LASER IN DER MEDIZIN

Medical Applications of Lasers: Diversity is Key to Success

Therapy, clinical tests or device fabrication: Diverse lasers ensure optimum results
Medical applications for lasers are incredibly diverse, encompassing three broad areas: therapeutic procedures, clinical testing/diagnostics, and medical device manufacturing. Supporting such varied applications in turn requires a wide array of laser technology. This article discusses representative applications from all of these areas, and reviews key laser attributes and recent technological developments for each.

AMD Treatment
Age-related macular degeneration (AMD) is the leading cause of blindness in the world. There are two distinct forms of AMD, both of which affect older patients. Dry form AMD is the more common and is characterized by a steady and usually slow decline of the visual field of view often beginning near the center of the eye. Until recently, there was no drug or interventional treatment for this disorder, but an ultrafast laser based method is now showing excellent promise. Wet form AMD is an episodic disorder characterized by blood vessels periodically bursting in the retina causing a sudden and dramatic loss in vision. Early stages of wet AMD can be treated by lasers in two possible ways. Where the problem blood vessels are grouped behind the fovea (yellow spot), a type of Photodynamic Therapy (PDT) is preferred. If the blood vessels are outside the fovea and are allowing blood leakage into the eye, photocoagulation is usually a recommended treatment. In photocoagulation, the laser produces controlled, local

THE aUTHOR
maTTHIas sCHUlZE Matthias Schulze is Director Marketing OEM Components & Instrumentation for Coherent Inc. He joined Coherent in 1995 as a sales engineer in Germany and subsequently was holding various positions in marketing. First at Coherent in Luebeck and later in companywide responsibilities. He holds a PhD in physics from the Technical University in Berlin, Germany.

Therapeutic Procedures
With wavelengths optimized for human tissue interactions, lasers are now found in many therapeutical segments. This wavelength selectivity allows to address particular parts of the biological tissue, leaving others unaffected. This is important for many applications in, e.g., dermatology. In ophthalmology it was crucial, that laser radiation can be transmitted by the vitreous body. That enabled the development of an entire new class of none invasive treatments with much less pain for the patient.
FIGURE 1: A 577 nm OPSL laser delivers superior photocoagulation for wet-form AMD sufferers because this wavelength matches a strong absorption peak in oxy-hemoglobin.

Dr. Matthias Schulze Coherent Inc. 5100 Patrick Henry Drive Santa Clara, CA 95054 Tel. +493030100786 Matthias.schulze@coherent.com www.coherent.com

cauterization, destroying the tiny culprit vessels and preventing further bleeding. Photocoagulation is also used to treat diabetic macular edema (DME). A key to successful photocoagulation is tissue selectivity; that is, closing the target vessels without damaging surrounding tissue in any way and with minimum discomfort to the patient, i.e. with minimal thermal loading of the eye. The main differentiator between the leaking vessel and other tissue is blood, so this can best be achieved by using a laser wavelength that is preferentially absorbed by blood. Photocoagulation also needs a visible laser in order to permit the beam to pass benignly through the transparent front of the eye. The main component of blood with visible absorption is oxy-hemoglobin, and until recently, the most commonly used laser wavelength has been 532 nm which is close to a weaker absorption
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peak in oxy-hemoglobin. But the absorption of oxy-hemoglobin actually peaks at 577 nm (see Figure 1). A laser that emits precisely at this wavelength can be constructed using optically pumped semiconductor laser (OPSL) technology. So to better treat wet-form AMD, Coherent developed the Genesis laser family, which delivers sufficient cw output power at 577 nm. First released in 2008, this yellow laser is enabling improved vessel closure with reduced thermal loading on the eye. Besides wavelength scalability, OPSL technology offers another advantage for photocoagulation. Specifically, the short upper state lifetime of OPSL gain medium enables these lasers to be fast pulsed directly (at tens of kilohertz and beyond) simply by switching the current supply to the pump diodes on and off. The development of pulsed OPSLs for this application has enabled an innovative photocoagulation approach using microsecond pulses without the expense or complexity of an external modulator. This fast pulsing provides extreme dosing control that appears to enable laser treatment to initiate a wound-healing response without actually causing any trauma.

FIGURE 2: Guided by a computer program, the excimer laser reshapes the cornea to correct nearsightedness. The laser trims the corneas center, making it flatter. For farsightedness, a doughnut shaped-ring of tissue is removed. (Photo: VSDAR)

LASIK
Laser in Situ Keratomileusis (LASIK) is arguably the single most popular elective medical procedure to date see Figure 2. Here a deep UV (193 nm) excimer laser is used to reshape the cornea and thus correct a patients eyesight for near-sightedness and/or astigmatism.

The first step in LASIK is to measure the shape of the cornea and determine a pattern to be ablated. In the actual procedure, the patient typically is mildly sedated. An incision is made in the cornea using a scalpel or sometimes an ultrafast laser, to enable a thin (typically < 160 microns) flap to be lifted from the center of the cornea, directly exposing the bulk material. This is then carefully ablated according to the predetermined pattern. The flap is then replaced. For many years, the most important laser parameters for this application were pulse to pulse energy stability and excellent beam uniformity; spatial hot spots or erratic pulse

energies can lead to uncontrolled ablation and a poor outcome. But recently, there has been equal emphasis placed on an increase in pulse repetition rate for two reasons. First this minimizes the duration for the procedure and thereby minimizes patient discomfort. Second, although the LASIK apparatus uses an eye-tracking system to follow inevitable natural movement of the eye, minimizing the overall treatment time minimizes any possibility of errors due to eye movement. To support this need, the latest generation of excimers for LASIK such as the Coherent ExciStar now provide pulse repetition rates up to 500 Hz.

THE COmpaNY Coherent Inc.

Coherent designs and manufactures a broad selection of lasers and supplies electro-optic instruments for laser test and measurement. The companys products include laser diodes and laser diode systems, carbon dioxide (CO2) lasers, excimer lasers, ion lasers, CW and Qswitched DPSS lasers and systems, ultrafast lasers and amplifiers. The company provides worldwide service and applications support. Contact: Petra Wallenta, PR Manager Europe Coherent GmbH phone: ++49 - 89 - 5892746-25 E-Mail: Petra.Wallenta@coherent.com www.coherent.de

FIGURE 3: Scheme of the Cellvizio system, a fibered confocal microscope (FCM) to obtain real-time fluorescent images. (Photo: Mauna Kea Technologies)

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Skin Resurfacing
Another elective medical application is fractional skin resurfacing. Here the goal is to modify the appearance of facial skin to restore a more youthful appearance. Laser treatments for this purpose date back many years but fractional skin resurfacing is a much less traumatic procedure than earlier methods, with less patient discomfort and a much shorter healing period. For example, physicians who offer this procedure typically claim only five days of healing are necessary. While generally considered to be primarily a cosmetic procedure, recently, this type of fractional skin resurfacing also has been used to successfully reduce the appearance of scars on burn victims. The laser of choice is a carbon dioxide laser with a power output of a few tens of watts. The output is chopped as the laser is scanned across the target skin in order to produce a closely spaced pattern of small holes with a typical depth of 2 mm. As these holes heal, the skin is tightened. In addition, the laser treatment promotes new collagen growth. The end result is a reduction in both fine and crease wrinkles. This treatment is now also used to reduce scar disfiguration in burn victims and to reduce acne scars.

ing through a positive lens matched to the numerical aperture of a fiber bundle. This bundle contains up to 30,000 individual fibers with a core diameter of 1.9 microns. With this arrangement, the beam is rastered over the input facet of the bundle at up to 12 frames per second. Because this is a coherent fiber bundle, the spatial mapping of the laser across the individual fibers is completely preserved at the distal end, which can be configured for surface or sub-surface confocal images see figure 4. Returned fluorescence follows the same path via the scanning mirrors. It is then spectrally filtered to eliminate laser backscatter before being focused on to an avalanche photodiode through a confocal aperture. The majority of applications require blue excitation, provided by an OPSL, the Coherent Sapphire 488 nm laser.

Retinal Scanning
Retinal scanning is used to survey the back of the eye for damage, evidence of disease or other problems. It is a much-preferred alternative to the fundus camera whose use typically causes patients discomfort due to the intense flash light source, and temporary over-sensitized vision. Moreover, a fundus

photograph requires the eye to be dilated which is not possible for some patients. In contrast, a retinal scanner obtains an image by rastering a collimated visible laser across the back of the eyeball and detecting backscatter using an avalanche photodiode (APD). Early instruments used a single laser, either green or near-IR. But recently, these instruments have incorporated three lasers (red, green and blue) in order to create a fullcolor image of the eye. These instruments have benefitted from the availability of economical OPSLs at arbitrary visible wavelengths, and their excellent (TEM00) beam quality and low noise characteristics. In cases where the scan or other evidence suggests a vascular type problem, another type of laser scanner may be used to perform a FA (fluorescein angiography) scan. For this test, the patients blood is fluorescently labeled with fluorescein dye. The FA retinal scanner then uses a 488 nm laser to provide the same rastered field of view and acquires detailed fluorescent images of the blood vessels at the back of the eye, including any leaking blood.

Clinical Testing and Diagnostics

In many cases, the use of lasers in this market segment takes advantage of technologies originally developed for other markets. An example is how laser based confocal microscopy paved the way towards endoscopic and retinal scanning applications.

Endoscopic Confocal Microscopy

Traditional endoscopy is widely used to examine both the gastrointestinal (GI) and respiratory tracts. During the exam, the physician may excise 30 or more different samples for subsequent analysis by microscope. Not only is this a time-consuming process, but sadly, this approach often fails to spot precancerous problems and small cancerous growths. In response companies such as Mauna Kea Technologies, have pioneered the development of the fibered confocal microscope (FCM) to obtain realtime fluorescent images during the actual procedure. Some products are already FDA approved for use in both bronchoscopy and GI endoscopy. Figure 3 schematically illustrates the main components of the Cellvizio FCM system from Mauna Kea. The laser beam is deflected with a pair of scanning mirrors before pass-

FIGURE 4: A selection of single frame images acquired with the Cellvizio. (a) In vivo mouse colon after instillation of acriflavine (Photo: D. Vignjevic, S. Robine, D. Louvard, Institut Curie, Paris, France). (b) In vivo reflectance imaging of human mouth mucosa. (c) Ex vivo Autofluorescence imaging in human lung (Photo: Dr. P. Validire, Institut Mutualiste Monsouris, Paris, France). (d) Microcirculation of the peritubular capillaries of a live mouse kidney. (Photo: I. Charvet, P. Meda, CMU, Geneva, Switzerland and L. Stoppini, Biocell Interface, Geneva, Switzerland).

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FIGURE 5: This low density polyethylene (LDPE) medical fluid container has been welded with a diode laser system.

Medical Device Manufacturing

Medical Device Manufacturing is a very diverse applications space that requires a similarly diverse range of laser solutions. Plastics welding and Micromachining are good examples illustrating this breadth.

Plastics Welding
A fast growing application area is laser welding of plastics using direct diode systems, usually fiber-coupled, with powers typically in the tens of watts range. Laser welding offers many advantages over other plastic-welding techniques, such as hot plate and ultrasonics. It can be used on many types of plastics that are commonly employed in the medical products, including polyethylene, polypropylene, acrylic, nylon and even Teflon (see Figure 5). In most cases laser welding of plastics relies on the so-called lap weld, where two sheets of material are overlapped. This creates a large area surface-to-surface join, rather than an edge-to-edge join achieved in a butt weld. The lap weld geometry yields a very strong joint, and can be implemented in a process known as transmission welding. With 100 watts of direct diode output, weld speeds can exceed 2000 mm/min even for weld widths of several millimeters.

mia. In this case, ablation catheters or mapping catheters are directed to the heart, via a femoral entrance. Different technologies may then be inserted to selectively kill tissue by heat or cold. Here, excimer-processing tasks may include stripping polymer insulation from the metal wires of cauterization devices to provide electrical access. Laser thinning (outer layer stripping) to increase the flexibility of devices is another technique that relies on Coherent excimer lasers. One emerging medical device application is the use of very high pulse energy excimers, such as the LambdaSX, to produce complete miniaturized circuits with a single laser pulse for use in disposable blood analyzers, Another developing process is the use of solid state ultraviolet lasers, such as the Coherent AVIA, series to produce miniature marks on medical products enabling suppliers to form unique device identification (UDI) marks. For example, individualized marks can be made on high value products, such as titanium surgical screws and plates, to help stem the growing problem of counterfeit and illegally transshipped products (see Figure 6). The main, overarching trend throughout medical device fabrication is for increased miniaturization, either to reduce product size or to increase the functionality/size ratio. Laser micromachining has proved to be a key technology supporting this by drilling, cutting, scribing and contouring materials as diverse as silicon, metals and plastics, with features as small as a few tens of microns. The goal of micromachining is spatial selectivity: producing micron-scale features while avoiding peripheral thermal damage. Until recently, precision micromachining has been powered by pulsed lasers with nanosecond pulse durations, either DPSS (diode-

pumped solid-state) lasers or excimer lasers. But now, the availability of fiber-based ultrafast lasers such as the Coherent Talisker is enabling even higher resolution and superior edge quality as well as virtually eliminating peripheral thermal effects (see Figure 7). The reason is that ultrafast (picosecond and femtosecond) lasers remove material by a combination of thermal and optical (multiphoton absorption) effects. The latter is a relatively cold ablative process. Moreover, multiphoton absorption allows the machining of several high bandgap materials (e.g.glass, certain polymers) that have low linear, optical absorption and so are difficult to process with existing, commercially available lasers. In addition, ultrafast lasers also provide greater control of depth and greater selectivity with respect to the bottom layer (in the case of thin films) because more material is removed as vapor and there is less thermal diffusion in the vertical direction.

Conclusion
Lasers are utilized in medical applications only when they provide superior value and results; a better outcome, faster healing, a lower cost test, or a less invasive procedure. The fact that diverse medical applications now utilize nearly every type of commercial laser technology, (including DPSS, OPSL, fiber, excimers, direct diode, ultrafast, and carbon dioxide) proves that laser manufacturers have universally risen to the challenge of delivering improved performance, reliability and value.

Micromachining
The breadth of laser machined medical devices is amazing, including stents, bioabsorbable stents, stent grafts, embolic filters, precision drug delivery devices, electrophysiology/ neurological devices, many types of catheters, intravascular radiation delivery devices, angioplasty balloons, and femoral closures. One of the most dynamic areas for these devices is electrophysiology, particularly to treat cardiac disorders such as aryth-

FIGURE 6: UV lasers can be used to create small encrypted identifying marks on parts as small as this titanium surgical screw head. (Photo: Stryker Micro Implants)

FIGURE 7: This hole was laser drilled with an ultrafast industrial fiber laser (Coherent Talisker) in 0.2 mm thick stainless steel. The edge quality would be near-impossible with any other commercial laser type.

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