, reflection mode (RM) using confocal laser scanning microscopy (CLSM), combined with differential interference contrast (DIC), was tested on polished sections. Second, two-photon fluorescence (TPF) and second harmonic signal (SHG) images were generated using a femtosecond-laser on the same rock section without impregnation by a fluorescent dye. CSLM results show that the silicate matrix is revealed with DIC and RM, while sulfides can be imaged in 3D at low resolution by RM. Sulfides yield strong autofluorescence from 392 to 715 nm with TPF, while SHG is only produced by the embedding medium. Simultaneous recording of TPF and SHG images enables efficient discrimination between different components of silicate rocks. Image stacks obtained with MPM enable complete reconstruction of the 3D structure of a rock slice and of sulfide morphology at submicron resolution, which has not been previously reported for 3D imaging of minerals. Our work suggests that MPM is a highly efficient tool for 3D studies of microstructures and morphologies of minerals in silicate rocks, which may find other applications in geosciences.

Near-IR, blue, and UV generation by frequency conversion of a Tm:YAP laser

NASA Astrophysics Data System (ADS)

Cole, Brian; Goldberg, Lew; Chinn, Steve

2018-02-01

We describe generation of near-infrared (944nm, 970nm), blue (472nm, 485nm), and UV (236 nm) light by frequency up-conversion of 2 μm output of a compact and efficient passively Q-switched Tm:YAP laser. The Tm:YAP laser source was near diffraction limited with maximum Q-switched pulse peak power of 190 kW. For second harmonic generation (SHG) of NIR, both periodically poled lithium niobate (PPLN) and lithium tri-borate (LBO) were evaluated, with 58% conversion efficiency and 3.1 W of 970 nm power achieved with PPLN. The PPLN 970nm emission was frequency doubled in 20mm long type I LBO, generating 1.1 W at 485nm with a conversion efficiency of 34%. With LBO used for frequency doubling of 2.3 W of 1888 nm Tm:YAP output to 944nm, 860mW was generated, with 37% conversion efficiency. Using a second LBO crystal to generate the 4th harmonic, 545mW of 472nm power was generated, corresponding to 64% conversion efficiency. To generate the 8th harmonic of Tm:YAP laser emission, the 472nm output of the second LBO was frequency doubled in a 7mm long BBO crystal, generating 110 mW at 236nm, corresponding to 21% conversion efficiency.

Effects of important parameters variations on computing eigenspace-based minimum variance weights for ultrasound tissue harmonic imaging

NASA Astrophysics Data System (ADS)

Haji Heidari, Mehdi; Mozaffarzadeh, Moein; Manwar, Rayyan; Nasiriavanaki, Mohammadreza

2018-02-01

In recent years, the minimum variance (MV) beamforming has been widely studied due to its high resolution and contrast in B-mode Ultrasound imaging (USI). However, the performance of the MV beamformer is degraded at the presence of noise, as a result of the inaccurate covariance matrix estimation which leads to a low quality image. Second harmonic imaging (SHI) provides many advantages over the conventional pulse-echo USI, such as enhanced axial and lateral resolutions. However, the low signal-to-noise ratio (SNR) is a major problem in SHI. In this paper, Eigenspace-based minimum variance (EIBMV) beamformer has been employed for second harmonic USI. The Tissue Harmonic Imaging (THI) is achieved by Pulse Inversion (PI) technique. Using the EIBMV weights, instead of the MV ones, would lead to reduced sidelobes and improved contrast, without compromising the high resolution of the MV beamformer (even at the presence of a strong noise). In addition, we have investigated the effects of variations of the important parameters in computing EIBMV weights, i.e., K, L, and δ, on the resolution and contrast obtained in SHI. The results are evaluated using numerical data (using point target and cyst phantoms), and the proper parameters of EIBMV are indicated for THI.

Second and third order nonlinear optical properties of conjugated molecules and polymers

NASA Technical Reports Server (NTRS)

Perry, Joseph W.; Stiegman, Albert E.; Marder, Seth R.; Coulter, Daniel R.; Beratan, David N.; Brinza, David E.

1988-01-01

Second- and third-order nonlinear optical properties of some newly synthesized organic molecules and polymers are reported. Powder second-harmonic-generation efficiencies of up to 200 times urea have been realized for asymmetric donor-acceptor acetylenes. Third harmonic generation chi(3)s have been determined for a series of small conjugated molecules in solution. THG chi(3)s have also been determined for a series of soluble conjugated copolymers prepared using ring-opening metathesis polymerization. The results are discussed in terms of relevant molecular and/or macroscopic structural features of these conjugated organic materials.

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

Modal method for Second Harmonic Generation in nanostructures

NASA Astrophysics Data System (ADS)

Héron, S.; Pardo, F.; Bouchon, P.; Pelouard, J.-L.; Haïdar, R.

2015-05-01

Nanophotonic devices show interesting features for nonlinear response enhancement but numerical tools are mandatory to fully determine their behaviour. To address this need, we present a numerical modal method dedicated to nonlinear optics calculations under the undepleted pump approximation. It is brie y explained in the frame of Second Harmonic Generation for both plane waves and focused beams. The nonlinear behaviour of selected nanostructures is then investigated to show comparison with existing analytical results and study the convergence of the code.

Optical second harmonic generation phase measurement at interfaces of some organic layers with indium tin oxide

NASA Astrophysics Data System (ADS)

Ngah Demon, Siti Zulaikha; Miyauchi, Yoshihiro; Mizutani, Goro; Matsushima, Toshinori; Murata, Hideyuki

2014-08-01

We observed phase shift in optical second harmonic generation (SHG) from interfaces of indium tin oxide (ITO)/copper phthalocyanine (CuPc) and ITO/pentacene. Phase correction due to Fresnel factors of the sample was taken into account. The phase of SHG electric field at the ITO/pentacene interface, ϕinterface with respect to the phase of SHG of bare substrate ITO was 160°, while the interface of ITO/CuPc had a phase of 140°.

Second-harmonic generation from a positive-negative index material heterostructure.

PubMed

Mattiucci, Nadia; D'Aguanno, Giuseppe; Bloemer, Mark J; Scalora, Michael

2005-12-01

Resonant cavities have been widely used in the past to enhance material, nonlinear response. Traditional mirrors include metallic films and distributed Bragg reflectors. In this paper we propose negative index material mirrors as a third alternative. With the help of a rigorous Green function approach, we investigate second harmonic generation from single and coupled cavities, and theoretically prove that negative index material mirrors can raise the nonlinear conversion efficiency of a bulk material by at least four orders of magnitude compared to a bulk medium.

Mapping the nonlinear optical susceptibility by noncollinear second-harmonic generation.

PubMed

Larciprete, M C; Bovino, F A; Giardina, M; Belardini, A; Centini, M; Sibilia, C; Bertolotti, M; Passaseo, A; Tasco, V

2009-07-15

We present a method, based on noncollinear second-harmonic generation, to evaluate the nonzero elements of the nonlinear optical susceptibility. At a fixed incidence angle, the generated signal is investigated by varying the polarization state of both fundamental beams. The resulting polarization charts allows us to verify if Kleinman's symmetry rules can be applied to a given material or to retrieve the absolute value of the nonlinear optical tensor terms, from a reference measurement. Experimental measurements obtained from gallium nitride layers are reported. The proposed method does not require an angular scan and thus is useful when the generated signal is strongly affected by sample rotation.

A Comparative Study of Vertebrate Corneal Structure: The Evolution of a Refractive Lens.

PubMed

Winkler, Moritz; Shoa, Golroxan; Tran, Stephanie T; Xie, Yilu; Thomasy, Sarah; Raghunathan, Vijay K; Murphy, Christopher; Brown, Donald J; Jester, James V

2015-04-01

Although corneal curvature plays an important role in determining the refractive power of the vertebrate eye, the mechanisms controlling corneal shape remain largely unknown. To address this question, we performed a comparative study of vertebrate corneal structure to identify potential evolutionarily based changes that correlate with the development of a corneal refractive lens. Nonlinear optical (NLO) imaging of second-harmonic-generated (SHG) signals was used to image collagen and three-dimensionally reconstruct the lamellar organization in corneas from different vertebrate clades. Second-harmonic-generated images taken normal to the corneal surface showed that corneal collagen in all nonmammalian vertebrates was organized into sheets (fish and amphibians) or ribbons (reptiles and birds) extending from limbus to limbus that were oriented nearly orthogonal (ranging from 77.7°-88.2°) to their neighbors. The slight angular offset (2°-13°) created a rotational pattern that continued throughout the full thickness in fish and amphibians and to the very posterior layers in reptiles and birds. Interactions between lamellae were limited to "sutural" fibers in cartilaginous fish, and occasional lamellar branching in fish and amphibians. There was a marked increase in lamellar branching in higher vertebrates, such that birds ≫ reptiles > amphibians > fish. By contrast, mammalian corneas showed a nearly random collagen fiber organization with no orthogonal, chiral pattern. Our data indicate that nonmammalian vertebrate corneas share a common orthogonal collagen structural organization that shows increased lamellar branching in higher vertebrate species. Importantly, mammalian corneas showed a different structural organization, suggesting a divergent evolutionary background.

Angle-Resolved Second-Harmonic Light Scattering from Colloidal Particles

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

Yang, N.; Angerer, W. E.; Yodh, A. G.

2001-09-03

We report angle-resolved second-harmonic generation (SHG) measurements from suspensions of centrosymmetric micron-size polystyrene spheres with surface-adsorbed dye (malachite green). The second-harmonic scattering profiles differ qualitatively from linear light scattering profiles of the same particles. We investigated these radiation patterns using several polarization configurations and particle diameters. We introduce a simple Rayleigh-Gans-Debye model to account for the SHG scattering anisotropy. The model compares favorably with our experimental data. Our measurements suggest scattering anisotropy may be used to isolate particle nonlinear optics from other bulk nonlinear optical effects in suspension.

Towards improved NDE and SHM methodologies incorporating nonlinear structural features

NASA Astrophysics Data System (ADS)

Chillara, Vamshi Krishna

Ultrasound is widely employed in Nondestructive Evaluation (NDE) and Structural Health Monitoring (SHM) applications to detect and characterize damage/defects in materials. In particular, ultrasonic guided waves are considered a foremost candidate for in-situ monitoring applications. Conventional ultrasonic techniques rely on changes/discontinuities in linear elastic material properties, namely the Young's modulus and shear modulus to detect damage. On the other hand, nonlinear ultrasonic techniques that rely on micro-scale nonlinear material/structural behavior are proven to be sensitive to damage induced microstructural changes that precede macro-scale damage and are hence capable of early damage detection. The goal of this thesis is to investigate the capabilities of nonlinear guided waves --- a fusion of nonlinear ultrasonic techniques with the guided wave methodologies for early damage detection. To that end, the thesis focuses on two important aspects of the problem: 1. Wavemechanics - deals with ultrasonic guided wave propagation in nonlinear waveguides; 2. Micromechanics - deals with correlating ultrasonic response with micro-scale nonlinear material behavior. For the development of efficient NDE and SHM methodologies that incorporate nonlinear structural features, a detailed understanding of the above aspects is indispensable. In this thesis, the wavemechanics aspect of the problem is dealt with from both theoretical and numerical standpoints. A generalized theoretical framework is developed to study higher harmonic guided waves in plates. This was employed to study second harmonic guided waves in pipes using a large-radius asymptotic approximation. Second harmonic guided waves in plates are studied from a numerical standpoint. Theoretical predictions are validated and some key aspects of higher harmonic generation in waveguides are outlined. Finally, second harmonic guided waves in plates with inhomogeneous and localized nonlinearities are studied and some important aspects of guided wave mode selection are addressed. The other part of the work focused on developing a micromechanics based understanding of ultrasonic higher harmonic generation. Three important aspects of micro-scale material behavior, namely tension-compression asymmetry, shearnormal coupling and deformation induced asymmetry are identified and their role in ultrasonic higher harmonic generation is discussed. Tension-compression asymmetry is identified to cause second (even) harmonic generation in materials. Then, shearnormal coupling is identified to cause generation of secondary waves of different polarity than the primary waves. In addition, deformation induced anisotropy due to the presence of residual stress/strain and its contribution to ultrasonic higher harmonic generation is qualitatively discussed. Also, the tension-compression asymmetry in the material is quantified using an energy based measure. The above measure is employed to develop a homogenization based approach amenable to multi-scale analysis to correlate microstructure with ultrasonic higher harmonic generation. Finally, experimental investigations concerning third harmonic SH wave generation in plates are carried out and the effect of load and temperature changes on nonlinear ultrasonic measurements are discussed in the context of SHM. It was found that while nonlinear ultrasound is sensitive to micro-scale damage, the relative nonlinearity parameter may not always be the best measure to quantify the nonlinearity as it is subject to spurious effects from changes in environmental factors such as loads and temperature.

Measurement of the quadratic hyperpolarizability of the collagen triple helix and application to second harmonic imaging of natural and biomimetic collagenous tissues

NASA Astrophysics Data System (ADS)

Deniset-Besseau, A.; Strupler, M.; Duboisset, J.; De Sa Peixoto, P.; Benichou, E.; Fligny, C.; Tharaux, P.-L.; Mosser, G.; Brevet, P.-F.; Schanne-Klein, M.-C.

2009-09-01

Collagen is a major protein of the extracellular matrix that is characterized by triple helical domains. It plays a central role in the formation of fibrillar and microfibrillar networks, basement membranes, as well as other structures of the connective tissue. Remarkably, fibrillar collagen exhibits efficient Second Harmonic Generation (SHG) so that SHG microscopy proved to be a sensitive tool to probe the three-dimensional architecture of fibrillar collagen and to assess the progression of fibrotic pathologies. We obtained sensitive and reproducible measurements of the fibrosis extent, but we needed quantitative data at the molecular level to further process SHG images. We therefore performed Hyper- Rayleigh Scattering (HRS) experiments and measured a second order hyperpolarisability of 1.25 10-27 esu for rat-tail type I collagen. This value is surprisingly large considering that collagen presents no strong harmonophore in its aminoacid sequence. In order to get insight into the physical origin of this nonlinear process, we performed HRS measurements after denaturation of the collagen triple helix and for a collagen-like short model peptide [(Pro-Pro- Gly)10]3. It showed that the collagen large nonlinear response originates in the tight alignment of a large number of weakly efficient harmonophores, presumably the peptide bonds, resulting in a coherent amplification of the nonlinear signal along the triple helix. To illustrate this mechanism, we successfully recorded SHG images in collagenous biomimetic matrices.

An analytical SMASH procedure (ASP) for sensitivity-encoded MRI.

PubMed

Lee, R F; Westgate, C R; Weiss, R G; Bottomley, P A

2000-05-01

The simultaneous acquisition of spatial harmonics (SMASH) method of imaging with detector arrays can reduce the number of phase-encoding steps, and MRI scan time several-fold. The original approach utilized numerical gradient-descent fitting with the coil sensitivity profiles to create a set of composite spatial harmonics to replace the phase-encoding steps. Here, an analytical approach for generating the harmonics is presented. A transform is derived to project the harmonics onto a set of sensitivity profiles. A sequence of Fourier, Hilbert, and inverse Fourier transform is then applied to analytically eliminate spatially dependent phase errors from the different coils while fully preserving the spatial-encoding. By combining the transform and phase correction, the original numerical image reconstruction method can be replaced by an analytical SMASH procedure (ASP). The approach also allows simulation of SMASH imaging, revealing a criterion for the ratio of the detector sensitivity profile width to the detector spacing that produces optimal harmonic generation. When detector geometry is suboptimal, a group of quasi-harmonics arises, which can be corrected and restored to pure harmonics. The simulation also reveals high-order harmonic modulation effects, and a demodulation procedure is presented that enables application of ASP to a large numbers of detectors. The method is demonstrated on a phantom and humans using a standard 4-channel phased-array MRI system. Copyright 2000 Wiley-Liss, Inc.

Harmonic Power Generation of IMPATT Diodes.

DTIC Science & Technology

1985-09-01

Performance of Si and GaAs Diodes Taking into Account the Thermal Effect (f = 23 GHz). 136 2.8 CW Results for Second-Harmonic Performance of the Si Uniform...Diode Obtained by Matching l-. Resistance (f = 23 GHz). 138 2.9 CW Results for Second-Harmonic Performance of the Si Uniform Diode Taking into Account ...at V = 28 V, V = 8 V, and Jdc = kA/cm 3. 1 3 181 2.21 Power Output for pin Diode . Taking into Account Circuit Matching Only. 194 2.22 CW Power

Concurrent Stabilization and Imaging of a Novel Polymer for Second Harmonic Generation via In Situ Photopolymerization

DTIC Science & Technology

1994-04-26

polymers bearing acrylatel 5. 16 ) or ethyny117 ) groups. Alternately, photoinduced crosslinking via a [2+2]cycloaddition of cinnamates , 18-21) a photo...groups.8 .9 Alternately, some improvement of stability has been achieved through photo-induced crosslinking via either a [2+2]cycloaddition of cinnamates ...2.5 x 2.5 cm) were dipped halfway into hydroiodic acid (55 % in water; 50 °C), for 30s to remove the ITO coating, polished with 0.5 g~m aluminum

Label-Free 3D Visualization of Cellular and Tissue Structures in Intact Muscle with Second and Third Harmonic Generation Microscopy

PubMed Central

Rehberg, Markus; Krombach, Fritz; Pohl, Ulrich; Dietzel, Steffen

2011-01-01

Second and Third Harmonic Generation (SHG and THG) microscopy is based on optical effects which are induced by specific inherent physical properties of a specimen. As a multi-photon laser scanning approach which is not based on fluorescence it combines the advantages of a label-free technique with restriction of signal generation to the focal plane, thus allowing high resolution 3D reconstruction of image volumes without out-of-focus background several hundred micrometers deep into the tissue. While in mammalian soft tissues SHG is mostly restricted to collagen fibers and striated muscle myosin, THG is induced at a large variety of structures, since it is generated at interfaces such as refraction index changes within the focal volume of the excitation laser. Besides, colorants such as hemoglobin can cause resonance enhancement, leading to intense THG signals. We applied SHG and THG microscopy to murine (Mus musculus) muscles, an established model system for physiological research, to investigate their potential for label-free tissue imaging. In addition to collagen fibers and muscle fiber substructure, THG allowed us to visualize blood vessel walls and erythrocytes as well as white blood cells adhering to vessel walls, residing in or moving through the extravascular tissue. Moreover peripheral nerve fibers could be clearly identified. Structure down to the nuclear chromatin distribution was visualized in 3D and with more detail than obtainable by bright field microscopy. To our knowledge, most of these objects have not been visualized previously by THG or any label-free 3D approach. THG allows label-free microscopy with inherent optical sectioning and therefore may offer similar improvements compared to bright field microscopy as does confocal laser scanning microscopy compared to conventional fluorescence microscopy. PMID:22140560

Photo-induced second-order nonlinearity in stoichiometric silicon nitride waveguides

NASA Astrophysics Data System (ADS)

Porcel, Marco A. G.; Mak, Jesse; Taballione, Caterina; Schermerhorn, Victoria K.; Epping, Jörn P.; van der Slot, Peter J. M.; Boller, Klaus-J.

2017-12-01

We report the observation of second-harmonic generation in stoichiometric silicon nitride waveguides grown via low-pressure chemical vapour deposition. Quasi-rectangular waveguides with a large cross section were used, with a height of 1 {\\mu}m and various different widths, from 0.6 to 1.2 {\\mu}m, and with various lengths from 22 to 74 mm. Using a mode-locked laser delivering 6-ps pulses at 1064 nm wavelength with a repetition rate of 20 MHz, 15% of the incoming power was coupled through the waveguide, making maximum average powers of up to 15 mW available in the waveguide. Second-harmonic output was observed with a delay of minutes to several hours after the initial turn-on of pump radiation, showing a fast growth rate between 10$^{-4}$ to 10$^{-2}$ s$^{-1}$, with the shortest delay and highest growth rate at the highest input power. After this first, initial build-up, the second-harmonic became generated instantly with each new turn-on of the pump laser power. Phase matching was found to be present independent of the used waveguide width, although the latter changes the fundamental and second-harmonic phase velocities. We address the presence of a second-order nonlinearity and phase matching, involving an initial, power-dependent build-up, to the coherent photogalvanic effect. The effect, via the third-order nonlinearity and multiphoton absorption leads to a spatially patterned charge separation, which generates a spatially periodic, semi-permanent, DC-field-induced second-order susceptibility with a period that is appropriate for quasi-phase matching. The maximum measured second-harmonic conversion efficiency amounts to 0.4% in a waveguide with 0.9 x 1 {\\mu}m$^2$ cross section and 36 mm length, corresponding to 53 {\\mu}W at 532 nm with 13 mW of IR input coupled into the waveguide. The according $\\chi^{(2)}$ amounts to 3.7 pm/V, as retrieved from the measured conversion efficiency.

Enhanced Second-Harmonic Generation Using Broken Symmetry III–V Semiconductor Fano Metasurfaces

DOE PAGES

Vabishchevich, Polina P.; Liu, Sheng; Sinclair, Michael B.; ...

2018-01-27

All-dielectric metasurfaces, two-dimensional arrays of subwavelength low loss dielectric inclusions, can be used not only to control the amplitude and phase of optical beams, but also to generate new wavelengths through enhanced nonlinear optical processes that are free from some of the constraints dictated by the use of bulk materials. Recently, high quality factor (Q) resonances in these metasurfaces have been revealed and utilized for applications such as sensing and lasing. The origin of these resonances stems from the interference of two nanoresonator modes with vastly different Q. Here we show that nonlinear optical processes can be further enhanced bymore » utilizing these high-Q resonances in broken symmetry all-dielectric metasurfaces. As a result, we study second harmonic generation from broken symmetry metasurfaces made from III–V semiconductors and observe nontrivial spectral shaping of second-harmonic and multifold efficiency enhancement induced by high field localization and enhancement inside the nanoresonators.« less

Second and third harmonic generation associated to infrared transitions in a Morse quantum well under applied electric and magnetic fields

NASA Astrophysics Data System (ADS)

Restrepo, R. L.; Kasapoglu, E.; Sakiroglu, S.; Ungan, F.; Morales, A. L.; Duque, C. A.

2017-09-01

The effects of electric and magnetic fields on the second and third harmonic generation coefficients in a Morse potential quantum well are theoretically studied. The energy levels and corresponding wave functions are obtained by solving the Schrödinger equation for the electron in the parabolic band scheme and effective mass approximations and the envelope function approach. The results show that both the electric and the magnetic fields have significant influence on the magnitudes and resonant peak energy positions of the second and third harmonic generation responses. In general, the Morse potential profile becomes wider and shallower as γ -parameter increases and so the energies of the bound states will be functions of this parameter. Therefore, we can conclude that the effects of the electric and magnetic fields can be used to tune and control the optical properties of interest in the range of the infrared electromagnetic spectrum.

Multipolar second-harmonic generation by Mie-resonant dielectric nanoparticles

NASA Astrophysics Data System (ADS)

Smirnova, Daria; Smirnov, Alexander I.; Kivshar, Yuri S.

2018-01-01

By combining analytical and numerical approaches, we study resonantly enhanced second-harmonic generation by individual high-index dielectric nanoparticles made of centrosymmetric materials. Considering both bulk and surface nonlinearities, we describe second-harmonic nonlinear scattering from a silicon nanoparticle optically excited in the vicinity of the magnetic and electric dipolar resonances. We discuss the contributions of different nonlinear sources and the effect of the low-order optical Mie modes on the characteristics of the generated far field. We demonstrate that the multipolar expansion of the radiated field is dominated by dipolar and quadrupolar modes (two axially symmetric electric quadrupoles, an electric dipole, and a magnetic quadrupole) and the interference of these modes can ensure directivity of the nonlinear scattering. The developed multipolar analysis can be instructive for interpreting the far-field measurements of the nonlinear scattering and it provides prospective insights into a design of complementary metal-oxide-semiconductor compatible nonlinear nanoantennas fully integrated with silicon-based photonic circuits, as well as methods of nonlinear diagnostics.

Linear and nonlinear Biot waves in a noncohesive granular medium slab: transfer function, self-action, second harmonic generation.

PubMed

Legland, J-B; Tournat, V; Dazel, O; Novak, A; Gusev, V

2012-06-01

Experimental results are reported on second harmonic generation and self-action in a noncohesive granular medium supporting wave energy propagation both in the solid frame and in the saturating fluid. The acoustic transfer function of the probed granular slab can be separated into two main frequency regions: a low frequency region where the wave propagation is controlled by the solid skeleton elastic properties, and a higher frequency region where the behavior is dominantly due to the air saturating the beads. Experimental results agree well with a recently developed nonlinear Biot wave model applied to granular media. The linear transfer function, second harmonic generation, and self-action effect are studied as a function of bead diameter, compaction step, excitation amplitude, and frequency. This parametric study allows one to isolate different propagation regimes involving a range of described and interpreted linear and nonlinear processes that are encountered in granular media experiments. In particular, a theoretical interpretation is proposed for the observed strong self-action effect.

Exploring Membrane Dynamics during Electric Pulse Exposure with Second Harmonic Generation

NASA Astrophysics Data System (ADS)

Moen, Erick; Ibey, Bennett; Beier, Hope; Armani, Andrea

Optical second harmonic generation (SHG) is a powerful tool for investigating the nanostructure of symmetry-breaking materials and interfacial layers. Recently, we developed an imaging technique based on SHG for quantifying and localizing nanoporation in the plasma membrane of living cells. Nanosecond pulsed electric fields (nsPEF) were used to controllably disrupt the membrane, and the observed changes were validated against an extensible cell circuit model. In this talk, I will discuss the development of this method and its application to various cell types and stimuli, with a specific focus on bipolar (BP) nsPEF. BP nsPEF hold special interest as a cellular insult because they allow for a unique exposition of transmembrane potential and membrane charging/relaxation. Using this approach, we examine the structural response of the membrane as the temporal spacing between pulse phases was varied over several orders of magnitude and compare these results to the response when the cell is exposed to a monopolar (MP) nsPEF. Disagreement of the experimental results with the model demonstrates that biological processes may play a larger role than previously thought. These findings could lead to a greater understanding of the fundamental processes essential to all electroporation.

Second Harmonic Generation Reveals Subtle Fibrosis Differences in Adult and Pediatric Nonalcoholic Fatty Liver Disease.

PubMed

Liu, Feng; Zhao, Jing-Min; Rao, Hui-Ying; Yu, Wei-Miao; Zhang, Wei; Theise, Neil D; Wee, Aileen; Wei, Lai

2017-11-20

Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Non-Linear Optical Microscopy Sheds Light on Cardiovascular Disease

PubMed Central

Caorsi, Valentina; Toepfer, Christopher; Sikkel, Markus B.; Lyon, Alexander R.; MacLeod, Ken; Ferenczi, Mike A.

2013-01-01

Many cardiac diseases have been associated with increased fibrosis and changes in the organization of fibrillar collagen. The degree of fibrosis is routinely analyzed with invasive histological and immunohistochemical methods, giving a limited and qualitative understanding of the tissue's morphological adaptation to disease. Our aim is to quantitatively evaluate the increase in fibrosis by three-dimensional imaging of the collagen network in the myocardium using the non-linear optical microscopy techniques Two-Photon Excitation microscopy (TPE) and Second Harmonic signal Generation (SHG). No sample staining is needed because numerous endogenous fluorophores are excited by a two-photon mechanism and highly non-centrosymmetric structures such as collagen generate strong second harmonic signals. We propose for the first time a 3D quantitative analysis to carefully evaluate the increased fibrosis in tissue from a rat model of heart failure post myocardial infarction. We show how to measure changes in fibrosis from the backward SHG (BSHG) alone, as only backward-propagating SHG is accessible for true in vivo applications. A 5-fold increase in collagen I fibrosis is detected in the remote surviving myocardium measured 20 weeks after infarction. The spatial distribution is also shown to change markedly, providing insight into the morphology of disease progression. PMID:23409139

Harmonic arbitrary waveform generator

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

Roberts, Brock Franklin

2017-11-28

High frequency arbitrary waveforms have applications in radar, communications, medical imaging, therapy, electronic warfare, and charged particle acceleration and control. State of the art arbitrary waveform generators are limited in the frequency they can operate by the speed of the Digital to Analog converters that directly create their arbitrary waveforms. The architecture of the Harmonic Arbitrary Waveform Generator allows the phase and amplitude of the high frequency content of waveforms to be controlled without taxing the Digital to Analog converters that control them. The Harmonic Arbitrary Waveform Generator converts a high frequency input, into a precision, adjustable, high frequency arbitrarymore » waveform.« less

Photovoltaic power converter system with a controller configured to actively compensate load harmonics

DOEpatents

de Rooij, Michael Andrew; Steigerwald, Robert Louis; Delgado, Eladio Clemente

2008-12-16

Photovoltaic power converter system including a controller configured to reduce load harmonics is provided. The system comprises a photovoltaic array and an inverter electrically coupled to the array to generate an output current for energizing a load connected to the inverter and to a mains grid supply voltage. The system further comprises a controller including a first circuit coupled to receive a load current to measure a harmonic current in the load current. The controller includes a second circuit to generate a fundamental reference drawn by the load. The controller further includes a third circuit for combining the measured harmonic current and the fundamental reference to generate a command output signal for generating the output current for energizing the load connected to the inverter. The photovoltaic system may be configured to compensate harmonic currents that may be drawn by the load.

Cascading second-order nonlinear processes in a lithium niobate-on-insulator microdisk.

PubMed

Liu, Shijie; Zheng, Yuanlin; Chen, Xianfeng

2017-09-15

Whispering-gallery-mode (WGM) microcavities are very important in both fundamental science and practical applications, among which on-chip second-order nonlinear microresonators play an important role in integrated photonic functionalities. Here we demonstrate resonant second-harmonic generation (SHG) and cascaded third-harmonic generation (THG) in a lithium niobate-on-insulator (LNOI) microdisk resonator. Efficient SHG in the visible range was obtained with only several mW input powers at telecom wavelengths. THG was also observed through a cascading process, which reveals simultaneous phase matching and strong mode coupling in the resonator. Cascading of second-order nonlinear processes gives rise to an effectively large third-order nonlinearity, which makes on-chip second-order nonlinear microresonators a promising frequency converter for integrated nonlinear photonics.

Second- and third-harmonic generation in metal-based structures

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

Scalora, M.; Akozbek, N.; Bloemer, M. J.

We present a theoretical approach to the study of second- and third-harmonic generation from metallic structures and nanocavities filled with a nonlinear material in the ultrashort pulse regime. We model the metal as a two-component medium, using the hydrodynamic model to describe free electrons and Lorentz oscillators to account for core electron contributions to both the linear dielectric constant and harmonic generation. The active nonlinear medium that may fill a metallic nanocavity, or be positioned between metallic layers in a stack, is also modeled using Lorentz oscillators and surface phenomena due to symmetry breaking are taken into account. We studymore » the effects of incident TE- and TM-polarized fields and show that a simple reexamination of the basic equations reveals additional, exploitable dynamical features of nonlinear frequency conversion in plasmonic nanostructures.« less

Phononic Crystal Waveguide Transducers for Nonlinear Elastic Wave Sensing.

PubMed

Ciampa, Francesco; Mankar, Akash; Marini, Andrea

2017-11-07

Second harmonic generation is one of the most sensitive and reliable nonlinear elastic signatures for micro-damage assessment. However, its detection requires powerful amplification systems generating fictitious harmonics that are difficult to discern from pure nonlinear elastic effects. Current state-of-the-art nonlinear ultrasonic methods still involve impractical solutions such as cumbersome signal calibration processes and substantial modifications of the test component in order to create material-based tunable harmonic filters. Here we propose and demonstrate a valid and sensible alternative strategy involving the development of an ultrasonic phononic crystal waveguide transducer that exhibits both single and multiple frequency stop-bands filtering out fictitious second harmonic frequencies. Remarkably, such a sensing device can be easily fabricated and integrated on the surface of the test structure without altering its mechanical and geometrical properties. The design of the phononic crystal structure is supported by a perturbative theoretical model predicting the frequency band-gaps of periodic plates with sinusoidal corrugation. We find our theoretical findings in excellent agreement with experimental testing revealing that the proposed phononic crystal waveguide transducer successfully attenuates second harmonics caused by the ultrasonic equipment, thus demonstrating its wide range of potential applications for acousto/ultrasonic material damage inspection.

Harmonic generation in metallic, GaAs-filled nanocavities in the enhanced transmission regime at visible and UV wavelengths.

PubMed

Vincenti, M A; de Ceglia, D; Roppo, V; Scalora, M

2011-01-31

We have conducted a theoretical study of harmonic generation from a silver grating having slits filled with GaAs. By working in the enhanced transmission regime, and by exploiting phase-locking between the pump and its harmonics, we guarantee strong field localization and enhanced harmonic generation under conditions of high absorption at visible and UV wavelengths. Silver is treated using the hydrodynamic model, which includes Coulomb and Lorentz forces, convection, electron gas pressure, plus bulk χ(3) contributions. For GaAs we use nonlinear Lorentz oscillators, with characteristic χ(2) and χ(3) and nonlinear sources that arise from symmetry breaking and Lorentz forces. We find that: (i) electron pressure in the metal contributes to linear and nonlinear processes by shifting/reshaping the band structure; (ii) TE- and TM-polarized harmonics can be generated efficiently; (iii) the χ(2) tensor of GaAs couples TE- and TM-polarized harmonics that create phase-locked pump photons having polarization orthogonal compared to incident pump photons; (iv) Fabry-Perot resonances yield more efficient harmonic generation compared to plasmonic transmission peaks, where most of the light propagates along external metal surfaces with little penetration inside its volume. We predict conversion efficiencies that range from 10(-6) for second harmonic generation to 10(-3) for the third harmonic signal, when pump power is 2 GW/cm2.

Two-Photon and Second Harmonic Microscopy in Clinical and Translational Cancer Research

PubMed Central

PERRY, SETH W.; BURKE, RYAN M.; BROWN, EDWARD B.

2012-01-01

Application of two-photon microscopy (TPM) to translational and clinical cancer research has burgeoned over the last several years, as several avenues of pre-clinical research have come to fruition. In this review, we focus on two forms of TPM—two-photon excitation fluorescence microscopy, and second harmonic generation microscopy—as they have been used for investigating cancer pathology in ex vivo and in vivo human tissue. We begin with discussion of two-photon theory and instrumentation particularly as applicable to cancer research, followed by an overview of some of the relevant cancer research literature in areas that include two-photon imaging of human tissue biopsies, human skin in vivo, and the rapidly developing technology of two-photon microendoscopy. We believe these and other evolving two-photon methodologies will continue to help translate cancer research from the bench to the bedside, and ultimately bring minimally invasive methods for cancer diagnosis and treatment to therapeutic reality. PMID:22258888

Ultrafast and nonlinear spectroscopy of brilliant green-based nanoGUMBOS with enhanced near-infrared emission

NASA Astrophysics Data System (ADS)

Karam, Tony E.; Siraj, Noureen; Zhang, Zhenyu; Ezzir, Abdulrahman F.; Warner, Isiah M.; Haber, Louis H.

2017-10-01

The synthesis, characterization, ultrafast dynamics, and nonlinear spectroscopy of 30 nm nanospheres of brilliant green-bis(pentafluoroethylsulfonyl)imide ([BG][BETI]) in water are reported. These thermally stable nanoparticles are derived from a group of uniform materials based on organic salts (nanoGUMBOS) that exhibit enhanced near-infrared emission compared with the molecular dye in water. The examination of ultrafast transient absorption spectroscopy results reveals that the overall excited-state relaxation lifetimes of [BG][BETI] nanoGUMBOS are longer than the brilliant green molecular dye in water due to steric hindrance of the torsional degrees of freedom of the phenyl rings around the central carbon. Furthermore, the second harmonic generation signal of [BG][BETI] nanoGUMBOS is enhanced by approximately 7 times and 23 times as compared with colloidal gold nanoparticles of the same size and the brilliant green molecular dye in water, respectively. A very clear third harmonic generation signal is observed from the [BG][BETI] nanoGUMBOS but not from either the molecular dye or the gold nanoparticles. Overall, these results show that [BG][BETI] nanoGUMBOS exhibit altered ultrafast and nonlinear spectroscopy that is beneficial for various applications including nonlinear imaging probes, biomedical imaging, and molecular sensing.

Label-free structural characterization of mitomycin C-modulated wound healing after photorefractive keratectomy by the use of multiphoton microscopy

NASA Astrophysics Data System (ADS)

Lo, Wen; Wang, Tsung-Jen; Chen, Wei-Liang; Hsueh, Chiu-Mei; Chen, Shean-Jen; Chen, Yang-Fang; Chou, Hsiu-Chu; Lin, Pi-Jung; Hu, Fung-Rong; Dong, Chen-Yuan

2010-05-01

We applied multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) microscopy to monitor corneal wound healing after photorefractive keratectomy (PRK). Our results show that keratocyte activation can be observed by an increase in its MAF, while SHG imaging of corneal stroma can show the depletion of Bowman's layer after PRK and the reticular collagen deposition in the wound healing stage. Furthermore, quantification of the keratocyte activation and collagen deposition in conjunction with immunohistochemistry and histological images demonstrate the effectiveness of mitomycin C (MMC) in suppressing myofibroblast proliferation and collagen regeneration in the post-PRK wound healing process.

Structural and molecular conformation of myosin in intact muscle fibers by second harmonic generation

NASA Astrophysics Data System (ADS)

Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

2009-02-01

Recently, the use of Second Harmonic Generation (SHG) for imaging biological samples has been explored with regard to intrinsic SHG in highly ordered biological samples. As shown by fractional extraction of proteins, myosin is the source of SHG signal in skeletal muscle. SHG is highly dependent on symmetries and provides selective information on the structural order and orientation of the emitting proteins and the dynamics of myosin molecules responsible for the mechano-chemical transduction during contraction. We characterise the polarization-dependence of SHG intensity in three different physiological states: resting, rigor and isometric tetanic contraction in a sarcomere length range between 2.0 μm and 4.0 μm. The orientation of motor domains of the myosin molecules is dependent on their physiological states and modulate the SHG signal. We can discriminate the orientation of the emitting dipoles in four different molecular conformations of myosin heads in intact fibers during isometric contraction, in resting and rigor. We estimate the contribution of the myosin motor domain to the total second order bulk susceptibility from its molecular structure and its functional conformation. We demonstrate that SHG is sensitive to the fraction of ordered myosin heads by disrupting the order of myosin heads in rigor with an ATP analog. We estimate the fraction of myosin motors generating the isometric force in the active muscle fiber from the dependence of the SHG modulation on the degree of overlap between actin and myosin filaments during an isometric contraction.

Cellular internalization of LiNbO3 nanocrystals for second harmonic imaging and the effects on stem cell differentiation

NASA Astrophysics Data System (ADS)

Li, Jianhua; Qiu, Jichuan; Guo, Weibo; Wang, Shu; Ma, Baojin; Mou, Xiaoning; Tanes, Michael; Jiang, Huaidong; Liu, Hong

2016-03-01

Second harmonic generation (SHG) nanocrystals have recently been reported to label cancer cells and other functional cell lines due to their unique double-frequency property. In this paper, we report for the first time the use of lithium niobate (LiNbO3, LN) nanocrystals as SHG labels for imaging stem cells. Rat mesenchymal stem cells (rMSCs) were labeled with LN nanocrystals in order to study the cellular internalization of the nanocrystals and the influence on stem cell differentiation. The results showed that LN nanocrystals were endocytosed by the rMSCs and the distribution of the internalized nanoparticles demonstrated a high consistency with the orientation of the actin filaments. Besides, LN-labeled rMSCs showed a concentration-dependent viability. Most importantly, rMSCs labeled with 50 μg per mL of LN nanocrystals retained their ability to differentiate into both osteogenic and adipogenic lineages. The results prove that LN nanocrystals can be used as a cytocompatible, near-infrared (NIR) light driven cell label for long-term imaging, without hindering stem cell differentiation. This work will promote the use of LN nanocrystals to broader applications like deep-tissue tracking, remote drug delivery and stem cell therapy.Second harmonic generation (SHG) nanocrystals have recently been reported to label cancer cells and other functional cell lines due to their unique double-frequency property. In this paper, we report for the first time the use of lithium niobate (LiNbO3, LN) nanocrystals as SHG labels for imaging stem cells. Rat mesenchymal stem cells (rMSCs) were labeled with LN nanocrystals in order to study the cellular internalization of the nanocrystals and the influence on stem cell differentiation. The results showed that LN nanocrystals were endocytosed by the rMSCs and the distribution of the internalized nanoparticles demonstrated a high consistency with the orientation of the actin filaments. Besides, LN-labeled rMSCs showed a concentration-dependent viability. Most importantly, rMSCs labeled with 50 μg per mL of LN nanocrystals retained their ability to differentiate into both osteogenic and adipogenic lineages. The results prove that LN nanocrystals can be used as a cytocompatible, near-infrared (NIR) light driven cell label for long-term imaging, without hindering stem cell differentiation. This work will promote the use of LN nanocrystals to broader applications like deep-tissue tracking, remote drug delivery and stem cell therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00785f

Coating barium titanate nanoparticles with polyethylenimine improves cellular uptake and allows for coupled imaging and gene delivery

PubMed Central

Dempsey, Christopher; Lee, Isac; Cowan, Katie; Suh, Junghae

2015-01-01

Barium titanate nanoparticles (BT NP) belong to a class of second harmonic generating (SHG) nanoprobes that have recently demonstrated promise in biological imaging. Unfortunately, BT NPs display low cellular uptake efficiencies, which may be a problem if cellular internalization is desired or required for a particular application. To overcome this issue, while concomitantly developing a particle platform that can also deliver nucleic acids into cells, we coated the BT NPs with the cationic polymer polyethylenimine (PEI) – one of the most effective nonviral gene delivery agents. Coating of BT with PEI yielded complexes with positive zeta potentials and resulted in an 8-fold increase in cellular uptake of the BT NPs. Importantly, we were able to achieve high levels of gene delivery with the BT-PEI/DNA complexes, supporting further efforts to generate BT platforms for coupled imaging and gene therapy. PMID:23973999

Third harmonic frequency generation by type-I critically phase-matched LiB3O5 crystal by means of optically active quartz crystal.

PubMed

Gapontsev, Valentin P; Tyrtyshnyy, Valentin A; Vershinin, Oleg I; Davydov, Boris L; Oulianov, Dmitri A

2013-02-11

We present a method of third harmonic generation at 355 nm by frequency mixing of fundamental and second harmonic radiation of an ytterbium nanosecond pulsed all-fiber laser in a type-I phase-matched LiB(3)O(5) (LBO) crystal where originally orthogonal polarization planes of the fundamental and second harmonic beams are aligned by an optically active quartz crystal. 8 W of ultraviolet light at 355 nm were achieved with 40% conversion efficiency from 1064 nm radiation. The conversion efficiency obtained in a type-I phase-matched LBO THG crystal was 1.6 times higher than the one achieved in a type-II LBO crystal at similar experimental conditions. In comparison to half-wave plates traditionally used for polarization alignment the optically active quartz crystal has much lower temperature dependence and requires simpler optical alignment.

Imaging rat esophagus using combination of reflectance confocal and multiphoton microscopy

NASA Astrophysics Data System (ADS)

Zhuo, S. M.; Chen, J. X.; Jiang, X. S.; Lu, K. C.; Xie, S. S.

2008-08-01

We combine reflectance confocal microscopy (RCM) with multiphoton microscopy (MPM) to image rat esophagus. The two imaging modalities allow detection of layered-resolved complementary information from esophagus. In the keratinizing layer, the keratinocytes boundaries can be characterized by RCM, while the keratinocytes cytoplasm (keratin) can be further imaged by multiphoton autofluorescence signal. In the epithelium, the epithelial cellular boundaries and nucleus can be detected by RCM, and MPM can be used for imaging epithelial cell cytoplasm and monitoring metabolic state of epithelium. In the stroma, multiphoton autofluorescence signal is used to image elastin and second harmonic generation signal is utilized to detect collagen, while RCM is used to determine the optical property of stroma. Overall, these results suggest that the combination of RCM and MPM has potential to provide more important and comprehensive information for early diagnosis of esophageal cancer.

Field-controllable second harmonic generation at a graphene oxide heterointerface

NASA Astrophysics Data System (ADS)

Fernandes, Gustavo E.; Kim, Jin Ho; Osgood, Richard, III; Xu, Jimmy

2018-03-01

We report on the voltage-dependent SHG signal obtained in a reduced-graphene oxide (rGO)/p-type Si heterointerface. A simple qualitative model considering the interaction between the heterointerface depletion region potential and the naturally occurring surface dipole layer on the rGO is introduced to account for the characteristics of the SHG signal, specifically, a minimum point at ≈ -3 V bias on the rGO side of the interface. This feature-rich system has the potential to provide field-controllable surface-dipole moments and second-order nonlinearities, which may find applications in tunable nonlinear photonic devices for realizing second-harmonic generation and optical-rectification.

In vitro and in vivo tissue harmonic images obtained with parallel transmit beamforming by means of orthogonal frequency division multiplexing.

PubMed

Demi, Libertario; Ramalli, Alessandro; Giannini, Gabriele; Mischi, Massimo

2015-01-01

In classic pulse-echo ultrasound imaging, the data acquisition rate is limited by the speed of sound. To overcome this, parallel beamforming techniques in transmit (PBT) and in receive (PBR) mode have been proposed. In particular, PBT techniques, based on the transmission of focused beams, are more suitable for harmonic imaging because they are capable of generating stronger harmonics. Recently, orthogonal frequency division multiplexing (OFDM) has been investigated as a means to obtain parallel beamformed tissue harmonic images. To date, only numerical studies and experiments in water have been performed, hence neglecting the effect of frequencydependent absorption. Here we present the first in vitro and in vivo tissue harmonic images obtained with PBT by means of OFDM, and we compare the results with classic B-mode tissue harmonic imaging. The resulting contrast-to-noise ratio, here used as a performance metric, is comparable. A reduction by 2 dB is observed for the case in which three parallel lines are reconstructed. In conclusion, the applicability of this technique to ultrasonography as a means to improve the data acquisition rate is confirmed.

Selective suppression of high-order harmonics within phase-matched spectral regions.

PubMed

Lerner, Gavriel; Diskin, Tzvi; Neufeld, Ofer; Kfir, Ofer; Cohen, Oren

2017-04-01

Phase matching in high-harmonic generation leads to enhancement of multiple harmonics. It is sometimes desired to control the spectral structure within the phase-matched spectral region. We propose a scheme for selective suppression of high-order harmonics within the phase-matched spectral region while weakly influencing the other harmonics. The method is based on addition of phase-mismatched segments within a phase-matched medium. We demonstrate the method numerically in two examples. First, we show that one phase-mismatched segment can significantly suppress harmonic orders 9, 15, and 21. Second, we show that two phase-mismatched segments can efficiently suppress circularly polarized harmonics with one helicity over the other when driven by a bi-circular field. The new method may be useful for various applications, including the generation of highly helical bright attosecond pulses.

Optical coherence tomography and non-linear microscopy for paintings - a study of the complementary capabilities and laser degradation effects.

PubMed

Liang, Haida; Mari, Meropi; Cheung, Chi Shing; Kogou, Sotiria; Johnson, Phillip; Filippidis, George

2017-08-07

This paper examines for the first time the potential complementary imaging capabilities of Optical coherence tomography (OCT) and non-linear microscopy (NLM) for multi-modal 3D examination of paintings following the successful application of OCT to the in situ, non-invasive examination of varnish and paint stratigraphy of historic paintings and the promising initial studies of NLM of varnish samples. OCT provides image contrast through the optical scattering and absorption properties of materials, while NLM provides molecular information through multi-photon fluorescence and higher harmonics generation (second and third harmonic generation). OCT is well-established in the in situ non-invasive imaging of the stratigraphy of varnish and paint layers. While NLM examination of transparent samples such as fresh varnish and some transparent paints showed promising results, the ultimate use of NLM on paintings is limited owing to the laser degradation effects caused by the high peak intensity of the laser source necessary for the generation of non-linear phenomena. The high intensity normally employed in NLM is found to be damaging to all non-transparent painting materials from slightly scattering degraded varnish to slightly absorbing paint at the wavelength of the laser excitation source. The results of this paper are potentially applicable to a wide range of materials given the diversity of the materials encountered in paintings (e.g. minerals, plants, insects, oil, egg, synthetic and natural varnish).

Nonlinear optical response of the collagen triple helix and second harmonic microscopy of collagen liquid crystals

NASA Astrophysics Data System (ADS)

Deniset-Besseau, A.; De Sa Peixoto, P.; Duboisset, J.; Loison, C.; Hache, F.; Benichou, E.; Brevet, P.-F.; Mosser, G.; Schanne-Klein, M.-C.

2010-02-01

Collagen is characterized by triple helical domains and plays a central role in the formation of fibrillar and microfibrillar networks, basement membranes, as well as other structures of the connective tissue. Remarkably, fibrillar collagen exhibits efficient Second Harmonic Generation (SHG) and SHG microscopy proved to be a sensitive tool to score fibrotic pathologies. However, the nonlinear optical response of fibrillar collagen is not fully characterized yet and quantitative data are required to further process SHG images. We therefore performed Hyper-Rayleigh Scattering (HRS) experiments and measured a second order hyperpolarisability of 1.25 10-27 esu for rat-tail type I collagen. This value is surprisingly large considering that collagen presents no strong harmonophore in its amino-acid sequence. In order to get insight into the physical origin of this nonlinear process, we performed HRS measurements after denaturation of the collagen triple helix and for a collagen-like short model peptide [(Pro-Pro-Gly)10]3. It showed that the collagen large nonlinear response originates in the tight alignment of a large number of weakly efficient harmonophores, presumably the peptide bonds, resulting in a coherent amplification of the nonlinear signal along the triple helix. To illustrate this mechanism, we successfully recorded SHG images in collagen liquid solutions by achieving liquid crystalline ordering of the collagen triple helices.

Type-I non-critically phase-matched second-harmonic generation in Gd1-xYxCa4O(BO3)3

NASA Astrophysics Data System (ADS)

Burmester, P. B. W.; Kellner, T.; Petermann, K.; Huber, G.; Uecker, R.; Reiche, P.

Second-harmonic generation was z-cut observed Gd1-xYxCa4O(BO3)3 (Gd1-xYxCOB) and the dependence of the phase-matching wavelength on the mixing ratio x has been investigated. The dependence on both temperature and angle tuning was examined as well. We found the suitable composition for noncritical frequency doubling at 930 nm, which is the lasing wavelength of Nd:YAlO3 on the 4F3/2?4I9/2 transition.

The Effects of Atmospheric Water Vapor Absorption on Infrared Laser Propagation in the 5 Micrometer Band.

DTIC Science & Technology

1983-05-01

which allows for thermal linedr expansion of the structure. 32 1 I 2. Second Harmonic Generation The second harmonic generation was achieved by mounting a...filter unit and then to the reference channel lock-in amplifier. C. TESTS 1 . DC Amplifier and A/D Calibration The Ectron DC amplifiers and the Altair A/D...AD-A130 788 THE EFFECTS OF ATMOSPHERIC WATER VAPOR ABSORPTION ON 1 / INFRARED LASER PRUPA..(U) OHIO STATE UNIV COLUMBUS ELECTROSCIENCE LAB L G WALTER

Polarization-insensitive ultralow-power second-harmonic generation frequency-resolved optical gating.

PubMed

Miao, Houxun; Weiner, Andrew M; Langrock, Carsten; Roussev, Rostislav V; Fejer, Martin M

2007-04-01

We demonstrate polarization-insensitive ultralow-power second-harmonic generation frequency-resolved optical gating (FROG) measurements with a fiber-pigtailed, aperiodically poled lithium niobate waveguide. By scrambling the polarization much faster than the measurement integration time, we eliminate the impairment that frequency-independent random polarization fluctuations induce in FROG measurements. As a result we are able to retrieve intensity and phase profiles of few hundred femtosecond optical pulses with 50 MHz repetition rates at 5.2 nW coupled average power without control of the input polarization.

Improving liver fibrosis diagnosis based on forward and backward second harmonic generation signals

NASA Astrophysics Data System (ADS)

Peng, Qiwen; Zhuo, Shuangmu; So, Peter T. C.; Yu, Hanry

2015-02-01

The correlation of forward second harmonic generation (SHG) signal and backward SHG signal in different liver fibrosis stages was investigated. We found that three features, including the collagen percentage for forward SHG, the collagen percentage for backward SHG, and the average intensity ratio of two kinds of SHG signals, can quantitatively stage liver fibrosis in thioacetamide-induced rat model. We demonstrated that the combination of all three features by using a support vector machine classification algorithm can provide a more accurate prediction than each feature alone in fibrosis diagnosis.

Extended phase matching of second-harmonic generation in periodically poled KTiOPO4 with zero group-velocity mismatch

NASA Astrophysics Data System (ADS)

König, Friedrich; Wong, Franco N. C.

2004-03-01

Under extended phase-matching conditions, the first frequency derivative of the wave-vector mismatch is zero and the phase-matching bandwidth is greatly increased. We present extensive three-wave mixing measurements of the wave-vector mismatch and obtain improved Sellmeier equations for KTiOPO4. We observed a type-II extended phase-matching bandwidth of 100 nm for second-harmonic generation in periodically poled KTiOPO4, centered at the fundamental wavelength of 1584 nm. Applications in quantum entanglement and frequency metrology are discussed.

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

Assessment of breast pathologies using nonlinear microscopy

PubMed Central

Tao, Yuankai K.; Shen, Dejun; Sheikine, Yuri; Ahsen, Osman O.; Wang, Helen H.; Schmolze, Daniel B.; Johnson, Nicole B.; Brooker, Jeffrey S.; Cable, Alex E.; Connolly, James L.; Fujimoto, James G.

2014-01-01

Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen. Imaging was performed on fresh, intact specimens without the need for fixation, embedding, and sectioning required for conventional histopathology. A visualization method to aid pathological interpretation is presented that maps NLM contrast from two-photon fluorescence and second harmonic signals to features closely resembling histopathology using hematoxylin and eosin staining. Mosaicking is used to overcome trade-offs between resolution and field of view, enabling imaging of subcellular features over square-centimeter specimens. After NLM examination, specimens were processed for standard paraffin-embedded histology using a protocol that coregistered histological sections to NLM images for paired assessment. Blinded NLM reading by three pathologists achieved 95.4% sensitivity and 93.3% specificity, compared with paraffin-embedded histology, for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. Interobserver agreement was κ = 0.88 for NLM and κ = 0.89 for histology. These results show that NLM achieves high diagnostic accuracy, can be rapidly performed on unfixed specimens, and is a promising method for intraoperative margin assessment. PMID:25313045

Strategic placement of stereogenic centers in molecular materials for second harmonic generation.

PubMed

Gangopadhyay, P; Rao, D Narayana; Agranat, Israel; Radhakrishnan, T P

2002-01-01

Basic aspects of the nonlinear optical phenomenon of second harmonic generation (SHG) and the assembly of molecular materials for SHG are reviewed. Extensive use of chirality as a convenient tool to generate noncentrosymmetricity in molecular lattices, an essential requirement for the development of quadratic nonlinear optical materials, is noted. An overview of our investigations of chiral diaminodicyanoquinodimethanes is presented, which provides insight into a systematic approach to the effective deployment of chirality to achieve optimal molecular orientations for enhanced solid state SHG. Extension of these ideas to the realization of strong SHG in materials based on helical superstructures is outlined.

Evaluation of area-based collagen scoring by nonlinear microscopy in chronic hepatitis C-induced liver fibrosis

PubMed Central

Sevrain, David; Dubreuil, Matthieu; Dolman, Grace Elizabeth; Zaitoun, Abed; Irving, William; Guha, Indra Neil; Odin, Christophe; Le Grand, Yann

2015-01-01

In this paper we analyze a fibrosis scoring method based on measurement of the fibrillar collagen area from second harmonic generation (SHG) microscopy images of unstained histological slices from human liver biopsies. The study is conducted on a cohort of one hundred chronic hepatitis C patients with intermediate to strong Metavir and Ishak stages of liver fibrosis. We highlight a key parameter of our scoring method to discriminate between high and low fibrosis stages. Moreover, according to the intensity histograms of the SHG images and simple mathematical arguments, we show that our area-based method is equivalent to an intensity-based method, despite saturation of the images. Finally we propose an improvement of our scoring method using very simple image processing tools. PMID:25909005

Evaluation of area-based collagen scoring by nonlinear microscopy in chronic hepatitis C-induced liver fibrosis.

PubMed

Sevrain, David; Dubreuil, Matthieu; Dolman, Grace Elizabeth; Zaitoun, Abed; Irving, William; Guha, Indra Neil; Odin, Christophe; Le Grand, Yann

2015-04-01

In this paper we analyze a fibrosis scoring method based on measurement of the fibrillar collagen area from second harmonic generation (SHG) microscopy images of unstained histological slices from human liver biopsies. The study is conducted on a cohort of one hundred chronic hepatitis C patients with intermediate to strong Metavir and Ishak stages of liver fibrosis. We highlight a key parameter of our scoring method to discriminate between high and low fibrosis stages. Moreover, according to the intensity histograms of the SHG images and simple mathematical arguments, we show that our area-based method is equivalent to an intensity-based method, despite saturation of the images. Finally we propose an improvement of our scoring method using very simple image processing tools.

Second Harmonic Hectometric Radio Emission at Jupiter

NASA Technical Reports Server (NTRS)

Menietti, J. D.; Gurnett, D. A.; Groene, J. B.

1998-01-01

Galileo has been in orbit around Jupiter since December 1995. The plasma wave instrument on board the spacecraft has occasionally detected a rotationally modulated attenuation band in the hectometric (HOM) emission that most likely is due to scattering of the radiation from density fluctuations along the Io L-shell, as reported earlier. The occurrence of the attenuation band is likely to be dependent on Io activity and the presence of density scattering centers along the Io-L-shell as well as the location of the source region. Some of the attenuation bands show clear indications of second harmonic emission. Without polarization measurements, it is difficult to place constraints on the local generation conditions based on the cyclotron maser instability, but the results imply that second harmonic emission could be present in the decametric (DAM) radiation as well. A survey of the data has revealed about 30 examples of second harmonic HOM.

Second Harmonic Hectometric Radio Emission at Jupiter

NASA Technical Reports Server (NTRS)

Menietti, J. D.; Gurnett, D. A.; Groene, J. B.

1998-01-01

Galileo has been in orbit around Jupiter since December 1995. The plasma wave instrument on board the spacecraft has occasionally detected a rotationally modulated attenuation band in the hectometric (HOM) emission that most likely is due to scattering of the radiation from density fluctuations along the Io L-shell, as reported earlier. The occurrence of the attenuation band is likely to be dependent on Io activity and the presence of density scattering centers along the Io L-shell as well as the location of the source region. Some of the attenuation bands show clear indications of second harmonic emission. Without polarization measurements, it is difficult to place constraints on the local generation conditions based on the cyclotron maser instability, but the results imply that second harmonic emission could be present in the decametric (DAM) radiation as well. A survey of the data has revealed about 30 examples of second harmonic HOM.

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.

Efficient Second-Harmonic Generation in Nanocrystalline Silicon Nanoparticles.

PubMed

Makarov, Sergey V; Petrov, Mihail I; Zywietz, Urs; Milichko, Valentin; Zuev, Dmitry; Lopanitsyna, Natalia; Kuksin, Alexey; Mukhin, Ivan; Zograf, George; Ubyivovk, Evgeniy; Smirnova, Daria A; Starikov, Sergey; Chichkov, Boris N; Kivshar, Yuri S

2017-05-10

Recent trends to employ high-index dielectric particles in nanophotonics are motivated by their reduced dissipative losses and large resonant enhancement of nonlinear effects at the nanoscale. Because silicon is a centrosymmetric material, the studies of nonlinear optical properties of silicon nanoparticles have been targeting primarily the third-harmonic generation effects. Here we demonstrate, both experimentally and theoretically, that resonantly excited nanocrystalline silicon nanoparticles fabricated by an optimized laser printing technique can exhibit strong second-harmonic generation (SHG) effects. We attribute an unexpectedly high yield of the nonlinear conversion to a nanocrystalline structure of nanoparticles supporting the Mie resonances. The demonstrated efficient SHG at green light from a single silicon nanoparticle is 2 orders of magnitude higher than that from unstructured silicon films. This efficiency is significantly higher than that of many plasmonic nanostructures and small silicon nanoparticles in the visible range, and it can be useful for a design of nonlinear nanoantennas and silicon-based integrated light sources.

Second-harmonic generation in substoichiometric silicon nitride layers

NASA Astrophysics Data System (ADS)

Pecora, Emanuele; Capretti, Antonio; Miano, Giovanni; Dal Negro, Luca

2013-03-01

Harmonic generation in optical circuits offers the possibility to integrate wavelength converters, light amplifiers, lasers, and multiple optical signal processing devices with electronic components. Bulk silicon has a negligible second-order nonlinear optical susceptibility owing to its crystal centrosymmetry. Silicon nitride has its place in the microelectronic industry as an insulator and chemical barrier. In this work, we propose to take advantage of silicon excess in silicon nitride to increase the Second Harmonic Generation (SHG) efficiency. Thin films have been grown by reactive magnetron sputtering and their nonlinear optical properties have been studied by femtosecond pumping over a wide range of excitation wavelengths, silicon nitride stoichiometry and thermal processes. We demonstrate SHG in the visible range (375 - 450 nm) using a tunable 150 fs Ti:sapphire laser, and we optimize the SH emission at a silicon excess of 46 at.% demonstrating a maximum SHG efficiency of 4x10-6 in optimized films. Polarization properties, generation efficiency, and the second order nonlinear optical susceptibility are measured for all the investigated samples and discussed in terms of an effective theoretical model. Our findings show that the large nonlinear optical response demonstrated in optimized Si-rich silicon nitride materials can be utilized for the engineering of nonlinear optical functions and devices on a Si chip.

Singularity-driven second- and third-harmonic generation at {epsilon}-near-zero crossing points

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

Vincenti, M. A.; Ceglia, D. de; Ciattoni, A.

We show an alternative path to efficient second- and third-harmonic generation in proximity of the zero crossing points of the dielectric permittivity in conjunction with low absorption. Under these circumstances, any material, either natural or artificial, will show similar degrees of field enhancement followed by strong harmonic generation, without resorting to any resonant mechanism. The results presented in this paper provide a general demonstration of the potential that the zero-crossing-point condition holds for nonlinear optical phenomena. We investigate a generic Lorentz medium and demonstrate that a singularity-driven enhancement of the electric field may be achieved even in extremely thin layersmore » of material. We also discuss the role of nonlinear surface sources in a realistic scenario where a 20-nm layer of CaF{sub 2} is excited at 21 {mu}m, where {epsilon}{approx} 0. Finally, we show similar behavior in an artificial composite material that includes absorbing dyes in the visible range, provide a general tool for the improvement of harmonic generation using the {epsilon}{approx} 0 condition, and illustrate that this singularity-driven enhancement of the field lowers the thresholds for a plethora of nonlinear optical phenomena.« less

Harmonic Structure Predicts the Enjoyment of Uplifting Trance Music.

PubMed

Agres, Kat; Herremans, Dorien; Bigo, Louis; Conklin, Darrell

2016-01-01

An empirical investigation of how local harmonic structures (e.g., chord progressions) contribute to the experience and enjoyment of uplifting trance (UT) music is presented. The connection between rhythmic and percussive elements and resulting trance-like states has been highlighted by musicologists, but no research, to our knowledge, has explored whether repeated harmonic elements influence affective responses in listeners of trance music. Two alternative hypotheses are discussed, the first highlighting the direct relationship between repetition/complexity and enjoyment, and the second based on the theoretical inverted-U relationship described by the Wundt curve. We investigate the connection between harmonic structure and subjective enjoyment through interdisciplinary behavioral and computational methods: First we discuss an experiment in which listeners provided enjoyment ratings for computer-generated UT anthems with varying levels of harmonic repetition and complexity. The anthems were generated using a statistical model trained on a corpus of 100 uplifting trance anthems created for this purpose, and harmonic structure was constrained by imposing particular repetition structures (semiotic patterns defining the order of chords in the sequence) on a professional UT music production template. Second, the relationship between harmonic structure and enjoyment is further explored using two computational approaches, one based on average Information Content, and another that measures average tonal tension between chords. The results of the listening experiment indicate that harmonic repetition does in fact contribute to the enjoyment of uplifting trance music. More compelling evidence was found for the second hypothesis discussed above, however some maximally repetitive structures were also preferred. Both computational models provide evidence for a Wundt-type relationship between complexity and enjoyment. By systematically manipulating the structure of chord progressions, we have discovered specific harmonic contexts in which repetitive or complex structure contribute to the enjoyment of uplifting trance music.

Harmonic Structure Predicts the Enjoyment of Uplifting Trance Music

PubMed Central

Agres, Kat; Herremans, Dorien; Bigo, Louis; Conklin, Darrell

2017-01-01

An empirical investigation of how local harmonic structures (e.g., chord progressions) contribute to the experience and enjoyment of uplifting trance (UT) music is presented. The connection between rhythmic and percussive elements and resulting trance-like states has been highlighted by musicologists, but no research, to our knowledge, has explored whether repeated harmonic elements influence affective responses in listeners of trance music. Two alternative hypotheses are discussed, the first highlighting the direct relationship between repetition/complexity and enjoyment, and the second based on the theoretical inverted-U relationship described by the Wundt curve. We investigate the connection between harmonic structure and subjective enjoyment through interdisciplinary behavioral and computational methods: First we discuss an experiment in which listeners provided enjoyment ratings for computer-generated UT anthems with varying levels of harmonic repetition and complexity. The anthems were generated using a statistical model trained on a corpus of 100 uplifting trance anthems created for this purpose, and harmonic structure was constrained by imposing particular repetition structures (semiotic patterns defining the order of chords in the sequence) on a professional UT music production template. Second, the relationship between harmonic structure and enjoyment is further explored using two computational approaches, one based on average Information Content, and another that measures average tonal tension between chords. The results of the listening experiment indicate that harmonic repetition does in fact contribute to the enjoyment of uplifting trance music. More compelling evidence was found for the second hypothesis discussed above, however some maximally repetitive structures were also preferred. Both computational models provide evidence for a Wundt-type relationship between complexity and enjoyment. By systematically manipulating the structure of chord progressions, we have discovered specific harmonic contexts in which repetitive or complex structure contribute to the enjoyment of uplifting trance music. PMID:28119641

Second harmonic generation and crystal growth of new chalcone derivatives

NASA Astrophysics Data System (ADS)

Patil, P. S.; Dharmaprakash, S. M.; Ramakrishna, K.; Fun, Hoong-Kun; Sai Santosh Kumar, R.; Narayana Rao, D.

2007-05-01

We report on the synthesis, crystal structure and optical characterization of chalcone derivatives developed for second-order nonlinear optics. The investigation of a series of five chalcone derivatives with the second harmonic generation powder test according to Kurtz and Perry revealed that these chalcones show efficient second-order nonlinear activity. Among them, high-quality single crystals of 3-Br-4'-methoxychalcone (3BMC) were grown by solvent evaporation solution growth technique. Grown crystals were characterized by X-ray powder diffraction (XRD), laser damage threshold, UV-vis-NIR and refractive index measurement studies. Infrared spectroscopy, thermogravimetric analysis and differential thermal analysis measurements were performed to study the molecular vibration and thermal behavior of 3BMC crystal. Thermal analysis does not show any structural phase transition.

Label-free three-dimensional imaging of cell nucleus using third-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Lin, Jian; Zheng, Wei; Wang, Zi; Huang, Zhiwei

2014-09-01

We report the implementation of the combined third-harmonic generation (THG) and two-photon excited fluorescence (TPEF) microscopy for label-free three-dimensional (3-D) imaging of cell nucleus morphological changes in liver tissue. THG imaging shows regular spherical shapes of normal hepatocytes nuclei with inner chromatin structures while revealing the condensation of chromatins and nuclear fragmentations in hepatocytes of diseased liver tissue. Colocalized THG and TPEF imaging provides complementary information of cell nuclei and cytoplasm in tissue. This work suggests that 3-D THG microscopy has the potential for quantitative analysis of nuclear morphology in cells at a submicron-resolution without the need for DNA staining.

Label-free three-dimensional imaging of cell nucleus using third-harmonic generation microscopy

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

Lin, Jian; Zheng, Wei; Wang, Zi

2014-09-08

We report the implementation of the combined third-harmonic generation (THG) and two-photon excited fluorescence (TPEF) microscopy for label-free three-dimensional (3-D) imaging of cell nucleus morphological changes in liver tissue. THG imaging shows regular spherical shapes of normal hepatocytes nuclei with inner chromatin structures while revealing the condensation of chromatins and nuclear fragmentations in hepatocytes of diseased liver tissue. Colocalized THG and TPEF imaging provides complementary information of cell nuclei and cytoplasm in tissue. This work suggests that 3-D THG microscopy has the potential for quantitative analysis of nuclear morphology in cells at a submicron-resolution without the need for DNA staining.

Optical Manifestations of the Electron-Electron Interaction

NASA Astrophysics Data System (ADS)

Portengen, Taco

1995-01-01

In this thesis, two optical manifestations of the electron-electron interaction are studied: the Fermi -edge singularity in doped quantum wells and quantum wires, and second-harmonic generation in mixed-valent compounds. First, we construct a theory of the Fermi-edge singularity that can systematically account for the finite mass of a hole created in the valence subband of a quantum well or quantum wire. The dynamical response for finite hole mass depends crucially on the dimensionality of the Fermi sea. Whereas in three dimensions the infrared divergence is suppressed, in two dimensions a one-over-square-root singularity survives, while in one dimension the spectrum is even more singular with recoil than without recoil. This explains the large optical singularities observed in quantum wires. Correlations change the prefactor, but not the exponent of the threshold behaviour in two and in three dimensions, while in one dimension, they affect neither the prefactor nor the exponent. Second, we apply our theory to the Frohlich polaron, a manifestation of the electron-phonon rather than the electron-electron interaction. The new method of calculating the Green's function removes unphysical features of the conventional cumulant expansion that had remained unnoticed in the literature up to now. Third, in an effort to investigate the impact of coherence on optical properties, we calculate the linear and nonlinear optical characteristics of mixed-valent compounds. Second -harmonic generation can only occur for solutions of the theoretical Falicov-Kimball model that have a built-in coherence between the itinerant d-electrons and localized f-holes. By contrast, second-harmonic generation cannot occur for solutions with f-site occupation as a good quantum number. The interaction between optically created quasiparticles leads to a threshold singularity in the absorption spectrum, and greatly enhances the second-harmonic conversion efficiency at half the gap frequency. As an experimental test of coherence we propose the measurement of the second-harmonic susceptibility of SmB_6..

Frequency modulation of high-order harmonic generation in an orthogonally polarized two-color laser field.

PubMed

Li, Guicun; Zheng, Yinghui; Ge, Xiaochun; Zeng, Zhinan; Li, Ruxin

2016-08-08

We have experimentally investigated the frequency modulation of high-order harmonics in an orthogonally polarized two-color laser field consisting of a mid-infrared 1800nm fundamental pulse and its second harmonic pulse. It is demonstrated that the high harmonic spectra can be fine-tuned as we slightly change the relative delay of the two-color laser pulses. By analyzing the relative frequency shift of each harmonic at different two-color delays, the nonadiabatic spectral shift induced by the rapid variation of the intensity-dependent intrinsic dipole phase can be distinguished from the blueshift induced by the change of the refractive index during self-phase modulation (SPM). Our comprehensive analysis shows that the frequency modulation pattern is a reflection of the average emission time of high-order harmonic generation (HHG), thus offering a simple method to fine-tune the spectra of the harmonics on a sub-cycle time scale.

Concept for power scaling second harmonic generation using a cascade of nonlinear crystals.

PubMed

Hansen, A K; Tawfieq, M; Jensen, O B; Andersen, P E; Sumpf, B; Erbert, G; Petersen, P M

2015-06-15

Within the field of high-power second harmonic generation (SHG), power scaling is often hindered by adverse crystal effects such as thermal dephasing arising from the second harmonic (SH) light, which imposes limits on the power that can be generated in many crystals. Here we demonstrate a concept for efficient power scaling of single-pass SHG beyond such limits using a cascade of nonlinear crystals, in which the first crystal is chosen for high nonlinear efficiency and the subsequent crystal(s) are chosen for power handling ability. Using this highly efficient single-pass concept, we generate 3.7 W of continuous-wave diffraction-limited (M(2)=1.25) light at 532 nm from 9.5 W of non-diffraction-limited (M(2)=7.7) light from a tapered laser diode, while avoiding significant thermal effects. Besides constituting the highest SH power yet achieved using a laser diode, this demonstrates that the concept successfully combines the high efficiency of the first stage with the good power handling properties of the subsequent stages. The concept is generally applicable and can be expanded with more stages to obtain even higher efficiency, and extends also to other combinations of nonlinear media suitable for other wavelengths.

Structural dynamics of the skeletal muscle fiber by second harmonic generation

NASA Astrophysics Data System (ADS)

Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

2008-02-01

The high degree of structural order in skeletal muscle allows imaging of this tissue by Second Harmonic Generation (SHG). As previously found (Vanzi et al., J. Muscle Cell Res. Motil. 2006) by fractional extraction of proteins, myosin is the source of SHG signal. A full characterization of the polarization-dependence of the SHG signal can provide very selective information on the orientation of the emitting proteins and their dynamics during contraction. We developed a line scan polarization method, allowing measurements of a full polarization curve in intact muscle fibers from skeletal muscle of the frog to characterize the SHG polarization dependence on different physiological states (resting, rigor and isometric tetanic contraction). The polarization data have been interpreted by means of a model in terms of the average orientation of SHG emitters.The different physiological states are characterized by distinct patterns of SHG polarization. The variation of the orientation of emitting molecules in relation to the physiological state of the muscle demonstrates that one part of SHG signal arises from the globular head of the myosin molecule that cross-links actin and myosin filaments. The dependence of the SHG modulation on the degree of overlap between actin and myosin filaments during an isometric contraction, provides the constraints to estimate the fraction of myosin heads generating the isometric force in the active muscle fiber.

The Effects of the Menstrual Cycle on Vibratory Characteristics of the Vocal Folds Investigated With High-Speed Digital Imaging.

PubMed

Kunduk, Melda; Vansant, Mathew B; Ikuma, Takeshi; McWhorter, Andrew

2017-03-01

This study investigated the effect of menstrual cycle on vocal fold vibratory characteristics in young women using high-speed digital imaging. This study examined the menstrual phase effect on five objective high-speed imaging parameters and two self-rated perceptual parameters. The effects of oral birth control use were also investigated. Thirteen subjects with no prior voice complaints were included in this study. All data were collected at three different time periods (premenses, postmenses, ovulation) over the course of one menstrual cycle. For five of the 13 subjects, data were collected for two consecutive cycles. Six of 13 subjects were oral birth control users. From high-speed imaging data, five objective parameters were computed: fundamental frequency, fundamental frequency deviation, harmonics-to-noise ratio, harmonic richness factor, and ratio of first and second harmonics. They were supplemented by two self-rated parameters: Reflux Severity Index and perceptual voice quality rating. Analysis included mixed model linear analysis with repeated measures. Results indicated no significant main effects for menstrual phase, between-cycle, or birth control use in the analysis for mean fundamental frequency, fundamental frequency deviation, harmonics-to-noise ratio, harmonic richness factor, first and second harmonics, Reflux Severity Index, and perceptual voice quality rating. Additionally, there were no interaction effects. Hormone fluctuations observed across the menstrual cycle do not appear to have direct effect on vocal fold vibratory characteristics in young women with no voice concerns. Birth control use, on the other hand, may have influence on spectral richness of vocal fold vibration. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Frequency-doubled vertical-external-cavity surface-emitting laser

DOEpatents

Raymond, Thomas D.; Alford, William J.; Crawford, Mary H.; Allerman, Andrew A.

2002-01-01

A frequency-doubled semiconductor vertical-external-cavity surface-emitting laser (VECSEL) is disclosed for generating light at a wavelength in the range of 300-550 nanometers. The VECSEL includes a semiconductor multi-quantum-well active region that is electrically or optically pumped to generate lasing at a fundamental wavelength in the range of 600-1100 nanometers. An intracavity nonlinear frequency-doubling crystal then converts the fundamental lasing into a second-harmonic output beam. With optical pumping with 330 milliWatts from a semiconductor diode pump laser, about 5 milliWatts or more of blue light can be generated at 490 nm. The device has applications for high-density optical data storage and retrieval, laser printing, optical image projection, chemical-sensing, materials processing and optical metrology.

Influence of crack opening and incident wave angle on second harmonic generation of Lamb waves

NASA Astrophysics Data System (ADS)

Yang, Yi; Ng, Ching-Tai; Kotousov, Andrei

2018-05-01

Techniques utilising second harmonic generation (SHG) have proven their great potential in detecting contact-type damage. However, the gap between the practical applications and laboratory studies is still quite large. The current work is aimed to bridge this gap by investigating the effects of the applied load and incident wave angle on the detectability of fatigue cracks at various lengths. Both effects are critical for practical implementations of these techniques. The present experimental study supported by three-dimensional (3D) finite element (FE) modelling has demonstrated that the applied load, which changes the crack opening and, subsequently, the contact nonlinearity, significantly affects the amplitude of the second harmonic generated by the fundamental symmetric mode (S0) of Lamb wave. This amplitude is also dependent on the length of the fatigue crack as well as the incident wave angle. The experimental and FE results correlate well, so the modelling approach can be implemented for practical design of damage monitoring systems as well as for the evaluation of the severity of the fatigue cracks.

Second Harmonic Generation Optical Rotation Solely Attributable to Chirality in Plasmonic Metasurfaces.

PubMed

Collins, Joel T; Hooper, David C; Mark, Andrew G; Kuppe, Christian; Valev, Ventsislav Kolev

2018-05-31

Chiral plasmonic nanostructures, those lacking mirror symmetry, can be designed to manipulate the polarization of incident light resulting in chiroptical (chiral optical) effects such as circular dichroism (CD) and optical rotation (OR). Due to high symmetry sensitivity, corresponding effects in second harmonic generation (SHG-CD and SHG-OR) are typically much stronger in comparison. These nonlinear effects have long been used for chiral molecular analysis and characterization, however both linear and nonlinear optical rotation can occur even in achiral structures, if the structure is birefringent due to anisotropy. Crucially, chiroptical effects resulting from anisotropy typically exhibit a strong dependence on structural orientation. Here we report large second-harmonic generation optical rotation of ±45°, due to intrinsic chirality in a highly anisotropic helical metamaterial. The SHG intensity is found to strongly relate to the structural anisotropy, however the angle of SHG-OR is invariant under sample rotation. We show that by tuning the geometry of anisotropic nanostructures, the interaction between anisotropy, chirality, and experiment geometry can allow even greater control over the chiroptical properties of plasmonic metamaterials.

Kilometric radiation power flux dependence on area of discrete aurora

NASA Technical Reports Server (NTRS)

Saflekos, N. A.; Burch, J. L.; Gurnett, D. A.; Anderson, R. R.; Sheehan, R. E.

1989-01-01

Kilometer wavelength radiation, measured from distant positions over the North Pole and over the Earth's equator, was compared to the area of discrete aurora imaged by several low-altitude spacecraft. Through correlative studies of auroral kilometric radiation (AKR) with about two thousand auroral images, a stereoscopic view of the average auroral acceleration region was obtained. A major result is that the total AKR power increases as the area of the discrete auroral oval increases. The implications are that the regions of parallel potentials or the auroral plasma cavities, in which AKR is generated, must possess the following attributes: (1) they are shallow in altitude and their radial position depends on wavelength, (2) they thread flux tubes of small cross section, (3) the generation mechanism in them reaches a saturation limit rapidly, and (4) their distribution over the discrete auroral oval is nearly uniform. The above statistical results are true for large samples collected over a long period of time (about six months). In the short term, AKR frequently exhibits temporal variations with scales as short as three minutes (the resolution of the averaged data used). These fluctuations are explainable by rapid quenchings as well as fast starts of the electron cyclotron maser mechanism. There were times when AKR was present at substantial power levels while optical emissions were below instrument thresholds. A recent theoretical result may account for this set of observations by predicting that suprathermal electrons, of energies as low as several hundred eV, can generate second harmonic AKR. The indirect observations of second harmonic AKR require that these electrons have mirror points high above the atmosphere so as to minimize auroral light emissions. The results provide evidence supporting the electron cyclotron maser mechanism.

High-harmonic generation by quantum-dot nanorings

NASA Astrophysics Data System (ADS)

Bâldea, Ioan; Gupta, Ashish K.; Cederbaum, Lorenz S.; Moiseyev, Nimrod

2004-06-01

Exact numerical results are obtained within the extended Hubbard Hamiltonian for nanorings consisting of Ag quantum dots (QD’s) with C6v symmetry which interact with a circularly polarized light. The results show that the high-harmonic generation (HHG) spectra obtained from such artificial “molecules” are more pronounced than the HHG spectra obtained from a real molecule such as benzene. Our studies show that the HHG spectra obtained from the QD nanorings consist of two plateaus while only one plateau appears for benzene. The role of electron correlations in the generation of the high-order harmonics is studied, and it is shown that it can increase the intensity of the high-order harmonics. Mainly affected are the harmonics which are located in the second plateau. Selection rules for the produced high harmonics and a new “synergetic” selection rule for the symmetry of the states contributing to the HHG spectrum, a combined effect of spatial and charge conjugation symmetries, are discussed.

Wide-bandgap III-Nitride based Second Harmonic Generation

DTIC Science & Technology

2014-10-02

fabrication process for a GaN LPS. Fig. 1: 3-step Fabrication process of a GaN based lateral polar structure. ( a ) Growth of a 20 nm AlN buffer layer...etching of the LT-AlN stripes. This results are shown in Fig. 2 ( a ) and (b). Fig. 2: AFM images of KOH ( a ) and RIE (b) patterned templates for lateral ...was varied between 0.6 - 1.0. FIG. 3: Growth process of AlGaN based Lateral Polar Structures. ( a ) RIE patterning. (b) Growth of HT- AlN. (c

Micro-/nanoscale multi-field coupling in nonlinear photonic devices

NASA Astrophysics Data System (ADS)

Yang, Qing; Wang, Yubo; Tang, Mingwei; Xu, Pengfei; Xu, Yingke; Liu, Xu

2017-08-01

The coupling of mechanics/electronics/photonics may improve the performance of nanophotonic devices not only in the linear region but also in the nonlinear region. This review letter mainly presents the recent advances on multi-field coupling in nonlinear photonic devices. The nonlinear piezoelectric effect and piezo-phototronic effects in quantum wells and fibers show that large second-order nonlinear susceptibilities can be achieved, and second harmonic generation and electro-optic modulation can be enhanced and modulated. Strain engineering can tune the lattice structures and induce second order susceptibilities in central symmetry semiconductors. By combining the absorption-based photoacoustic effect and intensity-dependent photobleaching effect, subdiffraction imaging can be achieved. This review will also discuss possible future applications of these novel effects and the perspective of their research. The review can help us develop a deeper knowledge of the substance of photon-electron-phonon interaction in a micro-/nano- system. Moreover, it can benefit the design of nonlinear optical sensors and imaging devices with a faster response rate, higher efficiency, more sensitivity and higher spatial resolution which could be applied in environmental detection, bio-sensors, medical imaging and so on.

Noninvasive intravital cellular diagnosis of atopic dermatitis by using harmonic optical virtual biopsy

NASA Astrophysics Data System (ADS)

Chen, Szu-Yu; Lee, Jyh-Hong; Chiang, Bor-Luen; Sun, Chi-Kuang

2007-02-01

Atopic dermatitis (AD) is now very common in people who live in cities, especially for babies and children. Since the cause of AD is still not completely understood and each person may have his own mixed symptoms that can change over time, diagnosis of AD can not be done precisely. Unlike some skin diseases, physical biopsy is rarely used in diagnosing AD on account of its low urgency. Thus, only indirect diagnoses, like asking for a medical history to learn about the symptoms and to rule out other diseases can be carried out. To gain insight into cellular details of AD for long-term diagnosing without physical biopsy, a noninvasive in vivo tool with a sub-micron subsurface resolution and high penetrability has to be used. In this presentation, we show that harmonic optical virtual biopsy can provide the required noninvasive cellular imaging, and is ideal for future clinical diagnosis of AD. Harmonic optical microscopy has been demonstrated to have the capability to reveal cellular morphology of human skin from epidermis to dermis layer. Third harmonic generation (THG), which is sensitive to inhomogeneous interfaces, can show the structures of skins, and can be used to reveal the morphological changes, for example, the thicken cuticle which is a common symptom of AD. Second harmonic generation (SHG), which occurs in non-centrosymmetric structures, has excellent contrast in collagen fibers and can show the pathological changes of dermis layer. Utilizing both THG and SHG, useful information may be given to facilitate the diagnosis of AD.

Ultrathin Nonlinear Metasurface for Optical Image Encoding.

PubMed

Walter, Felicitas; Li, Guixin; Meier, Cedrik; Zhang, Shuang; Zentgraf, Thomas

2017-05-10

Security of optical information is of great importance in modern society. Many cryptography techniques based on classical and quantum optics have been widely explored in the linear optical regime. Nonlinear optical encryption in which encoding and decoding involve nonlinear frequency conversions represents a new strategy for securing optical information. Here, we demonstrate that an ultrathin nonlinear photonic metasurface, consisting of meta-atoms with 3-fold rotational symmetry, can be used to hide optical images under illumination with a fundamental wave. However, the hidden image can be read out from second harmonic generation (SHG) waves. This is achieved by controlling the destructive and constructive interferences of SHG waves from two neighboring meta-atoms. In addition, we apply this concept to obtain gray scale SHG imaging. Nonlinear metasurfaces based on space variant optical interference open new avenues for multilevel image encryption, anticounterfeiting, and background free image reconstruction.

Quasi-phase-matching of only even-order high harmonics.

PubMed

Diskin, Tzvi; Cohen, Oren

2014-03-24

High harmonic spectrum of a quasi-monochromatic pump that interacts with isotropic media consists of only odd-order harmonics. Addition of a secondary pump, e.g. a static field or the second harmonic of the primary pump, can results with generation of both odd and even harmonics of the primary pump. We propose a method for quasi-phase matching of only the even-order harmonics of the primary pump. We formulate a theory for this process and demonstrate it numerically. We also show that it leads to attosecond pulse trains with constant carrier envelop phase and high repetition rate.

Multi-Photon Micro-Spectroscopy of Biological Specimens

DTIC Science & Technology

2000-07-01

Micro-spectroscopy, multi-photon fluorescence spectroscopy, second harmonic generation, plant tissues, stem, chloroplast, protoplast, maize, Arabidopsis...harmonic generation (SHG) in the plant cell 5wall. In this case, micro-spectroscopy provides a means of verification that, indeed, SHG occurs in plant ...fluorescence microscopy -the response of plant cells to high intensity illumination," Micron (in press) 2000. 3. H.-C. Huang and C. -C Chen, "Genome

3D full-field quantification of cell-induced large deformations in fibrillar biomaterials by combining non-rigid image registration with label-free second harmonic generation.

PubMed

Jorge-Peñas, Alvaro; Bové, Hannelore; Sanen, Kathleen; Vaeyens, Marie-Mo; Steuwe, Christian; Roeffaers, Maarten; Ameloot, Marcel; Van Oosterwyck, Hans

2017-08-01

To advance our current understanding of cell-matrix mechanics and its importance for biomaterials development, advanced three-dimensional (3D) measurement techniques are necessary. Cell-induced deformations of the surrounding matrix are commonly derived from the displacement of embedded fiducial markers, as part of traction force microscopy (TFM) procedures. However, these fluorescent markers may alter the mechanical properties of the matrix or can be taken up by the embedded cells, and therefore influence cellular behavior and fate. In addition, the currently developed methods for calculating cell-induced deformations are generally limited to relatively small deformations, with displacement magnitudes and strains typically of the order of a few microns and less than 10% respectively. Yet, large, complex deformation fields can be expected from cells exerting tractions in fibrillar biomaterials, like collagen. To circumvent these hurdles, we present a technique for the 3D full-field quantification of large cell-generated deformations in collagen, without the need of fiducial markers. We applied non-rigid, Free Form Deformation (FFD)-based image registration to compute full-field displacements induced by MRC-5 human lung fibroblasts in a collagen type I hydrogel by solely relying on second harmonic generation (SHG) from the collagen fibrils. By executing comparative experiments, we show that comparable displacement fields can be derived from both fibrils and fluorescent beads. SHG-based fibril imaging can circumvent all described disadvantages of using fiducial markers. This approach allows measuring 3D full-field deformations under large displacement (of the order of 10 μm) and strain regimes (up to 40%). As such, it holds great promise for the study of large cell-induced deformations as an inherent component of cell-biomaterial interactions and cell-mediated biomaterial remodeling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Centroid stabilization for laser alignment to corner cubes: designing a matched filter

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

Awwal, Abdul A. S.; Bliss, Erlan; Brunton, Gordon

2016-11-08

Automation of image-based alignment of National Ignition Facility high energy laser beams is providing the capability of executing multiple target shots per day. One important alignment is beam centration through the second and third harmonic generating crystals in the final optics assembly (FOA), which employs two retroreflecting corner cubes as centering references for each beam. Beam-to-beam variations and systematic beam changes over time in the FOA corner cube images can lead to a reduction in accuracy as well as increased convergence durations for the template-based position detector. A systematic approach is described that maintains FOA corner cube templates and guaranteesmore » stable position estimation.« less

Centroid stabilization for laser alignment to corner cubes: designing a matched filter

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

Awwal, Abdul A. S.; Bliss, Erlan; Brunton, Gordon

2016-11-08

Automation of image-based alignment of NIF high energy laser beams is providing the capability of executing multiple target shots per day. One important alignment is beam centration through the second and third harmonic generating crystals in the final optics assembly (FOA), which employs two retro-reflecting corner cubes as centering references for each beam. Beam-to-beam variations and systematic beam changes over time in the FOA corner cube images can lead to a reduction in accuracy as well as increased convergence durations for the template-based position detector. A systematic approach is described that maintains FOA corner cube templates and guarantees stable positionmore » estimation.« less

5D-intravital tomography as a novel tool for non-invasive in-vivo analysis of human skin

NASA Astrophysics Data System (ADS)

König, Karsten; Weinigel, Martin; Breunig, Hans G.; Gregory, Axel; Fischer, Peter; Kellner-Höfer, Marcel; Bückle, Rainer; Schwarz, Martin; Riemann, Iris; Stracke, Frank; Huck, Volker; Gorzelanny, Christian; Schneider, Stefan W.

2010-02-01

Some years ago, CE-marked clinical multiphoton systems for 3D imaging of human skin with subcellular resolution have been launched. These tomographs provide optical biopsies with submicron resolution based on two-photon excited autofluorescence (NAD(P)H, flavoproteins, keratin, elastin, melanin, porphyrins) and second harmonic generation by collagen. The 3D tomograph was now transferred into a 5D imaging system by the additional detection of the emission spectrum and the fluorescence lifetime based on spatially and spectrally resolved time-resolved single photon counting. The novel 5D intravital tomograph (5D-IVT) was employed for the early detection of atopic dermatitis and the analysis of treatment effects.

Dielectric Characterization of a Nonlinear Optical Material

PubMed Central

Lunkenheimer, P.; Krohns, S.; Gemander, F.; Schmahl, W. W.; Loidl, A.

2014-01-01

Batisite was reported to be a nonlinear optical material showing second harmonic generation. Using dielectric spectroscopy and polarization measurements, we provide a thorough investigation of the dielectric and charge-transport properties of this material. Batisite shows the typical characteristics of a linear lossy dielectric. No evidence for ferro- or antiferroelectric polarization is found. As the second-harmonic generation observed in batisite points to a non-centrosymmetric structure, this material is piezoelectric, but most likely not ferroelectric. In addition, we found evidence for hopping charge transport of localized charge carriers and a relaxational process at low temperatures. PMID:25109553

Absorption, fluorescence and second harmonic generation in Cr3+-doped BiB3O6 glasses

NASA Astrophysics Data System (ADS)

Kuznik, W.; Fuks-Janczarek, I.; Wojciechowski, A.; Kityk, I. V.; Kiisk, V.; Majchrowski, A.; Jaroszewicz, L. R.; Brik, M. G.; Nagy, G. U. L.

2015-06-01

Synthesis, spectral properties and photoinduced nonlinear optical effects of chromium-doped BiB3O6 glass are studied in the present paper. Absorption, excitation and time resolved luminescence spectra are presented and luminescence decay behavior is discussed. Detailed analysis of the obtained spectra (assignment of the most prominent spectral features in terms of the corresponding Cr3+ energy levels, crystal field strength Dq, Racah parameters B and C) was performed. A weak photostimulated second harmonic generation signal was found to increase drastically due to poling by proton implantation in the investigated sample.

Geometric effect on second harmonic generation from gold grating

NASA Astrophysics Data System (ADS)

Lu, Jiao; Ding, Baoyong; Huo, Yanyan; Ning, Tingyin

2018-05-01

We numerically investigate second harmonic generation from gold gratings of an ideal rectangular and ladder-shaped cross-section. The SHG efficiency from the gold gratings of the ladder-shaped cross-section is significantly enhanced compared with that from the ideal rectangular cross-section with a maximum enhancement factor of around two. The enhancement is ascribe to the nanostructure dependent local fundamental electric field, the nonlinear sources and thus the far field radiation. Our results have a practical meaning in the explanation of experimental SHG measurement, and the modulation of SHG response in the metallic nanostructure.

Spatial properties of odd and even low order harmonics generated in gas.

PubMed

Lambert, G; Andreev, A; Gautier, J; Giannessi, L; Malka, V; Petralia, A; Sebban, S; Stremoukhov, S; Tissandier, F; Vodungbo, B; Zeitoun, Ph

2015-01-14

High harmonic generation in gases is developing rapidly as a soft X-ray femtosecond light-source for applications. This requires control over all the harmonics characteristics and in particular, spatial properties have to be kept very good. In previous literature, measurements have always included several harmonics contrary to applications, especially spectroscopic applications, which usually require a single harmonic. To fill this gap, we present here for the first time a detailed study of completely isolated harmonics. The contribution of the surrounding harmonics has been totally suppressed using interferential filtering which is available for low harmonic orders. In addition, this allows to clearly identify behaviors of standard odd orders from even orders obtained by frequency-mixing of a fundamental laser and of its second harmonic. Comparisons of the spatial intensity profiles, of the spatial coherence and of the wavefront aberration level of 5ω at 160 nm and 6ω at 135 nm have then been performed. We have established that the fundamental laser beam aberrations can cause the appearance of a non-homogenous donut-shape in the 6ω spatial intensity distribution. This undesirable effect can be easily controlled. We finally conclude that the spatial quality of an even harmonic can be as excellent as in standard generation.

Tumor-associated macrophages and stromal TNF-α regulate collagen structure in a breast tumor model as visualized by second harmonic generation

NASA Astrophysics Data System (ADS)

Burke, Ryan M.; Madden, Kelley S.; Perry, Seth W.; Zettel, Martha L.; Brown, Edward B.

2013-08-01

Collagen fibers can be imaged with second harmonic generation (SHG) and are associated with efficient tumor cell locomotion. Preferential locomotion along these fibers correlates with a more aggressively metastatic phenotype, and changes in SHG emission properties accompany changes in metastatic outcome. We therefore attempted to elucidate the cellular and molecular machinery that influences SHG in order to understand how the microstructure of tumor collagen fibers is regulated. By quantifying SHG and immunofluorescence (IF) from tumors grown in mice with and without stromal tumor necrosis factor (TNF)-α and in the presence or absence of tumor-associated macrophages (TAMs), we determined that depletion of TAMs alters tumor collagen fibrillar microstructure as quantified by SHG and IF. Furthermore, we determined that abrogation of TNF-α expression by tumor stromal cells also alters fibrillar microstructure and that subsequent depletion of TAMs has no further effect. In each case, metastatic burden correlated with optical readouts of collagen microstructure. Our results implicate TAMs and stromal TNF-α as regulators of breast tumor collagen microstructure and suggest that this regulation plays a role in tumor metastasis. Furthermore, these results indicate that quantification of SHG represents a useful strategy for evaluating the cells and molecular pathways responsible for manipulating fibrillar collagen in breast tumor models.

Second harmonic generation microscopy analysis of extracellular matrix changes in human idiopathic pulmonary fibrosis

PubMed Central

Tilbury, Karissa; Hocker, James; Wen, Bruce L.; Sandbo, Nathan; Singh, Vikas; Campagnola, Paul J.

2014-01-01

Abstract. Patients with idiopathic fibrosis (IPF) have poor long-term survival as there are limited diagnostic/prognostic tools or successful therapies. Remodeling of the extracellular matrix (ECM) has been implicated in IPF progression; however, the structural consequences on the collagen architecture have not received considerable attention. Here, we demonstrate that second harmonic generation (SHG) and multiphoton fluorescence microscopy can quantitatively differentiate normal and IPF human tissues. For SHG analysis, we developed a classifier based on wavelet transforms, principle component analysis, and a K-nearest-neighbor algorithm to classify the specific alterations of the collagen structure observed in IPF tissues. The resulting ROC curves obtained by varying the numbers of principal components and nearest neighbors yielded accuracies of >95%. In contrast, simpler metrics based on SHG intensity and collagen coverage in the image provided little or no discrimination. We also characterized the change in the elastin/collagen balance by simultaneously measuring the elastin autofluorescence and SHG intensities and found that the IPF tissues were less elastic relative to collagen. This is consistent with known mechanical consequences of the disease. Understanding ECM remodeling in IPF via nonlinear optical microscopy may enhance our ability to differentiate patients with rapid and slow progression and, thus, provide better prognostic information. PMID:25134793

Inertial confinement fusion quarterly report, October--December 1992. Volume 3, No. 1

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

Dixit, S.N.

1992-12-31

This report contains papers on the following topics: The Beamlet Front End: Prototype of a new pulse generation system;imaging biological objects with x-ray lasers; coherent XUV generation via high-order harmonic generation in rare gases; theory of high-order harmonic generation; two-dimensional computer simulations of ultra- intense, short-pulse laser-plasma interactions; neutron detectors for measuring the fusion burn history of ICF targets; the recirculator; and lasnex evolves to exploit computer industry advances.

The Influence of Second Harmonic Phase and Amplitude Variation in Cyclically Pitching Wings

NASA Astrophysics Data System (ADS)

Culler, Ethan; Farnsworth, John

2017-11-01

From wind tunnel testing of a cyber-physical wing model, it has been found that the pitch trajectory for stall flutter is described by an array of higher harmonic frequencies with decaying energy content. These frequencies distort the stall flutter motion from that of a pure sinusoidal oscillation in pitch and can have a significant effect on the resulting force production. In order to understand how these higher harmonic frequencies contribute to the overall pitching moment characteristics of a wing in stall flutter, a rigid finite span wing model, with aspect ratio four, was pitched in the wind tunnel. The prescribed motion of the pitch cycle was varied by changing the amplitude ratio and phase of the second harmonic of the oscillation frequency. The second harmonic represents the second highest energy mode in the pitching cycle spectra. Pitching moment and planar particle image velocimetry data was collected. From these pitching trajectories, a significant dependence of pitching moment on both the phase and amplitude of the prescribed waveforms was found. Specifically, for the same amplitude ratio, variations in the phase produced changes of approximately 30 percent in the phase averaged pitching moment.

Fast determination of three-dimensional fibril orientation of type-I collagen via macroscopic chirality

NASA Astrophysics Data System (ADS)

Zhuo, Guan-Yu; Chen, Mei-Yu; Yeh, Chao-Yuan; Guo, Chin-Lin; Kao, Fu-Jen

2017-01-01

Polarization-resolved second harmonic generation (SHG) microscopy is appealing for studying structural proteins and well-organized biophotonic nanostructures, due to its highly sensitized structural specificity. In recent years, it has been used to investigate the chiroptical effect, particularly SHG circular dichroism (SHG-CD) in biological tissues. Although SHG-CD attributed to macromolecular structures has been demonstrated, the corresponding quantitative analysis and interpretation on how SHG correlates with second-order susceptibility χ(2) under circularly polarized excitations remains unclear. In this study, we demonstrate a method based on macroscopic chirality to elucidate the correlation between SHG-CD and the orientation angle of the molecular structure. By exploiting this approach, three-dimensional (3D) molecular orientation of type-I collagen is revealed with only two cross polarized SHG images (i.e., interactions of left and right circular polarizations) without acquiring an image stack of varying polarization.

Ultrasound imaging based on nonlinear pressure field properties

NASA Astrophysics Data System (ADS)

Bouakaz, Ayache; Frinking, Peter J. A.; de Jong, Nico

2000-07-01

Ultrasound image quality has experienced a significant improvement over the past years with the utilization of harmonic frequencies. This brings the need to understand the physical processes involved in the propagation of finite amplitude sound beams, and the issues for redesigning and optimizing the phased array transducers. New arrays with higher imaging performances are essential for tissue imaging and contrast imaging as well. This study presents measurements and simulations on a 4.6 MHz square transducer. The numerical scheme used solves the KZK equation in the time domain. Comparison of measured and computed data showed good agreement for low and high excitation levels. In a similar way, a numerical simulation was performed on a linear array with five elements. The simulation showed that the second harmonic beam is narrower than the fundamental with less energy in the near field. In addition, the grating lobes are significantly lower. Accordingly, selective harmonic imaging shows less near field artifacts and will lower the clutter, resulting in much cleaner images.

Surface diffusion of Sb on Ge(111) monitored quantitatively with optical second harmonic microscopy

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

Schultz, K.A.; Seebauer, E.G.

Surface diffusion of Sb on Ge(111) has been measured with the newly developed technique of optical second harmonic microscopy. In this method, concentration profiles at submonolayer coverage are imaged directly by surface second harmonic generation with 5 {mu} spatial resolution. A Boltzmann--Matano analysis yields the coverage dependence of the diffusivity {ital D} without parametrization. Experiments were performed at roughly 70% of the bulk melting temperature {ital T}{sub {ital m}}. In the coverage range 0{le}{theta}{le}0.6, the activation energy {ital E}{sub diff} remains constant at 47.5{plus minus}1.5 kcal/mol, but the pre-exponential factor {ital D}{sub 0} decreases from 8.7{times}10{sup 3{plus minus}0.4} to 1.6{times}10{supmore » 2{plus minus}0.4} cm{sup 2}/s. Both {ital E}{sub diff} and {ital D}{sub 0} are quite large, which is consistent with high-temperature measurements in other systems. The inadequacies of current theories for high-temperature surface diffusion are outlined, and a new vacancy model is proposed for low-coverage diffusion. The model accounts semiquantitatively for the large values of {ital E}{sub diff} and {ital D}{sub 0}, and suggests that these quantities may be manipulated using doping levels and photon illumination. An islanding mechanism is proposed to explain the decrease in {ital D}{sub 0} with {theta}.« less

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

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.

Second-harmonic generation at angular incidence in a negative-positive index photonic band-gap structure.

PubMed

D'Aguanno, Giuseppe; Mattiucci, Nadia; Scalora, Michael; Bloemer, Mark J

2006-08-01

In the spectral region where the refractive index of the negative index material is approximately zero, at oblique incidence, the linear transmission of a finite structure composed of alternating layers of negative and positive index materials manifests the formation of a new type of band gap with exceptionally narrow band-edge resonances. In particular, for TM-polarized (transverse magnetic) incident waves, field values that can be achieved at the band edge may be much higher compared to field values achievable in standard photonic band-gap structures. We exploit the unique properties of these band-edge resonances for applications to nonlinear frequency conversion, second-harmonic generation, in particular. The simultaneous availability of high field localization and phase matching conditions may be exploited to achieve second-harmonic conversion efficiencies far better than those achievable in conventional photonic band-gap structures. Moreover, we study the role played by absorption within the negative index material, and find that the process remains efficient even for relatively high values of the absorption coefficient.

Second-harmonic generation of ZnO nanoparticles synthesized by laser ablation of solids in liquids

NASA Astrophysics Data System (ADS)

Rocha-Mendoza, Israel; Camacho-López, Santiago; Luna-Palacios, Yryx Y.; Esqueda-Barrón, Yasmín; Camacho-López, Miguel A.; Camacho-López, Marco; Aguilar, Guillermo

2018-02-01

We report the synthesis of small zinc oxide nanoparticles (ZnO NPs) based colloidal suspensions and the study of second-harmonic generation from aggregated ZnO NPs deposited on glass substrates. The colloidal suspensions were obtained using the laser ablation of solids in liquids technique, ablating a Zn solid target immersed in acetone as the liquid medium, with ns-laser pulses (1064 nm) of a Nd-YAG laser. The per pulse laser fluence, the laser repetition rate frequency and the ablation time were kept constant. The absorption evolution of the obtained suspensions was optically characterized through absorption spectroscopy until stabilization. Raman spectroscopy, SEM and HRTEM were used to provide evidence of the ZnO NPs structure. HRTEM results showed that 5-8 nm spheroids ZnO NPs were obtained. Strong second-harmonic signal is obtained from random ZnO monocrystalline NPs and from aggregated ZnO NPs, suggesting that the high efficiency of the nonlinear process may not depend on the NPs size or aggregation state.

Transient regime in second harmonic generation

NASA Astrophysics Data System (ADS)

Szeftel, Jacob; Sandeau, Laure; Sandeau, Nicolas; Delezoide, Camille; Khater, Antoine

2013-09-01

The time growth of the electromagnetic field at the fundamental and double frequencies is studied from the very onset of the second harmonic generation (SHG) process for a set of dipoles lacking a symmetry centre and exhibiting a nonresonant coupling with a classical electromagnetic field. This approach consists first of solving the Schrödinger equation by applying a generalised Rabi rotation to the Hamiltonian describing the light-dipole interaction. This rotation has been devised for the resulting Hamiltonian to show up time-independent for both components of the electromagnetic field at the fundamental frequency and the second harmonic one. Then an energy conservation argument, derived from the Poynting theorem, is introduced to work out an additional relationship between the electromagnetic field and its associated electric polarisation. Finally this analysis yields the full time behaviour of all physical quantities of interest. The calculated results reproduce accurately both the observed spatial oscillations of the SHG intensity (Maker's fringes) and its power law dependence on the intensity of the incoming light at the fundamental frequency.

Pulsed Traveling-wave Quadrature Squeezing Using Quasi-phase Matched Lithium Niobate Crystals

NASA Astrophysics Data System (ADS)

Chen, Chao-Hsiang

Interests in generating higher quantum noise squeezing in order to develop methods to enhance optical measurement below the shot-noise limit in various applications has grown in recent years. The noise suppression from squeezing can improve the SNR in coherent optical systems when the returning signal power is weak, such as optical coherence tomography, LADAR, confocal microscopy and low-light coherent imaging. Unlike the generation of squeezing with a continuous wave, which is currently developed mainly for gravitational wave detection in LIGO project, the study of pulsed-traveling waves is focused on industrial, medical and other commercial interests. This dissertation presents the experimental results of pulsed traveling wave squeezing. The intention of the study is to explore the possibility of using quasi-phase matched crystals to generate the highest possible degree of quadrature squeezing. In order to achieve this goal, efforts to test the various effects from spatial Gaussian modes and relative beam waist placement for the second-harmonic pump were carried out in order to further the understanding of limiting factors to pulsed traveling wave squeezing. 20mm and 30mm-long periodically poled lithium noibate (PPLN) crystals were used in the experiment to generate a squeezed vacuum state. A maximum of 4.2+/-0.2dB quadrature squeezing has been observed, and the measured anti-squeezing exceeds 20dB.The phase sensitive amplification (PSA) gain and de-gain performance were also measured to compare the results of measured squeezing. The PPLN crystals can produce high conversion efficiency of second-harmonic generation (SHG) without a cavity. When a long PPLN crystal is used in a squeezer, the beam propagation in the nonlinear medium does not follow the characteristics in thin crystals. Instead, it is operated under the long-crystal criteria, which the crystal length is multiple times longer than the Rayleigh range of the injected beam i n the crystals. Quasi-phase matching was developed to overcome the limiting factor of both phase-mismatch and electric displacement walk off in second-harmonic generation. By using PPLN, the photorefractive damage threshold is the only limiting factor. For quantum noise squeezing with pulsed traveling-wave, the inhomogeneous nature of spatial and temporal modes are the constraining factors for further noise reduction.

Current developments in clinical multiphoton tomography

NASA Astrophysics Data System (ADS)

König, Karsten; Weinigel, Martin; Breunig, Hans Georg; Gregory, Axel; Fischer, Peter; Kellner-Höfer, Marcel; Bückle, Rainer

2010-02-01

Two-photon microscopy has been introduced in 1990 [1]. 13 years later, CE-marked clinical multiphoton systems for 3D imaging of human skin with subcellular resolution have been launched by the JenLab company with the tomograph DermaInspectTM. In 2010, the second generation of clinical multiphoton tomographs was introduced. The novel mobile multiphoton tomograph MPTflexTM, equipped with a flexible articulated optical arm, provides an increased flexibility and accessibility especially for clinical and cosmetical examinations. The multiphoton excitation of fluorescent biomolecules like NAD(P)H, flavins, porphyrins, elastin, and melanin as well as the second harmonic generation of collagen is induced by picojoule femtosecond laser pulses from an tunable turn-key near infrared laser system. The ability for rapid highquality image acquisition, the user-friendly operation of the system, and the compact and flexible design qualifies this system to be used for melanoma detection, diagnostics of dermatological disorders, cosmetic research, and skin aging measurements as well as in situ drug monitoring and animal research. So far, more than 1,000 patients and volunteers have been investigated with the multiphoton tomographs in Europe, Asia, and Australia.

Electromagnetic probes of molecular motors in the electron transport chains of mitochondria and chloroplasts

NASA Astrophysics Data System (ADS)

Miller, J. H., Jr.; Nawarathna, D.; Vajrala, V.; Gardner, J.; Widger, W. R.

2005-12-01

We report on measurements of harmonics generated by whole cells, mitochondria, and chloroplasts in response to applied sinusoidal electric fields. The frequency- and amplitude-dependence of the induced harmonics exhibit features that correlate with physiological processes. Budding yeast (S. cerevisiae) cells produce numerous harmonics, the amplitudes of which depend strongly on frequency. When the second or third harmonic amplitude is plotted vs. applied frequency, we observe two peaks, around 3 kHz and 12 kHz, which are suppressed by respiratory inhibitors. We observe similar peaks when measuring the harmonic response of B. indicas, a relative of the mitochondrial ancestor. In uncoupled mitochondria, in which most of the electron transport chain is active but the ATP-synthase molecular turbine is inactive, only one (lower frequency) of the two peaks is present. Finally, we find that harmonics generated by chloroplasts depend dramatically on incident light, and vanish in the absence of light.

Attosecond twin-pulse control by generalized kinetic heterodyne mixing.

PubMed

Raith, Philipp; Ott, Christian; Pfeifer, Thomas

2011-01-15

Attosecond double-pulse (twin-pulse) production in high-order harmonic generation is manipulated by a combination of two-color and carrier-envelope phase-control methods. As we show in numerical simulations, both relative amplitude and phase of the double pulse can be independently set by making use of multidimensional parameter control. Two technical implementation routes are discussed: kinetic heterodyning using second-harmonic generation and split-spectrum phase-step control.

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.

The collagen structure of equine articular cartilage characterized using polarization-sensitive optical coherence tomography and non-linear microscopy

NASA Astrophysics Data System (ADS)

Mansfield, Jessica C.; Ugryumova, Nadya; Knapp, Karen M.; Matcher, Stephen J.

2006-09-01

Equine articular cartilage has been imaged using both polarization-sensitive optical coherence tomography (PS-OCT) and non-linear microscopy. PS-OCT has been used to spatially map the birefringence in the cartilage and we have found that in the vicinity of the lesion the images display a characteristic disruption in the regular birefringence bands shown by normal cartilage. We also note that significant (e.g. x2) variations in the apparent birefringence of samples taken from young (18 month) animals that otherwise appear visually homogeneous are found over spatial scales of a few millimeters. We have also imaged the cartilage using non-linear microscopy and compare the scans taken with second harmonic generation (SHG) light and the two photon fluorescence (TPF) light. SHG images collected using 800 nm excitation reveals the spatial distribution of collagen fibers, whilst TPF images clearly shows the distribution of intracellular and pericellular fluorophores.

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.

Second harmonic generation quantitative measurements on collagen fibrils through correlation to electron microscopy

NASA Astrophysics Data System (ADS)

Bancelin, S.; Aimé, C.; Gusachenko, I.; Kowalczuk, L.; Latour, G.; Coradin, T.; Schanne-Klein, M.-C.

2015-03-01

Type I collagen is a major structural protein in mammals that shows highly structured macromolecular organizations specific to each tissue. This biopolymer is synthesized as triple helices, which self-assemble into fibrils (Ø =10-300 nm) and further form various 3D organization. In recent years, Second Harmonic Generation (SHG) microscopy has emerged as a powerful technique to probe in situ the fibrillar collagenous network within tissues. However, this optical technique cannot resolve most of the fibrils and is a coherent process, which has impeded quantitative measurements of the fibril diameter so far. In this study, we correlated SHG microscopy with Transmission Electron Microscopy to determine the sensitivity of SHG microscopy and to calibrate SHG signals as a function of the fibril diameter in reconstructed collagen gels. To that end, we synthetized isolated fibrils with various diameters and successfully imaged the very same fibrils with both techniques, down to 30 nm diameter. We observed that SHG signals scaled as the fourth power of the fibril diameter, as expected from analytical and numerical calculations. This calibration was then applied to diabetic rat cornea in which we successfully recovered the diameter of hyperglycemia-induced fibrils in the Descemet's membrane without having to resolve them. Finally we derived the first hyperpolarizability from a single collagen triple helix which validates the bottom-up approach used to calculate the non-linear response at the fibrillar scale and denotes a parallel alignment of triple helices within the fibrils. These results represent a major step towards quantitative SHG imaging of nm-sized collagen fibrils.

In situ SHG monitoring of dipolar orientation and relaxation in Disperse Red type/derivative urethane-urea copolymer

NASA Astrophysics Data System (ADS)

Samoc, A.; Holland, A.; Tsuchimori, M.; Watanabe, O.; Samoc, M.; Luther-Davies, B.; Kolev, V. Z.

2005-09-01

We investigated linear optical and second-order nonlinear optical (NLO) properties of films of urethane-urea copolymer (UU2) functionalised with a high concentration of an azobenzene chromophore. The polymer films on ITO-coated substrate were corona poled to induce a noncentrosymmetric organization of chromophore dipoles and data on the second harmonic generated with the laser beam (the fundamental wavelength 1053 nm, 6 ps/pulse, 20 Hz repetition rate) was acquired as a function of time and temperature. Second harmonic generation (SHG) was used to monitor in situ the polar alignment and relaxation of orientation of the side-chain Disperse Red-like chromophore molecules in the films poled at room temperature and high above the glass transition temperature (Tg 140-150oC). The deff coefficient was determined from the Maker-fringe method and corrected for absorption. A strong second harmonic effect with a fast relaxation was observed in "cold" (room temperature) poling experiments. A large second-order resonantly enhanced optical nonlinearity (d33 of the order of 200 pm/V) was obtained in high temperature poling. A strong and stable nonlinearity has persisted for years after the films were high-temperature poled.

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

Sasaki, S.; McNulty, I.; Shimada, T.

We investigate use of an APPLE-type undulator for generating Laguerre-Gaussian (LG) and Hermite-Gaussian (HG) mode beams. We find that the second harmonic radiation in the circular mode corresponds to an LG beam with l=1, and the second harmonic in the linear mode corresponds to an HG beam with l=1. The combination of an APPLE undulator and conventional monochromator optics may provide an opportunity for a new type of experimental research in the synchrotron radiation community.

Erratum: Sources of Image Degradation in Fundamental and Harmonic Ultrasound Imaging: A Nonlinear, Full-Wave, Simulation Study

PubMed Central

Pinton, Gianmarco F.; Trahey, Gregg E.; Dahl, Jeremy J.

2015-01-01

A full-wave equation that describes nonlinear propagation in a heterogeneous attenuating medium is solved numerically with finite differences in the time domain. This numerical method is used to simulate propagation of a diagnostic ultrasound pulse through a measured representation of the human abdomen with heterogeneities in speed of sound, attenuation, density, and nonlinearity. Conventional delay-and-sum beamforming is used to generate point spread functions (PSFs) that display the effects of these heterogeneities. For the particular imaging configuration that is modeled, these PSFs reveal that the primary source of degradation in fundamental imaging is due to reverberation from near-field structures. Compared with fundamental imaging, reverberation clutter in harmonic imaging is 27.1 dB lower. Simulated tissue with uniform velocity but unchanged impedance characteristics indicates that for harmonic imaging, the primary source of degradation is phase aberration. PMID:21693410

Giant enhancement of second harmonic generation in nonlinear photonic crystals with distributed Bragg reflector mirrors.

PubMed

Ren, Ming-Liang; Li, Zhi-Yuan

2009-08-17

We theoretically investigate second harmonic generation (SHG) in one-dimensional multilayer nonlinear photonic crystal (NPC) structures with distributed Bragg reflector (DBR) as mirrors. The NPC structures have periodic modulation on both the linear and second-order susceptibility. Three major physical mechanisms, quasi-phase matching (QPM) effect, slow light effect at photonic band gap edges, and cavity effect induced by DBR mirrors can be harnessed to enhance SHG. Selection of appropriate structural parameters can facilitate coexistence of these mechanisms to act collectively and constructively to create very high SHG conversion efficiency with an enhancement by up to seven orders of magnitude compared with the ordinary NPC where only QPM works. (c) 2009 Optical Society of America

Quasi-phase-matching of the dual-band nonlinear left-handed metamaterial

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

Liu, Yahong, E-mail: yhliu@nwpu.edu.cn; Song, Kun; Gu, Shuai

2014-11-17

We demonstrate a type of nonlinear meta-atom creating a dual-band nonlinear left-handed metamaterial (DNLHM). The DNLHM operates at two distinct left-handed frequency bands where there is an interval of one octave between the two center frequencies. Under the illumination of a high-power signal at the first left-handed frequency band corresponding to fundamental frequency (FF), second-harmonic generation (SHG) is observed at the second left-handed band. This means that our DNLHM supports backward-propagating waves both at FF and second-harmonic (SH) frequency. We also experimentally demonstrate quasi-phase-matching configurations for the backward SHG. This fancy parametric process can significantly transmits the SH generated bymore » an incident FF wave.« less

Electrical control of second-harmonic generation in a WSe 2 monolayer transistor

DOE PAGES

Seyler, Kyle L.; Schaibley, John R.; Gong, Pu; ...

2015-04-20

Nonlinear optical frequency conversion, in which optical fields interact with a nonlinear medium to produce new field frequencies, is ubiquitous in modern photonic systems. However, the nonlinear electric susceptibilities that give rise to such phenomena are often challenging to tune in a given material and, so far, dynamical control of optical nonlinearities remains confined to research laboratories as a spectroscopic tool. In this paper, we report a mechanism to electrically control second-order optical nonlinearities in monolayer WSe 2, an atomically thin semiconductor. We show that the intensity of second-harmonic generation at the A-exciton resonance is tunable by over an ordermore » of magnitude at low temperature and nearly a factor of four at room temperature through electrostatic doping in a field-effect transistor. Such tunability arises from the strong exciton charging effects in monolayer semiconductors, which allow for exceptional control over the oscillator strengths at the exciton and trion resonances. The exciton-enhanced second-harmonic generation is counter-circularly polarized to the excitation laser due to the combination of the two-photon and one-photon valley selection rules, which have opposite helicity in the monolayer. Finally, our study paves the way towards a new platform for chip-scale, electrically tunable nonlinear optical devices based on two-dimensional semiconductors.« less

Magnetization-induced second- and third-harmonic generation in transparent magnetic films

NASA Astrophysics Data System (ADS)

Ohkoshi, Shin-Ichi; Shimura, Jusuke; Ikeda, Katsuyoshi; Hashimoto, Kazuhito

2005-01-01

We describe the magnetization-induced second-harmonic (SH) generation in (FeIIxCrII1-x)1.5[CrIII(CN)6]. 7.5H2O and the magnetization-induced third-harmonic (TH) generation in Y1.5Bi1.5Fe3.8Al1.2O12 (Bi, Al:YIG). The polarization plane of a SH wave from a (FeIIxCrII1-x)1.5[CrIII(CN)6].7.5H2O film was rotated by an applied external magnetic field. This SH rotation is ascribed to the interaction between the electric polarization along the out-of-plane and spontaneous magnetizations. In particular, the magnetic linear term χijkLmagn(1) contributed to the SH rotation. Applying a longitudinal external magnetic field to a Bi,Al:YIG magnetic film rotated the polarization plane of the TH wave. This TH rotation is understood by the contribution of the magnetic term of χyxxxZmagn(1) in a third-order nonlinear optical susceptibility.

Characterization of muscle contraction with second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Prent, Nicole

Muscle cells have the ability to change length and generate force due to orchestrated action of myosin nanomotors that cause sliding of actin filaments along myosin filaments in the sarcomeres, the fundamental contractile units, of myocytes. The correlated action of hundreds of sarcomeres is needed to produce the myocyte contractions. This study probes the molecular structure of the myofilaments and investigates the movement correlations between sarcomeres during contraction. In this study, second harmonic generation (SHG) microscopy is employed for imaging striated myocytes. Myosin filaments in striated myocytes inherently have a nonzero second-order susceptibility, [special characters omitted] and therefore generate efficient SHG. Employing polarization-in polarization-out (PIPO) SHG microscopy allows for the accurate determination of the characteristic ratio, [special characters omitted] in birefringent myocytes, which describes the structure of the myosin filament. Analysis shows that the b value at the centre of the myosin filament, where the nonlinear dipoles are better aligned, is slightly lower than the value at the edges of the filament, where there is more disorder in orientation of the nonlinear dipoles from the myosin heads. Forced stretching of myocytes resulted in an SHG intensity increase with the elongation of the sarcomere. SHG microscopy captured individual sarcomeres during contraction, allowing for the measurement of sarcomere length (SL) and SHG intensity (SI) fluctuations. The fluctuations also revealed higher SHG intensity in elongated sarcomeres. The sarcomere synchronization model (SSM) for contracting and quiescent myocytes was developed, and experimentally verified for three cases (isolated cardiomyocyte, embryonic chicken cardiomyocyte, and larva myocyte). During contraction, the action of SLs and SIs between neighbouring sarcomeres partially correlated, whereas in quiescent myocytes the SLs show an anti-correlation and the SIs have no correlations. The characteristic correlation coefficients and amplitudes were obtained for each case, allowing for the characterization of the synchronization of sarcomere movement during muscle contraction. These investigations constitute the basis for studying the structure and physiology of muscle cell contractions with polarization SHG microscopy. Live dynamic imaging of myocytes is applicable for contractility research, drug discovery, and as a diagnostic tool for monitoring muscular diseases.

Watching stem cells at work with a flexible multiphoton tomograph

NASA Astrophysics Data System (ADS)

Uchugonova, Aisada; Hoffmann, Robert; Weinigel, Martin; König, Karsten

2012-03-01

There is a high demand for non-invasive imaging techniques that allow observation of stem cells in their native environment without significant input on cell metabolism, reproduction, and behavior. Easy accessible hair follicle pluripotent stem cells in the bulge area and dermal papilla are potential sources for stem cell based therapy. It has been shown that these cells are able to generate hair, non-follicle skin cells, nerves, vessels, smooth muscles etc. and may participate in wound healing processes. We report on the finding of nestin-GFP expressing stem cells in their native niche in the bulge of the hair follicle of living mice by using high-resolution in-vivo multiphoton tomography. The 3D imaging with submicron resolution was based on two-photon induced fluorescence and second harmonic generation (SHG) of collagen. Migrating stem cells from the bulge to their microenvironment have been detected inside the skin during optical deep tissue sectioning.

Method for determining surface properties of microparticles

DOEpatents

Eisenthal, Kenneth B.

2000-01-01

Second harmonic generation (SHG), sum frequency generation (SFG) and difference frequency generation (DFG) can be used for surface analysis or characterization of microparticles having a non-metallic surface feature. The microparticles can be centrosymmetric or such that non-metallic molecules of interest are centrosymmetrically distributed inside and outside the microparticles but not at the surface of the microparticles where the asymmetry aligns the molecules. The signal is quadratic in incident laser intensity or proportional to the product of two incident laser intensities for SFG, it is sharply peaked at the second harmonic wavelength, quadratic in the density of molecules adsorbed onto the microparticle surface, and linear in microparticles density. In medical or pharmacological applications, molecules of interest may be of drugs or toxins, for example.

Probing mixed tetragonal/rhombohedral-like monoclinic phases in strained bismuth ferrite films by optical second harmonic generation

NASA Astrophysics Data System (ADS)

Kumar, Amit; Denev, Sava; Zeches, Robert J.; Vlahos, Eftihia; Podraza, Nikolas J.; Melville, Alexander; Schlom, Darrell G.; Ramesh, R.; Gopalan, Venkatraman

2010-09-01

Epitaxial strain can induce the formation of morphotropic phase boundary in lead free ferroelectrics like bismuth ferrite, thereby enabling the coexistence of tetragonal and rhombohedral phases in the same film. The relative ratio of these phases is governed by the film thickness and theoretical studies suggest that there exists a monoclinic distortion of both the tetragonal as well as the rhombohedral unit cells due to imposed epitaxial strain. In this work we show that optical second harmonic generation can distinguish the tetragonal-like phase from the rhombohedral-like phase and enable detection of monoclinic distortion in only a pure tetragonal-like phase.

Second Harmonic Generation characterization of SOI wafers: Impact of layer thickness and interface electric field

NASA Astrophysics Data System (ADS)

Damianos, D.; Vitrant, G.; Lei, M.; Changala, J.; Kaminski-Cachopo, A.; Blanc-Pelissier, D.; Cristoloveanu, S.; Ionica, I.

2018-05-01

In this work, we investigate Second Harmonic Generation (SHG) as a non-destructive characterization method for Silicon-On-Insulator (SOI) materials. For thick SOI stacks, the SHG signal is related to the thickness variations of the different layers. However, in thin SOI films, the comparison between measurements and optical modeling suggests a supplementary SHG contribution attributed to the electric fields at the SiO2/Si interfaces. The impact of the electric field at each interface of the SOI on the SHG is assessed. The SHG technique can be used to evaluate interfacial electric fields and consequently interface charge density in SOI materials.

Efficient second harmonic generation of a diode-laser-pumped CW Nd:YAG laser using monolithic MgO:LiNbO3 external resonant cavities

NASA Technical Reports Server (NTRS)

Kozlovsky, William J.; Nabors, C. D.; Byer, Robert L.

1988-01-01

56-percent efficient external-cavity-resonant second-harmonic generation of a diode-laser pumped, CW single-axial-mode Nd:YAG laser is reported. A theory of external doubling with a resonant fundamental is presented and compared to experimental results for three monolithic cavities of nonlinear MgO:LiNbO3. The best conversion efficiency was obtained with a 12.5-mm-long monolithic ring cavity doubler, which produced 29.7 mW of CW, single-axial model 532-nm radiation from an input of 52.5 mW.

Quantitative biomarkers of colonic dysplasia based on intrinsic second-harmonic generation signal

NASA Astrophysics Data System (ADS)

Zhuo, Shuangmu; Zhu, Xiaoqin; Wu, Guizhu; Chen, Jianxin; Xie, Shusen

2011-12-01

Most colorectal cancers arise from dysplastic lesions, such as adenomatous polyps, and these lesions are difficult to be detected by the current endoscopic screening approaches. Here, we present the use of an intrinsic second-harmonic generation (SHG) signal as a novel means to differentiate between normal and dysplastic human colonic tissues. We find that the SHG signal can quantitatively identify collagen change associated with colonic dysplasia that is indiscernible by conventional pathologic techniques. By comparing normal with dysplastic mucosa, there were significant differences in collagen density and collagen fiber direction, providing substantial potential to become quantitative intrinsic biomarkers for in vivo clinical diagnosis of colonic dysplasia.

Experimental and theoretical debate on efficient second harmonic generation in Bis (Cinnamic acid): Hexamine cocrystal

NASA Astrophysics Data System (ADS)

Vijayalakshmi, S.; Kalyanaraman, S.; Ravindran, T. R.

2014-02-01

Second harmonic generation (SHG) in Bis (Cinnamic acid): Hexamine cocrystal was extensively analyzed through charge transfer (CT). The CT interactions through hydrogen bonding were well established with the aid of vibrational analysis and Natural Bond Orbital (NBO) analysis. The retentivity of coplanar nature of the cinnamic acid in the cocrystal was confirmed through UV-Visible spectroscopy and supported by Raman studies. Structural analysis indicated the quinoidal character of the given material presenting a high SHG efficiency. The first order hyperpolarizability value was calculated theoretically by density functional theory (DFT) and Hartree-Fock (HF) methods in support for the large value of SHG.

Second harmonic generation of template synthesized PbTiO 3 nanostructures

NASA Astrophysics Data System (ADS)

Chang, Ki-Seog; Park, Yong-Heon; Bu, Sang-Don; Hernandez, Bernadette A.; Fisher, Ellen R.; Dorhout, Peter K.

2007-09-01

The lead titanate (PbTiO3) nanotubes were prepared with a chelate sol-gel of titanium isopropoxide (Ti(OiPr)4) and lead acetate (Pb(OAc)2-3H2O) by using AlOx template. Whatman® anodisc membranes (with a 200 nm pore size) served as the template. The template was dipped into the precursor, PbTiO3 solution, allowed to air dry, and then calcined at 650 °C. Recently, we have characterized a signal of second harmonic generation (SHG); 532 nm on 1064 nm of Nd:YAG laser beam in the PbTiO3 nanotubes with AlOx template.

Extracting diagnostic stromal organization features based on intrinsic two-photon excited fluorescence and second-harmonic generation signals

NASA Astrophysics Data System (ADS)

Zhuo, Shuangmu; Chen, Jianxin; Xie, Shusen; Hong, Zhibin; Jiang, Xingshan

2009-03-01

Intrinsic two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals are shown to differentiate between normal and neoplastic human esophageal stroma. It was found that TPEF and SHG signals from normal and neoplastic stroma exhibit different organization features, providing quantitative information about the biomorphology and biochemistry of tissue. By comparing normal with neoplastic stroma, there were significant differences in collagen-related changes, elastin-related changes, and alteration in proportions of matrix molecules, giving insight into the stromal changes associated with cancer progression and providing substantial potential to be applied in vivo to the clinical diagnosis of epithelial precancers and cancers.

Promoting Spontaneous Second Harmonic Generation through Organogelation.

PubMed

Marco, A Belén; Aparicio, Fátima; Faour, Lara; Iliopoulos, Konstantinos; Morille, Yohann; Allain, Magali; Franco, Santiago; Andreu, Raquel; Sahraoui, Bouchta; Gindre, Denis; Canevet, David; Sallé, Marc

2016-07-27

An organogelator based on the Disperse Red nonlinear optical chromophore was synthesized according to a simple and efficient three-step procedure. The supramolecular gel organization leads to xerogels which display a spontaneous second harmonic generation (SHG) response without any need for preprocessing, and this SHG activity appears to be stable over several months. These findings, based on an intrinsic structural approach, are supported by favorable intermolecular supramolecular interactions, which promote a locally non-centrosymmetric NLO-active organization. This is in sharp contrast with most materials designed for SHG purposes, which generally require the use of expensive or heavy-to-handle external techniques for managing the dipoles' alignment.

Plasmonic modes in nanowire dimers: A study based on the hydrodynamic Drude model including nonlocal and nonlinear effects

NASA Astrophysics Data System (ADS)

Moeferdt, Matthias; Kiel, Thomas; Sproll, Tobias; Intravaia, Francesco; Busch, Kurt

2018-02-01

A combined analytical and numerical study of the modes in two distinct plasmonic nanowire systems is presented. The computations are based on a discontinuous Galerkin time-domain approach, and a fully nonlinear and nonlocal hydrodynamic Drude model for the metal is utilized. In the linear regime, these computations demonstrate the strong influence of nonlocality on the field distributions as well as on the scattering and absorption spectra. Based on these results, second-harmonic-generation efficiencies are computed over a frequency range that covers all relevant modes of the linear spectra. In order to interpret the physical mechanisms that lead to corresponding field distributions, the associated linear quasielectrostatic problem is solved analytically via conformal transformation techniques. This provides an intuitive classification of the linear excitations of the systems that is then applied to the full Maxwell case. Based on this classification, group theory facilitates the determination of the selection rules for the efficient excitation of modes in both the linear and nonlinear regimes. This leads to significantly enhanced second-harmonic generation via judiciously exploiting the system symmetries. These results regarding the mode structure and second-harmonic generation are of direct relevance to other nanoantenna systems.

Electric field measurements in a near atmospheric pressure nanosecond pulse discharge with picosecond electric field induced second harmonic generation

NASA Astrophysics Data System (ADS)

Goldberg, Benjamin M.; Chng, Tat Loon; Dogariu, Arthur; Miles, Richard B.

2018-02-01

We present an optical electric field measurement method for use in high pressure plasma discharges. The method is based upon the field induced second harmonic generation technique and can be used for localized electric field measurements with sub-nanosecond resolution in any gaseous species. When an external electric field is present, a dipole is induced in the typically centrosymmetric medium, allowing for second harmonic generation with signal intensities which scale by the square of the electric field. Calibrations have been carried out in 100 Torr room air, and a minimum sensitivity of 450 V/cm is demonstrated. Measurements were performed with nanosecond or faster temporal resolution in a 100 Torr room air environment both with and without a plasma present. It was shown that with no plasma present, the field follows the applied voltage to gap ratio, as measured using the back current shunt method. When the electric field is strong enough to exceed the breakdown threshold, the measured field was shown to exceed the anticipated voltage to gap ratio which is taken as an indication of the ionization wave front as it sweeps through the plasma volume.

Ultrafast third-harmonic generation from textured aluminum nitride-sapphire interfaces

NASA Astrophysics Data System (ADS)

Stoker, D. S.; Baek, J.; Wang, W.; Kovar, D.; Becker, M. F.; Keto, J. W.

2006-05-01

We measured and modeled third-harmonic generation (THG) from an AlN thin film on sapphire using a time-domain approach appropriate for ultrafast lasers. Second-harmonic measurements indicated that polycrystalline AlN contains long-range crystal texture. An interface model for third-harmonic generation enabled an analytical representation of scanning THG ( z -scan) experiments. Using it and accounting for Fresnel reflections, we measured the AlN -sapphire susceptibility ratio and estimated the susceptibility for aluminum nitride, χxxxx(3)(3ω;ω,ω,ω)=1.52±0.25×10-13esu . The third-harmonic (TH) spectrum strongly depended on the laser focus position and sample thickness. The amplitude and phase of the frequency-domain interference were fit to the Fourier transform of the calculated time-domain field to improve the accuracy of several experimental parameters. We verified that the model works well for explaining TH signal amplitudes and spectral phase. Some anomalous features in the TH spectrum were observed, which we attributed to nonparaxial effects.

Experimenting liver fibrosis diagnostic by two photon excitation microscopy and Bag-of-Features image classification.

PubMed

Stanciu, Stefan G; Xu, Shuoyu; Peng, Qiwen; Yan, Jie; Stanciu, George A; Welsch, Roy E; So, Peter T C; Csucs, Gabor; Yu, Hanry

2014-04-10

The accurate staging of liver fibrosis is of paramount importance to determine the state of disease progression, therapy responses, and to optimize disease treatment strategies. Non-linear optical microscopy techniques such as two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) can image the endogenous signals of tissue structures and can be used for fibrosis assessment on non-stained tissue samples. While image analysis of collagen in SHG images was consistently addressed until now, cellular and tissue information included in TPEF images, such as inflammatory and hepatic cell damage, equally important as collagen deposition imaged by SHG, remain poorly exploited to date. We address this situation by experimenting liver fibrosis quantification and scoring using a combined approach based on TPEF liver surface imaging on a Thioacetamide-induced rat model and a gradient based Bag-of-Features (BoF) image classification strategy. We report the assessed performance results and discuss the influence of specific BoF parameters to the performance of the fibrosis scoring framework.

Experimenting Liver Fibrosis Diagnostic by Two Photon Excitation Microscopy and Bag-of-Features Image Classification

PubMed Central

Stanciu, Stefan G.; Xu, Shuoyu; Peng, Qiwen; Yan, Jie; Stanciu, George A.; Welsch, Roy E.; So, Peter T. C.; Csucs, Gabor; Yu, Hanry

2014-01-01

The accurate staging of liver fibrosis is of paramount importance to determine the state of disease progression, therapy responses, and to optimize disease treatment strategies. Non-linear optical microscopy techniques such as two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) can image the endogenous signals of tissue structures and can be used for fibrosis assessment on non-stained tissue samples. While image analysis of collagen in SHG images was consistently addressed until now, cellular and tissue information included in TPEF images, such as inflammatory and hepatic cell damage, equally important as collagen deposition imaged by SHG, remain poorly exploited to date. We address this situation by experimenting liver fibrosis quantification and scoring using a combined approach based on TPEF liver surface imaging on a Thioacetamide-induced rat model and a gradient based Bag-of-Features (BoF) image classification strategy. We report the assessed performance results and discuss the influence of specific BoF parameters to the performance of the fibrosis scoring framework. PMID:24717650