Crecea V, Graf BW, Kim T
… +2 more, Popescu G, Boppart SA
IEEE J Sel Top Quantum Electron
· 2014 Mar · PMID 25400496
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We present a real-time multimodal near-infrared imaging technology that tracks externally induced axial motion of magnetic microbeads in single cells in culture. The integrated multimodal imaging technique consists of ph...We present a real-time multimodal near-infrared imaging technology that tracks externally induced axial motion of magnetic microbeads in single cells in culture. The integrated multimodal imaging technique consists of phase-sensitive magnetomotive optical coherence microscopy (MM-OCM) and multiphoton microscopy (MPM).MPMis utilized for the visualization of multifunctional fluorescent and magnetic microbeads, while MM-OCM detects, with nanometer-scale sensitivity, periodic displacements of the microbeads induced by the modulation of an external magnetic field. Magnetomotive signals are measured from mouse macrophages, human breast primary ductal carcinoma cells, and human breast epithelial cells in culture, and validated with full-field phase-sensitive microscopy. This methodology demonstrates the capability for imaging controlled cell dynamics and has the potential for measuring cell biomechanical properties, which are important in assessing the health and pathological state of cells.
Michalet X, Ingargiola A, Colyer RA
… +6 more, Scalia G, Weiss S, Maccagnani P, Gulinatti A, Rech I, Ghioni M
IEEE J Sel Top Quantum Electron
· 2014 Nov · PMID 25309114
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Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry and biophysics. The basic feature of this technique is to excite and collect light...Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry and biophysics. The basic feature of this technique is to excite and collect light from a very small volume and work in a low concentration regime resulting in rare burst-like events corresponding to the transit of a single molecule. Detecting photon bursts is a challenging task: the small number of emitted photons in each burst calls for high detector sensitivity. Bursts are very brief, requiring detectors with fast response time and capable of sustaining high count rates. Finally, many bursts need to be accumulated to achieve proper statistical accuracy, resulting in long measurement time unless parallelization strategies are implemented to speed up data acquisition. In this paper we will show that silicon single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection. We will review the key SPAD parameters and highlight the issues to be addressed in their design, fabrication and operation. After surveying the state-of-the-art SPAD technologies, we will describe our recent progress towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of this approach is illustrated with single-molecule Förster resonance energy transfer measurements.
IEEE J Sel Top Quantum Electron
· 2014 May · PMID 25309113
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We present an innovative surface-enhanced Raman spectroscopy (SERS) sensor based on a biological-plasmonic hybrid nanostructure by self-assembling silver (Ag) nanoparticles into diatom frustules. The photonic-crystal-lik...We present an innovative surface-enhanced Raman spectroscopy (SERS) sensor based on a biological-plasmonic hybrid nanostructure by self-assembling silver (Ag) nanoparticles into diatom frustules. The photonic-crystal-like diatom frustules provide a spatially confined electric field with enhanced intensity that can form hybrid photonic-plasmonic modes through the optical coupling with Ag nanoparticles. The experimental results demonstrate 4-6 and 9-12 improvement of sensitivities to detect the Raman dye for resonance and nonresonance SERS sensing, respectively. Such low-cost and high-sensitivity SERS sensors have significant potentials for label-free biosensing.
Li X, Li J, Jing J
… +11 more, Ma T, Liang S, Zhang J, Mohar D, Raney A, Mahon S, Brenner M, Patel P, Shung KK, Zhou Q, Chen Z
IEEE J Sel Top Quantum Electron
· 2014 Mar · PMID 24771992
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For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to...For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to remarkably increase diagnostic accuracy of vulnerable plaques. We have developed an integrated IVUS-OCT imaging apparatus, which includes the integrated catheter, motor drive unit, and imaging system. The dual-function imaging catheter has the same diameter of current clinical standard. The imaging system is capable for simultaneous IVUS and OCT imaging in real time. and experiments on rabbits with atherosclerosis were conducted to demonstrate the feasibility and superiority of the integrated intravascular imaging modality.
Vinegoni C, Lee S, Feruglio PF
… +1 more, Weissleder R
IEEE J Sel Top Quantum Electron
· 2014 Mar · PMID 24273405
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Intravital microscopy has emerged in the recent decade as an indispensible imaging modality for the study of the micro-dynamics of biological processes in live animals. Technical advancements in imaging techniques and ha...Intravital microscopy has emerged in the recent decade as an indispensible imaging modality for the study of the micro-dynamics of biological processes in live animals. Technical advancements in imaging techniques and hardware components, combined with the development of novel targeted probes and new mice models, have enabled us to address long-standing questions in several biology areas such as oncology, cell biology, immunology and neuroscience. As the instrument resolution has increased, physiological motion activities have become a major obstacle that prevents imaging live animals at resolutions analogue to the ones obtained in vitro. Motion compensation techniques aim at reducing this gap and can effectively increase the resolution. This paper provides a technical review of some of the latest developments in motion compensation methods, providing organ specific solutions.
Rogers JD, Radosevich AJ, Yi J
… +1 more, Backman V
IEEE J Sel Top Quantum Electron
· 2013 Sep · PMID 25587211
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Optical interactions with biological tissue provide powerful tools for study, diagnosis, and treatment of disease. When optical methods are used in applications involving tissue, scattering of light is an important pheno...Optical interactions with biological tissue provide powerful tools for study, diagnosis, and treatment of disease. When optical methods are used in applications involving tissue, scattering of light is an important phenomenon. In imaging modalities, scattering provides contrast, but also limits imaging depth, so models help optimize an imaging technique. Scattering can also be used to collect information about the tissue itself providing diagnostic value. Therapies involving focused beams require scattering models to assess dose distribution. In all cases, models of light scattering in tissue are crucial to correctly interpreting the measured signal. Here, we review a versatile model of light scattering that uses the Whittle-Matérn correlation family to describe the refractive index correlation function ( ). In weakly scattering media such as tissue, ( ) determines the shape of the power spectral density from which all other scattering characteristics are derived. This model encompasses many forms such as mass fractal and the Henyey-Greenstein function as special cases. We discuss normalization and calculation of optical properties including the scattering coefficient and anisotropy factor. Experimental methods using the model are also described to quantify tissue properties that depend on length scales of only a few tens of nanometers.
IEEE J Sel Top Quantum Electron
· 2012 Jul · PMID 23243386
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Recent advances in the use of diffuse optical techniques for monitoring the hemodynamic, metabolic and physiological signatures of the neoadjuvant breast cancer therapy effectiveness is critically reviewed. An extensive...Recent advances in the use of diffuse optical techniques for monitoring the hemodynamic, metabolic and physiological signatures of the neoadjuvant breast cancer therapy effectiveness is critically reviewed. An extensive discussion of the state-of-theart diffuse optical mammography is presented alongside a discussion of the current approaches to breast cancer therapies. Overall, the diffuse optics field is growing rapidly with a great deal of promise to fill an important niche in the current approaches to monitor, predict and personalize neoadjuvant breast cancer therapies.
Qiu L, Turzhitsky V, Chuttani R
… +7 more, Pleskow D, Goldsmith JD, Guo L, Vitkin E, Itzkan I, Hanlon EB, Perelman LT
IEEE J Sel Top Quantum Electron
· 2012 May · PMID 23087592
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This article reports the evolution of scanning spectral imaging techniques using scattered light for minimally invasive detection of early cancerous changes in tissue and cell biology applications. Optical spectroscopic...This article reports the evolution of scanning spectral imaging techniques using scattered light for minimally invasive detection of early cancerous changes in tissue and cell biology applications. Optical spectroscopic techniques have shown promising results in the diagnosis of disease on a cellular scale. They do not require tissue removal, can be performed in vivo, and allow for real time diagnoses. Fluorescence and Raman spectroscopy are most effective in revealing molecular properties of tissue. Light scattering spectroscopy (LSS) relates the spectroscopic properties of light elastically scattered by small particles, such as epithelial cell nuclei and organelles, to their size, shape and refractive index. It is capable of characterizing the structural properties of tissue on cellular and sub-cellular scales. However, in order to be useful in the detection of early cancerous changes which are otherwise not visible to the naked eye, it must rapidly survey a comparatively large area while simultaneously detecting these cellular changes. Both goals are achieved by combining LSS with spatial scanning imaging. Two examples are described in this article. The first reviews a clinical system for screening patients with Barrett's esophagus. The second presents a novel advancement in confocal light absorption and scattering spectroscopic (CLASS) microscopy.
IEEE J Sel Top Quantum Electron
· 2012 Jan · PMID 22899881
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Fiber lasers mode locked with large normal group-velocity dispersion have recently achieved femtosecond pulse durations with energies and peak powers at least an order of magnitude greater than those of prior approaches....Fiber lasers mode locked with large normal group-velocity dispersion have recently achieved femtosecond pulse durations with energies and peak powers at least an order of magnitude greater than those of prior approaches. Several new mode-locking regimes have been demonstrated, including self-similar pulse propagation in passive and active fibers, dissipative solitons, and a pulse evolution that avoids wave breaking at high peak power but has not been reproduced by theoretical treatment. Here, we illustrate the main features of these new pulse-shaping mechanisms through the results of numerical simulations that agree with experimental results. We describe the features that distinguish each new mode-locking state and explain how the interplay of basic processes in the fiber produces the balance of amplitude and phase evolutions needed for stable high-energy pulses. Dissipative processes such as spectral filtering play a major role in normal-dispersion mode locking. Understanding the different mechanisms allows us to compare and contrast them, as well as to categorize them to some extent.
Radosevich AJ, Rogers JD, Turzhitsky V
… +4 more, Mutyal NN, Yi J, Roy HK, Backman V
IEEE J Sel Top Quantum Electron
· 2012 Jul · PMID 24163574
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Since the early 1980's, the enhanced backscattering (EBS) phenomenon has been well-studied in a large variety of non-biological materials. Yet, until recently the use of conventional EBS for the characterization of biolo...Since the early 1980's, the enhanced backscattering (EBS) phenomenon has been well-studied in a large variety of non-biological materials. Yet, until recently the use of conventional EBS for the characterization of biological tissue has been fairly limited. In this work we detail the unique ability of EBS to provide spectroscopic, polarimetric, and depth-resolved characterization of biological tissue using a simple backscattering instrument. We first explain the experimental and numerical procedures used to accurately measure and model the full azimuthal EBS peak shape in biological tissue. Next we explore the peak shape and height dependencies for different polarization channels and spatial coherence of illumination. We then illustrate the extraordinary sensitivity of EBS to the shape of the scattering phase function using suspensions of latex microspheres. Finally, we apply EBS to biological tissue samples in order to measure optical properties and observe the spatial length-scales at which backscattering is altered in early colon carcinogenesis.
IEEE J Sel Top Quantum Electron
· 2012 Jun · PMID 25673966
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In this paper, we demonstrate high-resolution, multimodal imaging of human skin using optical coherence (OCM) and multiphoton microscopy (MPM). These two modalities are integrated into a single instrument to enable simu...In this paper, we demonstrate high-resolution, multimodal imaging of human skin using optical coherence (OCM) and multiphoton microscopy (MPM). These two modalities are integrated into a single instrument to enable simultaneous acquisition and coregistration. The system design and the OCM image processing architecture enable sufficient performance of both modalities for imaging of human skin. Examples of multimodal imaging are presented as well as time lapse imaging of blood flow in single capillary loops. By making use of multiple intrinsic contrast mechanisms this integrated technique improves the ability to noninvasively visualize living tissue. Integrated OCM and MPM has potential applications for diagnosis of various pathological skin conditions, such as skin cancer, as well as potential pharmaceutical and cosmetic research applications.
Chen Y, Huang SW, Zhou C
… +2 more, Potsaid B, Fujimoto JG
IEEE J Sel Top Quantum Electron
· 2012 May · PMID 22685379
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Optical coherence microscopy (OCM) is a promising technology for high-resolution cellular-level imaging in human tissues. Line-scanning OCM is a new form of OCM that utilizes line-field illumination for parallel detectio...Optical coherence microscopy (OCM) is a promising technology for high-resolution cellular-level imaging in human tissues. Line-scanning OCM is a new form of OCM that utilizes line-field illumination for parallel detection. In this study, we demonstrate improved detection sensitivity by using an achromatic design for line-field generation. This system operates at 830-nm wavelength with 82-nm bandwidth. The measured axial resolution is 3.9 μm in air (corresponding to ~2.9 μm in tissue), and the transverse resolutions are 2.1 μm along the line-field illumination direction and 1.7 μm perpendicular to line illumination direction. The measured sensitivity is 98 dB with 25 line averages, resulting in an imaging speed of ~2 frames/s (516 lines/s). Real-time, cellular-level imaging of scattering tissues is demonstrated using human-colon specimens.
IEEE J Sel Top Quantum Electron
· 2012 · PMID 26236147
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Optical coherence tomography (OCT) has great potential for deciphering the role of mechanics in normal and abnormal heart development. OCT images tissue microstructure and blood flow deep into the tissue (1-2mm) at high...Optical coherence tomography (OCT) has great potential for deciphering the role of mechanics in normal and abnormal heart development. OCT images tissue microstructure and blood flow deep into the tissue (1-2mm) at high spatiotemporal resolutions allowing unprecedented images of the developing heart. Here, we review the advancement of OCT technology to image heart development and report some of our recent findings utilizing OCT imaging under environmental control for longitudinal imaging. Precise control of the environment is absolutely required in longitudinal studies that follow the growth of the embryo or studies comparing normal versus perturbed heart development to obtain meaningful results. These types of studies are essential to tease out the influence of cardiac dynamics on molecular expression and their role in the progression of congenital heart defects.
Liu Y, Tu H, Benalcazar WA
… +2 more, Chaney EJ, Boppart SA
IEEE J Sel Top Quantum Electron
· 2012 May · PMID 24187481
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Nonlinear microscopy has become widely used in biophotonic imaging. Pulse shaping provides control over nonlinear optical processes of ultrafast pulses for selective imaging and contrast enhancement. In this study, nonli...Nonlinear microscopy has become widely used in biophotonic imaging. Pulse shaping provides control over nonlinear optical processes of ultrafast pulses for selective imaging and contrast enhancement. In this study, nonlinear microscopy, including two-photon fluorescence, second harmonic generation, and third harmonic generation, was performed using pulses shaped from a fiber supercontinuum (SC) spanning from 900 to 1160 nm. The SC generated by coupling pulses from a Yb:KYW pulsed laser into a photonic crystal fiber was spectrally filtered and compressed using a spatial light modulator. The shaped pulses were used for nonlinear optical imaging of cellular and tissue samples. Amplitude and phase shaping the fiber SC offers selective and efficient nonlinear optical imaging over a broad bandwidth with a single-beam and an easily tunable setup.
IEEE J Sel Top Quantum Electron
· 2012 · PMID 28053498
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Clinical outcome of patients diagnosed with primary brain tumor has been correlated with the extent of surgical resection. In treating this disease, the neurosurgeon must balance between an aggressive, radical resection...Clinical outcome of patients diagnosed with primary brain tumor has been correlated with the extent of surgical resection. In treating this disease, the neurosurgeon must balance between an aggressive, radical resection and minimizing the loss of healthy, functionally significant brain tissue. Numerous intra-operative methodologies and technological approaches have been explored as a means to improve the accuracy of surgical resection. This paper presents an overview of current conventional techniques and new emerging technologies with potential to impact the area of image-guided surgery of brain tumors. Emphasis is placed on techniques based on endogenous fluorescence lifetime contrast and their potential for intraoperative diagnosis of brain tumors.
Field JJ, Sheetz KE, Chandler EV
… +6 more, Hoover EE, Young MD, Ding SY, Sylvester AW, Kleinfeld D, Squier JA
IEEE J Sel Top Quantum Electron
· 2012 · PMID 27390511
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Multifocal multiphoton microscopy (MMM) in the biological and medical sciences has become an important tool for obtaining high resolution images at video rates. While current implementations of MMM achieve very high fram...Multifocal multiphoton microscopy (MMM) in the biological and medical sciences has become an important tool for obtaining high resolution images at video rates. While current implementations of MMM achieve very high frame rates, they are limited in their applicability to essentially those biological samples that exhibit little or no scattering. In this paper, we report on a method for MMM in which imaging detection is not necessary (single element point detection is implemented), and is therefore fully compatible for use in imaging through scattering media. Further, we demonstrate that this method leads to a new type of MMM wherein it is possible to simultaneously obtain multiple images and view differences in excitation parameters in a single shot.
IEEE J Sel Top Quantum Electron
· 2012 · PMID 23869163
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Recent progress in the development of femtosecond-pulse fiber lasers with parameters appropriate for nonlinear microscopy is reviewed. Pulse-shaping in lasers with only normal-dispersion components is briefly described,...Recent progress in the development of femtosecond-pulse fiber lasers with parameters appropriate for nonlinear microscopy is reviewed. Pulse-shaping in lasers with only normal-dispersion components is briefly described, and the performance of the resulting lasers is summarized. Fiber lasers based on the formation of dissipative solitons now offer performance competitive with that of solid-state lasers, but with the benefits of the fiber medium. Lasers based on self-similar pulse evolution in the gain section of a laser also offer a combination of short pulse duration and high pulse energy that will be attractive for applications in nonlinear bioimaging.
IEEE J Sel Top Quantum Electron
· 2011 Jul · PMID 23833549
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Improved methods for imaging and assessment of vascular defects are needed for directing treatment of cardiovascular pathologies. In this paper, we employ magnetomotive optical coherence tomography (MMOCT) as a platform...Improved methods for imaging and assessment of vascular defects are needed for directing treatment of cardiovascular pathologies. In this paper, we employ magnetomotive optical coherence tomography (MMOCT) as a platform both to detect and to measure the elasticity of blood clots. Detection is enabled through the use of rehydrated, lyophilized platelets loaded with superparamagnetic iron oxides (SPIO-RL platelets) that are functional infusion agents that adhere to sites of vascular endothelial damage. Evidence suggests that the sensitivity for detection is improved over threefold by magnetic interactions between SPIOs inside RL platelets. Using the same MMOCT system, we show how elastometry of simulated clots, using resonant acoustic spectroscopy, is correlated with the fibrin content of the clot. Both methods are based upon magnetic actuation and phase-sensitive optical monitoring of nanoscale displacements using MMOCT, underscoring its utility as a broad-based platform to detect and measure the molecular structure and composition of blood clots.
Isikman SO, Bishara W, Mudanyali O
… +6 more, Sencan I, Su TW, Tseng D, Yaglidere O, Sikora U, Ozcan A
IEEE J Sel Top Quantum Electron
· 2011 Jul · PMID 24478572
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Lensfree on-chip holographic microscopy is an emerging technique that offers imaging of biological specimens over a large field-of-view without using any lenses or bulky optical components. Lending itself to a compact, c...Lensfree on-chip holographic microscopy is an emerging technique that offers imaging of biological specimens over a large field-of-view without using any lenses or bulky optical components. Lending itself to a compact, cost-effective and mechanically robust architecture, lensfree on-chip holographic microscopy can offer an alternative toolset addressing some of the emerging needs of microscopic analysis and diagnostics in low-resource settings, especially for telemedicine applications. In this review, we summarize the latest achievements in lensfree optical microscopy based on partially coherent on-chip holography, including portable telemedicine microscopy, cell-phone based microscopy and field-portable optical tomographic microscopy. We also discuss some of the future directions for telemedicine microscopy and its prospects to help combat various global health challenges.
Kang H, Jiao JJ, Lee C
… +3 more, Le MH, Darling CL, Fried D
IEEE J Sel Top Quantum Electron
· 2010 Jul · PMID 21660217
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New methods are needed for the nondestructive measurement of tooth demineralization and remineralization to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to...New methods are needed for the nondestructive measurement of tooth demineralization and remineralization to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anticaries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10 µm, it is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper, a review of the use of polarization-sensitive-OCT for the measurement of tooth demineralization is provided along with some recent results regarding improved methods for the detection of caries lesions in the earliest stages of development. Automated methods of analysis were used to measure the depth and severity of demineralized bovine enamel produced using simulated caries models that emulate demineralization in the mouth. Significant differences in the depth and integrated reflectivity from the lesions were detected after only a few hours of demineralization. These results demonstrate that cross-polarization-OCT is ideally suited for the nondestructive assessment of early demineralization.