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Wednesday, January 21, 2004

Intelligent Agents for Diagnosis of Dementia

Maurice Cohen, Ph.D.
Donna Hudson, Ph.D.

Signal analysis data, especially electrocardiogram (ECG) and electroencephalogram (EEG) data, provide important information for clinical decision-making. In order to arrive at a diagnosis, it is often necessary to combine these results with other clinical parameters. A promising approach utilizes intelligent agents, a procedure that involves the development of a central mechanism that provides communications among differing methodologies and different information types to produce a comprehensive solution to the problem. Specific agent methodologies include knowledge-based approaches, neural networks, and chaotic modeling of nonlinear dynamical systems. The combined system has been shown to provide accurate diagnosis of cardiac disorders in a series of studies done over the last five years. In addition to the diagnostic results, the model supplies a list of weighted parameters relevant to the decision. Each of these three components of the model is based on new theoretical developments. These methodologies will be illustrated in a decision model for diagnosis of dementia, emphasizing new approaches for pre-processing and determination of summary measures for EEG data.

Dr. Maurice Cohen is Professor of Radiology at UCSF, and a faculty member in both the Graduate Group in Biological and Medical Informatics and the Joint Graduate Group in Bioengineering, UCSF and UC Berkeley and is also Professor of Mathematics at California State University. Dr. Cohen has a Ph.D. in applied mathematics and theoretical physics. For the past two decades he has been applying these methods to applications in biomedicine, including expert systems, neural network modeling and chaos theory, and has over 200 publications in this area. Dr. Cohen is a Fellow of the American Institute for Medical and Biological Engineering and the recipient of a number of research awards. He is also an internationally recognized and award-winning artist and exhibits his painting in Paris as well as California.

Dr. Donna Hudson is Professor of Family and Community Medicine at UCSF and a faculty member in both the Graduate Group in Biological and Medical Informatics and the Joint Graduate Group in Bioengineering, UCSF and UC Berkeley. Dr. Hudson has a Ph.D. in Computer Science from UCLA and has over 200 publications in the areas of computer decision support, artificial intelligence applied to medicine, neural network modeling, and analysis of biomedical signals. Dr. Hudson is Past-President of the International Society for Computers and Their Applications, Vice President for Financial Affairs for the IEEE Engineering in Medicine and Biology Society, Fellow of the American Institute for Medical and Biological Engineering, and Fellow of the IEEE.

Wednesday, February 18, 2003

Cell-Based Biosensor Systems for Toxin Detection and Drug Discovery

Gregory T. A. Kovacs, M.D., Ph.D.
Associate Professor of Electrical Engineering and, by courtesy, Medicine

Update: Substitute Speaker: Lauren Giovangrandi, Ph.D.

For many years, researchers have been able to grow living cells on integrated circuit substrates, and their qualitative responses to pharmaceutical agents have long been demonstrated. However, little work has been done to use this technology in realistic, repeatable, and quantitative instruments. Complete sensor systems can now be built that include full microenvironments for the cells and are field portable. These instruments include the sensor-containing substrates on which cells are grown, sensors for closed-loop microincubator control, dual cell chambers (for control and test samples), and all of the necessary fluidic interfaces. Cultured cells can be transported into the field and maintained in a sterile environment essentially identical to that found in a conventional incubator. These technologies can be applied not only to the detection of chemical and biological warfare agents, but also to the discovery of new pharmaceuticals. This presentation will cover advances in the areas of cellular/electronic interfaces, engineered cells, signal interpretation algorithms, and system integration leading to the development and field testing of a self-contained, hand-held cell-based biosensor.

Doctor Kovacs is an Associate Professor of Electrical Engineering at Stanford University with a courtesy appointment in the Department of Medicine. His present research areas include biomedical instruments and sensors, miniaturized spaceflight hardware, and biotechnology. In addition, Dr. Kovacs is the Director of Medical Device Technologies for the Astrobionics Program at the NASA Ames Research Center, and for the Stanford-NASA National Biocomputation Center. He helps direct a variety of projects spanning wearable physiologic monitors, biosensor instruments for detection of chemical and biological warfare agents and space biology applications, and free-flyer experiment payloads. He is involved in hands-on field testing of NASA wearable monitors in high altitude conditions. He is currently serving as the Investigation Scientist for the debris team of the Columbia Accident Investigation Board, having worked for the first four months after the accident at the Kennedy Space Center, Florida.

He has published extensively in technical literature, including authorship of a popular engineering textbook. He is a long-standing member of the Defense Sciences Research Council (DARPA), and has served as Associate Chair and Chairman. He also has extensive industry experience including co-founding several companies, most recently Cepheid in Sunnyvale, CA. He received an NSF Young Investigator Award, held the Noyce Family Chair, and was a Terman and then University Fellow at Stanford. He is a Fellow of the American Institute for Medical and Biological Engineering. Dr. Kovacs is a private pilot, scuba diver, and a Fellow National of the Explorers Club. Dr. Kovacs received a BASc degree in Electrical Engineering from the University of British Columbia, an MS degree in Bioengineering from the University of California, Berkeley, and a PhD and an MD degree from Stanford University.

Lauren Giovangrandi will stand in for Greg Kovacs due to a schedule conflict. Doctor Giovangrandi is in his third year of postdoctoral work in Greg Kovacs' lab, extending his Ph.D. studies of cell-based biosensors, mainly using electrogenic cells on microelectrode arrays, and development of associated device technology, signal processing, and system design.

Wednesday, March 17, 2004

The Evolution of the Intraocular Lens
Reza Zadno

The primary cause of blindness in the developed world is cataracts. In 2002 there were more than 6 million cataract procedures performed worldwide. This number includes over 3 million surgeries in the United States.

Incredible technological leaps have been made, in both material development and lens design, in the 50 years since the first IOL was implanted. Technology improvements which had been centered on returning functional vision to elderly patients, will now provide both elderly and middle aged patients, the ability to conduct their day to day lives without the aid of glasses or contacts.

The inability to read at near distance due to aging is known as Presybopia. Patients who have experienced excellent vision, during their early life, are forced to begin wearing glasses. As with all other segments of this aging generation, the "Baby Boomers" will demand the highest quality of life. Patients seeking surgical treatments to regain both near and distance vision will rise dramatically during the next ten to twenty years.

The agenda of the meeting is to briefly review the evolution of the intraocular lens. We will discuss changes and improvements in materials, and present new technologies such as multi-focal IOL's, adjustable IOL's and accommodating IOL's. These changes will gradually transform the cataract procedure into a refractive procedure as well as dramatically expand this segment of the vision market.

Reza Zadno was most recently at Three Arch Partners, working as entrepreneur in residence. Prior to joining Three Arch, he was with PercuSurge, Inc. which he co-founded in 1995, and where he served as VP of R&D and CTO until August 2000. PercuSurge developed, manufactured and marketed systems to contain and remove dislodged emboli during percutaneous vascular interventions, and was acquired by Medtronic in 2000.

Prior to PercuSurge, Reza was with Cardiac Pathways Corp. from the company's very early development stage until 1995, and served as the Director of Advanced Development Group. Cardiac Pathways developed, manufactured and marketed mapping and ablation systems for treatment of arrhythmia (IPO in 1996 and acquired by Boston Scientific in 2001).

From 1984-1992 Reza was with Raychem Corp. and worked in France, Belgium and USA as R&D Engineer and Project Manager. At Raychem, he developed Nitinol alloys and products in applications such as laparoscopy instruments, guide wire materials, dental arches, and industrial products including electrical connectors.

Reza holds MSc and PhD in Metallurgy from Ecole Nationale Superieure des Mines de Paris and has filed more than 100 US and international patent applications.

Wednesday, April 21, 2004

Recent advances in non-invasive MR imaging of the coronary arteries

Phillip Yang, MD
Clinical Instructor and Staff Physician
Division of Cardiovascular Medicine
Stanford University School of Medicine

This talk will review the current state-of-the-art of MR coronary angiography. Challenges inherent in MR coronary angiography include optimal spatial and temporal resolution, accurate motion compensation, wide anatomical coverage, and high signal and contrast to noise ratios. Fundamental problems with coronary angiography are small artery size (<4mm), tortuosity, competing MR signals from adjacent epicardial fat and myocardium, and the constant dysynchrony between cardiac and respiratory motions.

Significant technical developments have occurred in recent years in order to address these problems. Both two- and three-dimensional image acquisitions have become possible. Acquisition strategies have evolved from rectilinear segmented k-space to more complex echo planar and spiral imaging. Motion compensation has evolved from simple breath-hold to more complex navigator-based techniques. Other strategies to enhance contrast, signal, and imaging speed have also been developed to implement MR coronary angiography as a routine clinical test.

Phillip Yang received B.A.S. and M.A. degrees in biology and East Asian studies from Stanford University in 1984, and an MD degree from Yale University School of Medicine in 1989. He subsequently completed residency in internal medicine in 1993 at UCLA Hospital and fellowship in cardiovascular medicine in 1999 at Stanford University Hospital. In 1999 he joined the Division of Cardiovascular Medicine at Stanford University, where he is now a clinical instructor and staff physician. His research and clinical interests are in cardiovascular imaging using MRI and ultrasound. His research has focused on new technologies in cardiovascular and in vivo molecular and cellular imaging using MRI.

Downloads (PDF) associated with this subject matter:
American College of Cardiology reprint
New England Journal of Medicine reprint

Wednesday, May 19, 2004

Optical Biopsy in Gastroenterology

Professor Jacques Van Dam and Professor George Springer
Stanford University

After outlining the indications for small bowel imaging, this talk will review the limitations of standard endoscopic and radiographic techniques, and provide an overview of the GIVEN endoscopy technology including recent data on its clinical utility.

The GIVEN capsule is a swallowable, disposable camera system for endoscopic use. The objective is to develop a wireless gastric endocapsule for making clinical diagnoses without the need of an invasive endoscope. The capsule, about the size of a large vitamin pill, is swallowed by the patient. Via telemetry, stereoscopic (three dimensional) images of the stomach lining are transmitted to a screen. Visual inspection of the images of the gastric mucosa enables the operator to detect ulcers, bleeding, or tumors.

The endocapsule is moved to the required location by microthrusters, controlled remotely by the physician.

The current objective of this project is to design and construct a 5:1 scale working prototype of the gastric endocapsule. This prototype will enable the research team to work with the various components, all of which will ultimately be reduced to the size necessary to be swallowed by the patient.

Dr. Jacques Van Dam is Professor of Medicine at Stanford University School of Medicine and Clinical Chief of the Division of Gastroenterology and Hepatology at Stanford University Medical Center. He received his M.D. and Ph.D. degrees from Georgetown University School of Medicine and completed his postgraduate medical training at Harvard Medical School, where he remained on the faculty for more than ten years. Dr. Van Dam is an NIH-funded investigator and is the author of more than 300 scientific papers, reviews and abstracts.

Dr. Van Dam's graduate students at Stanford who contribute to this project include Eric Allison, a Ph.D. candidate at the Department of Aeronautics and Astronautics, and Zsolt Kiraly, a Ph.D. candidate at the Department of Aeronautics and Astronautics.

Dr. George S. Springer earned his BE in Mechanical Engineering from the University of Sydney in 1959, and completed his graduate work at Yale University where he earned a MEng in 1960, an MS in 1961, and a PhD in 1962, all in Mechanical Engineering. He was on the faculties of the Massachusetts Institute of Technology and the University of Michigan before becoming a professor of Aeronautics and Astronautics at Stanford University in 1983. He served as chairman of that department from 1990 to 2001, and was appointed Paul Pigott Professor of Engineering in 1994.

Dr. Springer is a fellow of the American Society of Mechanical Engineers (ASME), the American Institute of Aeronautics and Astronautics (AIAA),and the Society for the Advancement of Materials and Process Engineering, as well as a member of the Society of Automotive Engineers, and the American Physical Society. He has authored thirteen books and over two hundred technical papers, and is the owner of two U.S. Patents. He was elected to the National Academy of Engineering (NAE) in 1994, when he also received the ASME's Worcester Reed Warner Medal, and was honored with the AIAA Engineer of the Year Award in 1995. Also in 1995 he was made a Foreign Member of the Hungarian Academy of Science. In 1999 he received the Medal of Excellence in Composite Materials from the University of Delaware Center for Composite Materials. In 2000 he was the recipient of the AIAA Structures, Structural Dynamics and Materials Award.

Dr. Springer's current research focuses on biomedical devices, including hip replacements, aortic stems, and wireless gastric endocapsules.

Wednesday, June 16, 2004

The Artificial Synapse Chip: Towards an Electronic Prosthetic Retina

Harvey A. Fishman, M.D., Ph.D.
Senior Research Scientist
Director of Ophthalmic Tissue Engineering
Department of Ophthalmology
Stanford University School of Medicine

Age-related macular degeneration (AMD) is the most common form of severe and irreversible blindness in the U.S. Our research program consists of a highly interdisciplinary effort between physicians, engineers, and scientists to develop a neural interface that will connect the output from a digital camera to individual retinal cells in patients with AMD, thus bypassing injured cells.

Present prosthetic devices stimulate neurons electrically with limited spatial control and without cell type specificity. Our purpose is to explore whether neuronal growth from a specific retinal cell layer can be directed onto a chip where focal neurotransmitter or electrical stimulation would provide a more physiologic and neuron-specific transfer of information. To accomplish this, we are adapting BioMEMs technology to construct an artificial nerve connection that will be fashioned from flexible biomaterials and upon which the microcircuitry of retinal cells will be re-grown.

Specifically, neurites from retinal cells can be directed to the surface of a flexible, polymeric chip where micropatterns of growth factors cause the cells to grow toward focal stimulation sites. Cells and their neurites can be directed to grow to either (1) apertures that are connected to a microfluidics system that pulse neurotransmitters or (2) microelectrodes made from carbon nanotubes. Transmitter and electrical stimulation are shown to cause a calcium increase along the neurite and in the cell soma, indicating transmission of signal to the cell soma.

The ability to direct the growth of retinal-cell neurites and to stimulate them with a microfluidic neurotransmitter delivery system demonstrates the feasibility of a visual prosthesis interface based on direct neuronal stimulation with physiologically appropriate neurotransmitters. This neural interface represents a new paradigm in the field of electronic prosthetic retinas that are being developed worldwide. In addition to advancing the treatment of AMD, this method will have wide-reaching applications in spinal cord injuries and in the field of tissue engineering. These bioengineering technologies will help bring basic science discoveries into clinical realities and bridge the gap from bench to bedside.

Harvey A. Fishman, M.D., Ph.D., Director of Ophthalmic Tissue Engineering and Retinal Prosthesis Laboratory, Department of Ophthalmology, Stanford University School of Medicine. Dr. Fishman received his Baccalaureate degree in Chemistry. He then earned a Ph.D. in Chemistry with an emphasis in Neuroscience from Stanford University working under the guidance of Professors Richard N. Zare and Richard H. Scheller. He then earned an M.D. degree from Stanford University. He completed a medical internship at St. Mary's Hospital in San Francisco and is currently a licensed Physician in the State of California. Dr. Fishman then returned to Stanford where he now holds dual positions as both the Director of Ophthalmic Tissue Engineering and Chief Ophthalmology Resident (July 2004) in the department of Ophthalmology.

Dr. Fishman's area of expertise is translational research that uses a multidisciplinary approach to develop novel therapies for blinding diseases in the eye--in particular, Age-Related Macular Degeneration. His research bridges the gaps between tissue engineering, surface science, nanofabrication, chemistry, neuroscience and retinal transplantation biology in Ophthalmology. His background in new technologies and medical science is diverse including bioMEMS, chip-based microfluidics and confocal and time-lapse microscopy, neuroscience/nerve cell regeneration and macular diseases in Ophthalmology. He has made contributions in the fields of microfluidics, laser-induced fluorescence detection, separation science, and biosensors.

Wednesday, September 15, 2004

Presentation and Tour of Boston Scientific Corporation in Fremont
by Douglas Petty, Director of Strategic Marketing for the Imaging Group

Location: Boston Scientific in Fremont. The address is 47900 Bayside Parkway, Building 4.

Time: 6:00-7:30 pm

6:00 pm Talk on Boston Scientific Corporation by Mr. Douglas Petty (overview and biography below)
6:30 pm Career opportunities at BSC (speaker from Human Resources)
6:40 pm Tour of BSC facility - Highlights include viewing of the clean room (from outside the window) and walk through the instrument production floor.
7:10 pm. Refreshments at Building 4
7:30 pm Wrap-Up and Discussion

Mr. Petty will provide an overview of the Bay Area Boston Scientific business franchises and their respective markets, which include Interventional Cardiology, Interventional Neuroradiology & Neurosurgery and Electrophysiology.

Mr. Petty is the Director of Strategic Marketing for the Imaging Group at Boston Scientific based in Fremont, CA. The Strategic Marketing Group evaluates the clinical needs in new and emerging markets and evaluates business opportunities. He has worked in the Medical Device Industry for more than 20 years in both large and small companies. Mr. Petty is a Graduate of the University of Illinois School of Business Administration.

Wednesday, October 20, 2004, 7:30 pm
Cochlear Implants for Profound Hearing Loss - Signal Processing Considerations
Presented by Dr.-Ing. Bernhard Seeber

In recent years cochlear implants developed into the most successful sensory prosthesis. Cochlear implants replace the function of the inner ear, the cochlea, by direct electrical stimulation of the auditory nerve with a signal derived from the acoustical information. Early cochlear implants transformed the sound signal into an analog electrical signal for stimulation at one electrode. Recent models process the acoustical information infrequency bands and stimulate at multiple electrodes using current pulses.

A brief overview of the auditory system will be given in the beginning of the talk. In the main part the talk will focus on signal processing in cochlear implants from early models to current multichannel implants and its impact on speech perception and sound quality. Acoustical demonstrations of cochlear implant simulations will illustrate this development. Current approaches and problems for an improvement of the perceptual quality of cochlear implants will be highlighted. If time permits the view will be extended to the processing and perception of binaural, directional information with cochlear implants.

Bernhard Seeber obtained his diploma (MA) in Electrical Engineering and Information Technology from the University of Technology Munich, Germany in 1999. His diploma thesis focused on the masking effect in Psychoacoustics. In 1997 he worked with Rich Cox and Jont Allen at AT&T Labs Research (former Bell Labs) on the simulation of masking and loudness using a numerical model of the cochlea. From 1995 to 2002 he led his own company for sales and consulting in musical electronics and computer technology. In 2003 he received his Ph.D. in acoustics and psychoacoustics from the University of Technology Munich. He developed a new method for auditory localization studies. Using this method he showed that localization is possible with bilateral cochlear implants and for patients with a cochlear implant in one ear and a hearing aid in the other.

Dr. Seeber received several awards and grants for his work including a three year research funding from the Deutsche Forschungsgemeinschaft, two poster awards at the meetings of the German Acoustical Society in 2001 and 2003, and a young scientists conference attendance award from the International Commission for Acoustics in 2004. A list of publications can be found at

Wednesay, November 17, 7:30 pm
A Medical Device Entrepreneur's Guide to Understanding and Creating Value
Presented by Richard M. Ferrari, MBA
De Novo Ventures

Dinner: 6:15pm in the Stanford Hospital Cafeteria (No RSVP, just drop by, optional)
Meeting: 7:30-8:30pm in room M114 of the Medical School (follow overhead signs from the Cafeteria to the meeting room, near "M" on this map:

Maximizing value of a start-up is clearly one of the key topics that are not only on the Venture Capitalist's mind but also on the minds of the funders and the employees. Case studies that we will review point to the fact that there are 7 key characteristics to maximizing value for an early stage company. Furthermore it is fairly evident that success can be engineered by focusing on these 7 key elements. Rich Ferrari, with a distinguished and successful career in nurturing medical device company start-ups, will provide his insights on these seven necessary elements for successful entrepreneurship in medicine.

Richard M. Ferrari is a Managing Director of De Novo Ventures, a healthcare investment firm with $350 million under management. He has BS from Ashland University and an MBA from the University of South Florida. Early in his career, Rich held the position of Executive Vice President and General Manager of ADAC Laboratories. Rich was also the co-founder of Integrated Vascular Systems (which was recently purchased by Abbott) an early stage femoral artery closure company and Angiosense, a needle-free, jet injection, local drug delivery company.

1991, Rich became the CEO of Cardiovascular Imaging Systems. As CEO, he orchestrated a successful IPO and ultimately sold the company to Boston Scientific for $125 million. In 1996 he founded Saratoga Ventures, a venture capital partnership that has provided seed financing to several successful companies, including Atrionix, Oratec, Enteric Medical, Trivascular, and Endotex. Oratec, a portfolio company of which Rich was Chairman, went public and was ultimately acquired by Smith & Nephew.

Rich was co-founder of CardioThoracic Systems Inc. (CTSI), the market leader in disposable instruments and systems for beating heart bypass surgery, which was acquired by Guidant for $313 million in November of 1999. As CEO, he led the company to an initial public offering in only 7 months, the fastest of any medical technology company in history.

Following De Novo’s investment in Cryovascular Systems in 2000, Rich joined the initial five-person team as the start-up CEO. He built the company to 22 employees, was instrumental in developing the clinical and product strategies, and hired the executive team. In 2002, Rich led Paracor Medical, another De Novo portfolio company. He grew Paracor from its initial 4 to 22 employees, refined the product strategy, raised its Series B round, and hired his replacement CEO.

Rich is the recipient of the Mallinckrodt Award for Excellence in Medicine and twice a finalist for the Entrepreneur of the Year Award. He is currently on six medical company boards.

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