Vanderbilt University Department of Biomedical Engineering

Vanderbilt University Department of Biomedical Engineering NCIIA Grant Proposal: Hadamard Transform Imaging 04 November 2004 Team Members: Paul Holcomb Tasha Nalywajko Melissa Walden Project Description Brain tumors are among the most lethal types of cancer, with an average mortality rate of 71% of diagnosed cases.1 Studies have shown a correlation between complete or near-complete tumor resection and improved prognosis, both in adults and children.2-4 In order for optimal tumor resection to be performed, however, an imaging modality is needed to distinguish between normal and cancerous tissue, especially at the tumor margins Optical spectroscopy, specifically fluorescence and diffuse reflectance, has been found effective in differentiating between normal and tumor tissue, both in vitro and in vivo.5-7 Implementation of this technique in spectral imaging has not been examined for use in guidance of surgical resectioning Spectral imaging techniques are currently limited by the low level of autofluorescence of tissue; the weak signal obtained from current spectral imaging modalities requires long image acquisition and analysis times in order to resolve the image with the degree of clarity necessary for it to be useful The proposed tool, a Hadamard transform-based spectral imaging system using a digital micro-mirror device (DMD), has the potential to increase signal to noise ratio within the imaging system substantially, thus reducing the image acquisition and analysis time This will allow for near real-time intra-operative imaging of brain tumors and their margins, and will contribute to higher survival rates for patients Currently, three methods are widely used for spectral imaging: line scanning using motors and a spectrograph, wavelength scanning using filter wheels or electronically tunable filters, and multiplexing methods using Fourier interferometry Line-scanning methods, though ideal for small areas of interest, are relatively slow when large areas must be scanned and the motors can induce motion artifacts within the images While wavelength-scanning systems are rugged and simple to construct, filter wheels only allow spectral measurement at a limited number of wavelengths within the spectrum Electronically tunable filters can spectrally resolve emission over broad wavelength ranges, but they only transmit a narrow band of the emission at a time, and the transmission within this band generally peaks around 65% Multiplexing via Fourier interferometry increases the signal-to-noise ratio over wavelength scanning methods by collecting 50% of the emission, but the application of the inverse Fourier transform during post-processing significantly increases the overall acquisition time Through application of Hadamard transform multiplexing, many of the problems Figure 1: Schematic of a Hadamard Spectral Imaging System with the previous imaging techniques can be resolved The implementation of this technique (DMD – Digital Micromirror Device) With this design, the ydimension of the spectral image is encoded in successive CCD is made possible by the use of a digital micro- images The removable mirrors allow rapid switching between mirror device, which consists of an array spectral and real-time spatial imaging (1024x768) of 13μm x 13μm micro-mirrors that can be independently positioned to reflect light at two discrete angles (0º and 12º) relative to the normal axis of the mirror (see Figure 1) A Hadamard matrix, an array of ones and negative ones, can be implemented by positioning these mirrors for the application of the Hadamard transform to our image The mirrors are controlled using CMOS technology, and can change position within 20μs, allowing for rapid repositioning of the Hadamard matrix during image acquisition Nearly all of the light passed to the DMD can be transmitted to the next stage of the system, as the micro-mirrors are almost 100% reflective, which provides an advantage over previous Hadamard systems which employed liquid-crystal transmission masks After application of the Hadamard transform, the two reflected images (0º and 12º, or and -1 of the Hadamard transform) are individually compressed in separate system “legs” to one dimensional line images using cylindrical optics and then passed to a dispersion grating The grating disperses the spectral components of each line image along an axis perpendicular to the image, and the resulting two-dimensional images (one dimension of emitted wavelength and one of 1D spatial position within the target area) are collected by a CCD camera The number of image samples required for this technique is equal to the order of our Hadamard matrix (n) In order to acquire a full three-dimensional image (height, width, spectrum), all columns of the DMD are set to a single column of the Hadamard matrix, a sample is acquired, and all columns are then shifted to the next Hadamard matrix column until the entire matrix has been traversed After all sampling has been accomplished, the inverse Hadamard transform can be applied and the second spatial dimension of our image recovered This inversion consists of addition and subtraction of matrix components, making the process much faster than the inverse Fourier transform which relies on multiplication and division By assigning a color gradient to the image based on the wavelength acquired, the output can be overlaid on a standard camera image or optical microscope view for real-time use in surgery Initially, testing of the Hadamard transform imaging system will be performed on tissue phantoms and in vitro tissue samples using a single-leg system This testing will examine only one output image from the digital micro-mirror device and comparisons will be made with data acquired from a tunable filter spectral imaging system on the same sample A type of Hadamard matrix called an S-matrix will be used to transform the output data; the S-matrix is essentially a binary form of the Hadamard matrix, allowing for the mirrors to be represented as either “on” or “off” depending upon their state.9 This initial testing procedure allows for reduced cost at the outset, as well as a reduction in time required for alignment and testing As both outputs of the DMD will eventually be passed through identical optical compression systems, the design of this single-leg system can be easily extended to the full Hadamard application Size of our system is also another important consideration, as the device must be small enough to be used conveniently in an operating environment Scaling down of the system will be accomplished through reflective optics, thereby reducing the distance between optical components Many aspects of the Hadamard transform imaging technique make it ideal for use in spectral imaging The high transition rate of the DMD micro-mirrors and the rapid application of the inverse Hadamard transform leads to decreased time between image acquisition and display By using the reflective properties of the digital micro-mirror device to implement the Hadamard matrix in a two leg system, 100% of the light from our image can be used, as opposed to other spectral imaging techniques which use a maximum of 50% The use of the Hadamard transform also leads to increased signal-to-noise ratio (SNR) of the output; theoretically, the SNR of the image can be improved by a factor of √n, where n is equal to the order of the Hadamard matrix Application of the S-matrix, as is the case for our preliminary testing, still yields a SNR increase by a factor of √n/2 This signal improvement has been confirmed experimentally in several studies.8,10-11 A higher signal to noise ratio creates more accurate edges in our image, guaranteeing better tumor margin visualization The application of a Hadamard transform-based spectral imaging technique for brain tumor and tumor margin demarcation during tumor resection is a novel concept with potentially high impact This system is faster and more accurate than previous spectral imaging modalities, making it ideal for use in a clinical setting Implementation of this technique during resection will allow for precise, real-time visualization of the tumor and its margins with high resolution, leading to more complete tumor removal Consequently, recurrence of tumors will decrease and patient life expectancy will increase Unnecessary excision of normal brain tissue will also be prevented, leading to less damage to the brain and better quality of life for the patient Market Potential Because of the near real-time imaging that this design provides, the Hadamard transform imaging system will be used in conjunction with operating microscopes during brain surgery Ideally, this system will augment the operating microscopes already in place, thus reducing cost to the consumer As operating microscopes are used by almost all hospitals for microsurgical procedures, and especially for neurosurgical procedures, the potential market is very large The hardware for the Hadamard transform-based spectral imaging system is not a disposable product; we will be marketing an operating device that should not need replacing, however the opportunity for technical support is available Updates to the DMD control and image processing software allows for possible avenues of profit after product deployment Testing this device will require minimal paperwork, as image acquisition is completely non-invasive and has no foreseeable negative effects on the patient This technique also has the potential for marketing in any situation where tissues can be differentiated by their spectral properties, allowing for a more diverse customer base and higher profitability References [1] National Cancer Institute, “Adult Brain Tumor Treatment”, http://www.nci.nih.gov/cancertopics/pdq/treatment/adultbrain/healthprofessional [2] Bucci MK et al., “Near complete surgical resection predicts a favorable outcome in pediatric patients with nonbrainstem, malignant gliomas…” Cancer 101(4):817-24, 2004 [3] Lacroix, Michel et al., “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival”, J Neurosurg 95: 190-198, 2001 [4] Jaing TH et al., “Multivariate analysis of clinical prognostic factors in children with intracranial ependymomas” J Neurooncol 68(3):255-61, 2004 [5] Lin WC et al., “Brain tumor demarcation using optical spectroscopy; an in vitro study” J Biomed Opt 5(2):214-20, 2000 [6] Lin WC et al., “In vivo brain tumor demarcation using optical spectroscopy” Photochem Photobiol 73(4):396-402, 2001 [7] Marcu, Laura et al., “Fluorescence Lifetime Spectroscopy of Glioblastoma Multiforme” Photochem Photobiol 80: 98-103, 2004 [8] Hanley QS et al., “Three-dimensional spectral imaging by Hadamard transform spectroscopy in a programmable array microscope” J Microscopy 197(1): 5-14, 2000 [9] Harwit, Martin, Hadamard Transform Optics, Ch & 3, New York: Academic Press, 1979 [10] DeVerse RA et al., “Realization of the Hadamard Multiplex Advantage Using a Programmable Optical Mask…”, Applied Spectroscopy 54(12): 1751-1758, 2000 [11] Hanley QS et al., “Spectral Imaging in a Programmable Array Microscope by Hadamard Transform Fluorescence Spectroscopy”, Applied Spectroscopy 53(1): 1-10, 1999 Design Team Dr Anita Mahadevan-Jansen joined the faculty of the Biomedical Engineering Department in the fall of 1998 Her expertise is in the area of optical diagnosis of clinical physiology and pathology She has been working in the area of optical spectroscopy and imaging and specifically on the application of fluorescence and Raman spectroscopy for the diagnosis of cancers and precancers for the last eight years Dr Mahadevan-Jansen will be performing as research advisor and principal investigator on this project Dr Paul King, Associate Professor of Biomedical Engineering and Mechanical Engineering at Vanderbilt University, will serve as design instructor and assist in advising on this project Dr King's current work involves development of the design thrust of the VaNTH ERC in Biomedical Engineering Education His primary interests involve the undergraduate and masters of engineering design course and the application of computers to problems in medicine Steven Gebhart is a Ph.D graduate student in biomedical engineering at Vanderbilt University Three years of experience in biomedical optics research, specifically in spectroscopy and spectral imaging for brain tissue diagnosis, have given Steven the tools to advise the undergraduate students in their design and testing of the Hadamard Transform spectral imaging system Along with Anita Mahadevan-Jansen, Steve will serve to oversee and direct the development of the Hadamard transform imaging system as well as to bridge gaps between teams of undergraduate students who are ultimately involved with the project Paul Holcomb is a senior biomedical engineering student at Vanderbilt University Four years of management experience and previous group leadership positions have provided Paul with experience in budgeting, time management, and networking His previous research experience includes examination of the role of the EphA2 receptor in tumor angiogenesis with Dr Jin Chen at Vanderbilt University Medical Center (2003-present) Besides assisting with development of the design for the imaging system, Paul will be organizing the assembly timeline and acting as liaison between the team and advisory and support staff After graduating, Paul will be pursuing a PhD in neural engineering Tasha Nalywajko is a senior biomedical engineering and molecular biology double major at Vanderbilt University She has performed research for the past two years in intracellular engineering, focusing on microarrays and dynamic hybridization Most recently, her work includes dynamic virus attachment and detection Tasha’s skills include image acquisition and analysis, as well as knowledge of imaging equipment For this project, Tasha has contributed ideas and calculations for the optical design, and will assist with system assembly and data analysis She hopes to pursue a career in biotechnology Melissa Walden is a senior biomedical engineering student at Vanderbilt University She has experience working with computers, including webpage design and use of several programming languages She also has strong electrical engineering skills, especially dealing with bioelectrical components of nerves and stimuli in the body Melissa’s role in the project includes design and design calculations, implementation and assembly of the design, and maintaining technical contacts for the team web presence After graduation, she hopes to attend medical school and pursue rural and family practice medicine Timeline September October November December January February February March April May June July August Design X X X X Build (Single-Leg) Calibration/Testing Data Analysis Calibration/Testing X X X Data Analysis X X X Miniaturization Build (Dual-Leg) X X X X X X X X X X X X X X X X March and April will also be spent writing and preparing for presentation of our design and results at the Senior Design Day poster session on April 27, 2005 Equipment/Resources Needed Laboratory facilities have been provided by the Vanderbilt University Biomedical Engineering department, as have the digital micro-mirror device and CCD camera The components required for the single-leg portion of the build have been purchased using grant money provided by Dr Anita Mahadevan-Jansen Additional components for the dual-leg device and scaling down of the system have not been purchased Appendix Budget Expense Budgeted Cost Narrative Justification Equipment Optical components $2,000 Project development will require optical lenses and mirrors, lens and mirror mounts, dispersion gratings and mounts, etc for the imaging system design While most of these items have already been purchased for the first leg of the prototype benchtop system, additional components will be required for its successful completion, for the second leg of the prototype, and for the portable system which will ultimately be tested in the operating room Laptop computer $3,000 Prototype benchtop system testing can be completed using a current desktop workstation However, once the benchtop prototype is complete, the imaging system must be converted to a portable system for use in the clinical setting of the operating room This will require a laptop computer and docking station to control the digital micro-mirror device and excitation optics and and communicate with the CCD camera CCD Camera $9,000 The single-leg prototype benchtop system currently possesses a 512 x 512 pixel CCD camera for testing However, development of the full, two-leg system will require a camera with a 1024 x 512 pixel array While the listed cost will not cover the full cost of this item, it will help defray the expense Stipends Summer Research Student $3,000 In conjunction with the Vanderbilt School of Engineering Summer Internship program, this stipend will pay towards half of an undergraduate student (Paul Holcomb) to continue project development during Summer 2005 Conference Presentation $2,000 Travel and registration expenses to present project results at a major biomedical optics conference Technical Services Machining Costs $1,000 Once the benchtop prototype is complete, the imaging system must be converted to a portable system for use in the clinical setting of the operating room This will require the technical expertise of skilled machinists in the Vanderbilt Physics Machine Shop Total Requested Budget $20,000 Travel NAME POSITION TITLE Anita Mahadevan-Jansen Assistant Professor of Biomedical Engineering and Neurological Surgery EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION University of Bombay, Bombay, India University of Bombay, Bombay, India The University of Texas at Austin, Austin, TX The University of Texas at Austin, Austin, TX DEGREE (if applicable) YEAR(s) B.Sc M.Sc M.S Ph.D 1988 1990 1993 1996 FIELD OF STUDY Physics Physics Biomedical Engineering Biomedical Engineering RESEARCH AND PROFESSIONAL EXPERIENCE: April 2003 onwards Secondary Appointment, Assistant Professor, Department of Neurological Surgery, Vanderbilt University September 1998 onwards Assistant Professor, Department of Biomedical Engineering, Vanderbilt University, Nashville, TN Research Associate, Department of Biomedical Engineering, Vanderbilt University, Nashville, TN Postdoctoral Fellow, Biomedical Engineering Program, University of Texas at Austin, Austin, TX Research Assistant, Biomedical Engineering Program, University of Texas at Austin, Austin, TX July 1997 - August 98 May 1996 – December 1996 August 1990 – April 1996 Honors & Awards: Scholarships SPIE Continuing Education Scholarship, SPIE, Bellingham (August 1996) Nikon Precision Inc Scholarship (August 1996) University continuing fellowship, University of Texas, Austin (Sept 1994 - May 1995) Competitive academic fellowship, University of Texas, Austin (Sept 1990 - Aug 1991) University merit scholarship, University of Bombay, India (June 1988 - May 1990) National merit scholarship, Govt of India (June 1983 - May 1988) Best Basic Science Paper, Annual meeting American Society for Lasers Surgery & Medicine (ASLMS) (2004) Awards Distinction, Merit List of Physics Graduates, University of Bombay (1990) Merit List of Physics Graduates, University of Bombay (1988) Professional Affiliation American Society for Laser Medicine and Surgery (ASLMS) - fellow International Society for Optical Engineering (SPIE) - member Biomedical Optics Society (BiOS) - member and co-chair Optical Society of America (OSA) - member American Society for Engineering Education (ASEE) – member Society for Applied Spectroscopy (SAS) – fellow Society of Women Engineers (SWE) - member Professional Activities Reviewer - Journals – Journal of Biomedical Optics, Applied Optics, Applied Physics A, Photochemistry and Photobiology, Lasers in Medicine and Surgery, Optics Letters, Journal of Raman Spectroscopy, Applied Spectroscopy, Vibrational Spectroscopy, Applied Physics A, Optics Express, Biophysics Journal etc Proposals – ad-hoc member for NIH, NSF, Canadian Research Council, UK Cancer Research, Dutch Cancer Research amongst others Chair and Organizer - Biomedical Optics, In: 2nd Tennessee Biomedical Engineering Conference, Nashville, TN, 1999 Conference Chair Biomedical Spectroscopy and Other Novel Techniques, In: BiOS 2000, San Jose, CA, 2000 Program Committee - Biomedical Optical Spectroscopy and Diagnostics, Biomedical Topical Meetings 2000, Optical Society of America, Miami, FL, 2000 Program Committee - Biomedical Diagnostic, Guidance, and Surgical Assist Systems In: BiOS 2001, San Jose, CA, 2001 and In: BiOS 2003, San Jose, CA 2003, In: BiOS 2004, San Jose CA 2004 Program Committee Technical Program Committee for Medical and Biological Applications of CLEO/QELS Conference 2004, 2005 Conference Chair Biomedical Vibrational Spectroscopy, In: BiOS 2002, San Jose, CA, 2002 and In: BiOS 2004, San Jose, CA, 2004 Conference Chair Spectral Imaging In: BiOS 2005 Student Counselor - Society of Women Engineers, 1998 - current Secretary Vanderbilt Women's Faculty Organization, 1998-1999 Selected Publications: Peer Reviewed Journal Articles: 1) Wells JD, Kao C, Jansen ED, Konrad PE, Mahadevan-Jansen A, Physiologic validity and utility of optical stimulation for in vivo neural activation, Journal of Neuroscience Methods, (in preparation), 2004 2) Wells JD, Kao C, Jansen ED, Konrad PE, Mahadevan-Jansen A, Assessment of laser parameters for optical stimulation of peripheral nerves in vivo, Applied Optics, (in review), 2004 3) Wells JD, Kao C, Mariappan K, Albea J, Jansen ED, Konrad PE, Mahadevan-Jansen A, Optical stimulation of neural tissue in vivo, Optics Letters, (in press), 2004 4) Buttemere CR, Chari RS, Anderson CD, Mahadevan-Jansen A, Lin WC, “In vivo assessment of thermal damage in the liver using optical spectroscopy”, Journal of Biomedical Optics, (in press) 2004 5) Anderson CD, Lin WC, Buttemere CR, Mahadevan-Jansen A, Phillips DJ, Pierce J, Nicoud I, Chari RS, Realtime spectroscopic assessment of thermal damage: implications for radiofrequency ablation Journal of Gastrointestinal Surgery, (in press), 2004 6) Anderson CD, Lin WC, Buttemere CR, Mahadevan-Jansen A, Phillips DJ, Pierce J, Nicoud I, Chari RS, Fluorescence spectroscopy accurately detects irreversible cell damage during hepatic radiofrequency ablation Surgery, (in press), 2004 7) Lin WC, Buttermere C, Mahadevan-Jansen A, “Effect of thermal damage on the optical characteristics of liver tissues”, IEEE Journal of Selected Topics in Quantum Electronics, 9(2), p 162-170, 2003 8) Viehoever Robichaux, Anderson D, Jansen ED, Mahadevan-Jansen A, “Organotypic raft cultures as an effective in vitro tool for understanding Raman spectral analysis of tissue”, Photochemistry and Photobiology, 78(5), p 517-524, 2003 9) Lieber CA, Mahadevan-Jansen A, “Automated Method for Subtraction of Fluorescence from Biological Raman Spectra”, Applied Spectroscopy, 57(11), p 1363-1367, 2003 10) Lin WC, Toms SA, Jansen ED, Mahadevan-Jansen A, Elimination of blood contamination effect on optical spectroscopic guidance of surgeries, IEEE Journal of Selected Topics in Quantum Electronics 7(6), 2002 11) Utzinger U, Mahadevan-Jansen A, Hinzelman D, Follen M, Richards-Kortum R Near Infrared Raman Spectroscopy for In Vivo Detection of Cervical Precancers, Applied Spectroscopy, 55(8), 2001 12) Lin WC, Toms SA, Johnson M, Jansen ED, Mahadevan-Jansen A, In vivo brain tumor demarcation using optical spectroscopy, Photochemistry and Photobiology, 73(4), 396-402, 2001 13) Jansen ED, Mahadevan-Jansen A, Lin WC, Brophy SP, Mackanos MA, Development and implementation of an interactive instructional module for light distribution in tissue, 2001 ASEE Annual Conference Proceedings, 2000 14) Ramanujam N, Richards-Kortum R, Thomsen S, Mahadevan-Jansen A, Follen M, Chance B, Low temperature fluorescence imaging of freeze-trapped human cervical tissues, Optics Express, 8(6), 335-343, December 2000 15) Lin WC*, Toms SA, Motamedi M, Jansen ED, Mahadevan-Jansen A - Brain Tumor Demarcation using Optical Spectroscopy: An , Journal of Biomedical Optics, 5(2), April, 2000 16) Mahadevan-Jansen A, Mitchell MF, Richards-Kortum R Development of a Fiber Optic Probe to measure NIR Raman Spectra of Cervical Tissue in vivo, Photochemistry and Photobiology, 68(3), 427-431, 1998 17) Mahadevan-Jansen A, Mitchell MF, Ramanujam N, Malpica A, Thomsen S, Richards-Kortum R NearInfrared Raman Spectroscopy for the Diagnosis of Cervical Precancers Photochemistry and Photobiology, 68(1), 123-132, 1998 18) Ramanujam N, Mitchell MF, Mahadevan-Jansen A, Thomsen S, Staerkel G, Malpica A, Wright T, Atkinson A, Richards-Kortum R Cervical precancer detection using a multivariate statistical algorithm based on laserinduced fluorescence spectra at multiple excitation wavelengths, Photochemistry and Photobiology, 64(4), 720735, 1996 19) Ramanujam N, Mitchell MF, Mahadevan A, Thomsen S, Malpica A, Wright T, Atkinson A, Richards-Kortum R Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN) in vivo using laser-induced fluorescence spectra at multiple excitation wavelengths, Lasers in Surgery and Medicine, 19(1), 63-74, 1996 20) Ramanujam N, Mitchell MF, Mahadevan A, Thomsen S, Malpica A, Wright T, Atkinson A, Richards-Kortum R Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo, Lasers in Surgery and Medicine, 19(1), 46-62, 1996 21) Mahadevan-Jansen A, Richards-Kortum R Raman Spectroscopy for the Detection of Cancers and Precancers Journal of Biomedical Optics, 1(1), 40-79, 1996 Patents 1) Mahadevan-Jansen A, Konrad PE, Mariappan K, Optical stimulation of neural tissue, (provisional patent filed) 2) Lin WC, Mahadevan-Jansen A, Toms SA, Jansen ED, Brain tumor demarcation using optical spectroscopy (patent granted, issuance number pending) 3) Lin WC, Toms SA, Mahadevan-Jansen A, Phillips PJ, Johnson M, Weil RJ, Detection of radiation injury using optical spectroscopy, (Filed on 7/4/2003) 4) Lin WC, Mahadevan-Jansen A, Optical spectroscopic detection of cell and tissue death, (Provisional patent application filed on 9/30/2003) 5) Lin WC, Mahadevan-Jansen A, Konrad PE, Kao CC, Multi-modal 3-D targeting in deep brain stimulation, (Provisional patent application filed on 6/5/2002) Books and Book Chapters 1) Mahadevan-Jansen A, Raman Spectroscopy: from benchtop to bedside, Chapter 30: Biomedical Photonics Handbook, Editor: Vo-Dinh T, CRC Press, Boca Raton, FL, 2002 Biographical Sketch: Paul H King, Ph.D., P.E (i) Professional Preparation A list of the individual's undergraduate and graduate education and postdoctoral training as indicated below: Undergraduate Institution(s) Case Institute of Technology Major Engineering Degree & Year BS 1963 Science Graduate Institution(s) Case Institute of Technology Vanderbilt U Engineering Mechanical Engineering Postdoctoral Institution(s) ORAU Positron Emission Inclusive Dates (years) 1978Tomography 1979 Degree & Year MS 1965 Ph.D 1968 (ii) Appointments 1972-date Associate Professor of Biomedical and Mechanical Engineering 1987-2002 Associate Professor of Anesthesiology 1968-1972 Assistant Professor of Mechanical Engineering 1969-1972 Assistant Professor of Biomedical Engineering (iii) Publications King, Paul H, Kinser, D., Barnett, J, Dozier, A, Massengill, L “ Development of a Joint BME, ME, and EE/CE Senior Engineering Design Seminar”, presentation at June 2004 ASEE meeting, Salt Lake City, published in conference CD Walker, J M T., King, P H., “Concept Mapping as a Form of Student Assessment and Instruction in the Domain of Biomedical Engineering”, Journal of Engineering Education, Volume 19, No 2, pgs 167-179, April 2003 King, P.H., Fries, R.F., “Designing Biomedical Engineering Design Courses.” International Journal of Engineering Education, Volume 19, Issue 2, pgs 346-353, 2003 John Enderle, John Gassert, Susan Blanchard, Paul King, David Beasley, Paul Hale, and Dayne Aldridge, “The ABCs of Preparing for ABET: Accreditation Issues for Biomedical Engineering Programs Undergoing the “Engineering Criteria” Review Process”, IEEE EMBS Magazine July/August 2003, V22, #4, pgs 122-132 King, Paul H., and Fries, Richard C Design of Biomedical Devices and Systems, Marcel Dekker Press, New York, 2002 King, P.H., Pierce, D., Higgins, M., Beattie, C., Waitman, L C “A Proposed Method for the Measurement of Anesthetist Care Variability”, Journal of Clinical Monitoring and Computing, 16 (2): 121-125, 2000 King, P.H., “Freshman Biomedical Engineering Design Projects: What Can Be Done?” 2002 ASEE Conference and Exposition Proceedings, Montreal Canada, June 16-19 2002 Joan M.T Walker, Paul H King, & David S Cordray “The use of concept mapping as an alternative form of instruction in a capstone biomedical engineering design course”, 2003 ASEE Conference CD Proceedings Paul King, Stacy Klein, and Sean Brophy, “Orienting students to important features of ECG cycle and measurement”, 2003 ASEE Conference CD Proceedings Paul H King, Joan Walker, Sean Brophy, Jay Goldberg, Rich Fries, John Gassert, “Outcomes of a Biomedical Engineering Design Education Workshop”, 2003 ASEE Conference CD Proceedings King, P.H., Christiansen, W., “Teaching Safety Through Design In Biomedical Engineering Design” 2002 ASEE Conference and Exposition Proceedings, Montreal Canada, June 16-19 2002 (iv) Synergistic Activities Related activities include the continued development of a design (Biomedical and Biological Engineering) related web site (vubme.vuse.vanderbilt.edu/King/design_education.htm ) Other activities involve the polling of faculty and industry on components of the design process, and some recent work in the development of concept mapping tools for the teaching and evaluation of our design course We are in the process of developing a list of “best practices” in design, one of the results from this work has been the development of a design project scoring rubric, which closely mimics the ABET requirements A design education workshop was held in October 2003 in collaboration with Paul Yock of Stanford, with sponsorship by the NCIIA and the Whitaker Foundation We have modified our design sequence via the addition of a design seminar and through the addition of collaboration with a marketing class (v) Collaborators & Other Affiliations (a) Collaborators and Co-Editors: Sean Brophy, Vanderbilt Wayne Christianson, Christensen Consulting for Safety Excellence, LTD Jerry Collins, Vanderbilt David Cordray, Vanderbilt Rich Fries, Datex-Ohmeda John Gassert, Milwaukee School of Engineering Jay Goldberg, Marquette Stacy Klein, University School and Vanderbilt Jack Linehan, the Whitaker Foundation Joan Walker, Vanderbilt Phil Weilerstein, NCIIA Paul Yock, Stanford John Enderle, U Conn (b) Graduate and Postdoctoral Advisors James Reswick, address unknown, MS advisor William Roy Baker, PhD advisor, deceased (c) Thesis Advisor and Postgraduate-Scholar Sponsor Lemuel Russell Waitman, MS, May 1998, Vanderbilt Yuh-Show Tsai, Ph.D Dissertation, August 1998, faculty member at Chung Yuan University, Taiwan Neal W Sanders, Ph.D Dissertation, May 2000 Vanderbilt Lemuel Russell Waitman, Ph.D Dissertation, December 2001, faculty member at Vanderbilt U Michael Shane Jones, December 2002, Passport Health, Nashville TN Paul Clayton, December 2002, last with MicroNova Technology, Nashville Ross Fuller, M.E., May 2003, Michelle L Miller, M.S., August 2003, Geriatrix, Inc The total number of graduate students advised is: 36 as first reader, no postdoctoral scholars sponsored Steven C Gebhart CONTACT INFORMATION  5824 Stevenson Center Department of Biomedical Engineering Vanderbilt University Nashville, TN 37232 Office: (615) 343-4216 Cell: (770) 823-9311 Fax: (615) 343-7919 Email: steven.gebhart@vanderbilt.edu SUMMARY  Extensive experience in development and in vitro and in vivo testing of macroscopic spectral imaging systems for real-time brain tissue diagnosis Clinical experience acquiring single-point spectroscopy and spectral imaging data during neurosurgery Indepth knowledge of various spectral imaging modalities, including tunable-filter, Fourier transform, and Hadamard transform imaging Moderate experience with GUI development for system control and data analysis Familiarity with image-guided surgery systems and techniques and ultrasound imaging for flow quantification EDUCATION  Doctor of Philosophy in Engineering, (expected December 2005) Biomedical Engineering, Vanderbilt University, Nashville, Tennessee Research Advisor: Dr Anita Mahadevan-Jansen, Ph.D Master of Science in Engineering, December 2001 Biomedical Engineering, Vanderbilt University, Nashville, Tennessee Thesis title: "Dynamic, three-dimensional optical tracking of the Vanderbilt Free-Electron Laser" Research Advisor: Dr Robert L Galloway, Ph.D Bachelor of Science in Engineering, May 1999 Biomedical Engineering, Duke University, Durham, North Carolina Summa Cum Laude with Departmental Honors GPA: 3.9/4.0 TECHNICAL SKILLS  Extensive experience in MATLAB Familiar with: C/C++, LabView, UNIX, Windows NT/2000/XP, Fast Light Toolkit PROFESSIONAL EXPERIENCE  Vanderbilt University Nashville, TN Graduate research assistant Fall 2001 - Present Performing research work towards completion of Ph.D degree for design, construction, and clinical testing of a spectral imaging system optimized for real-time brain tumor demarcation Vanderbilt University Nashville, TN Teaching and research assistant Fall 1999 – Spring 2001 Taught senior laboratory and instrumentation laboratory courses while conducting research work towards completion of Master’s degree for optical tracking of an ablative laser beam during image-guided surgery Vanderbilt University Nashville, TN Research Assistant Summer 1999 Developed interactive Windows-based program to construct MRI and CT tomograms from individual DICOM images Duke University Durham, NC Research Assistant Spring 1998 – Spring 1999 Implemented ultrasound speckle tracking with four parallel-receive beams for multidimensional blood flow quantification using Matlab, as part of the Duke ERC Undergraduate Fellowship Program Duke University Durham, NC Research Assistant Summer 1997-Spring 1998 Design and trouble-shooting of circuitry driving high-amplitude, focused ultrasound for hyperthermic cancer therapy PUBLICATIONS  REFEREED JOURNALS: Bohs, L-N, B-J Geiman, M-E Anderson, S-C Gebhart, and G-E Trahey Speckle tracking for multi-dimensional flow estimation Ultrasonics, 38: 369-375, 2000 Bohs, L-N, S-C Gebhart, M-E Anderson, B-J Geiman, and G-E Trahey 2-D Motion Estimation Using Two Parallel Receive Beams IEEE Trans Ultrason Ferroelectr Freq Control, 48: 392-408, 2001 S-C Gebhart, E-D Jansen, R-L Galloway Three-dimensional optical tracking of an ablative laser beam Medical Physics (accepted September 2004) S-C Gebhart, A Mahadevan-Jansen, W-C Lin Experimental and Simulated Angular Profiles of Fluorescence and Diffuse Reflectance Emission from Turbid Media Applied Optics (in review) S-C Gebhart, W-C Lin, A Mahadevan-Jansen In Vitro Determination of Normal and Neoplastic Human Brain Tissue Optical Properties using Inverse Adding-Doubling TBA (to be submitted)  CONFERENCE PROCEEDINGS: Gebhart, S-C, R-L Galloway, E-D Jansen Optical Tracking of the Three-Dimensional Position of an Ablative Focused Laser Beam SPIE Proceedings of Photonics West 2003: Biomedical Optics, v 4958: p 225-234, 2003 Gebhart, S-C, W-C Lin, A Mahadevan-Jansen Characterization of a Spectral Imaging System SPIE Proceedings of Photonics West 2003: Biomedical Optics, v 4959: p 34-45, 2003 Gebhart S-C, R-L Galloway, E-D Jansen Dynamic, Three-Dimensional Optical Tracking of an Ablative Laser Beam SPIE Proceedings of Medical Imaging 2003, v 5029: p 292-302, 2003 Gebhart S-C, D-L Stokes, T Vo-Dinh, A Mahadevan-Jansen Instrumentation considerations in spectral imaging for tissue demarcation: comparing three methods of spectral resolution SPIE Proceedings of Photonics West 2005, (accepted November 2004), 2005  ABSTRACTS: Harris, S-S, S-C Gebhart, E Donnelly, R-L Galloway Towards Image-Guided Gene Therapy Delivery Accepted at IEEE EMBS/BMES Conference, Houston, TX, October 2002 HONORS & ACTIVITIES  • Edwin L Jones Memorial Scholar (Duke), 1996-1999 • Tau Beta Pi (Duke), initiated 1998 • Phi Beta Kappa (Duke), initiated 1998 • Dean's list (Duke), 1995-1999 • NSF/ERC Undergraduate Fellow (Duke), 1998-1999 • Collowick Honor Fellow (Vanderbilt) • Harold Sterling Vanderbilt Honor Fellow (Vanderbilt) • New Student Orientation Committee (Vanderbilt), 1999-2001 • TA of the Year for Department of Biomedical Engineering (Vanderbilt), 2000-2001 • Biomedical Engineering Graduate Development Committee (Vanderbilt), 2002-2003 • Biomedical Engineering Graduate Student Council (Vanderbilt), 2002-2003 REFERENCES  Available upon request Last updated on December 3, 2004 PA U L S H O L C O M B 2014 Linden Ave Apt Nashville, TN 37212 (615) 364-9392 (cell) transcendent@yahoo.com OBJECTIVE To gain greater understanding of biomedical engineering principles and practice by attending graduate school, with the intent of starting my own company in the field of neural engineering within 10 years EXPERIENCE 2003-Present Dr Jin Chen, Vanderbilt Medical Center Nashville, TN Research Assistant  Use yeast two-hybrid system to screen for EphA2-interacting proteins  Clone plasmids for use in experimentation  Maintain lab stock solutions, ordering, and website 2002-2003 Toys ‘R Us Charleston, WV World Leader, ‘R Zone Electronics Department  Managed sales floor and ‘R Zone employees  Implemented company-wide marketing and promotions  Maintained daily task lists and high level of customer service 1998–2001 Gamestop, Inc Charleston, WV Senior Sales Associate 2) Managed store accounts, sales floor, and marketing  Created marketing and promotional ideas to boost sales  Created schedules and daily task lists for associates EDUCATION 2001-Present Vanderbilt University Nashville, TN 3) BE in Biomedical Engineering expected May, 2005 4) Current GPA: 3.195 1999-2000 West Virginia University Morgantown, WV  Majored in Mechanical Engineering  Presidential Award for Academic Excellence  Inducted into the National Society for Collegiate Scholars  GPA: 3.80 SKILLS  Excellent leadership and team management skills  Keen attention to detail  Well-versed in customer relations and marketing  Experienced with many lab techniques, such as PCR, Western Blotting, DNA extraction and transformation, cloning  Extensive PC computer knowledge, both hardware and software, and can learn new software very quickly  Knowledgeable in several programming languages: HTML, C, PHP, Matlab  Member, National Society of Collegiate Scholors  Deans List with Honors: Fall 2002, Fall 2003 (Vanderbilt) 1999, Spring 2000 (West Virginia University)  Deans List with High Honors: Spring 2004 (Vanderbilt) AWARDS & HONORS Fall REFERENCES Dr Jin Chen Assistant Professor of Medicine, Cancer Biology, and Cell & Developmental Biology, Vanderbilt Ingrim Cance Center Dr Adam Anderson Associate Professor, Biomedical Engineering ,Vanderbilt University Dr Franz Baudenbacher Assistant Professor, Biomedical Engineering and Physics, Vanderbilt University A4323 MCN 1161 21st Ave S Nashville, TN 37232 (615) 343-3820 jin.chen@vanderbilt.edu 5824 Stevenson Center Vanderbilt University Nashville, TN 37232 (615) 322-8353 adam.anderson@vanderbilt.edu 5824 Stevenson Center Vanderbilt University Nashville, TN 37232 (615) 322-6361 f.baudenbacher@vanderbilt.edu V A N D E R B I LT P L A C E B O X B • N A S H V I L L E , T N PHONE (615) 364-6398 • E-MAIL T A S H A N A LY W A J K O @ V A N D E R B I LT E D U T A S H A N A LY W A J K O EDUCATION Vanderbilt University, Nashville, TN Bachelor of Engineering, Biomedical Engineering, May 2005 Molecular Biology, May 2005 5) GPA 3.265/4.0, Deans List Fall 2000 – Spring 2002 SELECTED COURSES Biomechanics, Biomedical Instrumentation, Circuit Analysis, Biological Transport Phenomena, Thermodynamics, Genetics I/II, Cell Biology, Biochemistry I/II, Biomedical Engineering Lab, Biomedical Optics RESEARCH PROJECT Capillary Design in Spot Variation in Microarrays, Dr Rick Haselton, Biomedical Engineering Worked with Dr Haselton in device design; Constructed various capillary printing pins; Tested pins and determined performance based on analyzed data; Presented data to BME faculty (Fall 2003) L AB EXPERIENCE Research Internships in Science & Engineering – University of Maryland, College Park, MD Undergraduate Research Scholar, Summer 2004 • Worked in group setting with three undergraduate scholars • Prepared semi-conductors for treatment with DNA • Performed radiation tests with a nuclear reactor, X-ray diffraction, and X-ray spectroscopy Presented at symposium (Aug 6, 2004) • Intracellular Engineering Laboratory – Vanderbilt University, Nashville, TN Undergraduate Lab Assistant, Summer 2002 – Spring 2003 • Constructed labeled DNA probe fragments using PCR techniques • Quantified labeled DNA for microarray testing • Created hybridization arrays on glass and silicon slides • Performed static hybridizations • Scanned & analyzed data from hybridizations EXTRACURRICUL AR ACTIVITIES Biomedical Engineering Society, Member 2000 – 2003 Alpha Phi Omega, Member 2002 – present; Fellowship Chair 2004 COMPUTER SKILLS Microsoft Office (Word, Excel, PowerPoint), HTML/Web design, some MATLAB T HE S IS C IRC L E A P T A RA L E I G H , N C 7 MELISSA 828-699-1708 M E L I S S A A W A L D E N @ V A N D E R B I LT E D U WALDEN OBJECTIVE PREVIOUS EMPLOYMENT To obtain a position in the medical field to further my experiences and prepare me for medical school Summer 2003 Asheville, NC Continental Teves 6) Assembly line worker 2003 Tutor TGI-Friday’s Staffing Service North Carolina State University Raleigh, NC 7) Organic Chemistry tutor 8) General Chemistry tutor EDUCATION HOSPITAL VOLUNTEERING CLUBS AND ACTIVITIES 1997-2001 North Henderson High SchoolHendersonville, NC 9) Graduated Valedictorian Summer 2000 Duke University Durham, NC 10) Summer school through Pre-college program 2001-2003 North Carolina State University Raleigh, NC 11) Worked toward undergraduate degree in Biomedical Engineering 2003-present Vanderbilt University Nashville, TN 12) Rising senior working toward Bachelor’s of Engineering in Biomedical Engineering, with a pre-medical tract 2003 - Worked with the new Vanderbilt Children’s Hospital Setting up and testing new equipment Circle K International Active member and Lt Gov West for the Kentucky-Tennessee district for the 2004-2005 academic year BMES - Biomedical Engineers Society Active member SWE – Society of Women Engineers Active member and Engineering Council Representative for the 2004-2005 academic year Skull & Bones, Pre-health society Active member VSVS – Vanderbilt Students Volunteer for Science Active member and team leader for the 2004-2005 academic year V-SMAC - Vanderbilt Students Meeting for the Awareness of Cancer Active Member  ... Surgery, Vanderbilt University September 1998 onwards Assistant Professor, Department of Biomedical Engineering, Vanderbilt University, Nashville, TN Research Associate, Department of Biomedical Engineering, ... Professor of Biomedical and Mechanical Engineering 1987-2002 Associate Professor of Anesthesiology 1968-1972 Assistant Professor of Mechanical Engineering 1969-1972 Assistant Professor of Biomedical. .. Fellow (Vanderbilt) • Harold Sterling Vanderbilt Honor Fellow (Vanderbilt) • New Student Orientation Committee (Vanderbilt) , 1999-2001 • TA of the Year for Department of Biomedical Engineering (Vanderbilt) ,