Laser emission modulation for treatment of calculi

Abstract

Laser-based systems and methods for treating calculi. The system may include a laser configured to emit pulsed laser energy; and a controller configured to control the laser device. The laser may be modulated to operate in one of a pulverization, fragmentation, or reduced backlash mode of operation. One or more of the operating modes includes a pulse composed of sub-pulses.

Description

[0001] Related applications

[0002] This application claims priority to U.S. Provisional Application Serial No. 63 / 440,191, filed on January 20, 2023, entitled “LASER EMISSION MODULATION FORTREATMENT OF HARD TISSUE,” the contents of which are hereby incorporated by reference in their entirety. Background Art Technical Field

[0003] The technical field generally relates to laser treatment of stones, and more particularly to modulated pulsed laser energy in treating stones.

[0004] Background Discussion

[0005] Kidney stone disease is a common condition, affecting an estimated 12% of the world's population. While most patients pass their stones naturally, the condition can be severe enough to require medical intervention. This can lead to extreme pain, nausea, vomiting, infection, blocked urinary flow, and loss of kidney function. Laser lithotripsy is a procedure used to treat kidney stones in which light energy, directed by an optical fiber, is used to break the stones into smaller pieces that can pass naturally.

[0006] Optimal targeting of stones, such as calculi, and minimizing the risk of unintended damage to surrounding intact soft tissue are two major issues in laser lithotripsy. Therefore, a technical solution is needed that addresses both issues by optimizing the temporal structure of the laser output.

[0007] Until recently, related laser sources (e.g., Ho:YAG lasers) were extremely limited in their ability to be modulated. However, the advent of newer laser sources (e.g., diode laser-pumped Tm fiber lasers and Tm:YAG lasers) has opened up the possibility of modulating laser light over a wider range of outputs. Summary of the Invention

[0008] Various aspects and embodiments are directed to methods and systems for using pulsed laser energy to modulate laser emission for treating stones.

[0009] According to an exemplary embodiment, a laser system for treating stones is provided, the laser system comprising: a laser configured to emit pulsed laser energy having a wavelength in the range of 1.85 micrometers (μm) to 2.2 μm, inclusive; and a controller configured to control the laser so that the pulsed laser energy is emitted as a sequence of sub-pulse groups separated in time by a pulse repetition interval, and each sub-pulse group comprises at least two sub-pulses separated in time by a sub-pulse interval in the range of 0 to 10 milliseconds (ms), wherein each sub-pulse of the sub-pulse group has a pulse duration in the range of 0.001 ms to 5 ms, inclusive, each sub-pulse of the sub-pulse group has an energy in the range of 0.001 joules (J) to 1 J, inclusive, and the pulse repetition interval is in the range of 1 ms to 1000 ms, inclusive.

[0010] According to another exemplary embodiment, a method for treating stones is provided, the method comprising: generating pulsed laser energy having a wavelength in the range of 1.85 micrometers (μm) to 2.2 μm, inclusive; emitting the pulsed laser energy as a sequence of sub-pulse groups separated in time by a pulse repetition interval, wherein each sub-pulse group comprises at least two sub-pulses separated in time by a sub-pulse interval in the range of 0 to 10 milliseconds (ms), inclusive, each sub-pulse of the sub-pulse group having a pulse duration in the range of 0.001 milliseconds (ms) to 5 ms, inclusive, each sub-pulse of the sub-pulse group having an energy in the range of 0.001 joules (J) to 1 J, inclusive, and the pulse repetition interval in the range of 1 ms to 1000 ms, inclusive; and directing the pulsed laser beam to a treatment area of ​​the stone.

[0011] In one example, the sub-pulse group includes 2 to 1000 sub-pulses. In another example, the sub-pulse group includes 2 to 100 sub-pulses. In another example, the sub-pulse group includes 2 to 10 sub-pulses.

[0012] In one example, the total energy of the sub-pulse group is in the range of 0.2 J to 5 J, inclusive. In another example, the total energy of the sub-pulse group is in the range of 0.5 J to 2 J, inclusive.

[0013] In one example, the energy of each sub-pulse is in the range of 0.01 J to 1 J, inclusive. In another example, the energy of each sub-pulse is in the range of 0.2 J to 1 J, inclusive.

[0014] In one example, the sub-pulse interval is in the range of 0.01 ms to 5 ms, inclusive. In another example, the sub-pulse interval is in the range of 0.01 ms to 1 ms, inclusive.

[0015] In one example, the duration of each sub-pulse is in the range of 0.1 ms to 1 ms, inclusive.

[0016] In one example, the pulsed laser energy has an average power in the range of 2 watts (W) to 120 W, inclusive. In another example, the average power is in the range of 2 W to 40 W, inclusive. In another example, the average power is in the range of 5 W to 40 W, inclusive.

[0017] In one example, the pulse repetition rate within the sub-pulse group is in the range of 0.5 Hz to 500 Hz, inclusive.

[0018] In one example, the peak power of the sub-pulses of the sub-pulse group is in the range of 250 W to 20,000 W, inclusive. In another example, the peak power of the sub-pulses of the sub-pulse group is in the range of 500 W to 5,000 W, inclusive.

[0019] In one example, at least one sub-pulse of the group of sub-pulses has a pulse shape such that the power of the at least one sub-pulse increases monotonically from the start of the sub-pulse to the end of the sub-pulse.

[0020] In one example, the laser is a thulium fiber laser, a thulium solid-state laser, or a holmium solid-state laser.

[0021] In one example, the size of the fragments of the stone after exposure to the pulsed laser beam is less than 1 mm in its largest cross-sectional dimension.

[0022] According to another exemplary embodiment, a laser system for treating stones is provided, the laser system comprising: a laser configured to emit pulsed laser energy having a wavelength in the range of 1.85 micrometers (μm) to 2.2 μm, inclusive; and a controller configured to control the laser so that each pulse of the emitted pulsed laser energy comprises two groups of sub-pulses separated in time by a sub-pulse group interval, wherein each group of sub-pulses comprises at least two sub-pulses separated in time by a sub-pulse interval in the range of 0 to 1 millisecond (ms), inclusive, the first group of sub-pulses having sufficient total energy, total pulse length, and average power to generate mechanical stress in the target stone, and the second group of sub-pulses having sufficient total energy, total pulse length, and average power to generate thermomechanical shock in the target stone, wherein the total energy of the two groups of sub-pulses is in the range of 2 joules (J) to 70 J, inclusive, and the repetition rate of the two groups of sub-pulses is in the range of 0.5 hertz (Hz) to 10 Hz, inclusive.

[0023] According to another exemplary embodiment, a method for treating stones is provided, the method comprising: generating pulsed laser energy having a wavelength in the range of 1.85 micrometers (μm) to 2.2 μm, inclusive; emitting the pulsed laser energy as two groups of sub-pulses separated in time by a sub-pulse interval, the sub-pulse interval being in the range of 0 to 1 millisecond (ms), inclusive, and the two groups of sub-pulses being configured such that the first group of sub-pulses has sufficient total energy, total pulse length, and average power to produce mechanical stress in the target stone, the second group of sub-pulses has sufficient total energy, total pulse length, and average power to produce thermomechanical shock in the target stone, the total energy of the two groups of sub-pulses being in the range of 2 joules (J) to 70 J, inclusive, and the repetition rate of the two groups of sub-pulses being in the range of 0.5 hertz (Hz) to 10 Hz, inclusive; and directing the pulsed laser beam toward the target stone.

[0024] In one example, the target stone fragments after exposure to the pulsed laser energy have a maximum cross-sectional dimension of at least 1 mm. In another example, the target stone fragments after exposure to the pulsed laser energy have a maximum cross-sectional dimension in the range of 1 mm to 5 mm. In another example, the target stone fragments after exposure to the pulsed laser energy have a maximum cross-sectional dimension in the range of 1 mm to 3 mm.

[0025] In one example, the energy of the first group of sub-pulses is in the range of 1 J to 65 J, inclusive. In another example, the energy of the first group of sub-pulses is in the range of 6.5 J to 65 J, inclusive.

[0026] In one example, the energy of the second group of sub-pulses is in the range of 1 J to 6.5 J, inclusive.

[0027] In one example, the target stone has an ablation threshold and the energy of the first group of sub-pulses does not exceed the ablation threshold. In another example, the target stone has an ablation threshold and the energy of the first group of sub-pulses is less than the ablation threshold multiplied by a factor of 1.5.

[0028] In one example, the first group of sub-pulses has an average power in the range of 50 Watts (W) to 200 W, inclusive.

[0029] In one example, the first group of sub-pulses includes at least two sub-pulses separated in time by a sub-pulse interval. In another example, the sub-pulse interval has a duration that prevents fluid penetration of the area of ​​the target stone that has been exposed to the pulsed laser energy.

[0030] In one example, the first group of sub-pulses includes 1 to 100 sub-pulses.

[0031] In one example, the peak power of the second group of sub-pulses is in the range of 500 W to 20,000 W, inclusive. In another example, the peak power of the second group of sub-pulses is in the range of 500 W to 1500 W, inclusive.

[0032] In one example, the laser is a thulium fiber laser or a solid-state laser.

[0033] Other aspects, embodiments and advantages of these example aspects and embodiments are discussed in detail below. In addition, it should be understood that both the above information and the detailed description below are merely illustrative examples of various aspects and embodiments, and are intended to provide an overview or framework for understanding the nature and characteristics of the claimed aspects and embodiments. The embodiments disclosed herein may be combined with other embodiments, and references to "embodiment," "example," "some embodiments," "some examples," "alternative embodiments," "various embodiments," "one embodiment," "at least one embodiment," "this embodiment and other embodiments," "certain embodiments," etc. are not necessarily mutually exclusive and are intended to indicate that the specific features, structures, or characteristics being described may be included in at least one embodiment. The appearance of such terms herein does not necessarily all refer to the same embodiment. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Various aspects of at least one embodiment are discussed below with reference to the accompanying drawings, which are not intended to be drawn to scale. These drawings are included to provide illustration and a further understanding of the various aspects and embodiments and are incorporated into and constitute a part of this specification, but are not intended to be a definition of limitations on any particular embodiment. The drawings, together with the rest of the specification, serve to explain the principles and operation of the described and claimed aspects and embodiments. Each identical or nearly identical component illustrated in various figures is represented by the same number in the figures. For clarity, not every component may be labeled in every figure. In the drawings:

[0035] Figure 1A is a chart illustrating one example of a pulse sequence optimized for a calcareous stone pulverization protocol according to one or more aspects of the present invention;

[0036] Figure 1B is a chart illustrating another example of a pulse sequence optimized for a calcareous stone pulverization protocol according to one or more aspects of the present invention;

[0037] Figure 1C is a chart illustrating another example of a pulse sequence optimized for a calcareous stone pulverization protocol according to one or more aspects of the present invention;

[0038] Figure 2A is a chart illustrating one example of a pulse sequence optimized for a calculus stone fragmentation protocol according to one or more aspects of the present invention;

[0039] Figure 2B is a chart illustrating another example of a pulse sequence optimized for a calculus stone fragmentation protocol according to one or more aspects of the present invention;

[0040] Figure 3A and Figure 3B are images captured from a high-speed video of a calculus ablation procedure according to aspects of the present invention and illustrating the distribution and amount of ablation products between the calculus and the distal end of an optical fiber;

[0041] Figure 4 are three images taken from a high-speed video of a calculus ablation procedure according to aspects of the present invention and showing thermal radiation at the distal end of an optical fiber;

[0042] Figure 5 is a graph illustrating one example of transmission oscillations over time according to aspects of the present invention;

[0043] Figure 6 is a graph illustrating one example of the number of transmission oscillations over time according to aspects of the present invention;

[0044] Figure 7A is a graph showing one example of a pulse optimized for recoil reduction according to the prior art;

[0045] Figure 7B is a graph illustrating one example of a pulse sequence optimized for recoil reduction according to one or more aspects of the present invention;

[0046] Figure 7C is a graph illustrating another example of a pulse sequence optimized for recoil reduction according to one or more aspects of the present invention;

[0047] Figure 8 is a graph showing one example of a pulse profile according to aspects of the present invention;

[0048] Figure 9 is a diagram showing one example of a pulse configuration according to aspects of the present invention; and

[0049] Figure 10 is a block diagram of a laser system for treating stones according to one or more aspects of the present invention. DETAILED DESCRIPTION

[0050] According to one or more embodiments, specific systems and methods for modulating laser emission are considered below for the specific purpose of treating stones. As used herein, the term "stone" refers to stones (stone-like stones) present in anatomical locations such as the ureter, kidney, or bladder. Stones include all types of stone-like stones in the human or animal body. One or more aspects of the present disclosure can be used for diode-pumped thulium (Tm) and holmium (Ho) doped crystal or fiber lasers with output wavelengths in the range of 1.85 μm and 2.2 μm, including the end values. In some embodiments, a Tm fiber laser or a Tm:YAG laser can be used. In some embodiments, a solid-state laser such as Tm:YAG or Ho:YAG can be used. According to various embodiments, a thulium fiber laser, a thulium solid-state laser, or a holmium solid-state laser can be used in the systems and methods described herein.

[0051] Maximize the efficiency of the calcareous stone pulverization protocol (pulverization mode of operation)

[0052] The primary goal of a calculus pulverization procedure is to produce the smallest possible calculus fragments in the shortest possible time period. The clinical goal of pulverization is to break up calculus into particles less than 1 mm in size (preferably less than 0.25 mm, which is considered "fine pulverization") to ensure that all fragments are naturally expelled within a few weeks after the procedure to prevent the formation of new calculus stones. According to the pulverization mode described herein, according to at least one embodiment, the maximum cross-sectional dimension of the fragments of the stone after exposure to the pulsed laser beam is less than 1 mm (if the fragments are round, this will be the diameter), and in some embodiments, the maximum cross-sectional dimension is less than 0.25 mm. Conventional laser pulverization procedures utilize regular pulses generated by a laser that is not configured with any kind of special modulation. For example, regular pulses generated by thulium fiber lasers widely used in clinical practice have rectangular or flat-top pulse shapes. Typically, these pulses have spurious modulation associated with relaxation oscillations, which manifest themselves as spikes with pulse lengths of 0.01 microseconds (μs) to 5 μs. However, the typical energy of these spikes is below the threshold for stone ablation and the impact of these spikes is negligible. The pulse structures and pulse shapes disclosed and described herein will be defined without considering the presence of such spikes.

[0053] At a fixed average power, using the conventional high pulse energy / low repetition rate mode of operation results in relatively large fragments that must be further broken down. In the alternative, using the conventional low pulse energy / high repetition rate mode of operation produces reasonably small fragments but lacks stone ablation efficiency and, therefore, results in increased procedure times. Both outcomes are suboptimal.

[0054] According to certain embodiments, two mechanisms of pulverization are proposed.

[0055] (1) Adiabatic vaporization of water in the spaces between the crystallites forming the stone-like stones, in the clusters of crystallites, and in the stone-like stone pores and other stone-like stone defects filled with water. The vapor pressure of the water vaporization causes the stone-like stones to break into crystallites with a size ranging from 0.01 μm to 50 μm, inclusive, or into clusters with a size ranging from 10 μm to 1000 μm, inclusive. To maximize the efficiency of this mechanism, in some embodiments, the pulse width is shorter than the thermal relaxation time of the space between the crystallites or clusters filled with water (thermally constrained), and preferably shorter than the relaxation time of the vapor pressure (acoustically constrained). According to at least one embodiment, the laser pulse energy and energy density are above the water vaporization energy threshold.

[0056] (2) Micro-fragmentation (delamination) of small fragments from the bottom of the laser crater due to a thermomechanical gradient of pressure perpendicular to the surface of the bottom of the laser crater. The thickness of the micro-fragmentation is approximately equal to the penetration depth of the laser light in the calcareous stone, which is defined by the absorption coefficient of water. The pulse width (pulse duration) should be shorter than the thermal relaxation time of the calcareous stone layer with a thickness corresponding to the penetration depth. Another mechanism of laser-induced delamination of small fragments from the bottom of the laser crater may be due to the formation of a dry layer of calcareous stone after the laser pulse, the penetration of the energy of the subsequent pulse into this layer, and the ablation of the wet calcareous stone layer below the dry layer.

[0057] The laser systems and methods disclosed herein are based on the applicant's discovery that modulation of the laser pulse structure provides a significant increase in pulverization rate and a reduction in mean fragment size. This discovery was made as a result of comparing various pulse structures and shapes generated by the laser with modulated pulse structures using preclinical and clinical settings and standard experimental methods. The pulse structure and shape, energy range, power and pulse spacing, pulse length and other characteristics are defined based on significant (greater than 25%) improvements compared to existing (conventional) conventional pulse treatments. According to at least one embodiment, pulses structured as a sequence of relatively low energy or optimal sub-pulses (micropulses) are used to perform the pulverization procedure. In some embodiments, the sub-pulses or micropulses are implemented with short intervals between the sub-pulses to prevent cooling of the stone-like stones via water infiltration between the sub-pulses. As used herein, the term "sub-pulse" or "micropulse" refers to a short pulse, multiple of which together form the resulting pulse. In one embodiment, the sequences of low energy sub-pulses are combined into groups of 2 to 1000, in another embodiment, into groups of 2 to 100, and in yet another embodiment, into groups of 2 to 10. According to at least one embodiment, the stone is less than 0.25 mm in diameter.

[0058] exist Figure 1AA non-limiting example of two sub-pulse groups used in a pulse sequence for calcite pulverization is shown in FIG. The term "sub-pulse group" refers to a number of sub-pulses that, when delivered, are temporally separated by a sub-pulse interval. Sub-pulse groups are temporally separated by a pulse repetition interval. According to at least one embodiment, a sub-pulse group is initiated by one or more lower peak power sub-pulses to minimize the recoil effect, i.e., when calcite fragments migrate away from the energy source. In some embodiments, the peak power can be increased after the initial one to three pulses. The presence of multiple short, low-energy micropulses produces sufficiently small fragments, while the high cumulative energy generated by the pulse sequence delivered in relatively short time intervals ensures high ablation efficiency. After ablation by each micropulse, the bottom of the laser crater is covered with a thin layer of dry calcite material and vaporized water. This layer can then be removed by the next pulse, due to the ablation of the wet calcite material beneath the dry layer, by causing micro-fractures or delamination of the calcite material at the bottom of the laser crater. For high ablation efficiency, it is critical to keep the interval between pulses below the penetration time of water in the dry layer, which occurs between micropulses and cools the stone-like stone material. According to some embodiments, the sub-pulse interval is in the range of 0 to 10 ms, inclusive, in some embodiments, in the range of 0.01 ms to 5 ms, inclusive, in some embodiments, in the range of 0.01 ms to 1 ms, inclusive, in some embodiments, in the range of 0.01 ms to 0.2 ms, inclusive, and in some embodiments, in the range of 0.01 ms to 1 ms, inclusive. According to certain embodiments, one or more of the sub-pulse intervals in a sub-pulse group may vary. For example, in Figure 1A In the embodiment, the first sub-pulse group includes four sub-pulses, wherein the sub-pulse interval between the first sub-pulse and the second sub-pulse is 0 (which means that the first sub-pulse and the second sub-pulse are connected, as shown in FIG. Figure 1A ), and the first sub-pulse interval is a value different from the duration of other sub-pulse intervals in the sub-pulse group.

[0059] Some embodiments may include Figure 1A For example, the first few pulses in the sequence may have gradually increasing amplitudes (peak powers) in order to further minimize recoil and shift the residual fragment size distribution toward smaller particles. Figure 1B One non-limiting example of such a set of pulses configured in such a sequence is shown in , which is another example of a pulse sequence that may be used in a calculus stone pulverization protocol.

[0060] exist Figure 1CAn additional example of a pulse sequence that can be used for a pulverization protocol is shown in In accordance with at least one embodiment, at least one sub-pulse of the set of sub-pulses has a pulse shape such that the power of the at least one sub-pulse increases monotonically from the start of the sub-pulse to the end of the sub-pulse. Figure 1C The second pulse, the third pulse, and the fourth pulse of the sub-pulse group in are non-limiting examples of such a power profile having a monotonically increasing function. This configuration and other examples are discussed in further detail below.

[0061] Return to Figure 1C As an example, each sub-pulse can be optimized to have a pulse shape that maximizes the effect of stone ablation and dust formation. In experimental work using high-speed photography, the applicant discovered that laser beam attenuation increases during the laser pulse, and this effect increases with the peak power of the rectangular pulse. Two mechanisms may explain this phenomenon.

[0062] The first mechanism is that the scattering and absorption of the laser beam on the ablation product flow (the effect of shielding the laser crater) increases with the increase of laser power. Figure 3A and Figure 3B In FIG, two video frames of the ablation crater and ablation product flow (i.e., particle-dust flow) of a COM stone-like concretion exposed to rectangular laser pulses generated by a thulium fiber laser with a wavelength of 1.94 μm, an energy of 0.5 J, and a peak power of 250 W ( Figure 3A ) and 2000W peak power ( Figure 3B ), with particular attention paid to the situation at the end of the laser pulse. As can be seen from the figure, for low peak power ( Figure 3A ) is larger than that for higher peak powers ( Figure 3B ) of the ablation particle flow, but with the angle of 2000W ( Figure 3B ) compared to 250W( Figure 3A ), the amount and density of particles as well as beam scattering and absorption are low.

[0063] Depend on Figure 4 Illustrating the second mechanism discovered, the figure shows three frames ((i), (ii), and (iii)) of video captured using a high-speed camera and including video frames of the ablation crater and the condition of the fiber tip used to deliver the ablation crater. Figure 3A and Figure 3BLaser energy for the same fiber (i.e., a thulium fiber laser directed toward a COM stone-like calculus), but with peak powers of 500 W (i), 1000 W (ii), and 2000 W (iii) at the end of a rectangular pulse, and an energy of 2 J. These figures indicate that the fiber tip is emitting visible light due to thermal radiation from the fiber tip, which is heated to a high temperature due to initial absorption of laser energy by ablation products that have contaminated the distal end of the fiber tip. The intensity of this thermal radiation in the visible spectrum increases with the temperature of the tip. Figure 4 The images shown indicate that for 500 W peak power (i) there is no thermal radiation from the fiber tip, for 1000 W (ii) there is low thermal radiation and for 2000 W (iii) there is very intense thermal radiation. For 500 W the temperature of the tip at the end of the pulse is below 400°C, for 1000 W it is between 600°C and 900°C and for 2000 W it is above 1300°C. It is known that heating a silica fiber to temperatures greater than 800°C induces an effect in the silica material that sharply increases the absorption of the silica material. This in turn increases the attenuation of the laser energy delivered to the stone-like calculus for ablation and reduces the ablation efficiency. Generally, increasing the peak power or rectangular pulses at a given energy leads to an increase in ablation efficiency, but the additional influence of the two discovered mechanisms can offset or even reverse this effect. When comparing Figure 4 When considering (i), (ii) and (iii) of FIG. 1 , it is apparent that, at an equal laser energy of 2 J, the size of the pit for the higher peak power (iii) is greater than the size of the pit for the lower peak power (i). Due to the combination of such mechanisms under each given condition (such as the local composition and structure of the stone, the laser pulse energy, the fiber diameter, and the distance between the fiber tip and the stone), there should be an optimal peak power that provides the maximum ablation efficiency. Since this optimal peak power depends on different factors that can vary during stone treatment, according to at least one embodiment, the pulse shape causes the power to vary within a certain range during the pulse to ensure that the range contains the optimal peak power for each location on the stone surface, the varying gaps, and other variables during treatment.

[0064] In accordance with at least one embodiment, at least one sub-pulse of the group of sub-pulses has a pulse shape such that the power of the at least one sub-pulse increases from the beginning of the sub-pulse to the end of the sub-pulse. In accordance with various embodiments, the increase can be monotonic or non-monotonic. The increase can follow one or more functions, such as a step function, a linear function, a polynomial function, or an exponential function. Figure 1CThe second, third, and fourth pulses of the sub-pulse group in are non-limiting examples of such a power profile having a monotonically increasing function. In some embodiments, the energy of such sub-pulses can be in the range of 0.2 J to 1 J, inclusive. In some embodiments, to prevent water from penetrating into the laser crater between sub-pulses, the spacing between such sub-pulses is in the range of 0.01 ms to 5 ms, inclusive.

[0065] According to at least one embodiment, the optimal laser parameters for the pulsed pulverization mode of operation as described above are as follows:

[0066] Energy per sub-pulse: 0.001 J to 1 J, inclusive, in some embodiments 0.01 J to 1 J, inclusive, in another embodiment 0.2 J to 1 J, inclusive, and in some embodiments sub-pulse energies can vary within a sub-pulse group, e.g., a first sub-pulse in a sub-pulse group can have lower energy than a second sub-pulse;

[0067] Total energy of the pulse (energy of a group of sub-pulses): 0.2 J to 5 J, inclusive, preferably 0.5 J to 2 J, inclusive;

[0068] Pulse width (sub-pulse duration): 0.001 ms to 5 ms, inclusive, preferably 0.1 ms to 1 ms, inclusive, and in some embodiments, the sub-pulse duration may vary within a sub-pulse group, e.g., within a sub-pulse group, the first sub-pulse may have a longer duration than the second sub-pulse;

[0069] Interval between micropulses (subpulse interval): 0 to 10 ms, inclusive, 0.01 ms to 5 ms, inclusive, preferably 0.01 ms to 1 ms, inclusive;

[0070] The average power depends on the anatomical location, and the irrigation and aspiration rates, typically in the ureters in the range of 2 W to 120 W inclusive, preferably in the range of 5 W to 15 W inclusive, in the kidneys in the range of 2 W to 40 W inclusive, and in the bladder in the range of 5 W to 40 W inclusive and 5 W to 60 W inclusive;

[0071] Pulse repetition interval: in the range of 1 ms to 1000 ms (inclusive);

[0072] Pulse repetition rate (within a sub-pulse group): in the range of 0.5 Hz to 500 Hz (inclusive);

[0073] Peak power (of sub-pulses in a sub-pulse group): in the range of 250 W to 20,000 W inclusive, preferably in the range of 500 W to 5000 W inclusive, and in some embodiments the peak power may vary within a sub-pulse group, for example, a first sub-pulse may have a lower or higher peak power than a second sub-pulse in a sub-pulse group.

[0074] Maximize the efficiency of the stone fragmentation protocol (fragmentation mode of operation)

[0075] The primary goal of a calculus fragmentation procedure is to break the calculus into fragments small enough to be removed by a retrieval basket or other tool, such as suction (typically, for fragments about 3 mm or less in size), especially when using rigid instruments. Based on theoretical modeling, experimental work, and clinical trials performed by the applicant, a new mechanism for calculus fragmentation has been proposed and demonstrated and disclosed herein. To this end, according to at least one embodiment, the optimal scenario for treatment is to: (1) first generate a temperature gradient in the calculus to produce mechanical stress in the calculus structure by slowly releasing residual laser energy transferred to the heating energy, and (2) then apply an intense thermomechanical shock to the stressed calculus structure by a relatively short high-energy pulse to produce cracking (typically, along one-dimensional line defects (dislocations), two-dimensional surface defects (grains, microcrystal clusters or domains, boundaries and free surfaces), and three-dimensional volume defects (pores), or other surfaces that separate regions of different structure in the calculus), thereby ultimately causing the calculus to fragment. In certain embodiments, this can be achieved using laser pulses consisting of two parts: a first (initial) group of sub-pulses for generating mechanical stress (in the target stone), and a second (subsequent) group of sub-pulses for generating thermomechanical shock (i.e., cleavage of the mechanically stressed stony stone (target stone)). As used herein, the term "mechanical stress" refers to structural stress within the stone caused by pressure changes or thermal gradients within the stone, and such stress can cause the stone itself to fracture. As used herein, the term "thermomechanical shock" refers to stone fracture caused by thermal strain energy and stress, which develops much faster during interaction with the first group of sub-pulses (as described in further detail below).

[0076] According to one embodiment, the technique is to initially pump sufficient laser energy into the stony calculi without causing substantial ablation, and then utilize intense pulses to deliver the aforementioned thermomechanical shock. It should be noted that the recoil effect is less important for the fragmentation mode than for the pulverization mode, as typically only sufficiently large stony calculi (approximately 8 mm or larger) are targets for fragmentation. According to the fragmentation mode described herein, according to at least one embodiment, the size of the fragments of the calculi after exposure to the pulsed laser energy has a maximum cross-sectional dimension of at least 1 mm (in the case of round fragments, this would be the diameter), and in some embodiments, the size of the fragments of the calculi after exposure to the pulsed laser energy has a maximum cross-sectional dimension in the range of 1 mm to 5 mm, and in preferred embodiments, the maximum cross-sectional dimension is in the range of 1 mm to 3 mm.

[0077] In one embodiment, the desired effect can be achieved by applying a first group of sub-pulses (1 to 100) wherein each sub-pulse of the first group of sub-pulses has a relatively small energy and the sub-pulse interval (the interval between sub-pulses) is short enough to prevent water (fluid) from penetrating the treatment area of ​​the stone during the sub-pulse interval used to cool the stone-like stone structure. A high energy pulse is then applied at a higher peak power (for simplicity, this may be referred to herein as the second group of sub-pulses). Thus, in some embodiments, the emitted pulsed laser energy includes two groups of sub-pulses separated in time by the sub-pulse group interval. In certain embodiments, the first group of sub-pulses has a sub-pulse group interval of a duration that prevents fluid penetration of the area of ​​the target stone that has been exposed to the pulsed laser energy. In some embodiments, each group of sub-pulses includes at least two sub-pulses separated in time by a sub-pulse interval that is in the range of 0 to 1 ms (inclusive). A sub-pulse interval having a value of 0 indicates that the two sub-pulses are connected (e.g., see Figure 2B The second group of sub-pulses may also have a sub-pulse spacing of zero, indicating that the sub-pulses are contiguous (see, for example, Figure 2B According to some embodiments, the first and second groups of sub-pulses can be grouped together into pulse groups, which can be transmitted sequentially, and the pulse groups are separated by a pulse repetition interval, such as Figure 2A shown.

[0078] exist Figure 2AA non-limiting example of a fragmentation pattern for treating stones is shown in FIG. During a first set of sub-pulses for treating a stone using the treatment, residual heating energy from each sub-pulse propagates inside the stone structure to produce a non-uniform temperature distribution and mechanical stress around the treatment area where the laser pulse propagates and is absorbed by the stone. According to at least one embodiment, the first group of sub-pulses has sufficient total energy (i.e., the combined energy of all sub-pulses included in the first group of sub-pulses), total pulse length (i.e., the combined pulse length (duration) of all sub-pulses included in the first group of sub-pulses), and average power (i.e., the average power of the sub-pulses included in the first group of sub-pulses) to produce mechanical stress in the target stone. If the energy of each individual sub-pulse is below the ablation threshold, only the phenomenon of mechanical stress occurs. If the energy of each individual sub-pulse is above the ablation threshold, pulverization occurs in addition to stone ablation. In accordance with at least one embodiment, the second group of subpulses has sufficient total energy (i.e., the combined energy of all subpulses included in the second group of subpulses), total pulse length (i.e., the combined pulse length (duration) of all subpulses in the second group of subpulses), and average power (i.e., the average power of the subpulses included in the second group of subpulses) to produce a thermomechanical shock in the target stone. This latter effect is explained in more detail below. The combined effect enables the ability to fragment the target stone into fragments larger than 1 mm.

[0079] According to an alternative embodiment, the group of sub-pulses can be replaced by a single pulse having a sufficiently low peak power and a sufficiently long duration, wherein the power is below or not significantly (<1.5 times) above the ablation threshold. In some embodiments, the target stone has an ablation threshold, and the energy of the first group of sub-pulses does not exceed the ablation threshold. In another embodiment, the energy of the first group of sub-pulses does not exceed the ablation threshold multiplied by a factor of 1.5.

[0080] exist Figure 2B A non-limiting example of another fragmentation mode for treating stones is shown in FIG. Preheating via a first set of sub-pulses with lower power results in increased mechanical stress around the laser-irradiated stone region, resulting in an increased absorption coefficient of the stone or mineral or organic components of the stone matrix due to heating to temperatures above 100°C to 250°C. A second set of sub-pulses with higher power will be more efficiently absorbed by the stone material and produce more efficient thermomechanical damage and stress due to better absorption compared to the first set of sub-pulses. The higher peak power of the second set of sub-pulses, combined with the initial mechanical stress in the stone around the laser-irradiated region, results in an increased probability that the stone will break into larger pieces.

[0081] According to the two methods described above, in certain embodiments, the shape structure of the two groups of sub-pulses described can be configured with high energy (up to 70 J) and low repetition rate (0.5 Hz to 5 Hz). Applicants have found that such higher energy pulses are also less damaging when accidentally impacting soft tissue than "conventional" lower energy pulses with higher repetition rate and the same average power as the two groups of sub-pulses disclosed. This makes the disclosed stone treatment safer compared to conventional laser operating parameters for stone fragmentation.

[0082] According to at least one embodiment, the optimal laser parameters for the fragmentation mode of operation using pulse shape modulation as described above are as follows:

[0083] The total pulse energy including the first and second groups of sub-pulses is 2 J to 70 J, inclusive, preferably 2 J to 4 J, inclusive for ureteral calculi and 7 J to 60 J, inclusive for kidney and bladder calculi

[0084] The energy of the first group of sub-pulses is 1 J to 65 J, inclusive, in some embodiments 6.5 J to 65 J, inclusive, in some embodiments 1 J to 3 J, inclusive for ureteral calculi, and 7 J to 60 J, inclusive for kidney and bladder calculi

[0085] The energy of the second group of sub-pulses is 1 J to 10 J, inclusive, in some embodiments 1 J to 6.5 J, inclusive, in some embodiments 1 J to 3 J, inclusive for ureteral calculi, and 3 J to 10 J, inclusive for kidney and bladder calculi

[0086] The average power of the first group of sub-pulses is 50W to 200W, inclusive

[0087] The peak power of the second group of sub-pulses of the pulse is 500W to 20,000W, inclusive, preferably 500W to 1500W, inclusive

[0088] The repetition rate of the two groups of sub-pulses is 0.5 Hz to 10 Hz, inclusive, preferably 0.5 Hz to 5 Hz, inclusive, for ureterolithic stones and 0.5 Hz to 2 Hz for renal or bladder lithiasis

[0089] oscillation

[0090] It is conventionally known that during a laser pulse in water, water vaporizes, resulting in the formation of a vapor channel (Moses channel) between the distal end of the optical fiber and the surface of the stone. Experiments conducted by the applicant have revealed that the channel first expands in size, creating a vapor channel from the distal end of the optical fiber to the stone surface, and then collapses. After collapsing, another channel is created during the laser pulse, and this process repeats for the entire duration of the laser pulse. This phenomenon, recognized by the applicant, is referred to as oscillation of the vapor (Moses) channel. This channel oscillation occurs because the laser energy input used to create the channel ceases when the channel is formed, and this energy is stored as increased potential energy in the surrounding water. This potential energy relaxes, causing the channel to collapse. The laser energy is coupled into the collapsing water, restarting the vaporization process, resulting in the formation of another channel. This process repeats for the duration of the laser pulse. Experiments conducted by the applicant have shown that the oscillation of the vapor (Moses) channel during the laser pulse causes the transmission of laser power to the stone to also oscillate during the laser pulse. Figure 5 The transmission of laser power through the oscillating steam channel (black curve) is shown when the fiber-stone distance is 0.8 mm and the laser power (marked in the figure) is 500 W within a 1 ms pulse duration (using a TFL laser with a peak power of 500 W and a pulse duration of 1 ms). The number of transmitted oscillations increases linearly with the pulse duration at a rate that depends on the fiber-stone distance, as shown in FIG. Figure 6 shown.

[0091] Reduce backlash (operation mode)

[0092] The water flow during channel formation and expansion, the steam pressure within the channel, and the water flow during and after channel collapse all act at different times on the stone. The net result is oscillatory movement of the stone that occurs synchronously with the channel oscillations. Applicants refer to this as the "trapping" effect. Experiments conducted by the applicants have demonstrated that for stone sizes of approximately 5 mm, the amplitude of the stone oscillations during the trapping effect is much less than 1 mm. For larger and smaller stones, smaller and larger oscillation amplitudes are expected, respectively. The non-oscillatory movement of the stone following the laser pulse depends on the characteristics and timing of the final channel collapse. The final channel collapse generates a water flow, which is the primary source of unwanted stone recoil. The direction of the flow depends on the final channel conditions, namely, the channel shape and the velocity and pressure differences at its boundaries. For example, symmetric channel collapse does not produce any net fluid momentum that can be transferred to the stone. Conversely, a properly formed channel can collapse to provide negative and positive stone movement toward and away from the optical fiber, respectively. The state of the final channel can be controlled by the laser power and pulse profile. The use of a combination of two sub-pulses to reduce kickback is known in the art, examples of which are given in Figure 7A, which is an example from PCT application No. PCT / US2019 / 042491, published as WO 2020 / 033121 and owned by the applicant, and incorporated herein by reference in its entirety. The first sub-pulse or portion is used to initiate channel formation between the optical fiber and the calculus, ablation of the calculus, and preheating of the calculus around the ablation pit, depending on the distance of the optical fiber from the calculus. Recent experiments by the applicant have confirmed that the first sub-pulse can further reduce recoil if its duration is reduced to a small fraction of a single channel period. The recoil effect of such a pulse will be reduced because a more symmetrical channel and channel collapse occurs, and less momentum is transferred to the fluid. In Figure 7A In the example, T1 is the duration of the first sub-pulse or portion, and T2 is the duration of the second sub-pulse or portion. In addition, the energy or power profile of the first sub-pulse or portion may be at level P min constant, or in the form of a function, such as from P min Increase to P max A linear, exponential, or polynomial function of max is the peak power of the second sub-pulse or portion. Recent experiments by the applicant have demonstrated that a further reduction of recoil occurs when the power of the first sub-pulse is low and its duration is synchronized with the channel or bubble frequency.

[0093] Recent studies performed by the applicant have also demonstrated the importance of not only the leading edge of the pulse, but also the trailing edge. Specifically, the rate of collapse of the final Moses channel can be reduced using a lower power setting that delays the final collapse and reduces the collapsing water velocity. This is achieved by introducing an additional post-sub-pulse at a reduced power level, thereby generating a "triplet" pulse, i.e., three sub-pulses. In some embodiments, the controller is configured to adjust the laser power profile so that each emitted pulse energy includes three sub-pulses. Figure 7B A non-limiting example of such a "triplet" pulse is shown in FIG. Figure 7B As indicated, the first sub-pulse (energy) may increase according to any one of a linear, polynomial, and exponential function, and the third sub-pulse may decrease according to any one of a linear, polynomial, and exponential function. Additionally, the third sub-pulse (energy, power) may be at level P min Furthermore, some embodiments of the (energy, power) of the "triplet" pulse may involve the use of oppositely tilted sub-pulses, a non-limiting example of which is Figure 7C. For example, in some embodiments, the respective slopes of the energies of the first and third sub-pulses are reciprocals of each other. In still other embodiments, the subsequent sub-pulse format may include a sequence of sub-pulses that are chirped (with reduced pulse duration and pulse power) to match the reduced Moses channel diameter and its duration (proportional to the channel diameter at a given ambient pressure).

[0094] In accordance with at least one embodiment, to reduce recoil and still ensure efficacy of the pulse for its intended purpose (pulverization, fragmentation, etc.), the following laser parameters are optimal for the leading (first) and trailing (third) sub-pulses:

[0095] Peak power: in the range of 50W to 200W, inclusive, preferably in the range of 100W to 130W, inclusive

[0096] Pulse energy: in the range of 0.005 J to 1 J, inclusive, preferably in the range of 0.01 J to 0.3 J, inclusive

[0097] • First sub-pulse duration: in the range of 100 μs to 1 ms, inclusive. According to some embodiments, the following laser parameters may be used in the reduced-recoil mode of operation:

[0098] The second sub-pulse has a higher energy than the first and third sub-pulses

[0099] Second sub-pulse energy: in the range of 0.01J to 10J, inclusive, in the range of 0.1J to 3J, inclusive

[0100] Second sub-pulse peak power: in the range of 400W to 4000W, inclusive, preferably in the range of 400W to 1500W, inclusive

[0101] Sub-pulse interval (duration between sub-pulses): in the range of 0 to 0.5 ms, inclusive

[0102] Sub-pulse interval: in the range of 0 to 300 μs

[0103] Sub-pulse duration: in the range of 0.1ms to 1ms

[0104] An additional embodiment includes the concept that if Figure 8 Increasing the laser power at the end of the pulse is shown, which causes the channel to recover more quickly, thus delivering more energy per pulse to the stone for ablation.

[0105] For stone-like stones that have moved away from the optical fiber (at a distance > 2 mm), Figure 8 The pulse profile shown is used to pull the stone back toward the fiber (negative recoil). Applicants refer to this process as stone "retraction." This occurs because eventually the Moses channel collapses in such a way that the water flows toward the fiber.

[0106] According to these embodiments, the following laser parameters may be used to enhance ablation efficiency / retraction mode of operation:

[0107] The first sub-pulse has lower energy than subsequent sub-pulses

[0108] Second sub-pulse energy for channel vaporization at intermediate power levels: in the range of 0.01 J to 10 J, inclusive, and in the range of 0.1 J to 3 J, inclusive

[0109] • The third sub-pulse is at the highest power level to create a higher pressure at the distal end of the channel (near the stone-like concretion) to make the asymmetric collapse greater at the distal end than at the proximal end (collapse towards the fiber).

[0110] Stones smaller than 5 mm in size can be trapped and oscillate during the laser pulse. The amplitude of the stone oscillation can be in the range of 0.1 mm to 3 mm, and the frequency of the Moses channel oscillation can be in the range of 0.5 kHz to 10 kHz, depending on the average fiber-stone distance. The above embodiments are methods for reducing or maintaining the average distance of stone from the fiber, which correspondingly improves ablation efficiency. An additional method for both improving ablation efficiency and reducing recoil allows for laser pulse power modulation (synchronized with the Moses channel oscillation) Figure 8 and reducing the amplitude of stone-like stone vibration to a range below 1 mm, preferably below 0.5 mm. This will improve ablation efficiency.

[0111] Applicants have observed that there are three important phases during the laser pulse: Phase 1 of duration T1, is the optimal power and duration for the start of channel formation, which affects the shape and dynamics of the channel close to the fiber. Phase 2 of duration T2, is the optimal power and duration for stone-like stone ablation (through a fully formed channel). Phase 3 of duration T3, is the optimal power and pulse duration for the final channel collapse at the end of the laser pulse. Therefore, the power during the laser pulse can be modulated and synchronized to the channel oscillation to improve ablation efficiency and simultaneously reduce recoil. Figure 9 A non-limiting example of such a pulse configuration is shown in FIG. Time period T1 is set at a power that affects the state of the Moses channel at the fiber end, T2 is set at a high power that achieves the best stone ablation rate, and T3 is set at a power level for obtaining symmetrical access conditions from the stone end to the fiber end to reduce recoil.

[0112] According to these embodiments, the following laser parameters may be used in this mode of operation:

[0113] Duration T1: in the range of 0.050 ms to 2 ms at a power in the range of 50 W to 250 W, inclusive, preferably in the range of 100 W to 130 W, inclusive

[0114] Duration T2: 0.050ms to 2ms at powers ranging from 50W to 4000W, inclusive

[0115] Duration T3: in the range of 0.050 ms to 2 ms at a power in the range of 50 W to 1000 W, inclusive, and a pulse energy in the range of 0.005 J to 1 J, inclusive

[0116] Duration T4: 1ms to 6ms at powers ranging from 50W to 4000W, inclusive

[0117] Laser system

[0118] Figure 10 is a block diagram illustrating one non-limiting example of a laser system configured to produce the laser pulse operating mode described above. It should be understood that other configurations may be used to achieve the aforementioned pulse mode.

[0119] The laser system 100 includes a power supply 103, a laser driver 125 that may include an optional energy storage device 120, a pump 115, a laser module 130, and a controller 150 (also referred to herein as a control module). Laser energy from the laser module 130 is directed to a target stone 160. The laser system 100 may also include a beam delivery system or module 145 and an optical coupler 140.

[0120] The pump 115 is configured with one or more diode lasers that provide energy to the laser 130. A power supply 103 supplies power to the system, and an optional energy storage device 125 (e.g., a capacitor and / or inductor) can be configured to store sufficient energy to form the laser pulses. The laser driver 125 of the pump 115 responds to control signals from the control module 150 to form electrical pulses with specified characteristics. The electrical pulses are received by one or more diodes of the pump 115, which form the optical pulses necessary to pump the lasing medium in the laser module 130. The output of the laser module 130 is coupled to a beam delivery system 145, and in some examples, this coupling occurs via an optical coupler 140.

[0121] One or more components of the laser system 100 are controlled by a controller 150 that is programmed with control signals for controlling the laser driver 125, the power supply 103, and / or the laser module 130. For example, the control signal from the controller 150 can be used to directly modulate the pump current of the driver 125 for the pump diode 115, as will be understood by those skilled in the art, to output a desired pulse energy, power, and temporal structure. In some embodiments, a single charge-discharge cycle of the energy storage device 120 can be used to modulate the diode current.

[0122] The aspects disclosed herein according to the present invention are not limited in their application to the construction details and component arrangements set forth in the following description or illustrated in the accompanying drawings. These aspects can assume other embodiments and can be practiced or executed in various ways. The examples of specific embodiments provided herein are for illustrative purposes only and are not restrictive. Specifically, the actions, components, elements, and features discussed in conjunction with any one or more embodiments are not intended to exclude similar roles in any other embodiment.

[0123] Likewise, the words and terms used herein are for descriptive purposes and should not be considered restrictive. Any reference to the examples, embodiments, components, elements or actions of the systems and methods mentioned herein in the singular may also include multiple embodiments, and any reference to any embodiment, component, element or action herein in the plural may also include only singular embodiments. References in the singular or plural form are not intended to limit the currently disclosed systems or methods, their components, actions or elements. "Include," "comprising," "having," "containing," "involving" and their variations used herein are intended to cover the items listed thereafter and their equivalents as well as additional items. References to "or" may be interpreted as inclusive, so that any term described using "or" may indicate any of the "single," "more than one," and "all" terms in the described terms. In addition, in the event of inconsistency in the usage of terms between this document and the documents incorporated herein by reference, the usage of terms in the incorporated references is a supplement to the usage of terms in this document; for irreconcilable inconsistencies, the usage of terms in this document shall prevail. Furthermore, headings or subheadings may be used in the specification for the convenience of the reader and this shall not affect the scope of the invention.

[0124] Thus, having described several aspects of at least one example, it should be understood that various variations, modifications, and improvements will readily occur to those skilled in the art. For example, the examples disclosed herein may also be used in other contexts. Such variations, modifications, and improvements are intended to be part of this disclosure and are intended to fall within the scope of the examples discussed herein. Therefore, the foregoing description and drawings are intended to be examples only.

Claims

1. A laser system for treating stones, comprising: a laser configured to emit pulsed laser energy having a wavelength in the range of 1.85 micrometers (μm) to 2.2 μm, inclusive; and a controller configured to control the laser so that the pulsed laser energy is emitted as a sequence of sub-pulse groups separated in time by a pulse repetition interval, and each sub-pulse group includes at least two sub-pulses separated in time by a sub-pulse interval in the range of 0 to 10 milliseconds (ms), wherein each sub-pulse of the sub-pulse group has a pulse duration in the range of 0.001 ms to 5 ms, inclusive, Each sub-pulse of the sub-pulse group has an energy in the range of 0.001 Joule (J) to 1 J, inclusive, and The pulse repetition interval is in the range of 1 ms to 1000 ms, inclusive. 2 . The laser system of claim 1 , wherein the sub-pulse group comprises 2 to 1000 sub-pulses.

3. The laser system of claim 2, wherein the sub-pulse group comprises 2 to 100 sub-pulses. The laser system of claim 3 , wherein the sub-pulse group comprises 2 to 10 sub-pulses.

5. The laser system of claim 1, wherein the total energy of the sub-pulse groups is in the range of 0.2 J to 5 J, inclusive.

6. The laser system of claim 6, wherein the total energy of the sub-pulse groups is in the range of 0.5 J to 2 J, inclusive.

7. The laser system of claim 1, wherein the energy of each sub-pulse is in the range of 0.01 J to 1 J, inclusive.

8. The laser system of claim 7, wherein the energy of each sub-pulse is in the range of 0.2 J to 1 J, inclusive.

9. The laser system of claim 1, wherein the sub-pulse interval is in the range of 0.01 ms to 5 ms, inclusive.

10. The laser system of claim 9, wherein the sub-pulse interval is in the range of 0.01 ms to 1 ms, inclusive.

11. The laser system of claim 1 , wherein the duration of each sub-pulse is in the range of 0.1 ms to 1 ms, inclusive.

12. The laser system of claim 1, wherein the pulsed laser energy has an average power in a range of 2 Watts (W) to 120 W, inclusive.

13. The laser system of claim 12, wherein the average power is in the range of 2 W to 40 W, inclusive.

14. The laser system of claim 13, wherein the average power is in the range of 5 W to 40 W, inclusive.

15. The laser system of claim 1, wherein a pulse repetition rate within the sub-pulse groups is in the range of 0.5 Hz to 500 Hz, inclusive.

16. The laser system of claim 1, wherein the peak power of the sub-pulses of the sub-pulse groups is in the range of 250 W to 20,000 W, inclusive.

17. The laser system of claim 16, wherein the peak power of the sub-pulses of the sub-pulse groups is in the range of 500 W to 5000 W, inclusive.

18. The laser system of claim 1, wherein at least one sub-pulse of the group of sub-pulses has a pulse shape such that a power of the at least one sub-pulse increases monotonically from a start of the sub-pulse to an end of the sub-pulse.

19. The laser system of claim 1, wherein the laser is a thulium fiber laser, a thulium solid-state laser, or a holmium solid-state laser.

20. A method for treating stones, comprising: generating pulsed laser energy having a wavelength in a range of 1.85 micrometers (μm) to 2.2 μm, inclusive; The pulsed laser energy is emitted as a sequence of sub-pulse groups separated in time by a pulse repetition interval, wherein each sub-pulse group comprises at least two sub-pulses separated in time by a sub-pulse interval in the range of 0 to 10 milliseconds (ms), inclusive, each sub-pulse of the sub-pulse group has a pulse duration in the range of 0.001 milliseconds (ms) to 5 ms, inclusive, Each sub-pulse of the sub-pulse group has an energy in the range of 0.001 Joule (J) to 1 J, inclusive, and The pulse repetition interval is in the range of 1 ms to 1000 ms, inclusive; and A pulsed laser beam is directed to the treatment area of ​​the stone.

21. The method of claim 20, wherein the fragments of the stone after exposure to the pulsed laser beam have a size of less than 1 mm in a largest cross-sectional dimension.

22. The method of claim 20, wherein the sub-pulse group comprises 2 to 1000 sub-pulses.

23. The method of claim 22, wherein the sub-pulse group comprises 2 to 100 sub-pulses.

24. The method of claim 23, wherein the sub-pulse group comprises 2 to 10 sub-pulses.

25. The method of claim 20, wherein the total energy of the sub-pulse groups is in the range of 0.2 J to 5 J, inclusive.

26. The method according to claim 25, wherein the total energy of the sub-pulse group is 0. In the range of 5J to 2J, inclusive.

27. The method of claim 20, wherein the energy of each sub-pulse is in the range of 0.01 J to 1 J, inclusive.

28. The method of claim 27, wherein the energy of each sub-pulse is in the range of 0.2 J to 1 J, inclusive.

29. The method of claim 20, wherein the sub-pulse interval is in the range of 0.01 ms to 5 ms, inclusive.

30. The method of claim 29, wherein the sub-pulse interval is in the range of 0.01 ms to 1 ms, inclusive.

31. The method of claim 20, wherein the duration of each sub-pulse is in the range of 0.1 ms to 1 ms, inclusive.

32. The method of claim 20, wherein the pulsed laser energy has an average power in a range of 2 Watts (W) to 120 W, inclusive.

33. The method of claim 32, wherein the average power is in the range of 2 W to 40 W, inclusive.

34. The method of claim 33, wherein the average power is in the range of 5 W to 40 W, inclusive.

35. The method of claim 20, wherein the pulse repetition rate within the sub-pulse groups is in the range of 0.5 Hz to 500 Hz, inclusive.

36. The method of claim 30, wherein the peak power of the sub-pulses of the sub-pulse groups is in the range of 250 W to 20,000 W, inclusive.

37. The method of claim 36, wherein the peak power of the sub-pulses of the sub-pulse groups is in the range of 500 W to 5000 W, inclusive.

38. The method of claim 20, wherein at least one sub-pulse of the group of sub-pulses has a pulse shape such that the power of the at least one sub-pulse increases monotonically from the beginning of the sub-pulse to the end of the sub-pulse.

39. The method of claim 20, further comprising providing a thulium fiber laser, a thulium solid-state laser, or a holmium solid-state laser for generating the pulsed laser energy.

40. A laser system for treating stones, the laser system comprising: a laser configured to emit pulsed laser energy having a wavelength in the range of 1.85 micrometers (μm) to 2.2 μm, inclusive; and a controller configured to control the laser so that each pulse of emitted pulsed laser energy comprises two groups of sub-pulses separated in time by a sub-pulse group interval, wherein each group of sub-pulses comprises at least two sub-pulses separated in time by a sub-pulse interval in the range of 0 to 1 millisecond (ms), inclusive, The first group of sub-pulses has sufficient total energy, total pulse length and average power to produce mechanical stress in the target stone, The second group of sub-pulses has sufficient total energy, total pulse length and average power to produce a thermomechanical shock in the target stone, wherein The total energy of the two groups of sub-pulses is in the range of 2 joules (J) to 70 J, inclusive, and The repetition rate of the two groups of sub-pulses is in the range of 0.5 Hertz (Hz) to 10 Hz, inclusive.

41. The laser system of claim 40, wherein the fragments of the target stone after exposure to the pulsed laser energy have a size of at least 1 mm in a maximum cross-sectional dimension.

42. The laser system of claim 40, wherein the size of the fragments of the target stone after exposure to the pulsed laser energy ranges from 1 mm to 5 mm in maximum cross-sectional dimension.

43. The laser system of claim 40, wherein the fragments of the target stone after exposure to the pulsed laser energy have a size ranging from 1 mm to 3 mm in maximum cross-sectional dimension.

44. The laser system of claim 40, wherein the energy of the first group of sub-pulses is in the range of 1 J to 65 J, inclusive.

45. The laser system of claim 44, wherein the energy of the first group of sub-pulses is in the range of 6.5 J to 65 J, inclusive.

46. ​​The laser system of claim 40, wherein the energy of the second group of sub-pulses is in the range of 1 J to 6.5 J, inclusive.

47. The laser system of claim 40, wherein the target stone has an ablation threshold and the energy of the first group of sub-pulses does not exceed the ablation threshold.

48. The laser system of claim 40, wherein the target stone has an ablation threshold and the energy of the first group of sub-pulses is less than the ablation threshold multiplied by a factor of 1.

5.

49. The laser system of claim 40, wherein the average power of the first group of sub-pulses is in the range of 50 Watts (W) to 200 W, inclusive.

50. The laser system of claim 40, wherein the first group of sub-pulses comprises at least two sub-pulses separated in time by a sub-pulse interval.

51. The laser system of claim 50, wherein the sub-pulse intervals have a duration that prevents fluid penetration of areas of the target stone that have been exposed to the pulsed laser energy.

52. The laser system of claim 50, wherein the first group of sub-pulses comprises 1 to 100 sub-pulses.

53. The laser system of claim 40, wherein the peak power of the second group of sub-pulses is in the range of 500 W to 20,000 W, inclusive.

54. The laser system of claim 53, wherein the peak power of the second group of sub-pulses is in the range of 500 W to 1500 W, inclusive.

55. The laser system of claim 40, wherein the laser is a thulium fiber laser or a solid state laser.

56. A method for treating stones, the method comprising: generating pulsed laser energy having a wavelength in a range of 1.85 micrometers (μm) to 2.2 μm, inclusive; The pulsed laser energy is emitted as two groups of sub-pulses separated in time by a sub-pulse interval in the range of 0 to 1 millisecond (ms), inclusive, and the two groups of sub-pulses are configured such that The first group of sub-pulses has sufficient total energy, total pulse length and average power to produce mechanical stress in the target stone, a second group of sub-pulses having sufficient total energy, total pulse length, and average power to produce thermomechanical shock in the target stone, The total energy of the two groups of sub-pulses is in the range of 2 joules (J) to 70 J, inclusive, and The two groups of sub-pulses have a repetition rate in the range of 0.5 Hertz (Hz) to 10 Hz, inclusive; and A pulsed laser beam is directed toward the target stone.

57. The method of claim 56, wherein the fragments of the target stone after exposure to the pulsed laser energy have a size of at least 1 mm in a largest cross-sectional dimension.

58. The method of claim 56, wherein the fragments of the target stone after exposure to the pulsed laser energy have a size ranging from 1 mm to 5 mm in maximum cross-sectional dimension.

59. The method of claim 56, wherein the fragments of the target stone after exposure to the pulsed laser energy have a size ranging from 1 mm to 3 mm in maximum cross-sectional dimension.

60. The method of claim 56, wherein the energy of the first group of sub-pulses is in the range of 1 J to 65 J, inclusive.

61. The method of claim 60, wherein the energy of the first group of sub-pulses is in the range of 6.5 J to 65 J, inclusive.

62. The method of claim 56, wherein the energy of the second group of sub-pulses is in the range of 1 J to 6.5 J, inclusive.

63. The method of claim 56, wherein the average power of the first group of sub-pulses is in the range of 50 Watts (W) to 200 W, inclusive.

64. The method of claim 56, wherein the target stone has an ablation threshold and the energy of the first group of sub-pulses does not exceed the ablation threshold.

65. The method of claim 56, wherein the target stone has an ablation threshold and the energy of the first group of sub-pulses is less than the ablation threshold multiplied by a factor of 1.

5.

66. The method of claim 56, wherein the first group of sub-pulses comprises at least two sub-pulses separated in time by a sub-pulse interval.

67. The method of claim 66, wherein the sub-pulse intervals have a duration that prevents fluid penetration of areas of the target stone that have been exposed to the pulsed laser energy.

68. The method of claim 56, wherein the first group of sub-pulses comprises 1 to 100 sub-pulses.

69. The method of claim 56, wherein the peak power of the second group of sub-pulses is in the range of 500 W to 20,000 W, inclusive.

70. The method of claim 69, wherein the peak power of the second group of sub-pulses is in the range of 500 W to 1500 W, inclusive.

71. The method of claim 56, further comprising providing a thulium fiber laser or a solid state laser for generating the pulsed laser energy.

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