1998 — 2006 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Physical Mechanisms of Pulsed Microbeam Ablation Processes @ University of California Irvine |
1 |
1999 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Physical Mechanisms of Pulsed Microbeam Ablation Processes: Fluorescent Images @ University of California Irvine
We have been successful in determining the optimal laser parameters necessary to encode and read out laser microbeam profiles in photochromic films. These films appear capable of giving accurate profiles of the spatial intensity distribution within microirradiated samples. Quantitative analysis of the confocal fluorescent images of these photochromic films indicate that the image contrast varies linearly with the local laser beam intensity. Line scans of these images in both longitudinal and lateral directions give profiles which possess excellent agreement with the theory of Gaussian beam propagation. We have also investigating schemes to accurately determine the pulse energy of a laser microbeam and are in the process of implementing a system to do so.
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1 |
1999 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Electromagnet Wave Propagat Model in Cells Using Finite Difference Time Domain @ University of California Irvine
The project uses a computational technique to describe the optical absorption and scattering of cells when interacting with a collimated or highly focused laser beam. The project makes use of the Finite Difference Time Domain to provide a numerical solution for Maxwell's equations. The results allow us to understand how the propagation of light is altered when passing through a cell and can be used to understand image quality in microscopy systems and the performance of optical trapping systems
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1 |
1999 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Monte Carlo Techniques: Diffuse Photon Migrat: Detect Structure Heterogeneity @ University of California Irvine
We are developing a novel method to compute, with high accuracy and sensitivity, the change in a diffuse reflectance signal induced by the introduction of a structural heterogeneity (e.g., a tumor) within a turbid tissue. The diffuse reflection is computed in both frequency and time-domain and provide insight into optical detection approaches which provide maximum detectability and contrast between heterogeneous structures embedded within a homogeneous turbid background.
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1 |
1999 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Monte Carlo Modeling of Diffuse Light Transport: Tissue Volume Computation @ University of California Irvine
Novel Monte Carlo techniques are being developed to quantitatively determine the tissue volume sampled by non-invasive diffuse imaging modalities. Novel features of these methods include the use of expected value estimators and the explicit consideration of the number and location of photon interactions within the turbid medium. The computation of tissue sampling volumes and its variation with tissue optical properties and instrument configuration parameters greatly aid in the design of novel probes customized for a particular application.
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1 |
2001 — 2005 |
Venugopalan, Vasan |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Photon Migration For Measurement of Small Tissue Volumes @ University of California Irvine
The overall goal of the proposed research is to develop non-invasive optical technologies for the real-time, quantitative measurement of optical and physiological properties in small tissue volumes. Currently, optical techniques that employ the detection of diffusely transmitted or reflected light are most often used in conjunction with diffusion-based optical transport models to either (a) image centimeter-thick, highly- scattering, heterogeneous tissues with approximately 5mm. spatial resolution or (b) quantify optical and physiological properties of large, highly-scattering, homogeneous tissue volumes (>50 mm[3]). Although such techniques can also be used to measure a volume-averaged impact of localized heterogeneous structures, the current inability to accurately characterize light transport on small length scales (equal to or < 5mm) significantly hampers the possibility of accurately quantifying optical properties in small, well-defined tissue volumes. Here, we propose a comprehensive theoretical, computational, and experimental approach to substantially extend diffusion approximation limits by enabling the assignment and quantification of optical and physiological properties to small localized tissue volumes (approximately 2-50 mm3) of arbitrary albedo. These properties have been shown to be sensitive, quantitative measures of cellular and extracellular morphology and biochemical composition. Such a capability will spur the development of novel, compact optical probes with broad application including early detection of dysplastic transformation of epithelial tissue structure and composition, intraoperative/endoscopic surgical guidance, as well as diagnostic feedback for real-time monitoring and control of photodynamic, hyperthermal, cryogenic, and coagulative therapies. Such probes are also valuable for basic biological studies in artificial tissue and pre-clinical animal models where the spatial scales probed are inherently small. The proposed research aims to fully develop both a novel optical modeling approach to describe light transport on sub-millimeter length scales as well as computational algorithms to determine optical properties from photon migration measurements made in small tissue volumes. These methods will be extensively tested and validated through the experimental measurement and computational processing of light signals that result from propagation through realistic tissue phantoms. We will apply these newly developed photon migration methods, in conjunction with thick-tissue microscopy techniques, to examine artificially- engineered tissue models for normal and dysplastic epithelia. This latter study will allow us to investigate the interrelationships between microscopic tissue morphology and composition and mesoscopic optical absorption, scattering and anisotropy coefficients provided by photon migration methods.
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1 |
2004 — 2011 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Perturbation Monte Carlo Techniques For Diffuse Photon Migration @ University of California Irvine |
1 |
2004 — 2005 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Poise Novel Approach For Determining Optical Properties of Turbid Media @ University of California Irvine
bioimaging /biomedical imaging; imaging /visualization /scanning
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1 |
2004 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Devel of Delta P1 &Higher Order Diffuse Models For Fdpm @ University of California Irvine |
1 |
2004 — 2011 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Monte Carlo Modeling of Diffuse Light Transport @ University of California-Irvine
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Novel Monte Carlo techniques are being developed to quantitatively determine the tissue volume sampled by non-invasive diffuse imaging modalities. Recent research activity has culminated with the development of a new transport-theoretic method for imaging and analyzing the conditional response of a detector, conditioned by passage through any designated tissue subvolume targeted for investigation. The new procedure relies on a generalized reciprocity theory for radiative transport that enables the computation to be performed efficiently using a pair of Monte Carlo simulations: one tracking photons from the source, and the second tracking backward-moving photons initiated at the detector. This "midway method" then pairs the forward and backward -moving photons in matched spatial-angular bins at the surface of the targeted volume. An integration over the target bounding surfaces produces the desired joint probability of both visiting the targeted volume and being detected. The method has been tested on a two-layer epithelial tissue model and the data derived from the simulations is used to compare the relative merits and efficiencies of competing probe designs. These preferences are then confirmed through the solution of inverse problems that indicate best probe designs for a given source-detector-target volume configuration. Future work will include the addition of variance reduction strategies and additional testing and model validation studies. The use of this conditional detector response information should aid greatly in the design of novel probes customized for a particular application.
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1 |
2005 — 2011 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Development of Delta P1 &Higher Order Diffuse Models For Fdpm @ University of California-Irvine
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are developing the delta-P1 and higher order diffusion based models to allow accurate processing of FDPM data in a broader number of clinical situations. Specifically, are making FDPM measurements to probe layered tissue structures as well as assess the properties of small tissue volumes. In both these applications, we require FDPM measurements to be made at small source-detector (S-D) separations. These delta-P1 and higher order diffusion based models accommodate spatially distributed collimated sources and provide accurate predictions at small s-d separations and over a broad range of albedo. We will compare these results to solutions derived using the standard diffusion approximation and experiment. We will also solve the new equations for steady and amplitude modulated collimated sources illuminating the surface of an infinite medium. Compare results with SODT and experiment. We are currently investigating the use of this theoretical models to solve th e in verse problem at small s-d separations.
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1 |
2005 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Green's Function of the Boltzmann Transport Equation to Solve Forward and Invers @ University of California Irvine |
1 |
2005 — 2006 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Methods For Image Reconstructions From Poise Data @ University of California Irvine |
1 |
2006 — 2008 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Physical Mechanisms of Pulsed Laser Microbeam Interactions With Cells @ University of California Irvine
Blood Plasma; CRISP; Cell Line; Cell Lines, Strains; CellLine; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytolysis; Electromagnetic, Laser; Fluorescence; Fluorescence Microscopy; Funding; Grant; Imagery; Individual; Institution; Investigators; Lasers; Lysis; Methods; Microscopy, Fluorescence; Microscopy, Light, Fluorescence; NIH; National Institutes of Health; National Institutes of Health (U.S.); Operation; Operative Procedures; Operative Surgical Procedures; Phase; Physiologic pulse; Plasma; Population; Process; Pulse; Pulse taking; Radiation, Laser; Range; Reporter; Research; Research Personnel; Research Resources; Researchers; Resources; Reticuloendothelial System, Serum, Plasma; Serum, Plasma; Source; Surgical; Surgical Interventions; Surgical Procedure; Time; United States National Institutes of Health; Visualization; cultured cell line; nano second; nanosecond; response; surgery; time use
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1 |
2006 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Green's Function of the Boltzmann Transport Equation to Solve Forward and Inver @ University of California Irvine |
1 |
2007 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Methods For Image Reconstruction From Poise Data @ University of California Irvine |
1 |
2007 — 2011 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Green?S Function of the Boltzmann Equation to Solve Problems in Photon Migration @ University of California-Irvine
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent developments in applied mathematics have yielded an analytic Green's function to the Boltmann Transport Equation (BTE) which provides an exact description for photon migration in turbid media. The use of a Green's function rather than Monte Carlo simulations promises to model important problems with much less computational expense. We are investigating approaches to utilizing this solutions to address important forward and inverse problems of photon migration in homogeneous and heterogeneous tissues using this approach. We are also working on incorporating the Green's function based ERT kernel into the Solver module of the Virtual Tissue Simulator.
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1 |
2007 |
Venugopalan, Vasan |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
An Automated Platform For Kinase Assays On Patient Cells @ University of California Irvine
DESCRIPTION (provided by applicant): An integrated laser microbeam-microscope system with time resolved imaging capabilities is proposed for studying laser induced tissue injury. Laser microbeams offer a fast, automated and non-contact means for cellular micromanipulation due to their ability to deposit energy with high spatial specificity and limited collateral damage. There is growing interest in their use for applications in tissue microprocessing and single cell analysis. However, research on basic mechanisms of laser-cell interactions is limited due to the small spatial scales and fast time scales over which they occur. The experimental platform we propose will image the dynamics of laser microbeam-induced injury with high spatial and temporal resolution in tissue engineered samples that mimic in-vivo systems. Focused nanosecond laser pulses will be delivered to the sample to cause injury at specific sites and the process will be imaged using time-resolved imaging on nanosecond to microsecond timescales. The contributions of the high-temperature plasma, Shockwave propagation and cavitation bubble expansion and collapse to cell injury will be determined from these images. Time-resolved images will also be used for quantitative estimation of cavitation bubble parameters such as bubble size, collapse time and bubble energy. The bubble dynamics will be used to estimate fluid velocity and shear stress at the tissue site. The biological effects of laser pulses will be monitored using fluorescence assays. A major goal would be to relate the physical effects from time-resolved imaging to the observed biological response. The hydrodynamic modeling will provide insights on cellular response to high shear fields on fast time scales to provide a biophysical characterization of the damage process. The platform will be designed to be scalable for general studies of laser microbeams and cavitation phenomena in biology. This research will be done primarily in Bangalore, India at the National Centre for Biological Sciences in collaboration with Dr. Kaustubh Rau as an extension of NIH grant R01-EB004436.
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1 |
2007 — 2011 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Poise: a Novel Approach For Determining Optical Properties of Turbid Media @ University of California Irvine |
1 |
2008 — 2011 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Monte Carlo Methods For Fiber Optic Probe Design @ University of California-Irvine
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The main goal of this project is to use Monte Carlo simulations in development of novel fiber optic endoscopes that can simultaneously probe the epithelial and stromal morphology using oblique collection fiber geometry. We will use previously reported scattering properties of human epithelium to predict and to characterize collection efficiency and depth resolution of different probe designs. Design parameters will include source-detector separation;various angles between illumination and collection fibers;fiber diameter;number of collection fibers, etc. We will change optical properties of the epithelium to reflect early cancer development and will optimize probe design to achieve the highest sensitivity to optical changes that are associated with an onset of carcinogenesis. Theoretical predictions will be tested using well defined multi-layered optical phantoms of human epithelium. Successful completion of the project can lead to development of a simple instrument for non-invasive, real time in vivo pre-cancer detection and monitoring via reflectance spectroscopy.
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1 |
2008 — 2011 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Fdtd Modeling of Light Scattering From Cells and Tissues @ University of California-Irvine
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We would like to incorporate aspects of our finite difference time-domain (FDTD) modeling of light scattering from cells into the Virtual Tissue Simulator. The FDTD method is an electromagnetic approach that enables accurate modeling of the complete light scattering properties of cells and other tissue components at the sub-micron scale. Although FDTD simulations are computationally demanding, it should be possible to create a database of scattering cross-sections and phase functions for a wide range of cellular structures and compositions that could be incorporated into macroscopic Monte Carlo methods. Such an approach would enable users to specify cellular and sub-cellular features of tissue components and then investigate how changes in the microscopic parameters translate to macroscopic optical changes.
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1 |
2009 — 2010 |
Venugopalan, Vasan Weed, Kent Richard |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Versatile System to Select and Expand Individual or Multiple Adherent-Type Cells @ Lightworks Optics, Inc.
DESCRIPTION (provided by applicant): The ability to select, isolate, and expand single adherent-type cells or cell colonies is critical in many areas of biological research. Our objective is to develop a novel technology that integrates pulsed laser microbeam irradiation and polymer microdevices for single cell selection, isolation, and expansion. Cell selection and isolation are achieved by culturing adherent cells on the top of discrete polymer micropallet (30-250-5m sides, 30-100-5m height) fabricated on top of a glass surface that facilitates biological imaging. Once an adherent cell of interest is identified (e.g., via morphological analysis or fluorescence microscopy), a pulsed laser microbeam is delivered proximal to the interface between the polymer and the underlying glass coverslip to release the cell and micropallet. Once collected the cell can, for example, be subject to genomic/proteomic analysis or cultured to form a monoclonal cell population. We aim to design and build an apparatus that can be integrated with standard biological microscopy platforms and operated by general users in both biomedical research and pharmaceutical/biotechnology industries. During phase I of this SBIR application, we will (a) develop methods to optimize the laser microbeam irradiation parameters (e.g., wavelength, pulse duration, pulse energy, and numerical aperture) to release the polymer micropallets while minimizing cellular exposure to physical stresses associated with the release process, (b) verify that the chosen laser microbeam parameters facilitate cell selection with minimal loss of cell viability/function;and (c) design, build, and test the prototype instrument. PUBLIC HEALTH RELEVANCE: This SBIR Phase I project will develop a novel technology integrating the use of laser radiation and polymer microdevices to enable the identification, selection and recultivation of single adherent-type cells or cell colonies. This technology will be designed for use by biomedical researchers as well as the biotechnology and pharmaceutical industries. An important application of this technology is that it provides a cost-effective approach to the formation of homogeneous (monoclonal) cell populations with specific characteristics and thus enable a variety of activities connected with understanding cellular behavior and disease progression as well as the evaluating the efficacy of potential therapeutic agents.
|
0.904 |
2012 — 2017 |
Khine, Michelle (co-PI) [⬀] Lander, Arthur (co-PI) [⬀] Prescher, Jennifer (co-PI) [⬀] Tromberg, Bruce (co-PI) [⬀] Venugopalan, Vasan |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Igert: Biophotonics Across Energy, Space, and Time (Best) @ University of California-Irvine
This Integrative Graduate Education and Research Traineeship (IGERT) award initiates a novel model for interdisciplinary graduate training in biophotonics across the biomedical sciences, physical sciences, and engineering. Biophotonics technologies provide powerful capabilities to probe and manipulate biological components and processes. Their utilization in the life sciences and medicine represents an estimated annual economic impact of $50 billion. This program aims to produce the next generation of biophotonics leaders to make transformative advances in the development and application of new tools for biological and medical discovery and maintain global U.S. leadership in biotechnology, pharmaceutical and medical device industries. Intellectual Merit: This IGERT award creates a hands-on training program that integrates physics, chemistry, engineering, and life-science principles across spatial and temporal scales. The interaction of, and collaboration between, biomedical scientists, physical scientists and engineers throughout the graduate traineeship will drive advances in biophotonics technologies, computational methods, and molecular probes to solve important problems in bio-molecular, cellular, tissue, and whole organismal systems. Broader Impacts: The BEST IGERT project will promote dissemination of an innovative education framework aimed towards a diverse cadre of scientists and engineers. Moreover, IGERT faculty and trainees will engage vigorously in a spectrum of outreach, dissemination, recruitment, retention, and career development activities that leverages the commitment of multiple units within UC-Irvine, industry in Southern California, and a nationwide network of faculty contacts, including those at minority serving institutions, to inform the public and broaden participation by students from underrepresented groups.
IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the interdisciplinary background, deep knowledge in a chosen discipline, and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to establish new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries, and to engage students in understanding the processes by which research is translated to innovations for societal benefit.
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1 |
2013 — 2017 |
Spanier, Jerome (co-PI) [⬀] Venugopalan, Vasan |
R25Activity Code Description: For support to develop and/or implement a program as it relates to a category in one or more of the areas of education, information, training, technical assistance, coordination, or evaluation. |
A National Short Course in Computational Biophotonics @ University of California-Irvine
DESCRIPTION (provided by applicant): This proposal aims to establish an Annual National Short Course in Computational Biophotonics that integrates biophysical concepts, mathematical, and computational approaches for the modeling of propagation and deposition of light in cells, tissues, and organisms. The Short Course will provide a foundation for modeling and simulating fundamental biophysical interactions and processes needed to make rapid, integrated advances in the field. The short course will help to release the full potential of opticl methods to provide unique approaches for imaging, physiological monitoring, manipulation and/or treatment of cells, tissues and organisms. The participating faculty of Laser Microbeam and Medical Program (LAMMP) at the UC, Irvine is ideally suited to host this annual workshop as it is one of only four NIH National Biomedical Technology Resource Centers (BTRCs) focused on the development and application of Optical Technologies in both Biology and Medicine. It is the only BTRC with a dedicated technology core devoted to modeling and computation. LAMMP draws upon substantial educational and research expertise - from a pool of more than 20 active faculty across 12 participating academic departments - to offer a training course to engage medical research fellows, graduate students, postdoctoral researchers, faculty and industrial scientists from diverse scientific disciplines who have nascent interest in engaging in Biomedical Optics research. Each day's program will be organized around a theme devoted to the application of specific Biophotonics processes to significant biomedical problems. This design provides the context for the exposition of fundamental optical processes, modeling and computational approaches needed for proper utilization of these methods and subsequent analysis of measured biophotonic signals. We expect significant demand for such a Short Course due to the growth and broadening scope of Biophotonic methods to impact biomedical research (e.g., functional microscopy, imaging of pre-clinical animal models, optogenetics) and clinical translation for functional imaging, optical diagnosis, and treatment. The course format will combine didactic lectures, practical computational laboratories featuring custom- designed software, and interactive trainee presentations and discussion of laboratory results. The content and format of the short course builds upon successful 21/2 day Virtual Photonics Workshops that we have held in each of the past three years. These have served well to introduce Biophotonics modeling and computation to a broad multi-disciplinary cadre of graduate student, post-doctoral, medical fellow and industrial participants. However, these workshops exposed to expand and deepen the instruction to provide time for absorption and reinforcement of the course material and secure interdisciplinary experiential group learning activities. Beyond providing an intensive on-site training course, all course materials and customized modeling and simulation software will be made available over the Internet at no cost in order to maximize distribution and outreach.
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1 |
2017 |
Venugopalan, Vasan |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Virtual Photonocs Technologies @ University of California-Irvine |
1 |
2018 — 2021 |
Potma, Eric (co-PI) [⬀] Venugopalan, Vasan |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Leveraging Light Scattering in Tissues For Improved Biomedical Imaging @ University of California-Irvine
Advances in laser-scanning optical microscopy, a high-resolution imaging technique, have made it possible to image the chemical and structural details of living cellular and tissue systems at high resolution. Unfortunately, microscopic variations in tissue composition scatter the laser light, causing degradation of the image quality and limits in imaging depth. In fact, light scattering is the main limitation of using laser-scanning microscopy for tissue imaging. A promising approach to improve image quality and depth is to use adaptive optics (e.g. deformable mirrors) to shape the laser beam in a way that counteracts the effects of light scattering in the tissue. While promising, adaptive optics techniques currently use optimization schemes that do not account for the mechanisms of scattering. This leaves the method prone to artifacts, especially as scattering becomes more severe at greater depths. Thus, a mechanistic (physical) insight into the scattering would be very helpful to guide and fundamentally improve adaptive optics optimization schemes. The goal of this project is to develop an integrated modeling, computational, and experimental approach--a Virtual Microscopy Simulator (VMS)--to determine the adaptive optics signal corrections necessary to fully correct for scattering induced distortions relevant to laser scanning microscopy. The outcomes of this work improve adaptive optics technics and allow imaging at greater depths in tissue materials, which will dramatically improve the impacts of optical microscopy in the biomedical sciences. Beyond making the VMS platform available to the science community, Education and Outreach plans include participating in a UC-HBCU summer research program and providing courses and mentorship within an NSF IGERT program in Biophotonics.
This goal of this project is to fundamentally improve optical imaging of tissues by delivering new insights in counteracting the effects of light scattering in tissues using a model-based approach to adaptive optics that will improve image quality and penetration depth. This approach addresses many of the limitations encountered by current technologies, including: a) constraint to superficial layers due to light scattering, b) non-unique solutions and artifacts when deeper layers are accessed via wavefront shaping based on empirically based optimization schemes, c) lack of beacon sensors that could provide information to generate a compensating phase pattern, d) production of distorted focal volumes, e) iterative optimization methods that make imaging slow and, most important, f) absence of methods to model wave-based light propagation in tissue materials of meaningful volumes, leaving no model-based support for adaptive optics in tissue imaging. The new framework will be used to compute the adaptive optics signal corrections necessary to fully correct for scattering induced distortions relevant to laser scanning microscopy, and nonlinear optical microscopy in particular. The Research Plan is organized under three objectives. OBJECTIVE 1 is to develop a Virtual Microscopy Simulator (VMS) to model focused beam propagation, (linear and nonlinear) signal generation, and signal detection in turbid tissues. The input module will allow users to provide input data such as microscopy type, lens data, incident beam parameters, scattering data, nonlinear susceptibility data, detector specifications and adaptive optics data (Deformable Mirrors or Spatial Light Modulators settings). The input data will be fed into the computational engine to execute the computations. The computational module will be designed to handle all computations: a) Signal Generation, b) Signal Emission and Detection, and c) Adaptive Optics Computations. The Output module will consist of text data files of 3D focal volume data, far-field radiation data, and image data. OBJECTIVE 2 is to perform experimental validation of the VMS in tissue-mimicking phantom systems with well-defined scattering and signal generation elements. Four classes of phantoms with nonlinear optical targets will be prepared to validate the VMS: a) agarose or Sylgard only (Non-scattering), b) agarose or Sylgard with microspheres, c) Collagen Hydrogel with and w/out microspheres, and d) hybrid specimens with a layer of agarose or Sylgard matrix and a layer of collagen hydrogel with microspheres. OBJECTIVE 3 is to establish model-based adaptive optics design principles through usage of the VMS to predict the input wavefronts necessary to counteract the dispersive effects of scattering media that impede diffraction-limited focal volume formation and signal generation in scattering. The aims of the objective are to a) examine potential differences between the corrected focal volume and a theoretical, undistorted volume, b) study the performance of the algorithms from the perspective of the ideal wavefront needed to correct the image, and c) develop an adaptive algorithm that reproduces the undistorted image, even in the presence of scatterers situated between the focal volume and the collecting lens.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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1 |
2018 — 2019 |
Venugopalan, Vasan |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Adaptive Optics Modeling in Nonlinear Microscopy to Improve Deep Tissue Imaging @ University of California-Irvine
Project Summary Coherent imaging technologies including as laser scanning confocal, multi-photon excited fluorescence (MPEF), second-harmonic generation (SHG), and coherent Anti-Stokes Raman scattering (CARS) microscopy have become powerful tools for biological research. However, the spatial heterogeneity of biological tissues presents a source of optical scattering that severely compromises the ability of these methods to acquire undistorted, high-resolution images at depths larger than a few hundred micrometers. Recently, investigators have sought to use an approach known as adaptive optics to mitigate scattering and optical system aberrations in microscopy. Adaptive optics represents an empirical approach to improve image quality by modifying the excitation wave front characteristics in order to improve the detected signal. This method has enabled some investigators to retrieve information at tissue depths that were previously inaccessible. However, the current implementations of adaptive optics, based on experimentally accessible parameters, do not ensure that the modification of the excitation signal properly corrects for the scattering- induced aberrations produced by tissue scattering. However it has been shown that adaptive optics optimization, using parameters measured from the detected optical signal, does not ensure that the modified excitation wave front characteristics properly corrected for the aberrations produced by the sample. We believe that a general and robust strategy to manage the depth and resolution limitations in optical microscopy must go beyond empirical optimization and be based on a mechanistic understanding of the light scattering. In this proposal, we propose to develop a fundamental ?bottom-up? approach to adaptive optics that utilizes a mechanistic treatment of scattering mechanisms in tissue that models how optical signal aberrations arise and propagate in optical microscopy. Using our recently developed Huygens? Fresnel Wave-based Electric Field Superposition (HF-WEFS) method that efficiently describes focused beam propagation in scattering media, we will mathematically model the effect of adaptive optics in two photon excited fluorescence (TPEF), SHG and CARS microscopy systems. We will apply these models to predict the effects of adaptive optics correction strategies when applied to the imaging of scattering media in above microscope techniques. We will verify our model predictions through experimental measurements. This project is expected to provide novel insights into an unexplored area of microscopy. We expect that the results of this investigation will not only fuel a better understanding of this process, but also will drive innovations to improve the capabilities in coherent optical imaging microscopy. This in turn will make possible improvements in the imaging of structural and functional information in thick tissues for use in studies spanning the fields of neurobiology, embryology, cell biology, developmental biology, cancer biology, and dermatology.
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1 |
2019 — 2020 |
Venugopalan, Vasan |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
A Biophotonics Platform For Mechanotransduction and Metabolic Microscopy @ University of California-Irvine
A Biophotonics Platform for Mechanotransduction and Metabolic Microscopy (M3) Project Summary: (30 lines) Mechanotransduction has emerged as one of the main regulators of biological function. While the downstream effects of cellular mechanotransduction have been widely studied, the interplay between cellular mechanotransduction and metabolism remains relatively unexplored. This proposal represents a multi-disciplinary collaboration between specialists in mechanobiology, laser-tissue interactions, and advanced fluorescence microscopy methods to develop a unique biophotonics technology platform that enables the precise application of impulsive force to 2-D cell cultures, 3-D tissue cultures, and live animal models to dynamically measure cellular mechanosensitivity and cellular mechanosignaling and correlate these with metabolic state, membrane fluidity, messenger RNA (mRNA) expression, as well as cell/matrix composition, morphology, organization, and stiffness. This will be achieved through a unique integration pulsed laser microbeam irradiation used for cell/tissue stimulation with laser scanning confocal (LSCM), multi-photon (MPM), fluorescence lifetime imaging (FLIM) microscopy, and multi- spectral imaging modalities. We will verify and demonstrate the capabilities of this platform in a variety of 2-D cell culture and 3-D tissue culture systems of varying complexity and material composition and stiffness. The proposed technology development will enable a unique capability to measure and examine the dynamic cellular interplay of sensitivity to mechanical cues, mechanosignalling, and other biological system characteristics including cellular metabolism, mRNA expression, and extracellular matrix remodeling. The proposed technology platform has broad applications for the study of normal tissue development and disease and for high-throughput drug screening.
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1 |