Harnessing Light Optical Science and Engineering for the 21st Century (1998) / Chapter Skim
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2 Optics in Health Care and the Life Sciences
2 Optics in Health Care and the Life Sciences
Pages 83-124
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From page 83... ...
The basic research in biology that leads to new insights into the treatment of disease has benefited from technical advances ranging from optical methods of gene sequencing to new and more precise microscopies. This broad use of optical techniques has led to new approaches to biological research problems, new methods of medical diagnosis, and new ways to treat d iseases.
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From page 84... ...
Optics has enabled laser surgery, optical diagnostic techniques, and visualization of the body's interior (see Figures 2.1 and 2.2 and Boxes 2.1 and 2.2~. Although the applications of optics to surgery and medicine have increased rapidly since the invention of the laser in 1960, a number of optical techniques were used before that time.
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From page 85... ...
Ophthalmology was the specialty that adapted and incorporated laser techniques into clinical practice most rapidly, in large part because the interior of the eye was optically accessible (Krause and Puliafito, 1995~. By the end of the 1 960s, some understanding of the mechanisms by which the laser interacts with the retina had been obtained, with both thermal and mechanical effects identified.
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From page 86... ...
Laparoscopic techniques also enable numerous other procedures, such as gall bladder removal, which is discussed later in the section on minimally invasive therapy. Medical applications spread from ophthalmology into the general area of surgery, with these applications generally developing around the most readily available lasers.
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From page 87... ...
The ability of pulsed lasers to cause a number of mechanical effects was recognized, studied, and used. Some of these photomechanical effects relied in turn on the ability of pulsed lasers to initiate nonlinear effects; specifically, the ability of pulsed lasers to produce optical breakdown in water was used to generate cavitation bubbles and launch stress waves.
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From page 88... ...
Water Photodynamic therapy Photodynamic therapy Tattoo removal Retinal photocoagulation, tissue welding Tissue cutting and coagulation, many surgical applications,tattoo removal Tissue cutting and shrinkage Skin resurfacing, hard and soft tissue cutting (experimental) Skin resurfacing, tissue cutting and coagulation, surgery l l H A R N E S S I N G L I G H T
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From page 89... ...
A number of feedback systems, based either on tissue temperature or on changes in tissue optical properties, have been studied in an attempt to obtain reliable laser-based tissue welding. If feedback control can enable tissue welding to be performed by most surgeons, it may complement sutures for applications, such as plastic surgery, where minimal scarring is desired.
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From page 90... ...
Role of Optics Video cameras Flexible endoscopes Rigid laparoscopes Laser sources Tissue characterization wavelengths of interest for therapeutic applications. An optical fiber can usually be added to an endoscope by passing it through one of the already available "channels" designed for irrigation and the passage of tools, resulting in an instrument that allows both viewing and laser irradiation.
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From page 91... ...
In some cases, the direct costs of an MIT procedure can be higher than those of the older, more-invasive technique because additional tools and more sophisticated equipment are required. Thus, the introduction of new MIT techniques will require that direct costs do not increase substantially or that patient demand is such that the minimally TABLE 2.2 Growth Patterns in Minimally Invasive Surgery Traditional anc Laparoscopic Cho~ecystectomies Year Traditional ProceduresLaparoscopic Procedures 1 988 537,0000 1 989 545,0001,000 1 990 535,00025,000 1 991 41 0,0001 25,000 1 992 1 50,000480,000 1 993 75,000525,000 1 994 85,000575,000 Source: W
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From page 92... ...
Approximately 25% of the population of the United States suffers from myopia (nearsightedness) and constitutes potential customers for excimer laser photorefractive keratectomy (PRK)
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From page 93... ...
The attractive feature of the laser in cardiovascular applications is its ability to deliver energy via an optical fiber to sites in very small vessels. Laser angioplasty, the use of lasers to remove blockages in arteries, is a well-known concept.
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From page 94... ...
With the discovery that excimer laser ablation of tissue led to minimal thermal damage, intense commercial activity was focused on developing excimer laser angioplasty systems. The success of these systems was limited by the restenosis problem common to all angioplasty procedures.
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From page 95... ...
, which was activated with 630-nm light, was used C h a p t e r 2 FIGURE2.3 Schematic diagram illustrating laser thrombolysis use of a laser to destroy a blood clot. (Courtesy of K Gregory, Oregon Medical Laser Center.)
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From page 96... ...
For many years, the standard light source for PDT was a dye laser pumped by an argon ion laser; more recently, the experimental use of diode lasers that emit red light has begun. Typical power requirements are of the order of 1 to 10 W and are currently available from commercial diodes at wavelengths of 660 nm and longer.
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From page 97... ...
Some optical techniques are well established in clinical practice, such as laser Doppler velocimetry to measure blood flow and the pulsed oximeter used in al I hospitals today. Ophthalmologists now use fundus cameras to obtain pictures of the retina and, with the use of fluorescent dyes, images of retinal blood flow.
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From page 98... ...
Glucose monitoring results in major improvements in the quality of life and in medical cost savings, but it requires periodic blood testing often several tests per day. Current glucose monitors are optically based instruments that require only a small blood sample, usually obtained by using a lances to prick a patient's finger.
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From page 99... ...
Previously, blood samples had to be sent out to be analyzed at a blood chemistry laboratory, causing delays of up to several hours. Optical Tumor Detection Initial studies of tumor detection demonstrated that fluorescencebased techniques using either exogenous marker dyes or endogenous (natural)
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From page 100... ...
An optically based mammography system could complement the existing technology if it were able to find the cancers that x-ray mammography misses. Today, a number of optical techniques aimed at this goal are being explored (see Figure 2.5~.
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From page 101... ...
Thus, to a very good approximation, near-infrared photons diffuse through human tissues and can be used for a variety of biomedical applications. In a typical measurement, the researcher uses an optical fiber to inject near-infrared photons into tissue or a tissue-like medium and a second optical fiber to detect photons at other locations.
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From page 102... ...
The optical method, in addition, has other criteria by which tumor growth may be observed: larger blood volume resulting from a larger number density and volume fraction of blood vessels residing within the tumor; blood deoxygenation arising from relatively high metabolic activity within the tumor; and increased concentration of cell organelles involved in metabolism, such as mitochondria. Recently, the first images of human breasts obtained using near-infrared light have been obtained; while these are early results, they do demonstrate the ability to detect relatively large tumors.
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From page 103... ...
The uses contemplated for these techniques are similar to those mentioned above: identification of internal bleeding and detection of breast tumors, among others. Optical Coherence Tomography Optical coherence tomography (OCT)
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From page 104... ...
Optical techniques for feedback control of therapeutic lasers are (Courtesy ofW.Happer, being applied to systems in which the laser effect occurs too rapidly to Princeton University.) al low manual control or in which more precise control than manual Iy possible is necessary to obtain the desired effect.
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From page 105... ...
NIH should establish a study section for RO1 grants devoted to biomedical applications of light and optical technology. An initiative to identify the human optical properties suitable for noninvasive monitoring should also be established.
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From page 106... ...
Many of these new approaches are strongly dependent on advances in laser technology, the development of sensitive detectors, improvements in optical components, and the development of advanced image processing hardware and software. Equally important for progress has been the creative development of optically based contrast-enhancing molecular probes, typically fluorescent molecules.
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From page 107... ...
A number of potential clinical applications are being investigated, however. Recently, several groups have developed scanning confocal microscopes designed C h a p t e r 2
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From page 108... ...
Two-Photon Microscopy Recently a non I i near absorption phenomenon has been used to obtain depth-resolved fluorescence microscopy images within biological samples without the necessity of confocal microscopy optics. The simultaneous absorption of two photons at sufficiently high light intensities was first predicted in 1931, but observation of these effects required the availability of intense pulsed laser sources.
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From page 109... ...
In the two-photon approach, red light, typically from a femtoseconddomain (about 1 o-~3 S) pulsed laser source, is used for the excitation of fl uorescence; two-photon absorption occu rs i n on Iy a smal I region around the focal spot of the objective.
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From page 110... ...
The spatial resolution is thus determined by aperture dimension rather than by diffraction, which becomes operative only in the far field. The optical tip can take a number of forms, including specially narrowed optical fibers and hand-crafted hollow metal guides.
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From page 111... ...
Much of the progress in fluorescence microscopy is linked to the development of ever more specific fluorescent probes, which may be chosen for their ability to intercalate into DNA or to label specific ions such as calcium. These fluorescent probes may be used to locate and examine specific sites by direct visualization with a microscope, or they may be sensed by a variety of optical techniques such as flow cytometry (discussed below)
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From page 112... ...
Combining photos/ability with the optical properties mentioned above provides a significant challenge. Measurement and Analysis Techniques The same sophisticated new optical probes that are so useful for biological visualization also make possible the application of optical measurement and analysis methods to such biological problems as gene sorting, mapping the human genome, and investigating cellular control and communication.
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From page 113... ...
The development of optically based measurement techniques and new probes occurred in parallel with the application of this technology to basic biological studies and routine clinical assays. Routine clinical applications of flow cytometry fall predominantly into two categories: immunophenotyping and DNA content measurement.
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From page 114... ...
The next generation of AIDS diagnostic techniques will focus on determining the concentration of free HIV in peripheral blood, the viral load. This diagnostic measurement has proven to be of great importance for developing promising new anti-HIV drugs, the protease inhibitors, and for determining effective therapies involving combinations of these antiviral drugs.
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From page 115... ...
Currently, there is no interdisciplinary degree program that adequately prepares either users or developers of the technology for the breadth of information and understanding that they need. Bioengineered Fluorescent Indicators A number of novel fluorescent indicators based on molecular biology have become available that serve as indicators of processes going on within living cells.
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From page 116... ...
By focusing laser light into narrow beams, researchers demonstrated that tiny particles, such as polystyrene spheres a few micrometers in diameter, could be displaced and even levitated against gravity using the force of radiation pressure. Under the right conditions, the intense light gradient near the focal region can achieve stable three-dimensional trapping of dielectric objects.
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From page 117... ...
The general strategy of all such instruments involves tagging the four distinct bases that occur in DNA with fluorescent dyes that have different emission wavelengths. Currently an argon ion laser is used to excite fluorescence.
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From page 118... ...
It binds most strongly to sites that match a portion of its DNA sequence, resulting in localized patches of high fluorescence. Laser scanning confocal microscopy, described previously, is rim - ~ l l H A R N E S S I N G L I G H T
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From page 119... ...
Applications envisioned for these probe arrays include rapid sequencing of DNA as well as the detection of mutations associated with resistance to antiviral drugs used in the treatment of AIDS. Although the commercial success of the DNA chip wi 11 depend on many factors, including the development of competing technologies, it illustrates the way sophisticated optical techniques, developed in part for the sem iconductor i Industry, are being used for biotechnology.
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From page 120... ...
Summary and Recommendations Surgery anti Metlicine Optics has enabled the development of rigid and flexible viewing scopes that allow minimally invasive diagnosis and treatment of numerous sites inside the body, such as the colon, the knee, and the uterus. Lasers have become accepted and commonly used tools for a variety of surgical applications.
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From page 121... ...
The disease-oriented structure of NIH does not encourage the funding of biomedical optical technology programs. Lasers and fiber-based instrumentation have enabled many new minimally invasive therapies that reduce total (direct plus lost time)
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From page 122... ...
NIH should establish a study section for R01 grants devoted to biomedical applications of light and optical technology. An initiative to identify the human optical properties suitable for noninvasive monitoring should also be established.
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From page 123... ...
1993. Lasers and Optical Fibers in Medicine.
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From page 124... ...
McDonnell.1995. Excimer laser photorefractive keratectomy.
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