Vanderbilt University

Department of

Biomedical Engineering

NCIIA Grant Proposal:

Hadamard Transform Imaging

04 November 2004

Team Members:Paul Holcomb

Tasha NalywajkoMelissa Walden

Project DescriptionBrain 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 with the previous imaging techniques can be resolved. The implementation of this technique is made possible by the use of a digital micro-mirror device, which consists of an array (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

Figure 1: Schematic of a Hadamard Spectral Imaging System. (DMD – Digital Micromirror Device). With this

design, the y-dimension of the spectral image is encoded in successive CCD images. The removable mirrors allow rapid

switching between spectral and real-time spatial imaging.

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.8 After application of the Hadamard transform, the two reflected images (0º and 12º, or 1 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.9 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. 1 & 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

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.

  Design Build (Single-Leg) Calibration/Testing Data AnalysisSeptember X      October X      November X X    December X X X XJanuary   X X XFebruary     X X  Build (Dual-Leg) Calibration/Testing Data Analysis MiniaturizationFebruary X      March X X X  April X X X  May   X X XJune       XJuly       XAugust       X

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.

Travel    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  

NAME

Anita Mahadevan-JansenPOSITION TITLE

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 DEGREE(if applicable) YEAR(s) FIELD OF STUDY

University of Bombay, Bombay, IndiaUniversity of Bombay, Bombay, IndiaThe University of Texas at Austin, Austin, TXThe University of Texas at Austin, Austin, TX

B.Sc.M.Sc.M.S.Ph.D.

1988199019931996

PhysicsPhysicsBiomedical EngineeringBiomedical 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.

July 1997 - August 98 Research Associate, Department of Biomedical Engineering, Vanderbilt University, Nashville, TN.

May 1996 – December 1996 Postdoctoral Fellow, Biomedical Engineering Program, University of Texas at Austin, Austin, TX.

August 1990 – April 1996 Research Assistant, Biomedical Engineering Program, University of Texas at Austin, Austin, TX.

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 AffiliationAmerican Society for Laser Medicine and Surgery (ASLMS) - fellowInternational Society for Optical Engineering (SPIE) - memberBiomedical Optics Society (BiOS) - member and co-chairOptical Society of America (OSA) - memberAmerican Society for Engineering Education (ASEE) – memberSociety for Applied Spectroscopy (SAS) – fellowSociety of Women Engineers (SWE) - member

Professional ActivitiesReviewer - 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 2005Student Counselor - Society of Women Engineers, 1998 - currentSecretary - 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, Real-time 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. Near- Infrared 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 laser-induced fluorescence spectra at multiple excitation wavelengths, Photochemistry and Photobiology, 64(4), 720-735, 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.

Patents1) 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 Chapters1) 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 Science

Degree & Year BS 1963

Graduate Institution(s) Case Institute of Technology Vanderbilt U.

EngineeringMechanical Engineering

Degree & Year MS 1965Ph.D. 1968

Postdoctoral Institution(s) ORAU Positron Emission Tomography

Inclusive Dates (years) 1978-1979

(ii) Appointments

1972-date Associate Professor of Biomedical and Mechanical Engineering1987-2002 Associate Professor of Anesthesiology1968-1972 Assistant Professor of Mechanical Engineering1969-1972 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 CenterDepartment of Biomedical EngineeringVanderbilt UniversityNashville, TN 37232

Office: (615) 343-4216Cell: (770) 823-9311Fax: (615) 343-7919Email: 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. In-depth 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, TennesseeResearch Advisor: Dr. Anita Mahadevan-Jansen, Ph.D.

Master of Science in Engineering, December 2001Biomedical Engineering, Vanderbilt University, Nashville, TennesseeThesis 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 1999Biomedical Engineering, Duke University, Durham, North CarolinaSumma Cum Laude with Departmental HonorsGPA: 3.9/4.0

TECHNICAL SKILLS

Extensive experience in MATLABFamiliar with: C/C++, LabView, UNIX, Windows NT/2000/XP, Fast Light Toolkit

PROFESSIONAL EXPERIENCE

Vanderbilt University Nashville, TNGraduate research assistant Fall 2001 - PresentPerforming 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, TNTeaching and research assistant Fall 1999 – Spring 2001Taught 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, TNResearch Assistant Summer 1999Developed interactive Windows-based program to construct MRI and CT tomograms from individual DICOM images.

Duke University Durham, NCResearch Assistant Spring 1998 – Spring 1999Implemented ultrasound speckle tracking with four parallel-receive beams for multi-dimensional blood flow quantification using Matlab, as part of the Duke ERC Undergraduate Fellowship Program.

Duke University Durham, NCResearch Assistant Summer 1997-Spring 1998Design 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.

P A U L S . H O L C O M B2014 Linden Ave. Apt. 5

Nashville, TN 37212 (615) 364-9392 (cell)

transcendent@yahoo.com

OBJECTIVETo 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.

EXPERIENCE2003-Present Dr. Jin Chen, Vanderbilt Medical Center

Nashville, TNResearch Assistant Use yeast two-hybrid system to screen for EphA2-

interacting proteins Clone plasmids for use in experimentation Maintain lab stock solutions, ordering, and website2002-2003 Toys ‘R Us Charleston, WVWorld 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

service1998–2001 Gamestop, Inc. Charleston, WVSenior Sales Associate2) Managed store accounts, sales floor, and marketing Created marketing and promotional ideas to boost sales Created schedules and daily task lists for associates

EDUCATION2001-Present Vanderbilt University

Nashville, TN3) BE in Biomedical Engineering expected May, 20054) 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

AWARDS & HONORS Member, National Society of Collegiate Scholors

Deans List with Honors: Fall 2002, Fall 2003 (Vanderbilt) Fall 1999, Spring 2000 (West Virginia University)

Deans List with High Honors: Spring 2004 (Vanderbilt)

REFERENCES

Dr. Jin ChenAssistant Professor of Medicine, Cancer Biology, and Cell & Developmental Biology, Vanderbilt Ingrim Cance Center

A4323 MCN1161 21st Ave. S.

Nashville, TN 37232(615) 343-3820

jin.chen@vanderbilt.edu

Dr. Adam AndersonAssociate Professor, Biomedical Engineering ,Vanderbilt University

5824 Stevenson CenterVanderbilt University

Nashville, TN 37232(615) 322-8353

adam.anderson@vanderbilt.edu

Dr. Franz BaudenbacherAssistant Professor, Biomedical Engineering and Physics, Vanderbilt University

5824 Stevenson CenterVanderbilt University

Nashville, TN 37232(615) 322-6361

f.baudenbacher@vanderbilt.edu

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T A S H A . N A L Y W A J K O @ V A N D E R B I L T . E D U

T A S H A N A L Y W A J K O

EDUCATION

Vanderbilt University, Nashville, TNBachelor of Engineering, Biomedical Engineering, May 2005Molecular Biology, May 20055) GPA 3.265/4.0, Deans List Fall 2000 – Spring 2002

SELECTED COURSESBiomechanics, Biomedical Instrumentation, Circuit Analysis, Biological Transport Phenomena, Thermodynamics, Genetics I/II, Cell Biology, Biochemistry I/II, Biomedical Engineering Lab, Biomedical Optics

RESEARCH PROJECTCapillary 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)

LAB EXPERIENCEResearch Internships in Science & Engineering – University of Maryland, College Park, MDUndergraduate 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, TNUndergraduate 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

EXTRACURRICULAR ACTIVITIESBiomedical Engineering Society, Member 2000 – 2003Alpha Phi Omega, Member 2002 – present; Fellowship Chair 2004

COMPUTER SKILLSMicrosoft Office (Word, Excel, PowerPoint), HTML/Web design, some MATLAB

MELISSA WALDEN

OBJECTIVE To obtain a position in the medical field to further my experiences and prepare me for medical school.

PREVIOUS EMPLOYMENT

Summer 2003 TGI-Friday’s Staffing ServiceAsheville, NC

Continental Teves6) Assembly line worker.

2003 North Carolina State University Raleigh, NCTutor

7) Organic Chemistry tutor.8) General Chemistry tutor.

EDUCATION 1997-2001 North Henderson High SchoolHendersonville, NC

9) Graduated Valedictorian.Summer 2000 Duke University

Durham, NC10) Summer school through Pre-college program.

2001-2003 North Carolina State University Raleigh, NC11) Worked toward undergraduate degree in

Biomedical Engineering.2003-present Vanderbilt University

Nashville, TN12) Rising senior working toward Bachelor’s of

Engineering in Biomedical Engineering, with a pre-medical tract.

HOSPITAL VOLUNTEERING

2003 - Worked with the new Vanderbilt Children’s Hospital. Setting up and testing new equipment.

CLUBS AND ACTIVITIES

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.

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