University of Texas
Optical Spectroscopy Laboratory
University of Texas
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Title: IGERT Training Grant in Optical BioMolecular Engineering Agency: NSF PI: Rebecca Richards-Kortum Abstract: This award establishes an inter-disciplinary new pathway to a graduate degree that synthesizes skills in optical engineering, biological chemistry and molecular biology in a single graduate degree. The degree program incorporates three important inter-disciplinary features. (1) A training grant gives students broad exposure to the field through research internships and a seminar course during their first two years. (2) Students pursue an inter-disciplinary PhD topic. A new structure for inter-disciplinary research requires a PhD advisory committee with broad participation from faculty in the Colleges of Engineering and Natural Sciences to meet regularly to advise the student and review their progress. Internships with industry and/or the national laboratories are pursued where appropriate. (3) Three new courses will give inter-disciplinary graduate education necessary to design and use optical instrumentation for visualization and manipulation of tissues and cells. 
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University of Texas
Optical Spectroscopy Laboratory
Title: The Biology, Clinical Performance, Acceptability, and Cost-Effectiveness of Fluorescence and Reflectance Spectroscopy and Quantitative Cytology and Histo-Pathology for Cervical Neoplasia Agency: NIH - Sub-Contract from MDACC PI: Rebecca Richards-Kortum Abstract: Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer mortality in women in developing countries. In the United States (U.S.) over $6 billion are spent annually in the evaluation and treatment of low-grade precursor lesions. Cervical cancer goes undetected in developing countries because of the cost of the tests and the lack of trained personnel and resources to screen and diagnose. In the U.S., resources are wasted on the evaluation and treatment of lesions not likely to progress to cancer. Both the screening and detection of cervical cancer could be vastly improved by technologies which improve, automate, and decrease the cost of screening and detection. The goal of this program project is to assess the emerging technologies of fluorescence and reflectance spectroscopy and quantitative cytology and histopathology for the diagnosis of cervical neoplasia. The program project seeks to address: (1) Biologic Plausibility, by examining the fluorescence/reflectance and quantitative images of cell lines, tissue cultures, and live tissue sections; (2) Technical Feasibility, by conducting large screening and diagnostic trials of fluorescence and reflectance spectroscopy and quantitative cytology and histopathology; (3) Intermediate Effects, by using the fluorescence and reflectance spectrometer in a randomized clinical trial; (4) Patient Outcomes, by assessing patient and provider acceptability of fluorescence and reflectance spectroscopy and quantitative cytology and histopathology; and (5) Societal Outcomes, by assessing the performance and cost-effectiveness of fluorescence and reflectance spectroscopy and quantitative cytology and histopathology in the screening and diagnostic setting. The four cores will support the projects by focusing on (A) Administration, (B) Biostatistics and Informatics, (C) Instrumentation, and (D) Pathology. The innovative aspects of this program project are three-fold: 1) the project uses the cervix, a small and accessible organ for which the dysplasia-carcinoma sequence is well-understood as the basis for examining emerging optical technologies, 2) optical spectroscopy and quantitative cytology and histopathologic analyses are evaluated for biological plausibility, effectiveness, acceptability, and cost-effectiveness, and 3) both technologies will have broad applications to other organ sites such as the oral cavity and lung, the digestive tract, the bladder, and skin.
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University of Texas
Optical Spectroscopy Laboratory
Title: Fiber Optic, In Vivo Confocal Microscopy Agency: NIH PI: Rebecca Richards-Kortum Abstract: The objectives of this project are to design, construct and test a fiber optic endoscope to obtain confocal reflected light images of human epithelial tissues in vivo with several micron resolution in near real time and to develop techniques t interpret the resulting tissue images to yield diagnostic information based on sub-cellular morphologic and biochemical changes. The application of the resulting system is to image epithelial tissues to aid in the diagnosis, and potentially screening, of epithelial pre-cancers. We will carry out a clinical trial to assess the capability of our device to measure tissue morphology and identify pre-cancer in vivo relative to the gold standard of histo-pathology in the uterine cervix. Successful completion of this project will provide a clinical tool which could dramatically improve recognition and monitoring of epithelial pre-cancer of the oral mucosa, uterine cervix, urinary bladder, colon and other organs with high incidences of epithelial cancer.
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University of Texas
Optical Spectroscopy Laboratory
Title: Multi-modal Miniature Microscopes for Detection of Pre-Cancer Agency: University of Arizona (through NSF) PI: Michael Descour Abstract: The goal of this interdisciplinary research project is to develop miniature microscopes that can utilize the interaction of light with tissues in many modalities to image morphology and cytochemistry in vivo, yielding tools that provide better delineation of tumors. We envision pen-sized, battery-powered multi-modal miniature microscopes (4Ms) designed to specifically image microscopic and molecular features of pre-cancer. The proposed miniature microscopes are being called multi-modal because of their potential for enabling different imaging modalities such as optical sectioning, 3-D spectral fluorescence imaging, and reflectance imaging. The size and cost of these microscopes will be small enough so that they can be used for wide-scale screening of disease. These tools will have broad applicability in many organ sites due to their very compact size and capability for imaging. We will first apply these tools to improve detection of oral-cavity pre-cancers because of the oral cavity’s easy accessibility. Furthermore, our assembled multidisciplinary expertise empowers us to treat the design of miniaturized imaging sensors in an all-inclusive manner: In addition to developing 4M devices, we will also design contrast agents specific for molecular alterations associated with pre-cancer that can be applied topically to significantly expand the imaging capability of miniature microscopes.
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University of Texas
Optical Spectroscopy Laboratory
Title: Molecular Based Diagnosis, Treatment and Prevention of Disease: Vertically Integrated Biomedical Engineering Education and Research Agency: Whitaker Foundation PI: Ken Diller Abstract: The University of Texas System has developed internationally recognized programs in Cellular and Molecular Biology, in Engineering, and in Molecular Medicine; we propose to integrate and expand these areas of excellence to form a Department of Biomedical Engineering at the University of Texas at Austin, emphasizing formal educational and research collaborations with the University of Texas Health Science Center in Houston and the University of Texas M.D. Anderson Cancer Center in Houston. This new department will train undergraduate and graduate students to understand the fundamental molecular bases of disease processes and to use this knowledge to engineer tools for the diagnosis, treatment and prevention of disease. We strongly feel that the next generation of Biomedical Engineers must be able to apply tools of (1) biomedical imaging, (2) biosensor design and (3) computational BME and bioinformatics across vertically-integrated systems spanning the molecular to the organismal levels; thus, these tools form the focus areas of research for this new department.
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University of Texas
Optical Spectroscopy Laboratory
Title: Biospecific Contrast Agents for Pre-Cancer Detection Agency: NSF PI: Rebecca Richards-Kortum Abstract: This proposal brings together scientists from very diverse areas with the goal of developing new photonic probes and contrast agents for highly sensitive and selective detection of pre-cancers in vivo. Dr. Andrew Ellington will use the approaches of combinatorial chemistry to develop a library of aptamer molecules specific for biomolecular targets on the surface of cervical cancerous and pre-cancerous cells. He will use well-established cervical cell lines at different stages of cancer development provided by Dr. Lotan. Drs. Brian Korgel and Konstantin Sokolov will develop new photonic probes based on quantum dots (BK) and metal nanoparticles (KS). They will utilize both the aptamers developed by Dr. Ellington as well as well-known antibodies currently used in clinical histopathology. Dr. Rebecca Richards-Kortum will test the conjugates as molecular specific contrast agents using optical microscopy and spectroscopy. She will use cervical cancer cell lines provided by Dr. Lotan, three-dimensional tissue phantoms and fresh cervical tissue slices from Dr. Follen. Experiments with all three biological systems representing properties of normal and neoplastic cervix at different levels of complexity will be used to assess and refine the performance and detection scheme for the new contrast agents. This refinement will include preparing bioengineered aptamers with high affinity to cancer specific targets, tailoring optical properties of metal nanoparticles and quantum dots, optimizing conjugation procedures, and developing optimal imaging geometries.
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University of Texas
Optical Spectroscopy Laboratory
Title: In Vivo Confocal Microscopy for Pre-Cancer Detection Agency: THECB PI: Rebecca Richards-Kortum Abstract: Cervical cancer is the 3rd most common cancer in women worldwide and the leading cause of cancer mortality in women in developing countries. The curable precursor to cervical cancer is cervical intra-epithelial neoplasia (CIN). In the U.S. over $6 billion are spent annually evaluating and treating CIN. Screening and detection could be vastly improved by optical technologies that image sub-cellular structure in vivo without need for expensive and painful tissue removal, processing, and examination. In vivo confocal imaging is a new technology under development at UT, which provides the ability to non-invasively image cervical epithelial cells using reflected light. In concept, this is similar to histologic analysis of biopsies, except that 3D sub-cellular resolution is achieved without removing tissue, and contrast is provided without stains. Pilot clinical trials show that confocalimaging has a sensitivity of 89% and a specificity of 91%, significantly better than the current clinical tool of colposcopy (average sensitivity 85%, specificity 69%). Further,our group has recently developed a small fiber optic confocal microscope that provides minimally invasive access to internal organ sites. Thus, we are at a stage where there is significant commercial potential for this new technology. The goals of this project are tocarry out research and development to transfer this technology to industry, and ultimately to routine clinical practice. We will achieve this goal through three aims: (1) we will obtain confocal images of normal and abnormal cervical tissue to create an atlas of cervical pathology before and after application of acetic acid using three optical systems. The resulting database will be used to develop and refine automated mage processing algorithms to recognize CIN. (2) Next, we will conduct a prospective in vivo clinical trial where images will be obtained from normal and abnormal cervix in vivo using our miniaturized fiber optic microscope. The algorithm developed in Aim 1 will be applied to these data to prospectively evaluate its sensitivity and specificity. (3) Finally, working with our industrial partner, we will develop a smaller, more stable, and manufacturable fiber optic microscope for use in future, multi-center clinical trials which will be necessary to obtain FDA approval for this new diagnostic technology.
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University of Texas
Optical Spectroscopy Laboratory
Title: Integrated Miniature Microscope for Pre-Cancer Detection Agency: University of Arizona (subcontract through NIH) PI: Michael Descour Abstract: The long-term goal of this research project is to develop a class of miniature microscopes that utilize the interaction of light with tissues in many modalities to image morphology and biochemistry in vivo, yielding tools that provide better delineation of tumors. We envision battery-powered, pen-sized multi-modal miniature microscopes (4Ms) designed to specifically image microscopic and molecular features of pre-cancer. The proposed miniature microscopes are multi-modal because of their potential for enabling different imaging modalities such as optical sectioning, 3-D spectral fluorescence imaging, and reflectance imaging. The size and cost of these microscopes can be eventually small enough so that they can aid in, for instance, guiding diagnostic biopsy and to aid in margin detection during tumor resection. 4M devices, suitably adapted, will have broad applicability in many organ sites due to their very compact size and capability for imaging. Because of the easy accessibility of the oral cavity and uterine cervix, we will first aim these tools to improve detection of pre-cancers in these organ sites.
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