Coherence is a central concept in optics and many techniques exist for its measurement.2 It is m... more Coherence is a central concept in optics and many techniques exist for its measurement.2 It is most com-monly measured using interferometry, which is a highly sensitive technique. However, accurate estimation of the visibility of fringes, which is the crucial parameter in ...
More than 85% of all cancers originate in the epithelium that lines the internal surfaces of orga... more More than 85% of all cancers originate in the epithelium that lines the internal surfaces of organs throughout the body. Although these are readily treatable provided they are diagnosed in one of the preinvasive stages, early lesions are often almost impossible to detect. Here we present a new optical-probe technique based on light-scattering spectroscopy that is able to detect precancerous and early cancerous changes in cell-rich epithelia.
Coherence is a central concept in optics and many techniques exist for its measurement.2 It is m... more Coherence is a central concept in optics and many techniques exist for its measurement.2 It is most com-monly measured using interferometry, which is a highly sensitive technique. However, accurate estimation of the visibility of fringes, which is the crucial parameter in ...
Laser-excited emission from YBa2Cu3O7–δ with 7.5% dysprosium nominally subsituted in place of ytt... more Laser-excited emission from YBa2Cu3O7–δ with 7.5% dysprosium nominally subsituted in place of yttrium is presented in the range 13 000–23 000 cm−1. In addition to the reported Raman lines in the CuO stretching region, a number of other spectral features were observed. These include a discrete luminescence with lines at 14 400 and 14 425 cm−1 and a broad emission with its peak position and band width varying with excitation wavelength. Additionally, an anti-Stokes scattering, which has no apparent counterpart in the Stokes region, was observed. These observations may be of significance in the elucidation of the mechanism of high-temperature superconductivity.
Geiger-mode photodiodes (GPD) act as binary photon detectors that convert analog light intensity ... more Geiger-mode photodiodes (GPD) act as binary photon detectors that convert analog light intensity into digital pulses. Fabrication of arrays of GPD in a CMOS environment simplifies the integration of signal-processing electronics to enhance the performance and provide a low-cost detector-on-a-chip platform. Such an instrument facilitates imaging applications with extremely low light and confined volumes. High sensitivity reading of small samples enables twodimensional imaging of DNA arrays and for tracking single molecules, and observing their dynamic behavior. In this work, we describe the performance of a prototype imaging detector of GPD pixels, with integrated active quenching for use in imaging of 2D objects using fluorescent labels. We demonstrate the integration of on-chip memory and a parallel readout interface for an array of CMOS GPD pixels as progress toward an all-digital detector on a chip. We also describe advances in pixel-level signal processing and solid-state photomultiplier developments.
IEEE Journal of Selected Topics in Quantum Electronics, 1999
We report an in situ method of probing the structure of living epithelial cells, based on light s... more We report an in situ method of probing the structure of living epithelial cells, based on light scattering spectroscopy with polarized light. The method makes it possible to distinguish between single backscattering from uppermost epithelial cells and multiply scattered light. The spectrum of the single backscattering component can be further analyzed to provide histological information about the epithelial cells such as the size distribution of the cell nuclei and their refractive index. These are valuable quantities to detect and diagnose precancerous changes in human tissues.
Light scattering spectroscopy (LSS) is a promising optical technique developed for quantitative c... more Light scattering spectroscopy (LSS) is a promising optical technique developed for quantitative characterization of tissue morphology as well as in vivo detection and diagnosis of disease such as early cancer. LSS employs a wavelength dependent component of light scattered by epithelial cells and other tissues to obtain information about subcellular structure. We present two novel modalities of LSS, LSS imaging and scattering angle sensitive LSS (a/LSS). LSS imaging provides quantitative information about the epithelial cell nuclei, such as nuclear size, degree of pleomorphism, hyperchromasia, and amount of chromatin. It allows mapping these histological properties over wide areas of epithelial lining. We show that LSS imaging can be used to detect precancerous lesions in optically accessible organs. Using a/LSS, which enables characterization of tissue components with sizes smaller than the wavelength of light, we show that the number of subcellular components with the sizes between 30 nm and few microns scales with the size according to an inverse power-law. We show that the size distribution exponent is an important parameter characterizing tissue organization, for example the balance between stochasticity and order, and has a potential to be applicable for early cancer diagnosis and characterization.
We have developed a light scattering technique to detect early pre-cancerous changes in the tissu... more We have developed a light scattering technique to detect early pre-cancerous changes in the tissues which, line the epithelial surfaces of the body. The majority of cancers are epithelial in nature. We use light reflection spectroscopy to observe the earliest sign, the enlargement of the index of the cells which, line this layer. Our method is based on the feature that single scattering in the backward direction retains the polarization of the light incident on nucleus in the epithelial layer whereas multiple scattering destroys the polarization. Collecting the backscattering spectral intensities of both polarizations, and taking their difference, we extract the single scattering component. The signals are analyzed to extract the nuclear density, size and the relative refractive index. The experimental results will be presented to illustrate the physical basis of the technique, and its biological application.
Biomedical imaging with light-scattering spectroscopy (LSS) is a novel optical technology develop... more Biomedical imaging with light-scattering spectroscopy (LSS) is a novel optical technology developed to probe the structure of living epithelial cells in situ without need for tissue removal. LSS makes it possible to distinguish between single backscattering from epithelial-cell nuclei and multiply scattered light. The spectrum of the single backscattering component is further analyzed to provide quantitative information about the epithelial-cell nuclei such as nuclear size, degree of pleomorphism, degree of hyperchromasia and amount of chromatin. LSS imaging allows mapping these histological properties over wide areas of epithelial lining. Because nuclear enlargement, pleomorphism and hyperchromasia are principal features of nuclear atypia associated with precancerous and cancerous changes in virtually all epithelia, LSS imaging can be used to detect precancerous lesions in optically accessible organs.
... Quantitative analysis of mucosal tissues in patients using light scattering spectroscopy (Pro... more ... Quantitative analysis of mucosal tissues in patients using light scattering spectroscopy (Proceedings Paper). Author(s): Lev T. Perelman; George I. Zonios; Vadim Backman; Rajan S. Gurjar; Irving Itzkan; Ramachandra R. Dasari; Jacques Van Dam; Michael S. Feld. ...
In this paper we present the details of a Diffuse Optical Tomographic (DOT) prototype instrument ... more In this paper we present the details of a Diffuse Optical Tomographic (DOT) prototype instrument developed and characterized at RMD for concurrent operation with Magnetic Resonance Imaging (MRI) to obtain high resolution spatial and functional images of hypoxic tumor tissue. We have developed a new system designed for in-vivo imaging of luminescent agents that respond to tissue oxygenation to improve the contrast and spatial resolution of functional optical images in deep tissue. High-resolution spatial and anatomical information obtained from MRI images is used to improve the accuracy of the reconstructed optical images. The time domain lifetime imaging module has parallel acquisition across a cooled 16-element avalanche photodiode (APD) array for high resolution and high throughput imaging. The low-cost, compact lifetime imager is compatible with high magnetic and RF fields associated with MR units in hybrid imaging systems. Using this APD module in a dual-modality imaging setup, phantom imaging was performed to obtain oxygenation images with high resolution and contrast. Optical image reconstruction is aided by spatial guidance obtained from the actual phantom dimensions to improve the accuracy of these images.
We present results of diffused phosphorescence lifetime tomography performed on tissue-simulating... more We present results of diffused phosphorescence lifetime tomography performed on tissue-simulating phantoms for high contrast imaging of hypoxic breast tumors. Oxygen sensitive phosphor embedded in a versatile nanoparticle matrix was used as contrast agent to identify simulated hypoxic tumors in phantoms. The surface of these nanoparticles was decorated with F3 peptide that targets cell surface receptors that is often overexpressed in aggressive breast tumors. The surface functionalization did not interfere with the embedded phosphor's characteristics. The phosphorescence intensity and lifetime was measured using single photon sensitive multi-pixel photon counting (MPPC) detectors in box-car geometry. The detection technique has a large dynamic range, high sensitivity and good resolution in oxygen concentration.
We present the design principles and performance characteristics of a prototype user-friendly she... more We present the design principles and performance characteristics of a prototype user-friendly shear force based Tip-Enhanced Raman Spectroscopy system. High numerical aperture reflective optics are utilized to optimize photon delivery and collection, while allowing for interrogation of samples with varying resistivities, thicknesses, and opacities. The integration of tips and tuning forks into manufacturable units is investigated to facilitate simple tip replacement. Finally we discuss methods to mitigate the remaining challenges to the technique becoming routine and user-friendly.
In this work, we present research performed to improve the receiver characteristics for underwate... more In this work, we present research performed to improve the receiver characteristics for underwater imaging applications using the hybrid lidar-radar detection technique. We report the development of the next-generation coherent heterodyne receiver using modulation of the optical receiver's amplifier gain. Significant advantages in the receiver specifications are achieved using a large-area, high gain, low-noise silicon avalanche photodiode (APD) as the photodetector cum frequency mixer-demodulator. We demonstrate that heterodyne detection by gain modulation of APD can be used to increase the signal-to-noise ratio, detection sensitivity and bandwidth for the hybrid receiver system.
We provide a detailed signal-to-noise analysis for 3D imaging of luminescence from a biomarker to... more We provide a detailed signal-to-noise analysis for 3D imaging of luminescence from a biomarker to detect hypoxic tumors in deep tissue. Preliminary studies on phantom tissues with inclusions and having homogeneous scattering and absorption coefficient of μs' ~ 15-20 cm-1 and μa ~ 2 cm-1 respectively, are reported as a function of oxygen tension, luminophore concentration, and tissue depth. The technique's sensitivity in terms of determination of spatial resolution is discussed.
In this work, we present research in using confocal optical techniques with femtolitre focal volu... more In this work, we present research in using confocal optical techniques with femtolitre focal volumes and obtain very high signal-to-noise and signal-to-background ratios for single molecule detection (SMD). We were able to achieve improved signal strength by using highly fluorescent quantum dots and nanopatterned substrates to obtain plasmon induced resonant fluorescence enhancement. A method to simultaneously using multiple excitation spots without the use of confocal apertures and an array of single photon sensitive Geiger mode avalanche photodiodes was used to increase the throughput of the detection system. Using this highly sensitive SMD system, we detect small quantities of synthetic DNA through hybridization eliminating the need of polymerase chain reaction.
We have developed the necessary theoretical framework and the basic instrumental design parameter... more We have developed the necessary theoretical framework and the basic instrumental design parameters to enable mapping of subsurface blood dynamics and tissue oxygenation for patients undergoing skin graft procedures. This analysis forms the basis for developing a simple patch geometry, which can be used to map by diffuse optical techniques blood flow velocity and tissue oxygenation as a function of depth in subsurface tissue.skin graft, diffuse correlation analysis, oxygen saturation.
Coherence is a central concept in optics and many techniques exist for its measurement.2 It is m... more Coherence is a central concept in optics and many techniques exist for its measurement.2 It is most com-monly measured using interferometry, which is a highly sensitive technique. However, accurate estimation of the visibility of fringes, which is the crucial parameter in ...
More than 85% of all cancers originate in the epithelium that lines the internal surfaces of orga... more More than 85% of all cancers originate in the epithelium that lines the internal surfaces of organs throughout the body. Although these are readily treatable provided they are diagnosed in one of the preinvasive stages, early lesions are often almost impossible to detect. Here we present a new optical-probe technique based on light-scattering spectroscopy that is able to detect precancerous and early cancerous changes in cell-rich epithelia.
Coherence is a central concept in optics and many techniques exist for its measurement.2 It is m... more Coherence is a central concept in optics and many techniques exist for its measurement.2 It is most com-monly measured using interferometry, which is a highly sensitive technique. However, accurate estimation of the visibility of fringes, which is the crucial parameter in ...
Laser-excited emission from YBa2Cu3O7–δ with 7.5% dysprosium nominally subsituted in place of ytt... more Laser-excited emission from YBa2Cu3O7–δ with 7.5% dysprosium nominally subsituted in place of yttrium is presented in the range 13 000–23 000 cm−1. In addition to the reported Raman lines in the CuO stretching region, a number of other spectral features were observed. These include a discrete luminescence with lines at 14 400 and 14 425 cm−1 and a broad emission with its peak position and band width varying with excitation wavelength. Additionally, an anti-Stokes scattering, which has no apparent counterpart in the Stokes region, was observed. These observations may be of significance in the elucidation of the mechanism of high-temperature superconductivity.
Geiger-mode photodiodes (GPD) act as binary photon detectors that convert analog light intensity ... more Geiger-mode photodiodes (GPD) act as binary photon detectors that convert analog light intensity into digital pulses. Fabrication of arrays of GPD in a CMOS environment simplifies the integration of signal-processing electronics to enhance the performance and provide a low-cost detector-on-a-chip platform. Such an instrument facilitates imaging applications with extremely low light and confined volumes. High sensitivity reading of small samples enables twodimensional imaging of DNA arrays and for tracking single molecules, and observing their dynamic behavior. In this work, we describe the performance of a prototype imaging detector of GPD pixels, with integrated active quenching for use in imaging of 2D objects using fluorescent labels. We demonstrate the integration of on-chip memory and a parallel readout interface for an array of CMOS GPD pixels as progress toward an all-digital detector on a chip. We also describe advances in pixel-level signal processing and solid-state photomultiplier developments.
IEEE Journal of Selected Topics in Quantum Electronics, 1999
We report an in situ method of probing the structure of living epithelial cells, based on light s... more We report an in situ method of probing the structure of living epithelial cells, based on light scattering spectroscopy with polarized light. The method makes it possible to distinguish between single backscattering from uppermost epithelial cells and multiply scattered light. The spectrum of the single backscattering component can be further analyzed to provide histological information about the epithelial cells such as the size distribution of the cell nuclei and their refractive index. These are valuable quantities to detect and diagnose precancerous changes in human tissues.
Light scattering spectroscopy (LSS) is a promising optical technique developed for quantitative c... more Light scattering spectroscopy (LSS) is a promising optical technique developed for quantitative characterization of tissue morphology as well as in vivo detection and diagnosis of disease such as early cancer. LSS employs a wavelength dependent component of light scattered by epithelial cells and other tissues to obtain information about subcellular structure. We present two novel modalities of LSS, LSS imaging and scattering angle sensitive LSS (a/LSS). LSS imaging provides quantitative information about the epithelial cell nuclei, such as nuclear size, degree of pleomorphism, hyperchromasia, and amount of chromatin. It allows mapping these histological properties over wide areas of epithelial lining. We show that LSS imaging can be used to detect precancerous lesions in optically accessible organs. Using a/LSS, which enables characterization of tissue components with sizes smaller than the wavelength of light, we show that the number of subcellular components with the sizes between 30 nm and few microns scales with the size according to an inverse power-law. We show that the size distribution exponent is an important parameter characterizing tissue organization, for example the balance between stochasticity and order, and has a potential to be applicable for early cancer diagnosis and characterization.
We have developed a light scattering technique to detect early pre-cancerous changes in the tissu... more We have developed a light scattering technique to detect early pre-cancerous changes in the tissues which, line the epithelial surfaces of the body. The majority of cancers are epithelial in nature. We use light reflection spectroscopy to observe the earliest sign, the enlargement of the index of the cells which, line this layer. Our method is based on the feature that single scattering in the backward direction retains the polarization of the light incident on nucleus in the epithelial layer whereas multiple scattering destroys the polarization. Collecting the backscattering spectral intensities of both polarizations, and taking their difference, we extract the single scattering component. The signals are analyzed to extract the nuclear density, size and the relative refractive index. The experimental results will be presented to illustrate the physical basis of the technique, and its biological application.
Biomedical imaging with light-scattering spectroscopy (LSS) is a novel optical technology develop... more Biomedical imaging with light-scattering spectroscopy (LSS) is a novel optical technology developed to probe the structure of living epithelial cells in situ without need for tissue removal. LSS makes it possible to distinguish between single backscattering from epithelial-cell nuclei and multiply scattered light. The spectrum of the single backscattering component is further analyzed to provide quantitative information about the epithelial-cell nuclei such as nuclear size, degree of pleomorphism, degree of hyperchromasia and amount of chromatin. LSS imaging allows mapping these histological properties over wide areas of epithelial lining. Because nuclear enlargement, pleomorphism and hyperchromasia are principal features of nuclear atypia associated with precancerous and cancerous changes in virtually all epithelia, LSS imaging can be used to detect precancerous lesions in optically accessible organs.
... Quantitative analysis of mucosal tissues in patients using light scattering spectroscopy (Pro... more ... Quantitative analysis of mucosal tissues in patients using light scattering spectroscopy (Proceedings Paper). Author(s): Lev T. Perelman; George I. Zonios; Vadim Backman; Rajan S. Gurjar; Irving Itzkan; Ramachandra R. Dasari; Jacques Van Dam; Michael S. Feld. ...
In this paper we present the details of a Diffuse Optical Tomographic (DOT) prototype instrument ... more In this paper we present the details of a Diffuse Optical Tomographic (DOT) prototype instrument developed and characterized at RMD for concurrent operation with Magnetic Resonance Imaging (MRI) to obtain high resolution spatial and functional images of hypoxic tumor tissue. We have developed a new system designed for in-vivo imaging of luminescent agents that respond to tissue oxygenation to improve the contrast and spatial resolution of functional optical images in deep tissue. High-resolution spatial and anatomical information obtained from MRI images is used to improve the accuracy of the reconstructed optical images. The time domain lifetime imaging module has parallel acquisition across a cooled 16-element avalanche photodiode (APD) array for high resolution and high throughput imaging. The low-cost, compact lifetime imager is compatible with high magnetic and RF fields associated with MR units in hybrid imaging systems. Using this APD module in a dual-modality imaging setup, phantom imaging was performed to obtain oxygenation images with high resolution and contrast. Optical image reconstruction is aided by spatial guidance obtained from the actual phantom dimensions to improve the accuracy of these images.
We present results of diffused phosphorescence lifetime tomography performed on tissue-simulating... more We present results of diffused phosphorescence lifetime tomography performed on tissue-simulating phantoms for high contrast imaging of hypoxic breast tumors. Oxygen sensitive phosphor embedded in a versatile nanoparticle matrix was used as contrast agent to identify simulated hypoxic tumors in phantoms. The surface of these nanoparticles was decorated with F3 peptide that targets cell surface receptors that is often overexpressed in aggressive breast tumors. The surface functionalization did not interfere with the embedded phosphor's characteristics. The phosphorescence intensity and lifetime was measured using single photon sensitive multi-pixel photon counting (MPPC) detectors in box-car geometry. The detection technique has a large dynamic range, high sensitivity and good resolution in oxygen concentration.
We present the design principles and performance characteristics of a prototype user-friendly she... more We present the design principles and performance characteristics of a prototype user-friendly shear force based Tip-Enhanced Raman Spectroscopy system. High numerical aperture reflective optics are utilized to optimize photon delivery and collection, while allowing for interrogation of samples with varying resistivities, thicknesses, and opacities. The integration of tips and tuning forks into manufacturable units is investigated to facilitate simple tip replacement. Finally we discuss methods to mitigate the remaining challenges to the technique becoming routine and user-friendly.
In this work, we present research performed to improve the receiver characteristics for underwate... more In this work, we present research performed to improve the receiver characteristics for underwater imaging applications using the hybrid lidar-radar detection technique. We report the development of the next-generation coherent heterodyne receiver using modulation of the optical receiver's amplifier gain. Significant advantages in the receiver specifications are achieved using a large-area, high gain, low-noise silicon avalanche photodiode (APD) as the photodetector cum frequency mixer-demodulator. We demonstrate that heterodyne detection by gain modulation of APD can be used to increase the signal-to-noise ratio, detection sensitivity and bandwidth for the hybrid receiver system.
We provide a detailed signal-to-noise analysis for 3D imaging of luminescence from a biomarker to... more We provide a detailed signal-to-noise analysis for 3D imaging of luminescence from a biomarker to detect hypoxic tumors in deep tissue. Preliminary studies on phantom tissues with inclusions and having homogeneous scattering and absorption coefficient of μs' ~ 15-20 cm-1 and μa ~ 2 cm-1 respectively, are reported as a function of oxygen tension, luminophore concentration, and tissue depth. The technique's sensitivity in terms of determination of spatial resolution is discussed.
In this work, we present research in using confocal optical techniques with femtolitre focal volu... more In this work, we present research in using confocal optical techniques with femtolitre focal volumes and obtain very high signal-to-noise and signal-to-background ratios for single molecule detection (SMD). We were able to achieve improved signal strength by using highly fluorescent quantum dots and nanopatterned substrates to obtain plasmon induced resonant fluorescence enhancement. A method to simultaneously using multiple excitation spots without the use of confocal apertures and an array of single photon sensitive Geiger mode avalanche photodiodes was used to increase the throughput of the detection system. Using this highly sensitive SMD system, we detect small quantities of synthetic DNA through hybridization eliminating the need of polymerase chain reaction.
We have developed the necessary theoretical framework and the basic instrumental design parameter... more We have developed the necessary theoretical framework and the basic instrumental design parameters to enable mapping of subsurface blood dynamics and tissue oxygenation for patients undergoing skin graft procedures. This analysis forms the basis for developing a simple patch geometry, which can be used to map by diffuse optical techniques blood flow velocity and tissue oxygenation as a function of depth in subsurface tissue.skin graft, diffuse correlation analysis, oxygen saturation.
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Papers by Rajan Gurjar