Vasan Venugopalan - Academia.edu (original) (raw)
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Papers by Vasan Venugopalan
Proceedings of SPIE, Jul 1, 2004
Proceedings of SPIE, Jul 23, 2003
Applied Physics B, Jun 25, 2013
Journal of the Optical Society of America, Apr 17, 2023
Journal of Biomedical Optics
Journal of the Optical Society of America A
The development and application of nonlinear optical (NLO) microscopy methods in biomedical resea... more The development and application of nonlinear optical (NLO) microscopy methods in biomedical research has experienced rapid growth over the past three decades. Despite the compelling power of these methods, optical scattering limits their practical use in biological tissues. This tutorial offers a model-based approach illustrating how analytical methods from classical electromagnetism can be employed to comprehensively model NLO microscopy in scattering media. In Part I, we quantitatively model focused beam propagation in non-scattering and scattering media from the lens to focal volume. In Part II, we model signal generation, radiation, and far-field detection. Moreover, we detail modeling approaches for major optical microscopy modalities including classical fluorescence, multi-photon fluorescence, second harmonic generation, and coherent anti-Stokes Raman microscopy.
Optical Tomography and Spectroscopy of Tissue XV
Journal of Biomedical Optics
We develop a computational framework to examine the factors responsible for scattering-induced di... more We develop a computational framework to examine the factors responsible for scattering-induced distortions of coherent anti-Stokes Raman scattering (CARS) signals in turbid samples. We apply the Huygens-Fresnel Wave-based Electric Field Superposition (HF-WEFS) method combined with the radiating dipole approximation to compute the effects of scattering-induced distortions of focal excitation fields on the far-field CARS signal. We analyze the effect of spherical scatterers, placed in the vicinity of the focal volume, on the CARS signal emitted by different objects (2μm diameter solid sphere, 2μm diameter myelin cylinder and 2μm diameter myelin tube). We find that distortions in the CARS signals arise not only from attenuation of the focal field but also from scattering-induced changes in the spatial phase that modifies the angular distribution of the CARS emission. Our simulations further show that CARS signal attenuation can be minimized by using a high numerical aperture condenser....
Nature Photonics, 2015
Luo et al. reply-We thank He et al. 1 for their Correspondence regarding our recent paper 2. They... more Luo et al. reply-We thank He et al. 1 for their Correspondence regarding our recent paper 2. They offer an alternate hypothesis for our observed microtsunami (μtsunami)initiated Ca 2+ signalling (μT-ICS) that differs from our claim of mechanical activation of stretch-sensitive G proteincoupled receptors (SS-GPCRs) by shear flow. Instead, they assert that μtsunami exposure initiates the release of Ca 2+ signalling molecules, including ATP, from the cell immediately below the site of laser radiation. These molecules then diffuse to neighbouring cells and activate purinergic receptors, including those coupled to GPCRs, resulting in a propagating intercellular Ca 2+ wave. They cite previous studies 3-5 that use femtosecondlaser microbeam irradiation to initiate Ca 2+ signalling in primary rat hippocampal cells and astrocytes as well as immortalized human kidney (HEK293T) and cervical cancer (HeLa) cells. These Ca 2+ waves have higher velocities (10-40 μm s −1) and smaller spatial extent (~200 μm radius) as compared with μT-ICS waves (4.5 μm s −1 and ~400 μm radius, respectively) reported in our paper. Importantly, our studies employed human vascular endothelial cells (HUVECs) whose physiological function requires mechanosensitivity to hemodynamic shear stress. The papers cited by He et al. 3-5 examine the roles of purinergic P2X (ligand-gated ion channels) and P2Y (GPCR) receptors in femtosecond laser microbeam induced Ca 2+ signalling. Cells were treated with pyridoxalphosphate-6-azophenyl-2ʹ,4ʹdisulfonic acid (PPADS) and Reactive Blue 2 (RB2) to provide broad inhibition of P2X and P2Y receptors, respectively. Because Ca 2+ signalling was unaffected by PPADS but reduced by more than 70% with RB2, the authors concluded that P2Y receptors play a central role in femtosecond laser induced signalling of astrocytes 5. However, purinergic receptor subtypes vary significantly between cell lines, as do their susceptibility to antagonists such as PPADS and RB2 (ref. 6). In fact, HUVECs express purinergic receptors P2X 1 , P2X 6 , P2X 7 , and P2Y 1 (refs 7,8) that are not susceptible to the action of these compounds 6,8. He et al. 1 suggest that 2-APB inhibition of μT-ICS does not elucidate the underlying signalling mechanisms because 2-APB acts at the IP 3 receptor well downstream of the activation of SS-GPCRs. Our demonstration of 2-APB suppression of Ca 2+ signalling in response to both exogenous ATP administration 9 and μtsunami exposure 2 ,
An overview is presented of recent trends in coherent anti-Stokes Raman scattering (CARS) microsc... more An overview is presented of recent trends in coherent anti-Stokes Raman scattering (CARS) microscopy. We briefly discuss the influence of tissue scattering on the CARS signal, methods for controlling the CARS emission and prospects for surface-enhancement of the CARS radiation.
Physical Review E, 2004
We demonstrate the use of Monte Carlo simulations to generate photon scattering density functions... more We demonstrate the use of Monte Carlo simulations to generate photon scattering density functions ͑PSDFs͒ that represent the tissue volume sampled by steady-state and frequency-domain photon migration. We use these results to illustrate how scaling laws can be developed to determine the mean sampling depth of the multiply scattered photons detected by photon migration methods that remain valid outside the bounds of the standard diffusion approximation, i.e., at small source-detector separations and in media where the optical absorption is significant relative to scattering. Using both the PSDF computation and the newly formulated scaling laws, we focus on a comprehensive description of the effects of source modulation frequency, optical absorption, and source-detector separation on the depth of the sampled tissue volume as well as the sensitivity of frequencydomain photon migration measurements to the presence of a localized absorption heterogeneity.
Journal of Biomedical Optics, 2007
The use of perturbation and differential Monte Carlo ͑pMC/ dMC͒ methods in conjunction with nonli... more The use of perturbation and differential Monte Carlo ͑pMC/ dMC͒ methods in conjunction with nonlinear optimization algorithms were proposed recently as a means to solve inverse photon migration problems in regionwise heterogeneous turbid media. We demonstrate the application of pMC/dMC methods for the recovery of optical properties in a two-layer extended epithelial tissue model from experimental measurements of spatially resolved diffuse reflectance. The results demonstrate that pMC/dMC methods provide a rapid and accurate approach to solve two-region inverse photon migration problems in the transport regime, that is, on spatial scales smaller than a transport mean free path and in media where optical scattering need not dominate absorption. The pMC/dMC approach is found to be effective over a broad range of absorption ͑50 to 400%͒ and scattering ͑70 to 130%͒ perturbations. The recovery of optical properties from spatially resolved diffuse reflectance measurements is examined for different sets of source-detector separation. These results provide some guidance for the design of compact fiber-based probes to determine and isolate optical properties from both epithelial and stromal layers of superficial tissues.
![Research paper thumbnail of Radiative transport in the delta-P[sub 1] approximation: accuracy of fluence rate and optical penetration depth predictions in turbid semi-infinite media](https://attachments.academia-assets.com/84609284/thumbnails/1.jpg)
](Journal of Biomedical Optics, 2004
Journal of Biomedical Optics
We present a Monte Carlo (MC) method to determine depth-dependent probability distributions of ph... more We present a Monte Carlo (MC) method to determine depth-dependent probability distributions of photon visitation and detection for optical reflectance measurements performed in the spatial frequency domain (SFD). These distributions are formed using an MC simulation for radiative transport that utilizes a photon packet weighting procedure consistent with the two-dimensional spatial Fourier transform of the radiative transport equation. This method enables the development of quantitative metrics for SFD optical sampling depth in layered tissue and its dependence on both tissue optical properties and spatial frequency. We validate the computed depth-dependent probability distributions using SFD measurements in a layered phantom system with a highly scattering top layer of variable thickness supported by a highly absorbing base layer. We utilize our method to establish the spatial frequency-dependent optical sampling depth for a number of tissue types and also provide a general tool to determine such depths for tissues of arbitrary optical properties.
Proceedings of SPIE, Jul 1, 2004
Proceedings of SPIE, Jul 23, 2003
Applied Physics B, Jun 25, 2013
Journal of the Optical Society of America, Apr 17, 2023
Journal of Biomedical Optics
Journal of the Optical Society of America A
The development and application of nonlinear optical (NLO) microscopy methods in biomedical resea... more The development and application of nonlinear optical (NLO) microscopy methods in biomedical research has experienced rapid growth over the past three decades. Despite the compelling power of these methods, optical scattering limits their practical use in biological tissues. This tutorial offers a model-based approach illustrating how analytical methods from classical electromagnetism can be employed to comprehensively model NLO microscopy in scattering media. In Part I, we quantitatively model focused beam propagation in non-scattering and scattering media from the lens to focal volume. In Part II, we model signal generation, radiation, and far-field detection. Moreover, we detail modeling approaches for major optical microscopy modalities including classical fluorescence, multi-photon fluorescence, second harmonic generation, and coherent anti-Stokes Raman microscopy.
Optical Tomography and Spectroscopy of Tissue XV
Journal of Biomedical Optics
We develop a computational framework to examine the factors responsible for scattering-induced di... more We develop a computational framework to examine the factors responsible for scattering-induced distortions of coherent anti-Stokes Raman scattering (CARS) signals in turbid samples. We apply the Huygens-Fresnel Wave-based Electric Field Superposition (HF-WEFS) method combined with the radiating dipole approximation to compute the effects of scattering-induced distortions of focal excitation fields on the far-field CARS signal. We analyze the effect of spherical scatterers, placed in the vicinity of the focal volume, on the CARS signal emitted by different objects (2μm diameter solid sphere, 2μm diameter myelin cylinder and 2μm diameter myelin tube). We find that distortions in the CARS signals arise not only from attenuation of the focal field but also from scattering-induced changes in the spatial phase that modifies the angular distribution of the CARS emission. Our simulations further show that CARS signal attenuation can be minimized by using a high numerical aperture condenser....
Nature Photonics, 2015
Luo et al. reply-We thank He et al. 1 for their Correspondence regarding our recent paper 2. They... more Luo et al. reply-We thank He et al. 1 for their Correspondence regarding our recent paper 2. They offer an alternate hypothesis for our observed microtsunami (μtsunami)initiated Ca 2+ signalling (μT-ICS) that differs from our claim of mechanical activation of stretch-sensitive G proteincoupled receptors (SS-GPCRs) by shear flow. Instead, they assert that μtsunami exposure initiates the release of Ca 2+ signalling molecules, including ATP, from the cell immediately below the site of laser radiation. These molecules then diffuse to neighbouring cells and activate purinergic receptors, including those coupled to GPCRs, resulting in a propagating intercellular Ca 2+ wave. They cite previous studies 3-5 that use femtosecondlaser microbeam irradiation to initiate Ca 2+ signalling in primary rat hippocampal cells and astrocytes as well as immortalized human kidney (HEK293T) and cervical cancer (HeLa) cells. These Ca 2+ waves have higher velocities (10-40 μm s −1) and smaller spatial extent (~200 μm radius) as compared with μT-ICS waves (4.5 μm s −1 and ~400 μm radius, respectively) reported in our paper. Importantly, our studies employed human vascular endothelial cells (HUVECs) whose physiological function requires mechanosensitivity to hemodynamic shear stress. The papers cited by He et al. 3-5 examine the roles of purinergic P2X (ligand-gated ion channels) and P2Y (GPCR) receptors in femtosecond laser microbeam induced Ca 2+ signalling. Cells were treated with pyridoxalphosphate-6-azophenyl-2ʹ,4ʹdisulfonic acid (PPADS) and Reactive Blue 2 (RB2) to provide broad inhibition of P2X and P2Y receptors, respectively. Because Ca 2+ signalling was unaffected by PPADS but reduced by more than 70% with RB2, the authors concluded that P2Y receptors play a central role in femtosecond laser induced signalling of astrocytes 5. However, purinergic receptor subtypes vary significantly between cell lines, as do their susceptibility to antagonists such as PPADS and RB2 (ref. 6). In fact, HUVECs express purinergic receptors P2X 1 , P2X 6 , P2X 7 , and P2Y 1 (refs 7,8) that are not susceptible to the action of these compounds 6,8. He et al. 1 suggest that 2-APB inhibition of μT-ICS does not elucidate the underlying signalling mechanisms because 2-APB acts at the IP 3 receptor well downstream of the activation of SS-GPCRs. Our demonstration of 2-APB suppression of Ca 2+ signalling in response to both exogenous ATP administration 9 and μtsunami exposure 2 ,
An overview is presented of recent trends in coherent anti-Stokes Raman scattering (CARS) microsc... more An overview is presented of recent trends in coherent anti-Stokes Raman scattering (CARS) microscopy. We briefly discuss the influence of tissue scattering on the CARS signal, methods for controlling the CARS emission and prospects for surface-enhancement of the CARS radiation.
Physical Review E, 2004
We demonstrate the use of Monte Carlo simulations to generate photon scattering density functions... more We demonstrate the use of Monte Carlo simulations to generate photon scattering density functions ͑PSDFs͒ that represent the tissue volume sampled by steady-state and frequency-domain photon migration. We use these results to illustrate how scaling laws can be developed to determine the mean sampling depth of the multiply scattered photons detected by photon migration methods that remain valid outside the bounds of the standard diffusion approximation, i.e., at small source-detector separations and in media where the optical absorption is significant relative to scattering. Using both the PSDF computation and the newly formulated scaling laws, we focus on a comprehensive description of the effects of source modulation frequency, optical absorption, and source-detector separation on the depth of the sampled tissue volume as well as the sensitivity of frequencydomain photon migration measurements to the presence of a localized absorption heterogeneity.
Journal of Biomedical Optics, 2007
The use of perturbation and differential Monte Carlo ͑pMC/ dMC͒ methods in conjunction with nonli... more The use of perturbation and differential Monte Carlo ͑pMC/ dMC͒ methods in conjunction with nonlinear optimization algorithms were proposed recently as a means to solve inverse photon migration problems in regionwise heterogeneous turbid media. We demonstrate the application of pMC/dMC methods for the recovery of optical properties in a two-layer extended epithelial tissue model from experimental measurements of spatially resolved diffuse reflectance. The results demonstrate that pMC/dMC methods provide a rapid and accurate approach to solve two-region inverse photon migration problems in the transport regime, that is, on spatial scales smaller than a transport mean free path and in media where optical scattering need not dominate absorption. The pMC/dMC approach is found to be effective over a broad range of absorption ͑50 to 400%͒ and scattering ͑70 to 130%͒ perturbations. The recovery of optical properties from spatially resolved diffuse reflectance measurements is examined for different sets of source-detector separation. These results provide some guidance for the design of compact fiber-based probes to determine and isolate optical properties from both epithelial and stromal layers of superficial tissues.
Journal of Biomedical Optics, 2004
Journal of Biomedical Optics
We present a Monte Carlo (MC) method to determine depth-dependent probability distributions of ph... more We present a Monte Carlo (MC) method to determine depth-dependent probability distributions of photon visitation and detection for optical reflectance measurements performed in the spatial frequency domain (SFD). These distributions are formed using an MC simulation for radiative transport that utilizes a photon packet weighting procedure consistent with the two-dimensional spatial Fourier transform of the radiative transport equation. This method enables the development of quantitative metrics for SFD optical sampling depth in layered tissue and its dependence on both tissue optical properties and spatial frequency. We validate the computed depth-dependent probability distributions using SFD measurements in a layered phantom system with a highly scattering top layer of variable thickness supported by a highly absorbing base layer. We utilize our method to establish the spatial frequency-dependent optical sampling depth for a number of tissue types and also provide a general tool to determine such depths for tissues of arbitrary optical properties.