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Press Releases Newsletters |
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Advances in Medical Technology at Physical Sciences Inc.Physical Sciences Inc. has devoted this unusually lengthy edition of the PSI newsletter to a survey of our rapidly growing research and development activities in the fields of medical and biomedical diagnostics. While the company has a long history of contributions to medical technologies, starting with studies of laser-tissue interactions and elimination of kidney stones with micro-mechanical devices, we have only recently exploited our full capabilities in biophotonics. This issue will also illustrate a basic requirement for relevant and successful research and development of medical techniques and devices, our close interaction and partnership with leading medical researchers and clinicians. PSI is fortunate to have many such partnerships in the Boston area and elsewhere in the biomedical community. Retinal ImagingOver the past several years, PSI's biomedical optics team, led by Dan Ferguson and Dan Hammer, with significant contributions by Teoman Ustun, John Magill, and Chad Bigelow, has developed a unique image stabilization system for use in scanning laser ophthalmoscopy. Working with colleagues at the Schepens Eye Institute of Harvard Medical School, and with continuing support from the National Eye Institute of the National Institutes of Health (NIH), we have successfully transitioned this technology from the laboratory to clinical settings. The Tracking, Scanning Laser Ophthalmoscope, or TSLO, is able to compensate for transverse eye movement and lock onto common features in the retina over nearly 1000 images. Retinal tracking has also been incorporated into a third generation commercial Optical Coherence Tomography (OCT) system manufactured by Carl Zeiss Meditec Inc., permitting blur-free, high resolution mapping of three-dimensional structures in the living eye. This capability will lead to a better understanding of disease processes and the improved specificity of diagnostic and therapeutic procedures.
Scanning laser ophthalmoscopy is a powerful research tool, but has seen limited use in ophthalmic clinics due in part to the size, cost, and complexity of the instruments. Conversely, low-cost retinal imaging devices have limited capabilities in scanning, detection, and diagnosis of disease. To fill the niche between these two, PSI, in collaboration with the Wellman Center for Photomedicine, Massachusetts General Hospital, has developed and tested a low-cost, hand-held line-scanning laser ophthalmoscope that does not require dilation. A dual TSLO/OCT has also been demonstrated, and the recent incorporation of adaptive optics has been shown to significantly enhance the system’s imaging capabilities.
Tissue changes that occur due to retinal laser injuries that may not be visible with standard photography can also be detected. Very recent developments at PSI and the Wellman Center have made it possible to combine these technologies into a single, affordable, field-deployable device, the Line-Scanning Laser Ophthalmoscope. Nick Iftimia has also shown that it may be possible to directly monitor red and white cell populations in retinal capillaries, and thereby provide a non-invasive diagnostic for several critical indicators of an individual's physiological status. Both military and civilian "telemedicine" applications have been identified. Optically-based Breath MonitorIn collaboration with Rice University and Johns Hopkins University, PSI is developing a compact, high sensitivity breath analysis system for the real-time monitoring of human physiology. The presence of specific molecules in exhaled breath has great potential for the determination of general physiologic condition, including radiation and toxin exposure. The PSI breath analysis system is based on a photonic biosensor technology that marries tunable laser sources and "cavity-enhanced" spectroscopy. With support from the National Cancer Institute, NASA, and the Air Force Office of Scientific Research, we have demonstrated the simultaneous measurement of both nitric oxide and carbon monoxide, which are bio-markers for airway inflammation. Under the direction of Mark Allen and Dave Rosen, these ongoing projects have shown the feasibility of monitoring many other molecules of diagnostic interest, including ethane, a key bio-marker of oxidative stress. Laryngeal Endoscope
Laryngeal video-endoscopy has become a basic clinical tool for assessing how the larynx functions to produce voice. To eliminate clinical examiner bias in the evaluation of laryngeal video recordings, PSI has added a light projection system for dimensional calibration of images obtained during flexible endoscopy. Led by Dave Rosen, and working with the Massachusetts Eye and Ear Infirmary and the Massachusetts General Hospital, PSI has completed preliminary human trials to establish the feasibility and practicality of the system. Under a continuing NIH grant, we are currently designing a device that is readily manufacturable and affordable to otolaryngologists and speech- language pathologists. Photodynamic Therapy MonitorIn photochemotherapy, also known as PhotoDynamic Therapy (PDT), a photosensitizer agent is injected into a cancer patient and is preferentially retained in tumor cells. The agent is then irradiated with visible to near infrared light, matching the wavelength of the light to the absorption band of the photosensitizer. The excited agent can pass its energy to oxygen molecules to generate "excited" oxygen, which can cause cell death. FDA approval has been granted for treatment of esophageal and certain lung cancers. PDT is also being used in clinical trials for bladder, brain, skin, and other cancers.
Monitoring excited molecular oxygen in real time can lead to a better understanding of the PDT process and to more precise and effective cancer treatment. Steve Davis and Seonkyung Lee have developed a fiber-coupled, diode laser-based monitor, and have recently demonstrated real-time detection in a rat prostate cancer cell line. Additional animal tests and clinical trials with human subjects are planned in collaboration with Dr. Tayyaba Hasan of the Massachusetts General Hospital. Protein Imaging in Living Cells
Under a NASA contract, low-power confocal imaging of protein interactions in living cells is being investigated by Anthony Ferrante. The goal is to develop a biological system that genetically labels intracellular structures in bone cell culture models. PSI has already demonstrated the feasibility of using recently commercialized Reef Coral Fluorescent Proteins (RCFPs) as markers for imaging experiments by genetically fusing them to cellular proteins. We have also developed a multiple wavelength strategy for simultaneously distinguishing up to three different RCFPs. Confocal microscopy, combined with compact diode-pumped, solid-state lasers, will enable researchers to study these systems in microgravity environments. Real time visualization of cellular processes may then enable the development of countermeasures to microgravity-induced changes in bone cells that result in bone loss during extended space flight. Zebrafish for Drug DiscoveryThere is strong interest in developing zebrafish as a model organism for use in high throughput drug discovery assays. Thus far, true high-throughput screening in zebrafish has been limited to embryos and very early larvae. With support from NIH, Anthony Ferrante and Dave Rosen have invented a novel technology that will be adaptable to standard image analysis systems that are already in use in drug discovery laboratories. This technology will allow researchers to generate clear side-views of older zebrafish larvae in microwell arrays. The PSI technology does not require confocal microscopy techniques or sophisticated image deconvolution algorithms, and can generate quality images in seconds, versus minutes required for other techniques. This should enable truly high throughput drug discovery of compounds that may reduce cholesterol and lipid levels, an important health care objective.
Miniature Electromechanical Devices for Orthopaedic Automation
Another ongoing medical technology project at PSI is a partnership with the Massachusetts General Hospital Department of Oral Surgery to develop an innovative device to encourage growth of the jaw bone. John Magill of PSI has developed a fully buried, automated actuator to produce the desired bone shape. By automating the process, patient responsibility is reduced and continuous motion is possible. Other applications of smart electromechanical devices to musculo-skeletal corrections are also being pursued. Compact Solid State Dye LaserDiode-pumped solid state dye lasers that are under development at PSI have multiple medical applications. Conventional dye lasers have been successfully used for clot removal in coronary arteries, tissue welding, photodynamic cancer therapy, and a variety of cosmetic surgery applications. The PSI Laser Technologies Group, under the direction of Henry Aldag and Dennis Pacheco, and with the support of the Department of Defense, has developed an efficient, diode-pumped, tunable solid state dye laser with excellent beam quality. An extremely compact device has recently been engineered, and will soon become available to the medical community.
Editor Donna Lamb lamb@psicorp.com Contributors D. Ferguson, D. Hammer, N. Iftimia, M. Allen, D. Rosen, J. Magill, A. Ferrante, H. Aldag, D. Rosen and R. Weiss A publication of
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