Laser-tissue interactions: fundamentals and applications


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Views Total views. Actions Shares. Embeds 0 No embeds. No notes for slide. Concepts such as the optical and thermal properties of tissue, and optical breakdown and its related effects, are treated in detail. You just clipped your first slide! Clipping is a handy way to collect important slides you want to go back to later. Now customize the name of a clipboard to store your clips. Visibility Others can see my Clipboard. Cancel Save. More information about this seller Contact this seller.

Brand New!. Seller Inventory VIB Markolf H. Publisher: Springer , This specific ISBN edition is currently not available. View all copies of this ISBN edition:. Synopsis About this title Medical practitioners, scientists and graduate students alike will find this exhaustive survey a vital learning tool. Buy New Learn more about this copy. Other Popular Editions of the Same Title. Springer, Hardcover. Search for all books with this author and title. As in all macromolecules, the ground and the excited electronic states are further split into several vibrational states. It was found by Kinoshita that the emission peak at nm decreases toward higher concentrations of HpD.

The lowest investigated concentration of 8. The time- 3. Data according to Yamashita Fig. Energy level diagram of HpD. Singlet 1 S and triplet 3 S states are shown. Dashed lines indicate higher excited states 54 3. For instance, Fig. Meanwhile, the results of several experiments and clinical applications have been collected.

It was found that other photosensitizers might even be more useful than HpD. According to Kessel , the primary adverse reaction of photodynamic therapy relates to the photosensitization of skin. Other disadvantages of HpD are: — since HpD absorbs very poorly in the red and near infrared spectrum, only tumors very close to the surface can be treated, — its concentration gradient among tumor and healthy cells could be steeper, — the production of HpD from calf blood is very expensive. However, the initial isolation in the period between injection of HpD and laser irradiation remains and is one of the biggest problems for patients.

This context also explains the injection of carotenoids immediately after laser irradiation. These agents act as a protection system on a molecular basis, because they reverse the production of singlet oxygen by means of a triplet carotenoid state compare Table 3. The protective property of carotenoids has been successfully tested by Mathews-Roth Currently, further photosensitive compounds of a so-called second generation are under investigation concerning their applicability for PDT.

In order to achieve a similar extent of tumor necrosis, it was reported by Gossner et al. Another interesting substance is 5-aminolaevulinic acid ALA which itself is not even a photosensitizer but a precursor of the endogeneous synthesis of porphyrins. According to Loh et al. Concentrations of HpD as labeled. The approximate decay durations are 2.


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Data according to Kinoshita 56 3. Interaction Mechanisms Gossner et al. The results are graphically summarized in Fig. The sensibility is measured in terms of a commonly used index of skin edema. It is interesting to observe that ALA induces least toxic skin damage. Thus, patients treated with DHE will have to remain in dark rooms for at least four weeks. Degree of skin sensibility after application of various photosensitizers as a function of time.

Data according to Gossner et al. Alternative photosensitizers such as mTHPC and ALA should be investigated in a large group of patients to further improve this type of treatment. Finally, an approved committee has to compare all results with those obtained with other minimally invasive methods of tumor treatment such as exposure to ionizing radiation. In several cases, observers have noticed improvements for the patients. Moreover, contradictory results were obtained in many experiments. However, often only very few patients were treated, and no clinical protocols were established.

In the area of such injuries, conditions are usually created preventing proliferation such as low oxygen concentration or pH. The exposure to red or near infrared light might thus serve as a stimulus to increase cell proliferation. One remaining open question is, which of the characteristics of laser radiation — coherence, narrow bandwidth, polarization — is of primary importance for biostimulation? Or, in other words, does it necessarily have to be a laser or would an incoherent light source serve as well? Usually, the controversy stems from our inability to specify the photochemical channels of potential reactions.

Detailed investigations in this area and reproducible experimental results are badly needed. Finally, the principles of laser-induced interstitial thermotherapy — a recently established treatment technique — are discussed. The histologic appearance of coagulated tissue is illustrated in Figs. In a histologic section, the coagulated area can be easily detected when staining the tissue with hematoxylin and eosin. In the second photograph, pulses from an Er:YAG laser were applied to an excised cornea. Again, the tissue was stained with hematoxylin and eosin.

A tooth was exposed to 20 pulses from an Er:YAG laser. During the ablation process, complete layers of tooth substance were removed leaving stair-like structures. This observation is attributed to the existence of so-called striae of Retzius which are layers with a high content of water molecules. Water strongly absorbs the Er:YAG wavelength at 2. The induced increase in pressure — water tries to expand in volume as it vaporizes — leads to localized microexplosions with results as demonstrated in the enlargement in Fig. The resulting ablation is called thermal decomposition and must be distinguished from photoablation which will be described in Sect.

In this case, however, too much energy was applied and carbonization occurred. Thus, the local temperature of the exposed tissue had been drastically increased. For medical laser applications, carbonization should be avoided in any case, since tissue already becomes necrotic at lower temperatures.

Thus, carbonization only reduces visibility during surgery. Finally, Figs. They originate from thermal stress induced by a local temperature gradient across the tooth surface. The edge of the interaction zone is shown in an enlargement in Fig. The temperature must have reached a few hundred degrees Celsius to melt the tooth substance which mainly consists of hydroxyapatite, a chemical compound of calcium and phosphate as will be discussed in Sect.

Interaction Mechanisms Fig. Photograph kindly provided by Dr. Kurek Heidelberg. Interaction Mechanisms Temperature certainly is the governing parameter of all thermal laser— tissue interactions. And, for the purpose of predicting the thermal response, a model for the temperature distribution inside the tissue must be derived.

The reaction with a target molecule A can be considered as a twostep process. Therefore, the temperature rise microscopically originates from the transfer of photon energy to kinetic energy. To answer this question, we have to consider both steps separately. First, absorption is facilitated due to the extremely large number of accessible vibrational states of most biomolecules. Second, the channels available for deactivation and thermal decay are also numerous, because typical energies of laser photons Er:YAG laser: 0. The spatial extent and degree of tissue damage primarily depend on magnitude, exposure time, and placement of deposited heat inside the tissue.

The deposition of laser energy, however, is not only a function of laser parameters such as wavelength, power density, exposure time, spot size, and repetition rate. For the description of storage and transfer of heat, thermal tissue properties are of primary importance such as heat capacity and thermal conductivity.

In biological tissue, absorption is mainly due to the presence of free water molecules, proteins, pigments, and other macromolecules as discussed in Sect. Therefore, the absorption spectrum of water — one important constituent of most tissues — is plotted in Fig. In this section of the spectrum and in the UV, absorption in tissue is higher than shown in Fig. Toward the IR range of the spectrum, however, 3.

Absorption of water. It should be borne in mind that the total attenuation in the UV is strongly enhanced by Rayleigh scattering as discussed in Sect. It originates from symmetric and asymmetric vibrational modes of water molecules as illustrated in Fig. According to Pohl , the resonance frequencies of these vibrational modes are 1. A similar argument applies for the wavelength of the Ho:YAG laser at 2. Flow chart with important parameters for modeling thermal interaction 3. Heat transport is solely characterized by thermal tissue properties such as heat conductivity and heat capacity.

We assume that a slab of tissue is exposed in air to a Gaussian-shaped laser beam as illustrated in Fig. For the sake of simplicity, a cylindrical geometry is chosen with z denoting the optical axis, and r the distance from this axis. From 3. Geometry of tissue irradiation 68 3. Interaction Mechanisms 3. Deposition of heat in tissue is due only to light that is absorbed in the tissue. According to Takata et al. In the case of water, i. In real laser—tissue interactions, however, there are losses of heat to be taken into account, as well.

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They are based on either heat conduction, heat convection, or heat radiation. Usually, the latter two can be neglected for most types of laser applications. One typical example 3. The perfusion rates of some human organs are summarized in Table 3. Heat radiation is described by the Stefan—Boltzmann law which states that the radiated power is related to the fourth power of temperature.


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Due to the moderate temperatures achieved in most laser—tissue interactions, heat radiation can thus often be neglected. Blood perfusion rates of some selected human organs. The dynamics of the temperature behavior of a certain tissue type can also be expressed by a combination of the two parameters k and c. With these mathematical prerequesites, we are able to derive the general heat conduction equation. Its combination with 3. With an additional heat source S like the absorption of laser radiation, 3. In cylindrical coordinates, 3.

The proof is straightforward. We simply assume that 3. The solution to the inhomogeneous heat conduction equation, 3. Usually, it is numerically evaluated assuming appropriate initial value and boundary conditions. For the sake of simplicity, we assume that the heat conduction parameters are isotropic4. In Table 3. Thermal penetration depths of water Time t Thermal penetration depth ztherm t 1 10 1 10 1 0.

By this means, the least possible necrosis is obtained. The scaling parameter for this time-dependent problem is the so-called thermal relaxation time according to Hayes and Wolbarsht and Wolbarsht Thermal relaxation times of water Because of 3. Interaction Mechanisms In Fig. After the laser pulse, i.

The thermally damaged zone is shorter than the optical absorption length. Thus, thermal damage to adjacent tissue can be kept small if a wavelength is selected that is strongly absorbed by the tissue. However, only a few groups like Andreeva et al. But their operation is not yet stable enough for clinical applications. Alternatives might soon arise due to recent advances in the development of tunable IR lasers such as the optical parametric oscillator OPO and the free electron laser FEL.

Tissue parameters according to Hayes and Wolbarsht and Weinberg et al. This procedure 3. Thus, for this period of time, temperature does not linearly increase as assumed in 3. Detailed simulations were performed by Weinberg et al. One example is found in Fig. The dependence of temperature on repetition rate of the laser pulses was modeled by van Gemert and Welch In this case, pulses from a picosecond Nd:YLF laser were focused on the same spot of a human tooth at a repetition rate of 1 kHz. In particular, the enlargement shown in Fig. In order to get a basic feeling for typical laser parameters, the following very simple calculations might be very useful.

Second, energy is transferred to vaporization heat. And third, the remaining energy leads to a further increase in temperature of the water vapor. This, however, is not always an easy task. In general, though, approximate values of achievable temperatures can often be estimated. As already stated at the beginning of this section, these can be manifold, depending on the type of tissue and laser parameters chosen. Furthermore, certain repair mechanisms of the cell are disabled.

Thereby, the fraction of surviving cells is further reduced. The corresponding macroscopic response is visible paling of the tissue. Due to the large increase in volume during this phase transition, gas bubbles are formed inducing mechanical ruptures and thermal decomposition of tissue fragments. Only if all water molecules have been vaporized, and laser exposure is still continuing, does the increase in temperature proceed.

To avoid carbonization, the tissue is usually cooled with either water or gas. All these steps are summarized in Table 3. For illustrating photographs, the reader is referred to Figs. Interaction Mechanisms Table 3. It is illustrated in Fig. The curve is derived from several empirical observations. In the example selected in Fig. Critical temperatures for the occurrence of cell necrosis. Data according to Henriques and Eichler and Seiler 3. But, according to Johnson et al.

The local degree of tissue damage is determined by the damage integral given in 3. This was performed by Weinberg et al. However, in Table 3. Typical lasers for coagulation are Nd:YAG lasers or diode lasers. CO2 lasers are very suitable for vaporization and the precise thermal cutting of tissue. Therefore, careful evaluation of the required laser parameters is essential.


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Reversible and irreversible tissue damage can be distinguished. Carbonization, vaporization, and coagulation certainly are irreversible processes, because they induce irrepairable damage. Hyperthermia, though, can turn out to be either a reversible or an irreversible process, depending on the type of tissue and laser parameters.

Since the critical temperature for cell necrosis is determined by the exposure time as shown in Fig. Thus, exposure energy, exposure volume, and exposure duration together determine the degree and extent of tissue damage. The coincidence of several thermal processes is illustrated in Fig. It was recently introduced to the treatment of various types of tumors such as in retina, brain, prostate, liver, or uterus, and has already become a well established tool in minimally invasive surgery MIS. The principal idea of LITT is to position an appropriate laser applicator inside the tissue to be coagulated, e.

As stated in Table 3. Due to the associated coagulation of blood vessels, severe hemorrhages are less likely to occur than in conventional surgery. This is of particular importance in the case of tumors, because they usually are highly vascularized. Thus, large volumes can be treated with temperature gradients not as steep as those associated with conventional thermotherapies based on heat conduction only.

Typical parameters of the procedure are 1—5 W of CW laser power for a period of several minutes and coagulation volumes with diameters of up to 40 mm. Especially in neurosurgery, it is very important to prevent injury from adjacent healthy tissue and sensitive structures. The spatial extent of the damage zone primarily depends on laser power, laser exposure, geometry of the laser applicator, and on thermal and optical tissue properties.

Since the optical penetration depth of laser light in the near infrared is very high, deeper zones are reached more easily by the mechanism of light scattering rather than by heat conduction. Therefore, laser applicators emitting their radiation through a scattering surface are favored compared to focusing optics.

Recently improved applicators scatter laser light isotropically into all spatial directions by means of a frosted rough surface as described by Roggan et al. In order to ensure isotropic scattering at the interface 82 3. Continuous emitting surfaces with active lengths up to 20 mm can be manufactured. Only then can large tissue volumes be safely coagulated at a rather moderate gradient of temperature. Experimental setup for laser-induced interstitial thermotherapy.

According to Roggan et al. Finally, i. The same target may be treated several times by LITT to increase the spatial extent of tissue necrosis. For large lesions, the distance between adjacent puncturing canals should not exceed 1. The whole procedure can be performed either intraoperatively or percutaneously. In both cases, it should be preceded by suitable irradiation planning to obtain best surgical results. This can be achieved with appropriate computer simulations by considering a variety of input parameters. Most important among these are the position, extent, and topology of the diseased volume as well as optical and thermal tissue parameters, and the rate of blood perfusion.

A choice of laser power and exposure duration should then be provided by the program. Detailed computer simulations for the laser treatment of liver tissue are illustrated in Figs. This is performed by dividing the tissue into consecutive shells and using a mathematical algorithm which takes into account the heat conduction from adjacent layers only.

After a few recursions of this algorithm, a steady-state solution is obtained expressing the desired temperature distribution. From Fig. Computer simulation and experimental results of LITT for liver tissue laser power: 4 W, surface of applicator: mm2. In the model of thermal interaction as described above, only absorption was taken into account. Especially during the process of coagulation, the optical properties of tissue are changed, leading to higher scattering but nearly the same absorption.

Each beamsplitter separates the incident laser beam into two laser beams with equal power. Using a total of three optical beamsplitters, a single input beam can be divided into four output beams. The coagulated volume visibly pales. Roggan Berlin Fig. As shown in Fig. He can thus adjust the coagulated volume to the geometry of a tumor. Some indications, e. In these cases, it is extremely important to avoid the coagulation of these organs at risk.

This task can be achieved by applying trapezoidal lesions.

Fundamentals and Applications

In volume scatterers, light is scattered by tiny scattering centers distributed throughout the whole volume of the applicator. Raw quartz is one of the basic materials used for volume scatterers. In raw quartz, the scattering centers consist of tiny gas bubbles. In Sect. For a further characterization of each method, the reader is referred to Sect. The removal of tissue was performed in a very clean and exact fashion without any appearance of thermal damage such as coagulation or vaporization.

This kind of UV light-induced ablation is called photoablation and will be discussed in this section. The ablation depth, i. The main advantages of this ablation technique lie in the precision of the etching process as demonstrated in Fig. Soon after, biological tissues were also ablated. Today, photoablation is one of the most successful techniques for refractive corneal surgery, where the refractive power of the cornea is altered in myopia, hyperopia, or astigmatism see Sect.

In this section, for the sake of simplicity, we will follow the explanations given by Garrison and Srinivasan in the case of synthetic polymer targets. Due to the homogeneity of these materials, their behavior under certain experimental conditions is easier to understand. Thus, experimental data on the ablative process are very reliable and theoretical modeling is strongly facilitated.

However, most of the theory applies for the more inhomogeneous biological tissues, as well. Organic polymers are made up of large molecules consisting of more than atoms, mainly carbon, hydrogen, oxygen, and nitrogen. A smaller molecular unit of up to 50 atoms is called a monomer. In Figs. The polymer is described by structureless monomer units held together by strong attractive forces. The interaction with laser radiation is simulated by allowing each monomer unit to undergo excitation directly from an attractive to a repulsive state.

This promotion is associated with a change in volume occupied by each monomer, leading to a transfer of momentum and, thus, to the process of ablation. For the sake of simplicity, a face-centered cubic fcc crystalline array is assumed. With a density of 1. The main attractive forces holding the monomer units together are the two carbon—carbon bonds along the chain. The strength of such a C—C bond is approximately 3. With these assumptions, the process of photoablation was simulated as shown in Fig. Computer simulation of photoablation showing the movement of PMMA monomers as a function of time.

In order to obtain a physical explanation of the photoablation process, let us assume that two atoms A and B are bound by a common electron. The corresponding energy level diagram of the ground and several excited states is shown in Fig. Due to the macromolecular structure, each electronic level is split into further vibrational states. Usually, the excitation is achieved by satisfying the Franck—Condon principle. Thus, transitions characterized by a vertical line in the energy level diagram are favored as indicated in Fig. Energy level diagram for photoablation If a UV photon is absorbed, the energy gain is usually high enough to access an electronic state which exceeds the bond energy.

In this case, the two atoms A and B may dissociate at the very next vibration. The dissociation energies of some typical chemical bonds are listed in Table 3. Moreover, the wavelengths and the corresponding photon energies of selected laser systems are given in Table 3. When comparing both tables, 92 3. Dissociation energies of selected chemical bonds. Therefore, the interaction mechanism of photoablation is limited to the application of UV light. The ejected photoproducts of excimer laser ablation have been analyzed in several studies, e.

It is interesting to add that the product composition was found to be wavelength-dependent. Srinivasan et al. Thus, the corresponding etched surface at nm is rougher and less predictable than at nm. If the incident intensity is moderate and such that the ablation depth is smaller than the corresponding optical absorption length, subsequent pulses will enter partially irradiated tissue as well as unexposed tissue underlying it.

After these, a linear relation between the number of applied pulses and the total etch depth is obtained. In practice, the etch depths are averaged over several pulses and noted as ablation depth per pulse. The physical principles of photoablation are summarized in Table 3. However, it is not limited to excimer lasers, since generating higher harmonics of other laser types can result in UV radiation, as well. The 4th harmonic of a solid-state laser, for instance, also induces photoablation as reported by Niemz et al. In both cases, the pulse duration at the fundamental wavelength was set to 30 ps.

The higher harmonics were induced by means of two BBO crystals. Whereas distinct impact sites of the focused laser beam are clearly visible in the section exposed to the second harmonic, a clean and homogeneous layer is ablated with the fourth harmonic. Enlargement of area exposed to the second harmonic right. Enlargement of area exposed to the fourth harmonic right 96 3. To evaluate the decrease in intensity, 3. This condition requires that a certain amount of energy must be absorbed per unit volume and time to achieve photoablation.

The threshold intensity Iph is determined by the minimal number of bonds that have to be dissociated to yield decomposition. The ablation depth d, i. The ablation curve of rabbit cornea is shown in Fig. The logarithmic dependence, i. This section of the ablation curve is observed in almost any kind of tissue. However, the threshold Iph is not as sharp as predicted by 3. This result most probably stems from the inhomogeneity in fragment 8 For a complete mathematical description of photoablation, the temporal shape of the applied laser pulses should also be taken into account.

Further details are found in the paper by Srinivasan a. The threshold varies around an average value according to the size of the ablated fragment. Imagine that such a fragment was bound to several molecules prior to ablation. As soon as a certain ratio of dissociated molecules is reached, the fragment will be released. Consequently, averaging of various fragment sizes leads to a smooth intercept with the abscissa. Ablation curve of rabbit cornea obtained with an ArF excimer laser pulse duration: 14 ns. Data according to Fantes and Waring Above a second threshold Ipl — the threshold of plasma generation — the ablation depth per pulse obviously saturates as shown in Fig.

All abundant energy thus dissipates to heat and does not contribute to a further increase in ablation depth. Therefore, the ablation curve saturates at high energy densities. Hence, 3. For a detailed discussion of plasma parameters and plasma shielding, the reader is referred to Sect. In the s, the question was raised whether photoablation is based on a photochemical or a photothermal process.

This discussion has led to 98 3. Interaction Mechanisms much controversy. Andrew et al. Today, it is well accepted that photoablation — or the synonym ablative photodecomposition in the sense of UV ablation — shall be considered as an interaction mechanism of its own that can certainly be distinguished from pure photochemical and thermal processes described in Sects. And only an ablation caused by UV photons should be regarded as photoablation9.

In order to distinguish photoablation or ablative photodecomposition from thermal interaction, we take a closer look once more at the energy level diagram shown in Fig.

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The photon energy is not high enough for the molecule to reach a repulsive state. The molecule is promoted only to a vibrational state within the ground level or to a rather low electronic state including any of its vibrational states.

Laser-Tissue Interactions: Fundamentals and Applications

By means of nonradiative relaxation, the absorbed energy then dissipates to heat, and the molecule returns to its ground state. It only states that an ablation occurs which is caused by photons, but it does not imply any further details. Photoablation in the common sense, though, is a very precise ablation caused by UV photons. In the cases of the ArF laser and the KrF laser, the slope of the curve strongly decreases above a certain threshold, i. Radiation from the XeCl laser, on the other hand, continues to act thermally even at higher energy densities.

However, the bottom line of the above observation — i. Therefore, we can conclude that ArF excimer lasers are probably the best choice when aiming at photoablation. XeCl laser could be used for thermal decomposition, although CW lasers might do a similar job. This statement has to be taken seriously, since laser surgery, of course, should not evoke new maladies when eliminating others. And it is also well known that this radiation can cause mutagenic alterations of cells, e. The major chemical change is the formation of a dimer from two adjacent pyrimidine bases.

Other products are also synthesized in the DNA that may have biological consequences. Cells are frequently able to repair dimers before any adverse responses occur. This is an indispensable mechanism of protection, since the DNA contains important genetic information. Thus, if these photoproducts are not repaired, erroneous information may be passed on to progeny cells when the cell divides. Several studies have been done in order to evaluate potential hazards from UV laser radiation. With these, most of the UV spectrum is covered. Only in some cases was radiation at nm found to be less cytotoxic than at nm.

Whereas the Hg 3. Data according to Rasmussen et al. Sister chromatid exchanges per cell after UV irradiation. When comparing the ArF laser at nm and the XeCl laser at nm, the latter is less cytotoxic. In the same study, the exchange of sister chromatids was measured. These can either be repaired by the cell or, in severe cases, lead to irreversible defects.

In the latter case, either cell necrosis or uncontrolled cell proliferation, i. The extent of sister chromatid exchange was investigated for the same UV sources and is shown in Fig. The required energy density at nm, for instance, is much less than at nm or nm. Moreover, the slope of the curve at nm is much steeper than the others.

Thus, another proof is given that radiation from a Hg lamp can be considered as being more mutagenic than ArF or XeCl lasers. We conclude that radiation from excimer lasers is less mutagenic than UV light from Hg lamps. This observation can probably be explained by the existence of proteins in the cell matrix which strongly absorb radiation at nm, before it reaches the cell nucleus containing the DNA.

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According to Green et al. Hence, the sensitive DNA inside the nucleus is shielded by the surrounding cytoplasm. However, potential risks should never be ignored when using ArF or XeCl lasers. Actually, a few altered cells might be enough to induce cancer in tissue. And, according to Rasmussen et al. For instance, a haze inside the cornea is frequently observed within a few years after refractive corneal surgery has been performed with excimer lasers. The origin of this haze is yet unknown.

It might well be attributed to cell alterations, even if corneal tumors do not occur. A bright plasma spark is clearly visible which is pointing toward the laser source. If several laser pulses are applied, a typical sparking noise at the repetition rate of the pulses is heard. In one case, a sample of corneal tissue was ablated with a picosecond Nd:YLF 3. The cross-sectional view shows a very precise excision without mechanical ruptures. Further details on potential applications are given in Sects.

Sometimes, plasma-induced ablation is also referred to as plasma-mediated ablation.

Laser-tissue interactions: fundamentals and applications Laser-tissue interactions: fundamentals and applications
Laser-tissue interactions: fundamentals and applications Laser-tissue interactions: fundamentals and applications
Laser-tissue interactions: fundamentals and applications Laser-tissue interactions: fundamentals and applications
Laser-tissue interactions: fundamentals and applications Laser-tissue interactions: fundamentals and applications
Laser-tissue interactions: fundamentals and applications Laser-tissue interactions: fundamentals and applications

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