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Lasers for Medical Applications: Diagnostics, Therapy and Surgery

Lasers for Medical Applications: Diagnostics, Therapy and Surgery

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Lasers for Medical Applications: Diagnostics, Therapy and Surgery

1,549 pagine
Sep 30, 2013


Lasers have a wide and growing range of applications in medicine. Lasers for Medical Applications summarises the wealth of recent research on the principles, technologies and application of lasers in diagnostics, therapy and surgery.

Part one gives an overview of the use of lasers in medicine, key principles of lasers and radiation interactions with tissue. To understand the wide diversity and therefore the large possible choice of these devices for a specific diagnosis or treatment, the respective types of the laser (solid state, gas, dye, and semiconductor) are reviewed in part two. Part three describes diagnostic laser methods, for example optical coherence tomography, spectroscopy, optical biopsy, and time-resolved fluorescence polarization spectroscopy. Those methods help doctors to refine the scope of involvement of the particular body part or, for example, to specify the extent of a tumor. Part four concentrates on the therapeutic applications of laser radiation in particular branches of medicine, including ophthalmology, dermatology, cardiology, urology, gynecology, otorhinolaryngology (ORL), neurology, dentistry, orthopaedic surgery and cancer therapy, as well as laser coatings of implants. The final chapter includes the safety precautions with which the staff working with laser instruments must be familiar.

With its distinguished editor and international team of contributors, this important book summarizes international achievements in the field of laser applications in medicine in the past 50 years. It provides a valuable contribution to laser medicine by outstanding experts in medicine and engineering.
  • Describes the interaction of laser light with tissue
  • Reviews every type of laser used in medicine: solid state, gas, dye and semiconductor
  • Describes the use of lasers for diagnostics
Sep 30, 2013

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Lasers for Medical Applications - Elsevier Science

Jelínková,     Prague


Introduction: the history of lasers in medicine

H. Jelínková,     Czech Technical University in Prague, Czech Republic


On the background of the history of laser medicine, the basic principles of the interaction of laser radiation with tissue are explained and the main factors influencing the results of the interaction are analyzed. After description of .laser radiation and tissue main characteristics, the primary factors of laser radiation interaction with tissue, including spectral reflection, refraction, absorption, scattering, and transmission, are defined. Secondary factors, i.e. photochemical or photothermal interaction (non-ablative heating, vaporization), photo-ablation, plasma-induced ablation, and photo-disruption are then mentioned.

Key words

laser medicine history

interaction of the laser radiation with tissue

1.1 Introduction

The application of the laser in medical treatment is based on the interaction of laser radiation with biological tissue. Laser radiation can be included in a large category of electromagnetic radiation generated by many types of radiation sources such as the sun, fire, bulbs, electric discharge, plasma, etc. From a historical point of view, the sun’s radiation has been used as a therapeutic tool for the treatment of various pathological phenomena or to improve health for many centuries. The ancient Egyptians are believed to have used ‘sunbathing’ as phototherapy, and the ancient Greeks and Romans used sunlight for phototherapy or heliotherapy (Bertolotti, 2005). Sun radiation also initiated the action of light-sensitive substances applied to the skin, leading to a particular tissue healing process. The Egyptians and Indians treated skin diseases such as vitiligo or leukoderma with the help of this method, which is today called photochemotherapy. The Chinese have historically used the sun in order to cure (or at least slow down) the progress of diseases such as rickets, skin cancer or even psychosis.

During the Middle Ages, the use of light for medical treatment was interrupted, possibly due to medieval morals prohibiting nudity in public. At the end of the nineteenth century, the Swiss healer Arnold Rikli reintroduced the medical profession to the positive effects of sunlight and used these effects as the basis of successful natural healing methods. Louis Kuhne and Heinrich Lahman also used heliotherapy for the care of some illnesses (Friedhelm and Wade, 1994). Significant work in phototherapy was done by Danish physician Niels Ryberg Finsen. His works ‘On the effects of light on the skin’ (1893), ‘The use of effects of light on the skin’ (1896), and ‘La Photothérapie’ (1899) were the basis on which Finsen was awarded the Nobel Prize¹ for his results in the treatment of patients with various cutaneous diseases.

Besides the knowledge of the positive medicinal effects of sun radiation, the negative impact of solar radiation on the human eye has also been known since the time of Plato and Socrates. A description of central vision loss from gazing at the sun was provided by Theophilus Bonetus in the seventeenth century. It was observed that solar radiation can damage the structure of the inner eye. The first experiments regarding retinal damage by sunlight were performed by Czerny in 1867. In the twentieth century, further experiments were performed by Maggiore (1927) and Moran-Salas (1940) (Palanker et al., 2011). The basic knowledge that light has the potential to damage the eye was slowly converted into a method of treating the eye structures. In 1949 G. Meyer-Schwickerath focused sunlight onto patients’ retinas to treat melanomas for the first time. Meyer-Schwickerath was also involved in the construction of the first eye photocoagulator, which used solar radiation to weld a detached part of the retina (1949); in the following years he developed treatments for retinal tears, macular holes, and diabetic retinopathy with the help of photocoagulation, and also solved other problems of the retina and macula using the Zeiss xenon arc light photocoagulator (Meyer-Schwickerath, 1989). A 1000 W arc lamp was used to direct light into the eye for 1 s intervals to form scars attaching the retina to the eyeball.

Red ruby laser radiation was generated for the first time by Theodore Maiman in May 1960 (Maiman, 1960) (see Chapter 2). Following this initial breakthrough, engineers and physicists began to test the possible applications of laser radiation. They found that it is possible to drill holes through razor blades using ruby laser radiation, suggesting that it might be suitable for other technological applications. Physicians also compared laser light with the other light sources that had been used in medical treatment up to this time. Because light radiation was already in widespread use for the treatment of diseases, mainly in dermatology and during the twentieth century also in ophthalmology (as was documented above, and see also Chapter 13), the first successful experiments using laser light for such treatments were carried out very soon after laser light was first generated.

The first real success in terms of laser technology was in the care of a detached retina. Arc-lamp radiation was replaced by millisecond red ruby laser pulses. After successfully treating rabbits for detached retina, the ophthalmologist Ch. J. Campbell and then Ch. Zweng² performed the first successful operations on a human patient (Koester and Campbell, 2003).

Ruby laser light interaction with the skin was also under investigation at this time. In 1961, Leon Goldman became the first researcher to use laser radiation to treat a human skin disease when he treated a skin melanoma. In 1963, Goldman and his co-workers published the first study on the effects of laser radiation on the skin, describing the selective destruction of skin pigmented structures (including hair follicles) using a ruby laser beam. They noted highly selective injury of pigmented structures (black hair) with no evident change in the white skin underneath (Goldman et al., 1963). This method later became popular for removing birthmarks, nevi and tattoos with minimal scarring. In 1966, Goldman supervised the first operation in which laser radiation was used to remove a tumor without causing bleeding. The laser’s pulses of light cut skin and cauterized blood vessels simultaneously, paving the way for several other applications (Goldmann, 1967; Waynant, 2002; Geiges, 2011). The difficulty lay in controlling the power output and the delivery rate of the laser radiation, as well as the relatively poor absorptive capacity of some types of tissue for ruby laser light. With the development of laser physics and successive discoveries of other aspects of laser technology³ such as the generation of new wavelengths, radiation with various energy levels, high power and small beam divergence, a new branch of science dealing with the applications of ‘laser medicine’ began to develop.

Other laser treatments in medicine followed almost in parallel with the news in laser science. Soon after the discovery of the Nd:glass laser, its near-infrared (IR) radiation was first used for medical treatment. For people with diabetes, a significant development occurred in 1968 when F. L’Esperance, E. Gordon, and E. Labuda successfully used an argon ion laser for the treatment of diabetic retinopathy (L’Esperance, 1969; L’Esperance and James, 1981). This laser has further potential applications in treating port-wine stain marks. Studies were also carried out on the possible treatment of vascular malformations using argon laser technology. The discovery of CO2 and Nd:YAG lasers in 1964 was also of great importance for medicine. These two lasers work in the near-IR (Nd:YAG) and far-IR (CO2) regions of the spectrum, and have been the most common laser devices in medical practice up to the present time. It was found that a Nd:YAG and CO2 laser beam could cut tissue like a scalpel, but with minimal blood loss. Using an out-of-focus beam created the potential for a larger spot size, making hemostasis possible. This made Nd:YAG and CO2 lasers a helpful tool in surgery on vasculated organs such as liver, oral mucosa and gynecological tissue. The surgical uses of CO2 lasers were investigated extensively from 1967 to 1970 by pioneers such as T. Polanyi and G. Jako, and the use of the CO2 laser in otolaryngology and gynecological surgery became well established in the early 1970s. Advances in this field were also made by V. C. Wright and I. Kaplan, who developed the application of CO2 lasers to general surgery (Wright, 1982; Kaplan, 1984).

Together with the discovery of new laser types, the development of new ways of using lasers influenced the discovery of new medical treatments. In 1962 Hellwarth and McClung discovered the potential for generating short, tens of nanoseconds (10–9 s) long, pulses, which provided a much higher power laser than those previously available. These pulses were therefore named ‘giant’ pulses (Hellwarth and McClung, 1962) (for an explanation of this phenomenon, see Chapter 5). Using such giant pulses, the most striking results have been obtained with the removal of tattoos and nevi. In 1964 Maher described the generation of the first spark produced by intense laser radiation. Laser pulses incorporating both high power levels and sparks generated in the tissue were subsequently used in ophthalmology for removing secondary cataracts (Krasnov, 1975; Fankhauser, 1982). When even shorter pulses in the range of picoseconds (10–12 s) appeared (Dienes et al., 1972), they were used for the same purpose (Aron-Rosa et al., 1980). Recent developments have given rise to the generation of femtosecond pulses (10–15 s), which are used in ophthalmology for cornea reshaping. In the twenty-first century, semiconductor lasers are used in medical applications, where their small dimensions and compactness are an asset.

With the development of so many types of laser, it is important to choose the laser with the optimal radiation parameters for a particular tissue treatment. A poor choice of laser may lead to null results or even to tissue damage. Therefore, a fundamental knowledge of laser technology is necessary before a laser is selected for a particular medical treatment.

After 50 years of laser radiation application in medicine, the background of the interaction between radiation and tissue is understood. Because these facts are common to all the medical treatments presented in this book (for therapeutics as well as for diagnostics), the relation of laser radiation properties to particular medical treatments is given in this first chapter. This part provides an overview of the interaction of laser radiation with tissue and describes the main active factors which must be taken into account before a laser is used in medicine. It provides readers with some background knowledge which can be used alongside the specialized descriptions of laser treatment in the third and fourth parts of this book in order to better understand the choice of individual lasers for diagnostics and therapy.

1.2 Interaction of laser radiation with tissue: main contributing factors

In all medical laser applications, the use of radiation for particular diagnostics or treatments should be based on a sound knowledge of the interactions of laser radiation with human tissue. A suitable choice of laser system for the necessary medical application requires a perfect knowledge of the biological processes taking place during the interaction.

Nevertheless, in medical procedures the biological effect caused by the laser radiation is based on the primary physical phenomenon (for example, tissue coagulation after thermal radiation). For this reason it is useful to look at such interactions from the physical point of view and to investigate the criteria that should be used for proper laser selection and to derive which factors and mechanisms are crucial in terms of laser radiation interaction with tissue.

Considering the effects of laser radiation on tissue as a necessary consequence of physical and biological processes, the following factors should be taken into account as having a potential influence on the outcome of laser–tissue interactions:

• laser radiation

• irradiated tissues

• mutual interaction processes.

1.3 Laser radiation

In order to understand the laser radiation interaction with the particular type of tissue, it is necessary to know about the main laser output radiation characteristics, such as the wavelength, pulse duration or possible interaction time interval, radiation energy, power, fluence, intensity and divergence. Hundreds of lasers generating radiation at wavelengths ranging from X-ray up to far IR currently exist (see Fig. 2.15). From the point of view of pulse duration, radiation can affect the tissue for time intervals from multiple seconds up to several femtoseconds (10− 15 s). Radiation energy can range in level from nanojoules (10–9 J) up to tens of joules. Depending on the interaction time, the radiation peak power can range from microwatts (10–6 W) to gigawatts (10⁹ W). The radiation can be focused to a small spot with a diameter of several micrometers, resulting in a high level of fluence or intensity (10⁶ J/cm² – 10¹² W/cm²) (for details see Chapter 2, Section 2.3.2).

1.4 Interacting tissue

Human tissue is heterogeneous matter made up of many different components. Using a very basic classification, it can be divided into hard tissue, soft tissue and biological fluids.

1.4.1 Hard tissues

These include mainly bone, dental enamel or dentine, and calcified tissue plates. In terms of its interaction with radiation, hard tissue can be characterized by its water content and by the OH-radicals of the hydroxyapatite.

1.4.2 Soft tissues

These include primarily muscles, nervous tissue, skin and adipose tissue. Soft tissue can be opaque or transparent and is predominantly composed of water, which is its main chromophore (a material or tissue component that absorbs a specific radiation wavelength). Soft tissue can also consist of many other types of molecules, such as the pigment melanin, lipids and carbohydrates.

1.4.3 Biological fluids

These are mainly represented by blood, which contains predominantly water and then proteins, leukocytes, thrombocytes and blood cells with hemoglobin.

Due to the complexity of the different types of tissue and their components, the results of tissue–radiation interaction are different in each part of the tissue. Molecules absorb photons of radiation with particular wavelengths, and their behavior after absorption is determined by the output characteristics of the interacting radiation: its fluence, intensity, power, and so on. In order to predict the result of laser radiation interactions with tissue, the fundamental properties of tissue must be understood. They can be divided into the optical (index of refraction, absorption coefficient, scattering coefficient, anisotropy factor) and thermal (mainly, thermal conductivity and thermal diffusivity) (for more details on this topic see Chapter 3).

1.5 Mutual interaction processes

Before the mutual interaction processes are explained, it should be mentioned that there are two purposes for laser irradiation of tissue: diagnostic and therapeutic. In the case of diagnostics, permanent changes in the tissue should not occur during irradiation, and only the condition of the examined, irradiated tissue is detected. The goal of the therapeutic application of laser radiation is to cause controlled, specific damage to occur in the irradiated tissue to improve the health of the patient.

A variety of therapeutic interaction mechanisms can occur during the application of laser light onto biological tissue. These can begin on delivery of the laser radiation (see Chapter 4) and can be generally divided into primary and secondary factors. Detailed investigation suggests that the primary factors of laser radiation interaction with tissue include spectral reflection, refraction, absorption, scattering, and transmission (see Chapter 3). Secondary factors include photochemical or photothermal interaction (non-ablative heating, vaporization), photoablation, plasma-induced ablation, and photodisruption.

1.6 Primary factors

1.6.1 Spectral reflection and refraction

Reflection and refraction are related to the Fresnel laws. Refraction plays a role when the radiation falls on some transparent tissue such as the cornea. In opaque tissue, absorption and scattering are more common than refraction. The dominant effect (reflection, absorption, or scattering) in the interaction depends on the type of material and on the characteristics of the incident radiation. Spectral reflection determines the amount of incident radiation that penetrates into the tissue.

1.6.2 Scattering of electromagnetic radiation

Scattering processes occur when the parameters of the incident radiation (direction, phase, wavelength, and polarization) change according to the type of scattering. The scattered light is emitted in all directions around the scattering centers. If this center is large, such that its size is comparable with the incident wavelength of the radiation (such as in a blood cell), it is called Mie scattering. Scattering dependent on light polarization is called Rayleigh scattering. The intensity of Rayleigh scattering is proportional to the fourth power of the incident radiation frequency. In both cases, scattered radiation has the same wavelength as the incident light. It is considered to be an elastic collision (that is, a photon is scattered without an energy change) and the scattered light is coherent. In addition to these processes, there is a third type of scattering in which inelastic collision occurs, resulting in a change in the scattered radiation frequency. Raman and Brillouin scattering are examples of this third type.

1.6.3 Spectral absorption and transmission

The ability of the receiving medium to absorb electromagnetic radiation plays a fundamental role in therapeutic treatment. This ability depends on several factors, mainly the electronic structure of the atoms and molecules, radiation wavelength, the thickness of the absorbing medium and its internal parameters (temperature, concentration of absorbing elements, etc.).

In biological tissue, spectral absorption is mainly caused by water molecules and secondly by macromolecules such as proteins and pigments. Water is the main component of human tissue, and absorption of radiation in water plays a fundamental role in the transmission of radiation into the tissue structures. Water is transparent to visible radiation, whereas radiation is absorbed by melanin and hemoglobin. The most significant absorption of radiation in water is in the ultraviolet (UV) and infrared (IR) parts of the spectrum. In the IR part of the spectrum, many absorption maxima can be found. The most significant peak is at the wavelength of 2.94 μm, which coincides with the Er:YAG laser output wavelength. Other tissue components affecting the penetration of radiation include proteins, pigment, melanin, and hemoglobin. Proteins have absorption peaks around the wavelength 0.28 μm. Melanin is the most important tissue and epidermal chromophore. It absorbs mainly in the UV and in the visible areas of the spectrum – its absorption coefficient decreases monotonically across the visible spectrum toward IR. Hemoglobin is the dominant compound of vascular tissue. It has absorption peaks around the wavelengths 0.28 μm, 0.42 μm, 0.54 μm, 0.58 μm, and 0.6 μm. For hard tissue treatment, except for water wavelength absorption dependence, hydroxyapatite also has to be taken into account. The maximum absorption of this substance is found in the far infrared area of the spectrum, around 10 μm. The dependence of the absorption of the main tissue components on the radiation wavelength is shown in Fig. 1.1 (Hale and Querry, 1973; Miseredino, 1995; Boulnois, 1986). The wavelengths of the most commonly used types of laser radiation in medicine are marked. In view of the fact that water is contained in most biological molecules, the water absorption dependence on the wavelength plays a significant role during decision-making about the applicability of a particular laser for a given treatment. The graph of water absorption dependence on the wavelength is therefore placed in all laser descriptions, in order to clarify at which wavelength the radiation can be absorbed (Part II, Chapters 5 to 8).

1.1 Main tissue components absorption dependence on radiation wavelength (adapted from Boulnois 1986, with Springer Science permission).

1.7 Secondary factors

Secondary factors involved in tissue–radiation interactions are determined by the power density dependence on the interaction time. Although the number of possible combinations of interaction parameters (i.e. laser radiation and tissue) is virtually unlimited, the secondary effects can be divided into five categories according to the results of this interaction, depending on the radiation power density and the interaction time. The interaction can be described as photochemical, thermal, photoablation, plasma-induced ablation, or photodisruption (Boulnois, 1986; Niemz, 2004). A schematic representation of the possible physical processes that can take place during tissue–radiation interaction is shown in Fig. 1.2. Double logarithmic dependence on the power density interaction time shows five basic types of interaction. The power density varies between 18 orders, and the exposition of laser radiation (almost identical to the interaction time) also varies between 18 orders. For power densities lower than 100 W/cm², heating of the tissue occurs. The power density level of 10² –10⁸ W/cm² can cause tissue evaporation, and for higher values of 10⁹ –10¹⁵ W/cm² plasma and rear shock waves are created, which can cause the tissue to tear. An interesting feature of the interaction mechanism is the fact that the energy densities can range between 1 and 1000 J/cm². Adjacent types of interactions cannot be viewed as completely separate mechanisms. For example, the effect on temperature can play an important role in photochemical interactions; plasma-induced ablation and photodisruption are seen to overlap in certain areas; ultrashort pulses, which themselves do not cause thermal changes in tissues, can cause thermal damage when they are applied with a high repetition rate (> 10 Hz).

1.2 Physical processes occurring during laser radiation interaction with the tissue. (adapted from Niemz 2004, with Springer Science permission)

1.7.1 Photochemical interaction

Photochemical reactions are metabolic processes that are activated by low-intensity light. The interaction occurs when the incident absorbed radiation photon energy is high enough to convert a quantum system to a higher quantum state, which subsequently causes the chemical reactions. Electrons with higher energy levels more easily overcome the forces binding them to the atomic nucleus. Such excited atoms or molecules can easily react with the surrounding molecules of tissue, with effects such as exchange or sharing of electrons taking place. The main physical characteristics of laser radiation that cause photochemical interactions follow from the requirement that the radiation must obviously interact in the higher levels of the tissue. Therefore, lasers generating radiation in the visible region (where the light is not absorbed by water) are used (i.e. gas lasers such as He-Ne (the wavelength λ = 0.635 μm), Rhodamine dye lasers (λ = 0.632 μm), semiconductor diode lasers (λ ~  0.7 − 0.9 μm), etc.). Regarding the power density and interaction time, very low values (typically 1 W/cm²) and long exposure times lasting from milliseconds (10− 6 s) to continuous exposition are used (see Fig. 1.2). The low power density should ensure negligible temperature rise in the tissue, while the long exposure time should increase the number of photons absorbed.

Photochemical interactions play a very important role in photodynamic therapy (details in Chapter 25), which is based on the application of photosensitive agents. These agents accumulate preferentially in rapidly proliferating cells (i.e. in a tumor) and, after exposure to laser light with the corresponding wavelength, they cause the destruction of a tumor cell. A second application of photochemical interaction is in biostimulation processes, for example wound healing and anti-inflammatory applications. The suitability of photochemical interactions for these applications has been investigated, and some of them are routinely used.

1.7.2 Photothermal interactions

A photothermal interaction is caused by the change of photon energy (absorbed by tissue fluids) into heat energy that arises as a result of molecular vibration and collisions between molecules. Part of the vibrational energy of excited molecules is transferred to the colliding molecule as translational kinetic energy, which is reflected on the macroscopic scale as a temperature increase. This can lead to photothermal effects on the tissue, such as coagulation (see Fig. 1.2), vaporization (thermal ablation), and even carbonization or melting. The main physical parameters of laser radiation used for photothermal interaction are determined by the required therapeutic goal to be obtained by this interaction. The thermal effect should take place inside the tissue as well as on the surface, and therefore various laser wavelengths are used, starting with the visible part of the spectrum (e.g. argon ion λ = 514 nm used for retina coagulation or port-wine-stain removal – see Part IV, Chapters 13 and 14), and moving through to the near-infrared Nd:YAG λ = 1.06 μm (cutting and coagulation – Part IV, Chapter 19), Nd:YAG pulsed λ = 1.06 μm, 1.44 μm (cutting or drilling – Part IV, Chapter 19), up to the mid- and far-infrared pulsed CTH:YAG λ = 2.01 μm, Er:YSGG λ = 2.78 μm, Er:YAG λ = 2.94 μm, and CO2 λ = 10.6 μm for cutting or drilling hard or soft tissue, bone, and so on (see Part IV, Chapters 13 to 21). Regarding the laser radiation parameters, the typical power densities 10–10⁶ W/cm² and exposition time 1 μs − 1 min are used.

1.7.3 Photoablation

The photoablation effect is based on the delivery of sufficient energy into the tissue to ablate it in a short time before any heat is transferred to the surrounding tissue. It is caused by molecules with an electron transition from low-energy orbital to higher (non-bounded) orbitals absorbing high-energy photons. This absorption causes an explosive expansion in the irradiated tissue volume, as well as tissue evaporation from the surface. The resulting tissue removal is primarily mechanical; it includes a thermoelastic expansion of the tissue. Therefore, lasers generating high-energy photons can be good candidates for photoablation (for example, excimer lasers generating light in the UV spectral region – see Chapter 6). Besides the UV lasers, there are also several lasers generating in the visible or near-infrared spectral region (ruby 0.69 μm or Nd:YAG 1.06 μm – see Chapter 5) that can be used, with a short pulse duration and a corresponding power density. Regarding the power density and interaction time, values of about 10⁷ –10¹⁰ W/cm² are used for photoablation, together with exposure times in the order of tens of nanoseconds to microseconds.

1.7.4 Laser-induced plasma ablation and photodisruption

Plasma-induced ablation refers to well-defined removal of tissue, without thermal or mechanical damage. If the peak power density of the laser radiation is high enough, localized micro-plasma is formed. In the focal volume, free electrons are generated by thermal or multi-photon ionization. These electrons absorb the incoming photons and consequently accelerate. If their kinetic energy is high enough, they ionize colliding molecules and generate new free electrons, repeating the process and starting an avalanche effect leading to the generation of free electrons and ions. A dielectric breakdown can occur in the tissue, leading to the formation of high-pressure plasma and causing either plasma-induced ablation of the tissue or photodisruption, depending on the value of the laser power density. For plasma-induced ablation, power density levels of 10¹¹ W/cm² to 10¹³ W/cm² are needed. (The laser pulse length should be approximately from 100 fs (10− 15 s) up to 500 ps (10− 12 s). In the case of photodisruption, values from 10¹¹ W/cm² up to 10¹⁶ W/cm² are applied (laser pulse length from 100 fs up to 100 ns (10− 9 s)). In the case of photodisruption, besides the creation of plasma, other physical effects can also occur, such as acoustic shock wave generation, Brillouin scattering, and multiple plasma generation.

As soon as the plasma appears, it can absorb all the incident energy. This effect is called plasma shielding and it has an important role in the medical application of laser technology; for example, in ophthalmology microsurgery for secondary cataract treatment, plasma shielding can be used to destroy the clouded posterior capsule membrane that often appears after primary cataract surgery (see Chapter 13). An important feature of plasma generation is that it can occur not only in pigmented tissue but also in transparent media, due to the increased absorption coefficient caused by the induced plasma. The laser-induced plasma and disruption effect has also been successfully used in lithotripsy to destroy urinary or biliary stones (see Chapter 16).

For laser-induced plasma ablation and photodisruption, lasers capable of generating a high power density are used. Excimer lasers, Ti:sapphire or Nd and Yb doped lasers have the potential for very short pulse length generation (see Chapters 2, 5). To destroy urinary stones, the high-energy Ho:YAG laser is used.

1.8 Conclusion

In conclusion, it can be said that that there is no longer a medical discipline in which lasers have not been used or at least tested. New possibilities offered by lasers in medical applications include the connection of various types of lasers with endoscopes, microscopes, or operating electro-coagulators. A prerequisite for the further development of laser systems in medicine is to deepen basic biological research into the interactions between lasers and living tissue at the cellular and molecular level. Sophisticated, highly manageable devices, along with better knowledge of the optical properties of tissue, will enable accurately determined destruction of pathological tissue and its treatment in the future.

1.10 References

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Dienes, A., Ippen, E.P., Shank, C.V. High-efficiency tunable CW dye laser. IEEE J. Quantum Electronics. 1972; 8:388.

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Krasnov, M.M. Laser-phakopuncture in the treatment of soft cataracts. Br. J. Ophthalmol.. 1975; 59:96–98.

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L’Esperance, F.A., James, W.A.Diabetic Retinopathy: Clinical Evaluation and Management. London: YB Medical Publishers, 1981.

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Meyer-Schwickerath, G.R. The history of photocoagulation. J. Ophthalmol.. 1989; 17:427–434.

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¹Niels Ryberg Finsen was awarded the Nobel Prize in 1903 in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation. He opened a new avenue for medical science.

²Charles J. Campbell treated the first human patient at the Harkness Eye Institute of Columbia University on 22 November 1961. Christian Zweng performed a similar operation in Palo Alto, California a week later.

³The following discoveries were hugely important for the development of laser medicine: Nd:glass laser (λ = 1.06 μm; E. Snitzer, 1961); continuously (cw) running red He-Ne laser (λ = 0.632 μm; A. White and D. Rigden, 1962); semiconductor laser (near infrared; R. Hall, 1962); green (pulsed and then cw) argon-ion laser (λ = 0.514 μm and 0.488 μm; W. Bridges and E. Gordon, 1964); CO2 laser (λ = 10.6 μm; K. Patel, 1964); Nd:YAG laser (λ = 1.06 μm; J. Geusic and LeGrand Van Uitert, 1964); helium-cadmium laser (λ = 0.442 μm; W. Silfvast and G. Fowles, 1965); first dye laser (P. Sorokin and F. P. Schaefer, 1966); pulsed UV xenon excimer laser (N. Basov, 1970); running continuously at room temperature semiconductor laser (Z. Alferov, 1970).

Part I

Laser–tissue interaction


Laser characteristics

H. Jelínková and J. Šulc,     Czech Technical University in Prague, Czech Republic


After some historical remarks, Chapter 2 gives a review of laser radiation fundamentals so as to understand how the laser operates. The fundamental parts of the laser system (the active medium, pumping, and open resonator) are mentioned and their function in the laser system is explained. It is shown that various laser systems operate on the same basic principles. The classification of lasers according to active medium, generated wavelength, and energy levels involved in stimulated emission, type of pumping, regime of operation, time development or safety precautions is shown. The main laser radiation characteristics – monochromaticity, directionality, coherence, and high brightness – are listed and the output beam characteristics are also described.

Key words


spontaneous emission


stimulated emission

light amplification

optical resonator

laser pumping

classification of lasers

2.1 Introduction: principle of the laser

The word LASER is an acronym of the words Light Amplification of Stimulated Emission of Radiation. The generation of laser radiation is based on the stimulated emission of light in an active material which is in an excited state caused by a pumping source. The first laser radiation was generated in May 1960 by T. Maiman, but the history of the laser goes back much further. To understand the origin of laser radiation, it is necessary to know some basic principles discovered in the twentieth century.

2.1.1 Light and matter interaction

At the turn of the twentieth century, Max Planck, in seeking to explain the shape of an absolutely blackbody radiation spectrum, hypothesized that, during the mutual interaction of the substance and light, the exchange of the energy (emission or absorption) is possible only over a discrete volume, which he called quanta, and that the size of these quanta of energy E is


where the constant of proportionality h is referred to as the Planck constant h = 6.626 × 18− 34 J/s. Energy E is expressed in Joules (J) and frequency v in Hertz (Hz), i.e. 1/s. Albert Einstein followed Planck’s research with studies of the photoelectric effect (1905), and he declared that the energy of light is transmitted in discrete quantum particles called photons. French physicist Louis de Broglie in 1924 attributed some wave properties to matter. His hypothesis was expressed by the equation


According to this equation, to each free matter with the momentum p is assigned a monochromatic plane-wave with the wavelength λ, while h is the Planck constant. This relationship confirmed the dual nature of light (wave–particle duality¹¹) – light can be seen as waves (radiation) or as particles (Fig. 2.1).

2.1 Demonstration of the dual nature of light. The light from the sun (or, generally, all electromagnetic radiation) propagates in accordance with the laws of general optics (reflection, refraction, absorption, scattering, transmission), and at the same time displays the properties of particles (it is possible to investigate the radiation power).

One of the principal parts of the laser is an active material. This material can be considered as a system of molecules, atoms, or ions consisting of mutually coupled–bounded elementary particles: protons, neutrons, and electrons. From the point of atom theory the so-called ‘stationary state’ of the atom can be defined (published by Niels Bohr in his ‘General assumptions’, 1915 (Bohr, 1934)). Every stationary state is characterized by a specific, well-defined energy. In the bound system of particles, more inner stationary states exist, corresponding to different values of energy. These discrete energy values are called energy levels (Fig. 2.2). The state corresponding to the smallest value of energy E0 is known as the ground state. Other states (with higher energy) are defined as excited states. Since the energy of stationary states of systems cannot take an arbitrary value (it is quantized), the system of the atoms, ions, or molecules is called a quantum system. The difference between the energy of the ground state and of the excited state is referred to as excitation energy. The highest energy level of the quantum system corresponds to an ionization energy (causing the disintegration of the atom to the free electron and ion) or to dissociation energy, which causes a molecule to split into simpler groups of atoms, single atoms, or ions.

2.2 Energy levels of quantum system (n is the number of energy level which corresponds to energy E).

In nature the system is affected by the surrounding environment. This external influence impacts on the internal structure of the system and causes changes to its stationary state. The change from one stationary state of the quantum system to another is called quantum transition. When a quantum system accepts energy (from an external light source or due to collisions of the atoms or molecules, etc.) then it is located in the excited state (excited level), and this process is called absorption. After a certain time the quantum system returns to its stable position, and during transition it releases the energy. This process is called spontaneous emission. The time interval for which the quantum system stays at the excited state is called the lifetime of this state. The excited state lifetime is typically a few nanoseconds (10− 9 s), but can be as short as a picosecond (10− 12 s) or as long as a few milliseconds (10− 3 s). The long-lived excited state is referred to as a metastable state (first investigated in excited helium by J. Franck and F. Reiche).

To satisfy the law of energy conservation, the energy that the quantum system exchanges with the surroundings must equal the energy difference between the initial and final states of the quantum system (ΔE = Einitial − Efinal). The exchanged energy may have the form of a photon (electromagnetic wave). The emitted photon has energy equal to ΔE, but all its other properties (such as direction, phase, and polarization) are random. The effects taking place in the quantum system can be described in the simplest form by two levels only (the so-called two-level approximation) (Fig. 2.3).

2.3 photons = particles @ waves.

In 1916, Einstein hypothesized that, as well as spontaneous emission, a stimulated, induced, or forced transition can exist (Einstein, 1916; Einstein, 1917). This emission occurs when the incoming photon (with the energy equal to the difference ΔE = E2 − E1) induces transition of quantum system from the excited to the ground state. The new emitted photon then not only has the same energy as the ‘stimulating’ photon, but it will propagate in the same direction, and it has the same phase. This emission is called stimulated, induced, or forced emission (Fig. 2.3(c)). This statement expresses the fundamental principle of the MASER (microwave amplification of stimulated emission of radiation) or the LASER (light amplification of stimulated emission of radiation). The basics of masers and lasers were thus given, but it took many years to successfully demonstrate the first amplification by stimulated emission of radiation.

2.1.2 Population inversion and light amplification

The experimental verification of stimulated emission was first obtained in 1928 in gas discharges (Kopfermann and Ladenburg, 1928). The basic model of the active material (when seen as a macroscopic system) is a set of N identical, independent quantum systems per unit volume (generally N > > 1). Although they are the same quantum systems, they can generally exist in many possible quantum states – i.e. in different internal configurations and at various energy levels Ei, where i = 0, 1, 2. . . . At every time, at the i-th energy level (with energy Ei) there exists a certain number of particles (Ni) out of the whole set of N. The statistical meaning of particle counts (Ni) per unit volume is called a population or occupancy of the i-th energy level. The sum of the population of all levels in the quantum system must be equal to N. If the quantum system does not interact with the surroundings (it is an isolated system), no macroscopic changes exist, and the system is in so-called thermodynamic equilibrium. In this case, the population of the levels is given by Boltzmann’s law


where N1, N2 expresses the occupancy of the energy levels E1 and E2, k = 1.381×10− 23 J/K is the Boltzmann constant, and T is the absolute temperature. The population of every energy level decreases exponentially with growing energy (Fig. 2.4(a)).

2.4 – atom/molecule in the ground state.)

In nature, most materials are in a state of thermodynamic equilibrium, which means that most quantum systems are in the ground state given by the structure of particular atoms or molecules. Hence, under natural conditions the probability of absorption is higher than the probability of stimulated emission of radiation and only spontaneous emission can occur.

In order to amplify the radiation, the population N2 on the upper level should be greater than the population N1 on the lower level (Fig. 2.4(b)) – the so called population inversion has to be established. To reach this population distribution, energy must be added to the quantum system. There are many possible ways to reach population inversion (see Fig. 2.13). This process is called quantum systems pumping

Attainment of a particular laser material population inversion depends on many factors, namely, on the usually rather complicated structure of the active material energy level as such.

To explain the pumping procedure, the two-level approximation of the quantum system is not sufficient, and therefore it is necessary to use a view in which higher excited levels are taken into account. Obviously they are compressed into one ‘pumping level’. Then so-called three-level or four-level models are defined (Fig. 2.5). In both these cases the laser transition takes place between the upper level 2 and terminal level 1.

2.5 – atom/molecule in the ground state)

In the case of three-level approximation, the pump causes an excitation from ground state 1 to the excited state 3 (Fig. 2.5(a)). This state is rather short-lived, and, therefore, the atom drops quickly (through the non-radiative transition) to the first excited level 2, which is considered as a metastable level. (During non-radiation transition the energy ΔE = Einitial − Efinal is released in the form of a non-radiative phonon, causing lattice vibration and consequently a heating of the material.) The transition from this metastable level to the ground state causes the release of quanta of radiation. When more photons are absorbed from the pumping source, the number of atoms in the metastable state can exceed the number of atoms in the ground state and population inversion occurs. The main representative of the three-level system is the ruby laser (Chapter 5).

At four-level approximation, the lower laser level is not the ground state (Fig. 2.5(b)). The pumping radiation causes transition from ground state 0 up to the second short-lived excited state 3, from which the quantum system decays to the metastable upper laser level 2. Laser transition occurs between this laser level 2 and the terminal level 1, which is a short-lived state and its population is near zero. (The transition from this level and ground state is quick non-radiative transition.) The population inversion between levels 2 and 1 can be achieved in a much easier way in comparison with the three-level energy system. The fact that the lower lasing transition for the three-level system is the ground state makes it rather difficult to reach efficient population inversion in comparison with the fourlevel system. A typical four-level laser is the Nd:YAG laser (Chapter 5) or the helium-neon (He-Ne) gas laser (Chapter 6).

The principle of radiation amplification is schematically described in Fig. 2.6 (for explanation the three-level model is used). The left-hand side of the figure (Fig. 2.6(a–c)) shows the interaction of photons with the unpumped materials (being originally in thermal equilibrium – Fig. 2.6(a)). The coming quanta with resonance pumping frequency vp (vp = (E3 – E1)/h) are mostly absorbed, and the quantum system will gradually reach the excited state (Fig. 2.6(c)). As seen on the right-hand side of the figure (Fig. 2.6(d–f)), the signal wave resonant photons interact with the active material which is in the excited state. The radiation from the external source with the signal energy Es (Es = E2 − E1) is passing through the excited material and stimulates the atoms to transition to the terminal level (Fig. 2.6(d)). As it spreads through the active material the avalanche process starts and the number of stimulated photons increases – original radiation is amplified (Fig. 2.6(e)). The quantum system then relaxes back to the state of thermodynamic equilibrium as at the beginning of the process (Fig. 2.6(f)).

2.6 – atom/molecule in the ground state). Left-hand side of the figure: initial state (a); absorption of the resonant radiation Ep and creation of population inversion (b, c); right-hand side: stimulated emission (d) amplification of the passing signal radiation Es (e); transition of the material to the thermodynamic equilibrium (f).

In 1939, V. A. Fabrikant predicted the use of stimulated emission for amplifying ‘short’ waves (Fabrikant, 1939; Lukishova, 2010). Together with his colleagues M. M. Vudynsky and F. A. Butaeva, he investigated amplification of electromagnetic radiation. The idea of amplifying radiation by stimulated emission was first proved in the microwave region. In 1953, J. Weber proposed a microwave amplifier which was based on stimulated emission in a paramagnetic solid (Weber, 1953). In 1954, a molecular device MASER (using molecules of ammonia in a resonant microwave cavity) for generating microwave radiation with a wavelength of 13 mm was built independently by N. G. Basov and A. M. Prokhorov, and by J. P. Gordon, H. J. Zeiger, and Ch. H. Townes (Basov and Prokhorov, 1954; Gordon et al., 1955). In 1958, a maser with a solid state medium – the ruby – was developed by Makov et al ). To generate shorter wavelengths even in the optical region, a special resonator based on the open Fabry–Pérot cavity was suggested by L. Schawlow and Ch. H. Townes. So, now all parts of the future laser were available (i.e. the active medium, pumping, and the open resonator). On 16 May 1960, T. Maiman generated the first ever optical laser radiation, using a ruby crystal. Pulsed operation was obtained and red radiation with a wavelength of 694.3 nm was generated (see Section 2.2). The system was named LASER (Maiman, 1960a, b). The abbreviation LASER was first used by G. Gould (see Taylor, 2000; Townes, 1999; Maiman, 2000). Since that time many other lasers with various active materials, different systems of pumping, and arrangements of Fabry–Pérot resonator have been designed, constructed, investigated, and even introduced into practice (see Chapters 5–8).

2.2 Fundamentals of lasers

The ruby laser worked on the following principle. When population inversion is established by pumping (the active elements – the atoms, ions, or molecules of the active material – are in an excited state), generation of laser radiation can start. Due to the effort of a quantum system to remain in thermal equilibrium, some of the quantum systems are returning to the lower state, with the emission of spontaneous photons, which are emitted with different polarizations in all directions and in a wide spectral range given by the laser active medium.

The spontaneous photons fulfil the role of the incoming stimulating photons (see Fig. 2.6(d)), causing induced transition of other excited quantum systems (atoms, ions, molecules) from the excited into the ground state with the emission of stimulated photons. As a result, every spontaneously emitted photon stimulates generation of other photons. While passing through active medium, as described above, the photons trigger an avalanche process and the number of stimulated photons increases. To further amplify the generated photon beam, the reflecting mirror is placed into the path of propagating photons. After reflection they pass through active medium once again and their number increases. When the second mirror – parallel to the first one, and obviously partially transmitting – is used on the opposite side of the active medium, the radiation is reflected and then passed through the active medium again. The system of two plan-parallel adjusted mirrors is called an ‘optical (open) resonator’, which is based on the above-mentioned Fabry–Pérot cavity. When pumping is still switched on (in the active medium there are sufficient systems in the excited state), the number of photons bouncing inside the resonator is growing, the laser beam is formed and it leaves the resonator through the partially reflecting mirror. The formation of laser radiation inside the resonator is graphically illustrated in Fig. 2.7. The photons moving in other directions than the direction perpendicular to the resonator mirrors do not return to the active medium, and they do not play a principal role in the laser radiation generation.

2.7 – atom/molecule in the ground state).

2.2.1 Basic laser components

From the previous paragraph it follows that the laser system consists of the following three main parts: an active material, a pumping source, and an optical (open) resonator. These parts form the head of the laser system.

1. Active material – a substance in which population inversion can be reached. This medium can be: ions in crystals (e.g. Fe² +, Dy² +, Cr³ +, Ti³ +, Nd³ +, Pr³ +, Dy³ +, Ho³ +, Er³ +, Tm³ +, Yb³ +); atoms (e.g. Cu, Ne, I), ions (e.g. Cd+, Ar+), or molecules (e.g. ArF, CO, CO2) in gases; dye molecules in solutions or solids (e.g. Rhodamine 6); electron–hole pairs in semiconductor material (e.g. InGaAs); or multi-ionized atoms in plasma (see Fig. 2.13). Detailed characteristics are given in chapters 5–8. All active media have a complicated inner structure of energy levels or bands (semiconductors).

2. Pumping energy source – supplies the necessary energy into the laser active medium to create population inversion of energy levels, which is the principal requirement for radiation amplification. Depending on the type of a particular active material, pumping requires either the light from a flash-lamp, radiation from another laser, or electrical discharge; or a chemical reaction, or electric current to cause electron collisions, etc. Detailed characteristics for particular lasers are also given in chapters 5–8.

3. Optical (open) resonator – creates optical feedback mechanism essential for formation of laser oscillations inside the resonator. It is a system of two or more reflective surfaces – mirrors or other reflecting optical elements (prisms, etc.) providing a possibility to establish standing waves with a wavelength λ much smaller than the geometric dimension of the mirrors and the distance between them (Fig. 2.8) (Siegman, 1986; Hodgson and Weber, 2005; Saleh and Teich, 1991; Silfvast, 1996; Svelto, 1998; Koechner, 1999).

2.8 Schematic of the standing waves inside the optical resonator and generated radiation transmitted by the partially transparent resonator mirror (L-resonator length, distance between resonator mirrors, λ-wavelength of generated radiation).

One of the resonator mirrors is fully reflective (its reflectivity is ~ 100%); the other is partly transparent (transparency is equal to 1% up to 99% according to the laser system). By this mirror (called output coupler) the laser light is coupled out from the resonator.

The fundamental function of the laser active material were explained in the previous section, and details for the particular laser types will be presented in chapters 5 to 8. Due to various active materials, there are numerous laser pumping systems, which are strongly dependent on the active medium properties. The fundamentals of the open resonators which are common to most lasers will be given in the following section.

In addition to the basic laser system components listed above (i.e. active medium, optical resonator, and pumping system), which can be found in every laser (see Fig. 2.9), laser systems for medical or technological purposes or for other applications typically contain an electronic system belonging to the set of pumping, and a cooling unit (usually used for solid-state lasers – see Fig. 5.2). (In some special cases, the laser system does not have a laser resonator (Cu, N2 lasers, plasma lasers). These lasers are working in the regime of amplification of spontaneous emission.) In the output there is a telescopic system forming the output laser beam or a delivery system transporting the laser radiation to the interaction place (see Chapter 4). Also, strong attention has to be paid to compactness of the whole system and reduced needs for adjustment and correction of the system. Automated security features, which protect the operator (in medical treatment, surgeons and patients) from possible reflected radiation, also have to be included. These are most of all the construction problems of every particular laser system.

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