A laser treatment device for living tissue

Abstract

The invention relates to a laser treatment device for treating living tissue (2), comprising a pulsed laser light source (4) with an emission power of 5 W to 100 W, the irradiation of the living tissue with laser light (1) being triggered by a trigger device via an applicator; a detection device (3) for measuring the volume change in relation to time caused by the absorption of the laser light in the living tissue (2); a computing unit (6) for issuing control commands to a control device for controlling the laser light (1) power irradiated onto the living tissue (2) depending on the evaluation of the detected volume change, wherein: a. each trigger causes a first heating laser pulse with a first laser power and a first laser pulse duration and a second heating laser pulse with a second laser power and a second laser pulse duration to be applied to the living tissue (2) at a predetermined pulse interval; b. the detection device (3) records the volume change caused by the rising and falling power gradient of the first laser pulse and provides the measured values to the computing unit (6); c. the computing unit (6) determines an estimate of the temperature rise of the living tissue (2) during the irradiation of the first heating laser pulse based on the measured values of the volume change and at least taking into account the predetermined rise of the power gradient of the first heating laser pulse; d. depending on the estimate, a command is issued to adjust the second power and / or the second laser pulse duration of the second laser pulse such that the irradiation of the second laser pulse heats the living tissue (2) to a predetermined target temperature.

Description

Technical Field

[0001] This invention relates to a laser treatment device for living tissue, comprising a pulsed laser source and automatic adjustment of irradiation power, and is an ophthalmic laser device for treating the posterior part of the eye. Background Technology

[0002] Lasers are used to treat various retinal diseases. During laser irradiation of the posterior segment of the eye, primarily the light-absorbing layers, the retinal pigment epithelium (RPE) and choroid, are heated, and heat diffuses from here into adjacent layers. Besides the absorbed laser energy, this diffusion depends on the pulse duration and the irradiated area. For each laser spot on the retina, the typical area has a diameter of approximately 100-500 μm, and the irradiation duration is typically 20-500 ms. The shorter the irradiation time, the less heat diffuses into the volume outside the irradiated area.

[0003] Depending on the treatment objective, different temperatures are required to avoid undertreatment (i.e., lack of therapeutic effect) or overtreatment (i.e., unintentional collateral damage). Within the stated time range, sublethal stimulation of the retina requires approximately 43-50°C (e.g., high-thermal tissue stimulation for prophylactic treatment of dry age-related macular degeneration (AMD), subvisible (subthreshold) 50-70°C or mild photocoagulation 70-90°C (e.g., diabetic macular lesions), and intense photocoagulation 90-120°C (for panretinal irradiation in diabetic retinopathy or retinal detachment). For selective thermomechanical destruction of the RPE (e.g., for serous central retinopathy), nanosecond to microsecond pulses are used, where temperatures >140°C occur only in the RPE (selective retinal therapy, SRT) and result in the selective generation of microvesicles on intracellular melanosomes. At pulse durations of 2 μs, thermal necrosis is observed in addition to rupture. Generally, pulse durations between 2 and 50 μs are considered a transitional region between thermomechanical and thermal effects.

[0004] Due to the large fluctuations in light transmission through the eye and the highly variable light absorption of the RPE (20-80% in the visible spectrum), the aforementioned temperature rise cannot be achieved with a fixed laser setting. Therefore, it is absolutely necessary to measure and regulate the temperature rise during irradiation.

[0005] To measure temperature, a photoacoustic method is known, for example, from US2003 / 032949 A1, in which a retinal absorber is thermoelastically excited by means of repetitive short-pulse laser radiation (pulse duration in the nanosecond range, repetition rate typically 1 kHz) superimposed on therapeutic laser radiation, and the pressure transients emitted on the cornea of ​​the eye can be picked up by an ultrasonic transducer. Due to the temperature dependence of the Grüneisen coefficient, the pressure amplitude increases with retinal temperature and, after prior calibration, indicates an increase in the current average temperature on the retina. Strictly speaking, it is possible to determine the temperature in this way only as long as the target tissue is reversibly heated but has not yet suffered thermal conversion and permanent damage. Nevertheless, concepts have been developed for assessing tissue damage caused by a sequence of laser pulses (“pulse trains”) and, in doing so, determining the temperature during the first portion of the pulse train sequence in order to adjust the laser during the application of a second portion of the same pulse train sequence, see, for example, US2010 / 292763 A1.

[0006] The goal is to allow the physician to precisely trigger the laser only once for each point to be treated, assuming that only intentional tissue damage occurs there without causing excessive collateral damage. Typically, with this "economical" laser treatment, only faint or even no visible damage appears on the retina. In this respect, there is no direct and objective way to assess the physician's effectiveness.

[0007] A significant drawback of the method in US2003 / 032949 A1 is that a separate laser is required in addition to the treatment laser, which increases the complexity and cost of the laser system.

[0008] Currently, continuous-emission high-power lasers with emission power on the order of 10W in the green spectral band are being developed for use on the retina. In the current context, this invention covers emission power on the order of 5W. It is anticipated that in the future, lasers with emission power on the order of 100W and approximately constant power over longer durations will also be used for medical purposes. When using such high power, the total irradiation time per laser point must be at a low μs interval (2-50 μs) or even lower and well-tuned to avoid causing severe, uncontrollable damage to the retina. More specifically, when using such lasers instead of laser pulse sequences, a single pulse may already be therapeutically effective.

[0009] The tissue's extremely rapid heating makes it impossible to use photoacoustic methods of the type described in US2003 / 032949 A1 for temperature control, because pressure transients always require up to approximately 20 μs to travel from the retina to the acoustic sensor in the contact glass. The measurement signal arrives too late to modulate the thermal laser pulse.

[0010] Alternatively, optical detection can be used to measure the instantaneous volume changes of the irradiated tissue during laser heating via reversible thermal expansion and contraction. Such methods have been tested, for example, in documents US2013 / 102894 A1 and US2015 / 011983A1, and these methods utilize interferometers, specifically envisioned for interferometry, measuring light sources typically reflected into the therapeutic laser beam. However, the main drawbacks here are the complexity and cost of the laser system.

[0011] The work by Xiahau Feng et al., "Self-temperature regulation of photothermal therapy by laser-shared photoacoustic feedback," Vol. 40, No. 19, October 1, 2015, *Optics Letters*, pp. 4492-2295, discloses a laser device with photoacoustic feedback for controlling the temperature of a target using only a single thermal laser. The laser operates in a pulse-modulated manner, where a linear chirped sequence of long heating pulses and short pulses for temperature measurement alternates continuously in time with a pressure transient and an ultrasonic transducer. This results in automatic adjustment of the irradiation dose on the target by modulating the pulse duration of the thermal laser, enabling the target to reach and maintain a predetermined temperature with high precision. In this work, the target is a phantom, the laser emission power is 1 W, and the pulse duration of the laser thermal pulses is in the range of milliseconds to seconds. The chirped sequence takes 40 microseconds, and there is no time delay to the ultrasound transducer. These simplified conditions do not allow for direct application to retinal treatment problems.

[0012] As described in US2010 / 292963 A1, the idea of ​​using the heated laser itself to determine the temperature is also followed here. Document DE 10 2009 016184A1 describes a method with alternating short measuring laser pulses and continuous, very long heating laser pulses from a combined laser source specifically designed for laser treatment of the posterior segment of the eye under temperature monitoring and adjustment.

[0013] Fei Gao et al., “Single laser pulse generates duel photo-acoustic signals for differential contrast photoacoustic imaging,” Scientific Reports 7:626, DOI:10.138 / s41598-017-00725-4, published online on April 4, 2017, discloses the possibility of photoacoustic imaging of biological tissues using only two pressure transients triggered and detected at the beginning and end of a long heated laser pulse. By allocating stress confinement while maintaining thermal confinement, they demonstrated that the pressure transients at the beginning and end of the heated laser pulse have opposite polarities and different amplitudes, which can provide information about the energy density deposited in the tissue during the pulse duration. Summary of the Invention

[0014] In view of the above background, the present invention proposes a laser treatment device for living tissue, which utilizes the relatively high power and pulse duration of laser pulses for self-adjusting treatment; the device also has objective effect evaluation.

[0015] The technical solution of this invention:

[0016] A laser therapy device for treating living tissue includes: a pulsed laser having an emission power of 5W to 100W; an applicator for guiding the laser; a triggering device for triggering the laser to irradiate the living tissue via the applicator; a detection device for measuring the volume change over time caused by laser absorption in the living tissue; and a computing unit for evaluating the detected volume change and issuing control commands to a control device to control the laser power irradiated onto the living tissue; wherein:

[0017] a. Each triggering of irradiation of living tissue results in a first heating laser pulse having a first laser power and a first laser pulse duration, and a second heating laser pulse having a second laser power and a second laser pulse duration, being applied to the living tissue at a predetermined pulse interval, wherein

[0018] b. The detection device optically or acoustically records the volume change caused by the rising and falling power gradients of the first laser pulse and provides the measured values ​​to the computing unit;

[0019] c. The computing unit determines an estimate of the temperature rise of the living tissue during irradiation by the first heating laser pulse, based on the measured value of the volume change and taking into account at least a predetermined increase in the power gradient of the first heating laser pulse.

[0020] d. Based on the estimated value, the computing unit sends a command to the control device, which causes the control device to adjust the second power and / or the duration of the second laser pulse, so that the irradiation of the second laser pulse heats the living tissue (2) to a predetermined target temperature. Attached Figure Description

[0021] Figure 1 A simplified diagram of a laser system with a processing unit and a detector for volume change signals is shown.

[0022] Figure 2 Experimental data on the gradient rise of a laser at various pulse durations and powers are shown for an example using a diode laser.

[0023] Figures 3a-3c Experimental measurements of (time-shifted) pressure transients are shown when laser pulses with comparable pulse durations are heated with different powers. Detailed Implementation

[0024] A laser therapy device for treating living tissue (2) includes: a pulsed laser (4) having an emission power of 5W to 100W laser (1); an applicator for guiding the laser (1); a triggering device for triggering the laser (1) to irradiate the living tissue (2) via the applicator; a detection device (3) for measuring the volume change over time caused by laser absorption in the living tissue (2); and a computing unit (6) for evaluating the detected volume change and issuing a control command to a control device to control the power of the laser (1) irradiating the living tissue (2), wherein:

[0025] a. Each trigger results in a first heating laser pulse having a first laser power and a first laser pulse duration, and a second heating laser pulse having a second laser power and a second laser pulse duration, being applied to the living tissue at a predetermined pulse interval (2), wherein

[0026] b. The detection device (3) optically or acoustically records the volume change caused by the rising and falling power gradients of the first laser pulse and provides the measured values ​​to the computing unit (6);

[0027] c. The computing unit (6) determines an estimated temperature rise of the living tissue (2) during irradiation by the first heating laser pulse, based on the measured value of the volume change and taking into account at least a predetermined rise in the power gradient of the first heating laser pulse.

[0028] d. Based on the estimated value, the computing unit (6) sends a command to the control device, which causes the control device to adjust the second power and / or the duration of the second laser pulse, so that the irradiation of the second laser pulse heats the living tissue (2) to a predetermined target temperature.

[0029] The dependent claims relate to advantageous embodiments, and more specifically to further developments in evaluating the effects.

[0030] To date, temperature measurements have typically used short, low-energy laser pulses that should not, or only minimally, contribute to the heating of the tissue. Where possible, the aim is generally to avoid altering the tissue condition during the condition determination process.

[0031] The device according to the invention now eliminates the need for short laser pulses or pulse trains of such laser pulses, instead applying only long heating laser pulses of medium to high power, each heating laser pulse causing a temperature rise of several degrees Celsius during its pulse duration. For treatment of a single laser point, particularly on the retina, very few pulses are required, preferably even only two pulses.

[0032] The first heating laser pulse at the heating laser point should preferably not trigger any sustained tissue damage (e.g., denaturation), but rather induce a sufficiently rapid volume change solely through the thermal expansion of the tissue at the start and its contraction at the end of the heating laser pulse, which can be recorded using an optical or acoustic detection device. In doing so, the detection device generates a volume change signal, which is sent to a processing unit capable of evaluating it.

[0033] This detection device can, for example, be used for optical recording of thermally triggered motion in irradiated tissue, which is made of light-diffusing or light-reflecting tissue layers, and can include an interferometer and at least one photodetector that measures the light intensity changing over time and emits it as a measurement. For this purpose, optical coherence tomography (OCT) can be used, for example, or a highly coherent light source (single longitudinal mode) with speckle recording can also be used. The therapeutic laser itself can also emit light with sufficiently high coherence so that a small fraction of the therapeutic light can simultaneously be the measurement light. Based on the determined motion, such as the change in distance between two diffuse tissue layers, the sought volumetric change can be directly inferred.

[0034] According to the invention, preferably, the detection device is configured to record heat-triggered pressure waves in irradiated living tissue and includes at least one ultrasonic transducer that records pressure transients and emits them as measurements. Sufficient time is provided for the ultrasound waves to propagate from the heated tissue to the ultrasound receiver during and between long pulses.

[0035] According to the present invention, it is envisioned that information from the first heating laser pulse is used to adjust the second heating laser pulse applied only after the volume change signal is recorded and evaluated.

[0036] Preferably, the interval between the durations of the first and second pulses is 2 to 50 microseconds. Other pulse durations are not excluded, more specifically, shorter pulse durations. The distinguishability-separability of the volume change signal at the start and end of the pulse depends on the detection type: optical detection can also achieve this for very short pulses. In terms of equipment, acoustic detection is generally simpler.

[0037] Pulse interval is typically defined as the time interval between two identical characteristics of two consecutive laser pulses, such as the same rising pulse gradient or pulse maximum value. Alternatively, in the case of several pulses each with a long pulse duration, it is advantageous to define the pulse interval as the pause duration between two pulses, i.e., the time interval between the falling gradient of the heating laser pulse and the rising gradient of the next heating laser pulse. Preferably, the time pulse interval between the first and at least the second heating laser pulses should be predetermined to be greater than the thermal relaxation time of living tissue.

[0038] Previous knowledge about thermal relaxation time exists in the literature, such as Brinkman and Birngruber, “Selective Retina Therapy”, *Z. Med. Phys.* 17 (2007), pp. 6–22. This paper states that the thermal relaxation time depends on the size and structure of the object being heated by the laser, and is approximately 64 μs for a hypothetical uniform RPE absorption layer of 4 μm thickness. The authors also conclude that a pulse duration of approximately 5–30 μs is suitable if the goal is to uniformly heat all RPE cells without significantly heating the environment. On the other hand, if a significant peak temperature is desired on the melanosomes, a pulse duration of <5 μs should be chosen. “At pulse durations >50 μs, a limited loss of cell temperature elevation occurs.” This also indicates the aforementioned preferred interval for pulse duration.

[0039] Particularly preferably, the time pulse interval is selected such that the temperature rise in the tissue achieved by the first heating laser pulse is greatly eliminated before the second pulse is triggered, that is, the tissue has returned to its basic temperature, typically 37°C, before irradiation begins.

[0040] However, according to the present invention, the first heating laser pulse is used to obtain information about the tissue in the selected laser point, and the second heating laser pulse causes heating only there to the target temperature to achieve a therapeutic effect. The energy of the second heating laser pulse is generally richer than that of the first heating laser pulse, that is, the product of the laser power and pulse duration of the second heating laser pulse is generally greater than that of the first heating laser pulse.

[0041] It is considered advantageous if the first and second heating laser pulses have the same pulse duration and the laser power is adjusted only for the second heating laser pulse. In high-performance laser diodes developed to date, this can be easily achieved by adjusting the direct power supply. Thus, expensive optical components, such as acousto-optic modulators, are not required for electronically controlled shielding or laser steering. However, the use of optical modulators or changes in the applied power are also covered by the framework of this invention.

[0042] Based on the condition that the emission power of the laser source exhibits sufficiently steep rising and falling gradients when the heating laser pulses are switched on and off, and a smooth, constant plateau process between them, only two significant volume change signals are actually generated if the energy irradiated during the gradient duration δt corresponds to the typical pulse energy of sample pulses detected to date. For photoacoustic detection, a sample pulse with a known energy of 5 μJ is sufficient. In P 最大 In the case of a laser power of 10W, this corresponds to a gradient duration of δt = 1μs, where the applied laser power increases linearly from zero to a maximum value in the first approximation, and then decreases again.

[0043] A particularly significant advantage of this invention is that the assessment of volumetric change resulting from the first heating laser pulse, used to determine an estimate of the temperature rise, can also be readily applied to at least the second heating laser pulse, resulting in an estimate of the actual therapeutically active target temperature induced by the laser after the laser treatment point has ended. This estimate can be displayed to the treating physician in real time, or recorded (i.e., electronically stored), and compared with the physician's desired target temperature. Therefore, the user can effectively monitor treatment protocols that can also serve as electronic proof of treatment or for recording treatment history and are available and stored upon request.

[0044] If a heating laser pulse with a laser power in the range of W is applied to absorbing tissue within a time range of μs, then during the laser power changes dp1 and dp2—when the rising (dp1) and falling (dp2) laser pulse gradients are well detectable—rapid volume changes occur through tissue expansion dV1 and contraction dV2 if the power changes occur sufficiently rapidly within the short gradient durations dt1 and dt2, respectively. Therefore, the heating laser pulse gradient determines the measurement signal to be recorded, i.e., the tissue's direct response to turning the laser on and off. In the case of pulses with a constant stationary process, considering the rise in laser power over the pulse gradient is sufficient for signal evaluation.

[0045] The expansion velocities dV1 / dt1 and contraction velocities dV2 / dt2 can be directly measured by optical interferometry, in which the positional displacement of the tissue layer (e.g., the tissue surface) is tracked. These velocities are at their maximum values ​​during the gradient of the heating laser pulse and allow for estimation of the tissue's coefficient of thermal expansion, which can be derived from preliminary work as temperature-dependent material parameters over a wide temperature range.

[0046] Simultaneously, rapid volume changes trigger pressure waves in the radiation region, which propagate through the tissue and can be recorded by an ultrasound receiver as a time-dependent pressure signal (pressure transient). In this case, the temperature dependence of the previously known Grüneisen coefficient is also used to directly extrapolate the temperature from the pressure transient. The specific measurements dD1 and dD2 can be, for example, the maximum amplitude of the pressure transient or the integral over the period of increasing amplitude, or the frequency of the pressure transient.

[0047] Experimentally, acoustic detection revealed that if the power change and gradient duration are the same at the ends of two pulses, the ratio of the pressure measurement signal from the end of the laser pulse to the pressure measurement signal at the beginning of the laser pulse during heating can be used as a measure of tissue heating. However, this is not usually the case. Nevertheless, the laser pulse gradient can be measured during each pulse, or, provided there is sufficient stability between laser pulses, based on previously available data from the laser source manufacturer.

[0048] In the case of different gradient processes at the beginning and end of the heating laser pulse, the ratio of the pressure measurement signal can be normalized to the gradient rise, for example, according to...

[0049]

[0050] The value ΔP can be introduced here as the maximum rise of the laser gradient. Alternatively, it can be represented as the average rise over the gradient duration δt. Other standardizations in this sense are also possible.

[0051] The steeper the change in laser power, the faster the tissue volume changes. This results in higher expansion and contraction rates and higher pressure amplitudes.

[0052] Regarding acoustic detection, the value α is deterministic; in other words, it represents the ratio of the energy of the pressure wave triggered to the energy of the irradiated laser in each case where the pulse end gradient and pulse start gradient are correlated. From the known temperature dependence of the ratio α and the Grüneisen coefficient of the tissue, the temperature rise produced by the tissue until the end of the pulse can be derived.

[0053] Especially when the pulse duration is less than the tissue's thermal relaxation time, a temperature gradient is generated along the radiation propagation direction z according to the absorption and diffusion of radiation μa(z) and μs(z). Therefore, the value α only results in the average weighted temperature value, which depends on all irradiation and tissue parameters.

[0054] To approximate the extrapolation of temperature rise, the temperature dependence of the Grüneisen coefficient and the initial temperature before irradiation (body temperature, room temperature) must be known. The temperature dependence of the Grüneisen coefficient can be approximated, for example, by a quadratic equation of the following form.

[0055]

[0056] For tissues within a temperature range of 0 to 100°C. For retinal tissue from pigs in a cuvette, the parabola T... m =105.4℃ and the maximum value of zero crossover T0 = -21℃ is approximate (see: Kandula et al., Journal of Biomedical Optics 11(4) 2006), where C is a proportionality constant.

[0057] Calculate the average temperature rise in the tissue One possibility is to calculate it directly through a fitted function. Based on the aforementioned parabolic approximation, the average temperature increase is...

[0058]

[0059] in

[0060]

[0061] T B This is the baseline temperature (e.g., room temperature or body temperature). To rise from the average temperature... Extrapolating the maximum temperature rise T, which is generally of more interest at higher temperatures, is possible. 最大 (T max), which can determine the constant f.

[0062]

[0063] Typically, the constant f depends on the irradiation geometry and duration, as well as the thermo-tissue parameters. In the case of a stretched, homogeneous absorber without diffusion, this results in f = 2 under irradiation with a pulse duration shorter than the thermal relaxation time. Generally, f for a specific sample type or, in this case, tissue category can be determined through theoretical models or experiments (e.g., using thermal sensors, temperature-dependent fluorescent nanoparticles, etc.).

[0064] In order to control the irradiation process at the defined target temperature T Ziel At least two heating laser pulses are applied, wherein the first heating laser pulse has an energy E1 that has not yet reached the target temperature and preferably will not cause thermal damage to the tissue. The temperature is then determined based on measurements taken after the first pulse. The energy E2 of the second auditory laser pulse can be adjusted by setting the power and / or pulse duration so that the target temperature is reached after the second pulse ends, for example, by...

[0065]

[0066] Several pulses can also be applied to approach the target temperature in stages.

[0067] As long as the heat absorbed by the laser and deposited in the tissue cannot leave the irradiated volume via a heat transport mechanism (thermal inclusion), it is in principle irrelevant whether the increased energy E2 is achieved by increasing the power or pulse duration of at least one second heating laser pulse. Initially, only the product of power and pulse duration is relevant. However, it can be seen that it is advantageous not to increase the second pulse duration but to set it equal to the first duration and only increase the power. Heat transport is time-dependent, and the transport process during the second heating laser pulse is naturally most similar to the transport process during the first heating laser pulse. Furthermore, it can be seen that the on-off process during power adjustment of the laser source can lead to different laser power processes for different pulse durations. Controlling the emission of a continuously activated laser by allocating an optical modulator and instead operating the laser with power pulses of different pulse durations does not necessarily assume maintaining the pulse form. This can complicate the evaluation of measurements and can be easily avoided if all pulse durations are chosen to be the same.

[0068] Advantageously, this pulse sequence is chosen so that the tissue is cooled to its base temperature as completely as possible between pulses. Alternatively, any remaining heat can be included in the calculations.

[0069] As already mentioned, a key advantage of this invention is its ability to measure the actual target temperature reached in the tissue because the detection device records the volume changes caused by the slopes of the increasing and decreasing second heating laser pulses, respectively, and provides the measurement results to a processing unit that determines, displays, and / or records an estimate of the temperature rise during the second heating laser pulse. Compared to therapeutic lasers used to date, this laser treatment's numerical and objective effectiveness assessment is considered a significant advancement.

[0070] Furthermore, the use of lasers with power in the range of 5W to 100W opens up pathways for thermomechanical therapy, which focuses on destroying cells through evaporation. Here, by simply expanding the software of the computing unit, treatment and even some effect monitoring using the same laser device according to the present invention are also possible.

[0071] Preferably, in this case, i.e., for a target thermomechanical tissue injury with a target temperature, for example, exceeding 140°C, at the start of the second pilot laser pulse, the computational unit is configured to determine and record the difference between the time at which volume change begins on the rising gradient of the heating laser pulse and the next time after the start of volume change. If the difference in this measurement is less than the duration of the second pulse, it indicates that the measurement signal of volume change arrived early and therefore cannot originate from the falling laser gradient. Instead, the volume change due to the formation of microbubbles in the tissue is recorded. Bubble formation is generally associated with pressure amplitude, which is two orders of magnitude larger than the pressure amplitude of purely thermal triggering when the gradient of the heating laser pulse is not steep. Therefore, they cannot be practically monitored, and the time at which they begin marks the start of bubble formation. In turn, the time difference between the start of bubble formation and the end of the heating laser pulse is measurable and can be used as a measurement of the thermomechanical treatment dose. Using the known pulse duration, this measurement can be directly seen from the time difference determined in the computational unit between the start of the laser pulse and the start of bubble formation.

[0072] The invention will now be described in more detail with reference to the accompanying drawings:

[0073] Figure 1 The diagram shown is a simplified representation of a laser device according to the invention in an embodiment for retinal treatment. In the schematic diagram, the light guide, the applicator, and the trigger for the applicator are not shown.

[0074] The laser (4) emits a heating pulse laser (1) onto the living tissue (2). The detection device records changes in the volume of the living tissue and generates electrical signals that are provided to the arithmetic unit (6). The arithmetic unit (6) can be a programmable microprocessor or a personal computer. It processes the raw data arriving from the detection device (3), stores the data in a non-volatile manner if necessary, and determines control commands for the laser (4) based on the processing results. The control device for the laser (4) is not shown separately but is typically integrated into the structural unit of the laser (4). As preferably assumed here, if the operating current intensity of the laser (4) is changed to control the laser power, the control device can be designed as a simple analog circuit that directly transmits voltage values ​​from the arithmetic unit (6) in the form of current. Alternatively, the control device can also be integrated into the arithmetic unit (6). The control device can also be designed to digitally receive meta-commands from the arithmetic unit (6), such as values ​​for pulse duration and pulse power, and convert these into analog signals to control the laser (4).

[0075] According to the invention, the laser (4) has an emission power in the range of 5W to 100W. Here, as an example, it is preferable, as integrated into the laser source (4) and not shown separately, to be at least a portion of the emission laser power used for time recording laser (1). The measured value of the detected laser power is provided to the arithmetic unit (6) for the arithmetic unit (6) to determine the power rise gradient of the laser pulse. This radiation monitoring is the current state of the technology. In the case of a very stable laser source, it is possible to consider compiling a table of gradients of laser pulses with different pulse durations and powers, rather than repeatedly measuring them.

[0076] The operating device (5) for inputting irradiation parameters into the arithmetic unit (6) is preferably configured to display user-selectable intervals of the irradiation parameters, wherein the intervals are hierarchically restricted depending on the user input. This means that the operating device (5) can be positioned to comply with certain safety rules and reject entries that contradict these rules. This can be especially beneficial in early-stage treatments when using power lasers with a high probability of causing damage, particularly in retinal therapy. As an example, and preferably, the operating device (5) can be designed to select the power of the first heating laser pulse based on the user's input of the pulse duration, in a manner that prevents the first heating laser pulse from causing any sustained tissue damage. It is also advantageous if the operating device (5) is designed to allow only user-inputted values ​​as the time pulse interval between the first and at least the second heating laser pulses, and which are greater than the thermal relaxation time of living tissue predetermined from the duration of the first pulse. Here, hierarchical dependence means that some user selection options are prioritized in the implementation, while other selection options are considered subordinate and subject to predetermined, for example, programmed safety rules, which are appropriately restricted depending on the higher-priority user input.

[0077] In this respect, the operating device (5) may include its own processor for data processing and data storage for non-volatile data storage.

[0078] The operating device (5) can be designed such that the user input includes at least the target temperature and laser pulse duration, for example, as a priority, and optionally, the duration of the first heating laser pulse, the laser pulse interval, and the first power. Furthermore, the processor of the operating device (5) can execute an encryption algorithm to encrypt the data sent by the arithmetic unit (6) along with the user input, thereby preserving it in an indivisible and unmodifiable manner. This secure data can then only be read together and can be used as an authenticated treatment protocol (also timestamped).

[0079] The gradient rise ratio ΔP2 / ΔP1 of the heating laser pulse was experimentally studied as a function of pulse duration and laser power. Figure 2 Measurements of pulse durations of 5 μs and 50 μs at powers up to 14 W are shown only as an example. The ratio of the pulse gradient rise and how the gradient rise itself changes with the applied power due to variations in the excitation conditions of the laser (including the pump flow). Clearly, pulsed measurements of the gradient rise are advantageous for the evaluations described herein if laborious calibration of the laser source is undesirable. Furthermore, laser aging effects are possible, making a one-time working calibration not always sufficient.

[0080] Figure 3a-c illustrates three examples of pressure transients measured at different laser powers. The pressure transient is the lower curve in each case, and the derivative of the heating laser pulse is the upper curve. To compare the representational quality across all plots, they are normalized such that the first maximum value of the first pressure transient, according to the numerical values, corresponds to the maximum gradient ΔP1 of the rising gradient of the first heating laser pulse. It is easy to see how much the temperature rise at the end of the heating laser pulse contributes to the pressure transient. For better representation, the acoustic duration from the sample to the sensor is removed, i.e., the pressure transient is shifted by this duration.

[0081] Figure 3a The pressure transient under irradiation at 614 mJ / cm² is shown: an irradiation pulse with a duration of 35 μs has two gradient increases ΔP1 and ΔP2, each triggering pressure transients A1 and A2. Here, the pressure transients are shown on the same time axis as the heating laser pulse, i.e., the signal duration from the retina to the ultrasonic transducer, which is a constant shift, for better allocation. Energy measurements dD1 and dD2 are assigned to the pressure transients, which are here determined, for example, from the maximum amplitudes of signals A1 and A2. The ratio α is thus calculated, and The temperature at the end of the pulse is 55°C. This short-duration temperature rise typically does not damage living retinal tissue. The curve shown represents an example of the first heating laser pulse according to the method of the present invention.

[0082] Figure 3b The pressure transient under irradiation of 1245 mJ / cm² is shown: when applied with Figure 3a Compared to a pulse with twice the power, the same signal with the increased value can be observed. The laser pulse gradient rises much faster, and the amplitude of the pressure transient is significantly increased. (Using...) Figure 3a The same calculations resulted in a temperature of 82°C at the end of the pulse, which is already within the typical range for the target temperature of photo-condensation. Therefore, Figure 3b This indicates a possible second heating laser pulse according to the present invention, which directly produces a therapeutic effect.

[0083] Figure 3c The pressure transient under irradiation at 1488 mJ / cm² is shown: this radiation causes bubbles to form in the tissue. A second pressure transient occurs before the laser power is reduced. Therefore, it is not based on thermoelastic relaxation during tissue cooling, but rather on material evaporation. The double arrow 1 indicates the time difference between the start and end of the acoustic signal. The modified scale is then compared with... Figure 3a and 3bA comparison was made. A tenfold increase in amplitude also indicates microbubble formation and confirms this hypothesis. Since the irradiation power and the microbubble formation time are known, it is possible to determine which irradiation intensity can achieve a microbubble formation temperature exceeding approximately 140°C. The duration of the thermomechanical interruption until the end of the heating laser pulse can also be used for dose measurement, and possibly, despite adjusting the laser, adjustments and optimizations can be made for subsequent laser pulses.

[0084] It should also be noted here that, Figure 3a The -c curves were not recorded at the same laser point. Therefore, the absorption coefficients of the tissues differed between experiments.

Claims

1. A laser treatment device for treating living tissue (2), comprising: A pulsed laser (4) having an emission power of 5 W to 100 W laser (1); An applicator for guiding a laser (1); a triggering device for triggering the laser (1) to irradiate a living tissue (2) via the applicator; a detection device (3) for measuring the volume change over time caused by laser absorption in the living tissue (2); and a processing unit (6) for evaluating the detected volume change and issuing control commands to the control device to control the power of the laser (1) irradiating the living tissue (2), characterized in that: a. Each triggering of irradiation of living tissue results in a first heating laser pulse having a first laser power and a first laser pulse duration, and a second heating laser pulse having a second laser power and a second laser pulse duration, being applied to the living tissue at a predetermined pulse interval (2), wherein b. The detection device (3) optically or acoustically records the volume change caused by the rising and falling power gradients of the first heating laser pulse and provides the measured values ​​to the computing unit (6). c. The computing unit (6) determines an estimated temperature rise of the living tissue (2) during irradiation by the first heating laser pulse, based on the measured value of the volume change and taking into account at least a predetermined rise in the power gradient of the first heating laser pulse. d. Based on the estimated value, the computing unit (6) sends a command to the control device, which causes the control device to adjust the second laser power and / or the duration of the second heating laser pulse, so that the irradiation of the second heating laser pulse heats the living tissue (2) to a predetermined target temperature.

2. The laser therapy device according to claim 1, characterized in that, The control device is configured such that all heating laser pulses applied at trigger have the same pulse duration.

3. The laser therapy device according to claim 1, characterized in that, The detection device (3) records the volume change caused by the rising and falling power gradients of the second heating laser pulse and provides the measured values ​​to the calculation unit (6), and the calculation unit (6) determines, displays and records the estimated value of the temperature rise during the irradiation of the second heating laser pulse.

4. The laser therapy device according to claim 1, characterized in that, Based on the time recording of the emitted laser power, at least a portion of the laser power measurement values ​​of the detected laser (1) are provided to the computing unit (6) to determine the rising power gradient of the heating laser pulse.

5. The laser therapy device according to any one of the preceding claims, characterized in that, The detection device (3) is designed to record thermally triggered pressure waves in irradiated living tissue and includes at least one ultrasonic transducer that records pressure transients and transmits them as measurements.

6. The laser therapy device according to any one of claims 1 to 4, characterized in that, The detection device (3) is designed for optically recording the thermally triggered motion of light-diffusing or reflective tissue layers in irradiated living tissue; it includes an interferometer and at least one photodetector, which records the light intensity that changes over time and emits it as a measurement value.

7. The laser therapy device according to claim 1, characterized in that, The computing unit is designed to determine and record the difference between the start time of the volume change on the rising power gradient of the heating laser pulse from the start of the second heating laser pulse and the start time of the next volume change.

8. The laser therapy device according to claim 1, characterized in that, The operating device (5) for the user to input irradiation parameters into the arithmetic unit (6) displays selectable intervals for the irradiation parameters, wherein the interval restriction levels depend on the user input.

9. The laser therapy device according to claim 8, characterized in that, The operating device (5) selects the power of the first heating laser pulse based on the user input of the duration of the first laser pulse and the duration of the second laser pulse, so that the first heating laser pulse does not cause any continuous tissue damage.

10. The laser therapy device according to claim 8 or 9, characterized in that, The operating device (5) allows the user to input a value greater than the thermal relaxation time of the living tissue as the time pulse interval between the first heating laser pulse and the second heating laser pulse.

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