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LASER: BASIC PRINCIPLES
Introduction:
During the last three decades, lasers became increasingly accepted as instruments of great usefulness for dermatologic therapy. The many clinical applications for lasers in the treatment of cosmetically important skin conditions were almost immediately recognized after development of laser in 1959 (Wheeland, 1991). Dermatologists have played an important role in the evolution of effective forms of therapy using many different laser systems and laser treatment techniques to assist patients with cutaneous problems for which no acceptable form of therapy had previously existed. As a consequence of the precise, reproducible, and controllable way by which laser light can be used, these instruments have gained the acceptance both by the physician and patients alike (Wheeland, 1991).
Basic laser principles:
Laser radiation is coherent, both "temporally" and "spatially". It is monochromatic and thought of as temporally coherent because all of the waves retain their same phase relationships. This permits selective optical absorption and consequent selective tissue heating. The laser light also has spatial coherence, that is not only in phase but in step. The distinction between coherent and incoherent light is analogous to comparing a marching band with a milling group of students. The band marches in parallel raws spatial coherence. Light from an incandescent bulb, which is of different wavelengths and is emitted in random directions, is incoherent in both respects (Berns et al., 1992).
The parallel rays of coherent light can be focused to a small size or propagated over a long distance "Collimation" with little beam spreading. A laser beam focused to a small spot carries an enormous amount of energy and allows an intense power density to be incident on a given target. All lasers have the following three basic elements : (1) the lasing medium. (2) the pumping system (Power supply or energy source). (3) an optical cavity containing mirrors (Berns et al., 1992).
Photons are the fundamental units of light, and they are the same whether produced by a light bulb or a laser. Light from the light bulb radiates in all different directions. As the distance from the light bulb increases, its intensity decreases as a function of the square of the distance. In the laser, the photons are emitted parallel or near parallel and in phase with each other as they travel toward infinity. This property is used by scientists to send a laser beam to the moon and back (Berns, 1974).
Another feature of light from the light bulb is that it is white or yellow-white in color. That is because it contains all the different colors and wavelengths in the visual portion of the electromagnetic spectrum. If a glass prism is put in front of the light bulb, it will refract the different wavelengths and the constituent colors will be seen. With the laser, the prism will produce light of one wave length (one color). The light from the laser is therefore pure or monochromatic. This property, under some circumstances, facilitates selective absorption of laser energy within the tissue; structures with high absorption at a laser wave length can be selectively altered or destroyed (Berns et al., 1992).
A third difference between the two light sources is in their intensity. The number of photons produced by the laser is much greater per unit area of emission than for any other light source. In fact, there are millions more photons emitted by a laser than by a comparable surface area of the sun. For example, peak powers of (1012 W) can be obtained with certain short pulsed lasers (Berns et al.,1992).
One can also vary the laser power over a large range and achieve quite different tissue effects. For example, a low power laser may be used to gently heat a tissue with the only change being an increase in some biochemical functions where as a high power pulsed laser may be used to achieve nonlinear optical effect (e.g.optical breakdown) causing explosions within the tissue (Boulnosis, 1986).
Simply, the laser beam is emitted when the number of photons trapped in a metastable energy level is sufficient beginning the stimulated emission of radiation as photons are released from their excited state to the ground state level. When a critical energy level is reached and photons arrive at a partially reflecting mirror, only a portion is reflected back; the rest emerge as a laser beam. The light may be released in pulsed or continuous fashion. In the pulsed laser, the energy is released quickly in discrete packages, similar to firing a gun. In the continuous type of laser, the energy is emitted in a continuous fashion and may be used as such or in short pulses by means of a shutter mechanism (Arndts and Noel, 1982).
To understand the lasing mechanism, it is necessary to explain some basic atomic physics. Two atoms existing in the lowest possible energy level, "the ground state" (fig.1). If electrons of these atoms are excited from the ground state by the input of energy, they may move to a higher energy level, called "the excited singlet state". The source of this energy or "pumping system" can be electrical, chemical, or light from a flashlamp or another laser. When the atoms are excited to the singlet state, they will drop very quickly to an in-between, long-lived energy level called the "metastable state". This explains why some materials can go through the "lasing" process and others cannot. Only atoms and molecules with a metastable state in the energy structure can undergo stimulated emission (Berns et al., 1992).
What happens next is a spontaneous event. Those atoms existing in the metastable state spontaneously, and randomly, return to the ground state with the loss of some energy. This loss of energy is in the form of light, the release of a photon. If the photon is in close proximity to another atom still in the metastable state, it will interact with the other atom. This interaction stimulates the second atom to return to its ground state and, in the process, emits a photon of light. This phenomenon is termed "Stimulated Emission of Radiation". Since both photons come from identical energy levels, they will be of the same wavelength (color) and also they will be moving parallel and in phase with each other (the property of coherence) (Berns et al., 1992). The foregoing events on a much grander scale are presented in (fig. 2). The atoms in the lasing medium are represented in the ground state by open circles and those in the metastable state by dark circles. Most atoms are initially in the ground state and are subsequently excited to the singlet state by a flash of light. They rapidly drop down to the metastable state (dark circles). Following this event, spontaneous emission occurs as described above. The two emitted photons interact with other atoms in the metastable state causing them to emit photons in parallel and in phase with those already present. This results within a fraction of a second in an intense buildup of many photons or "photon cascade". If the laser cavity has opposing reflective surfaces, the photons will be oscillated through the medium at the speed of light stimulating the emission of more photons. This buildup of intensity by oscillation between two reflecting surfaces results in the final process of lasing; amplification. By permitting the release of some photons by means of a partially reflective surface at one end of the cavity, the result is a bright, intense, monochromatic beam of light (Berns et al., 1992).
The regions in the electromagnetic spectrum where lasers can be used are shown in ( fig. 3). It can be seen that lasers occupy a relatively small region of the entire spectrum. However, this portion is expanding with the development of the free electron laser, which eventually may be manipulated from the infrared to the ultraviolet portions of the spectrum. In discussing different kinds of lasers, identification is made by the type of material inside the device that is undergoing the lasing process (Berns et al.,1992).
There are four categories of lasing materials solid, gas, liquid, and semiconductor. Examples of solid state lasers are the ruby and YAG (ytrium-aluminum-garnet). Examples of gas lasers are the helium-neon, argon, and carbon dioxide. Liquid lasers employ complex organic dyes in a solution or suspension, such as rhodamine and coumarin. Semiconductor lasers use two layers of semiconductor material, such as gallium arsenide. It is possible to obtain lasing action from any of these materials provided their atomic structures have metastable states that permit the stimulated emission process to occur (Berns et al., 1992).
There are also ways to modify the wavelengths obtainable from lasers. Certain asymmetric crystals interact with an intense laser beam, and interaction of these photons generates laser light with twice the frequency (half the wavelength) of the incident radiation. This is called "frequency doubling or harmonic generation". This complicated process can be used to double, triple, or quadruple the wavelengths from the primary laser source. If the primary laser is a tunable dye laser, then it is possible to increase greatly the number of wavelengths available by passing the laser output through the nonlinear crystals (Berns et al.,1992).
In summary, there is a wide range of lasers available for clinical use. They produce light from the far ultraviolet to the mid-infrared that can be matched to absorption peaks of tissue chromophores, thus permitting their selective destruction and subsequent tissue ablation (Berns et al., 1992). Laser light emitted from the standard medical device is generally characterized in terms of power, in units of watts. The energy (stated in joules) is defined as the power x time interval during which it is emitted (Berns et al., 1992).
Energy (joules) = Power (W) x Time (Sec).
For this type of beam, the spot size (radius = r) is defined as the distance from the center of the beam to the point on the edge where the power density is l/e2 of that for the center. The beam diameter is then twice the spot size. The power density or irradiance is then defined as the power applied per unit area of target tissue (Berns et al., 1992).
Power density = Power (W) / x R2 (cm2) Fluence is defined as the energy applied to an area of target tissue (Berns et al., 1992).
Fluence = Power density (W/cm2) x Time (Sec) = J/cm2
The effect of the laser beam on target tissue is affected by any one of three variables; power, spot size, or time. The effects of power and time are proportional whereas that of spot size is an inverse square. If either the power or time is doubled, the fluence increases by a factor of two. However, if the spot size "radius" is decreased by a factor of two, the fluence will increase by a factor of four. Doubling the spot size will result in a fourfold reduction in the fluence (Berns et al., 1992).
If the clinical objective is to make an incision, the physician should use a small spot with a high fluence because that will penetrate deeply into the tissues. However, if the intent is to ablate layer by layer from the surface, a larger spot size with a lower fluence should be used. This gives the surgeon a way to control the effect produced in the tissue by manipulating either the spot size or power of the laser beam. It is important to recognize this principle so that the desired clinical results can be achieved (Berns et al., 1992).
A continuous wave (CW) laser may be differentiated from a pulsed laser that provides bursts of energy. The CW laser undergoes minimal fluctuation with time, creating a steady flow of radiation. A pulsed laser delivers its energy in the form of a single pulse or a train of pulses. The frequency or pulse repetition rate is the number of pulses emitted in one second. Duration of the pulse, or "pulse width", is defined as the total time required for the pulse to rise from zero intensity, build to a maximum, and then fall to zero intensity again. For each pulse, the energy, irradiance, and fluence are calculated as for the CW laser described above (Berns et al., 1992). The average power produced by a train of pulses is determined by multiplying the pulse power by the pulse repetition rate and pulse width (Berns et al.,1992).
Average power = Pulse power (W) x pulse repetition rate ( 1/sec) x pulse width (sec) = W
The average irradiance and fluence are calculated in the same manner as described earlier. Several methods of creating pulses of laser light are available with pulse widths from tenths of seconds to femtoseconds (10-15 sec) (Berns et al., 1992).
Biological effects of Laser :
It is important to recognize that the interactions of laser radiation with living tissue are complex phenomena influenced not only by laser parameters, such as power, spot size, time, and wavelength, but also by tissue properties (Boulnosis, 1986).
If a laser beam is directed at a tissue, it may be reflected back toward the source or to another location. Since tissues reflect light, reflectance characteristics are important (Berns et al., 1992).
If reflectance is adequately accounted for, two additional things can happen other than absorption. The tissue itself can scatter light. The light literally bounces off particles and structures in the tissue and "scatters" to places where it is not wanted. Furthermore, the light might be transmitted right through the tissue with only a minimal amount being absorbed and/or scattered. Since every tissue has some reflective, scattering, and transmissive properties, their characterization is an important aspect of effective laser use (Berns et al., 1992).
Normally we think of lasers as producing heat, and in many of the clinical procedures, lasers produce some kind of local thermal event. However, heat is just one way that the energy of the photon can be dissipated ( fig. 4). When photons enter the tissue, those that are not reflected, scattered, or transmitted are absorbed. Their energy is transferred to some other molecule / group of atoms in the target tissue. The important point to remember is that when photon energy is absorbed, the absorbing structure or tissue has to dissipate that energy in some way, and it is the manner in which this energy is dissipated that brings about the different biological effects that are used clinically. In order to have light energy absorbed, it is necessary to have some absorbing molecule in the tissue. These molecules are generally referred to as chromophores. When light is absorbed by a chromophore, the photon energy is transferred to the chromophore. Haemoglobin has a high absorption in the violet and blue /green portions of the spectrum and declines in the red region of the spectrum. This is the rational for using an argon laser (which emits blue /green light) in the treatment for vascular lesions, such as haemangiomas and port wine stains. This may not be as selective as anticipated because even with absorption by the haemoglobin molecule, the heat that destroys the blood vessel (unless it is precisely confined just to this area), will radiate out in all directions and still may destroy the overlying skin layers or adjacent structures. Newer laser systems have been developed with pulsed modes where confining the energy to very short period of time will reduce the spread of the heat to surrounding structures (Anderson and Parrish, 1983).
Water, on the other hand, has no absorption in the visible portion of the spectrum and minimal absorption in the near infrared portions of the spectrum. However, further out in the infrared (past 2 um), water has significant absorption. This is why a carbon dioxide laser can have a direct effect on any tissue in the body. If used properly, the carbon dioxide laser can be compared clinically to performing a dermabrasion because the laser gradually removes cells layer by layer through the volatilization of water present in the tissue (Berns et al., 1992).
The photons of the Nd:YAG, on the other hand, are poorly absorbed by haemoglobin, water and other body pigments. This is why the Nd:YAG laser will penetrate much more deeply into tissue and affect a much greater volume of tissue than either the argon or CO2 lasers. In summary, the selection of the correct laser for particular clinical procedure requires an understanding of the absorptive as well as the reflective, scattering, and transmissive properties of the target tissue (Berns et al., 1992).
Laser tissue interactions:
1- Heat :
Given that one goal of Laser therapy is the precise control of thermal energy, one must first understand the process of tissue heating. The effect of temperature rise in a tissue being irradiated varies according to temperature gradients (fig. 5). As the temperature rises to 37-60°C, the tissue starts to retract. With a temperature above 60°C, there is protein denaturation and coagulation. From 90-100°C, carbonization and burning of tissue occurs. Above 100°C, the tissue is vaporized and ablated. Ideally from a clinical point of view, the physician should be able to confine the heating process to any one of these thermal ranges to produce the desired clinical result (Bohigian, 1986).
It is important to recognize that heat radiates in 360o around the crater produced by tissue vaporization. The result will be successive zones of carbonization, vacuolization, and oedema as the heat is dissipated (fig. 6). The zones of vacuolization and oedema may be irreversibly affected and eventually necrose and slough, or they may be repaired by the host. However, in some instances, it is desirable to have thermal spread to nearby capillaries, thus increasing haemostasis (Berns et al.,1992).
One way to maximize the spatial confinement of heat is to use a pulsed laser with a pulse width on the order of the thermal relaxation time of the tissue. This is defined as the time needed for a target structure to cool to one-half its initial temperature. Shorter pulse durations can confine the laser energy to progressively smaller targets (Anderson and Parrish, 1983).
2- Photochemistry:
Photon energy may also be dissipated by photochemistry. The basic concept of photochemistry is that certain molecules (natural or applied) can function as photosensitizers. The presence of these photosensitizers in certain cells make these cells vulnerable to light at wavelengths absorbed by the chromophore. The excited photosensitizer may subsequently transfer its energy to a molecular substrate, such as; oxygen, to produce "highly reactive" singlet oxygen, which causes irreversible oxidation of some essential cellular components. All of this occurs without generation of heat. The most common clinical use of this mechanism has been in the treatment of cancer after sensitization with haematoporphyrin derivatives (HPD). Although the mechanism of their selective localization in the malignant cells is uncertain, it is well established that the total time the HPD is retained in the malignant tissue is much longer than the nonmalignant tissue from which it is generally cleared, between 24-72 hours. Shortly after light administration, the tumor becomes necrotic and slough within few days (Dougherty, 1987).
3- Fluorescence:
Photon energy may be dissipated as the re-emission of light. If this happens within 10-6 sec after absorption, it is called "fluorescence". The fluorescent photon is emitted as the excited atom returns to the ground state. Many of the photosensitizing dyes used to induce photochemistry are also fluorescent. When using HPD, and a 400-nm blue/violet light of krypton laser used with an appropriate filter and detector, fluorescence can be observed in malignant tissue. It would then be possible to switch over to 630 nm red light and bring about the photochemical reaction to kill the cells containing the photosensitizer. This actualy has a great seal of promise clinically and in detection of occult lung tumors, determining the extent of superficial skin tumors (Benson and Farrow, 1982). Intravascularly, laser-induced fluorescence is being developed to distinguish normal from diseased (atherosclerotic) vessele (Berns et al., 1992).
4- Photoablation:
Photoablation occurs when pulsed, high energy ultraviolet photons (193 nm) produced by an excimer laser are absorbed on the surface of an organic substrate (Srinivasan, 1985). Since ultraviolet radiation is absorbed intensely by most biological molecules, the penetration depths are only a few microns (Parrish, 1985).
This combination of high absorption and high individual photon energy results in the direct transfer of energy within the absorbing molecule to the bonds that hold the molecule together. When the incoming ultraviolet energy exceeds the molecular bonding energy (the ablation threshold) the substrate will undergo random bond destruction and is reduced to its atomic constituents (Berns et al., 1992).
The rapid expansion created by this excitation and bond cleavage gives rise to the actual ejection of fragments at supersonic velocities or the ablation phenomenon. Although the question of heat generation in this process has not been resolved, it is clear that the tissue degradation process is by nonthermal process (Berns et al., 1992).
5- Ionization:
Ionization is the ejection of an electron from an atom, and it is generally felt that the individual photons generated from existing lasers do not have enough energy to cause the absorbing molecule to lose an electron. However, it is possible to have absorption of more than one photon simultaneously in a "multiphoton process". This has been observed in solutions and in living cells, but in most of the present clinical situations, ionization occurs only in laser-induced plasmas (Calmettes and Berns, 1983).
6- Plasma formation:
Plasma formation is one of the few laser-tissue interactions that does not obey the basic photobiological principles, meaning that the plasma formation is independent of the time period within which the photons are delivered i.e. it is power dependent. With the advent of Q-switched (nanosec) and short pulsed, mode-locked (picosec) lasers, it has become possible to generate very high fluences (gigawatts/cm2) in focal spots of 25-50 um. When these lasers are focused precisely on a small spot of tissue, it is possible to generate a "plasma", which is a gaseous cloud rich in free electrons (Boulnosis, 1986).
This plasma has been called the "fourth" state of matter. Its properties are different from those of solids, liquids, or gases. Due to the sudden production of an electrical field in 10-9-10-12 sec, an intense acoustical shock wave is generated in the medium. This acoustic wave originating from the focus carries potentialy damaging kinetic energy and has been used clinically in the eye to remove secondary cataracts in the posterior capsule as well as experimentaly to fracture recalcitrant urinary calculi (Berns et al., 1992).
7- Optical force generation:
In 1986, Arthur Ashkin of AT&T Bell labs described the uses of a microscope-focused laser beam to create an optical force that could be used to hold "trap"and move biological cells and organelles (Ashkin and Dziedzic, 1987). If laser light at a wavelength that is not absorbed by the tissue is focused on the target, it will be refracted. As a result, momentum will be transferred from the photon to the object. "Optical tweezers" have been used to trap bacteria (Block et al., 1989), individual sperm cells (Tadir et al., 1990), chromosomes (Berns et al., 1989), and even to hold cells together to facilitate cell fusion (Wiegand et al., 1991). Although still in the experimental stages of development, this new, nondestructive use of laser light may have exciting biological and clinical applications (Berns et al., 1992).