Method and apparatus for laser lithotripsy

Abstract

To solve a problem in which a need that exists for shaped pulsed laser lithotripsy that is performed by a laser system that operates to modulate pulse energy, peak power, pulse repetition frequency and pulse shape to provide an optimal condition for laser-stone interaction leading to decreased treatment time and cost.SOLUTION: A shaped pulse method and device for laser lithotripsy that provides high ablation rates while also minimizing ablation product regression. A method and laser system for treating stones in a human or animal body includes a laser that emits a sequence of laser pulses, and the laser can be operated in an amplitude modulated manner, in which laser pulses are emitted at a constant pulse frequency and with periodically varying peak power or pulse energy or peak power and pulse energy with an amplitude modulation period Na equal to the number of pulses in one amplitude period group.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] This disclosure generally relates to methods and laser systems for treating litholiths in the human or animal body, which increase the speed of litholith treatment according to various surgical procedures by controlling the temporal structure of the laser power. In particular, the present invention relates to methods and laser systems for treating litholiths with laser pulses having an improved temporal structure by modulation of pulse shape in addition to pulse energy, peak power, and repetition rate. [Background technology]

[0002] Pulsed laser sources may be used in lithotripsy to remove stones in humans and animals. Stones (also referred to herein as stones) are coagulated bodies of material that can form in the organs or ducts of the body. Urinary stones include nephroliths (also called intranephroliths or kidney stones) and bladder stones (also called intrabladder stones or bladder stones), and may have any one of several compositions, including mixed compositions. The main composition often includes calcium oxalate, calcium phosphate, magnesium ammonium phosphate, diammonium calcium phosphate, magnesium phosphate, cysteine, uric acid or urate, and xanthine. Stones of the gallbladder and bile ducts are called gallstones and arise mainly from bile salts and cholesterol derivatives. Stones can also form in other parts of the body, including the nasal passages, gastrointestinal tract, salivary glands, tonsils, and veins.

[0003] Laser lithotripsy is the use of lasers to induce the fracture of stones through various mechanisms. Typically, a fiber optic cable, traveling along the long axis of a rigid, flexible, or rib-shaped endoscope, transmits the laser beam for lithotripsy. The stones can be broken down (fragmented) into particles between 1 and 3-4 mm in size, which can then be removed through the working channel of a rigid instrument using a basket or similar device. Alternatively, the stones can be broken down into smaller particles (size <1 mm) in a process called dusting. A subdivision of dusting known as microdusting (particles <0.25-0.5 mm, depending on the stone composition and the shape of the dust particles) results in fragments small enough to be removed by a urinary flow or by a standard perfusion supplied by a water / saline bag suspended at a height of approximately 40 cm. Vaporization down to the molecular level is also possible. The efficiency of ablation depends on the conditions at the treatment site and can be substantially lower for large stones or when treating multiple stones in a single procedure. This problem is more typical for the treatment of large and multiple kidney stones by flexible ureteroscopy when the goal is to complete stone dusting in contact and non-contact modes during surgery.

[0004] Another problem is the movement of the stone during treatment due to recession. Recession is caused by the following phenomena: Light energy absorbed by water in the gap between the fiber and the stone generates a hydrostatic wave that pushes the stone away from the tip of the fiber. When laser energy is absorbed by the stone and stone ablation occurs, the rebound momentum of the ablation also causes the stone to displace away from the fiber. Recession prolongs the surgical time and makes it difficult for the surgeon to complete stone fragmentation or dusting to achieve a result free of residual stone particles. Increasing the average laser power and treatment time to compensate for the low ablation rate may be limited by the increased risk of soft tissue damage.

[0005] Several surgical techniques are known for performing laser lithotripsy, based, for example, on the relative position and displacement of the fiber tip and the stone to be treated. These techniques generally fall into one of the following categories: contact lithotripsy, semi-contact scanning (dancing), and non-contact (popcorn) techniques. When using lithotripsy, the fiber tip is positioned in contact with the center of the stone, and laser power is delivered to the stone until macro-fractures and fragmentation occur. In lithotripsy, the laser power is applied to one small area for a relatively long period of time. As a result of such a mode of operation, relatively deep drill holes and thermomechanical stress that induce macro-fractures of the stone are produced.

[0006] In the scanning technique, the fiber moves continuously across the stone surface in near-contact (0-1 mm distance) with the stone. Each pass across the stone surface results in the removal (excision) of a thin layer of stone. This technique is preferred for excising (dusting) stones into small fragments. If the possibility of operating in contact or near-contact mode due to retraction is not acceptable, a non-contact technique is used for treating stone fragments (typically less than 3 mm in size). In the non-contact technique, the fiber is positioned in a fixed position close to the location of the targeted stone fragment, and the laser is irradiated in a non-contact manner. As a result of vaporization and bubble implosion, water flows, causing the stone fragments to move. When such fragments enter the effective range of the distal end of the surgical fiber, further fragmentation / dusting occurs, resulting in even smaller stone fragments.

[0007] The ablation rate is determined by the ablation mechanism and depends on the chemical composition and structure of the stone, the operating parameters of the laser (e.g., wavelength, radiant energy, peak power, pulse width, and repetition frequency), the thickness of the interlayer between the end of the radiating fiber and the surface of the stone, and the optical properties (transparency) of the material in this interlayer. Various physical processes and mechanisms of ablation are associated with the aforementioned surgical procedures for stone fracture and include photomechanical, photothermal, and / or photochemical mechanisms.

[0008] The photomechanical mechanism, typical for laser pulses shorter than a few microseconds, posits that ablation begins when the laser-induced tensile stress exceeds the target's ultimate tensile strength. Key factors in this mechanism include the mechanical properties of the target material and the laser-induced stress. Transient tensile stress in solid materials can lead to the formation of microscopic cracks and other defects, and if the stress exceeds the material's effective strength, fracture and material ejection can occur (a process called fracturing). In addition, transient tensile stress in liquids can cause the medium to rupture, leading to a phenomenon known as cavitation. Cavitation involves the growth and collapse of cavities in a liquid, potentially causing damage to surrounding solid materials. Laser energy can also lead to plasma formation on an object. Plasma formation is achieved through high-speed object ionization accompanied by optical destruction, a nonlinear effect generated when laser radiation is strongly absorbed by the irradiated object and / or on the target at high power density. In liquid treatment environments, laser-induced bubble formation in the liquid is induced either directly or through plasma-mediated absorption. This absorption results in growing vapor bubbles. Although the growing vapor bubbles may not reach the stone, the energy from the pulse is further absorbed by the liquid. In this way, a bipolar pressure pulse (i.e., a shock wave) is formed in front of the growing bubbles, inducing cracking of the stone. The cavitation process with bubbles further contributes to shock wave growth. Thus, by focusing laser energy onto the target material, damage is inflicted through a series of optical breakdowns, plasma formation, shock wave generation, and induction of negative pressure during bubble cavitation.

[0009] The photothermal mechanism is typical for lasers with pulses longer than approximately 12 microseconds. For lithotripsy, where silica fibers are used for energy delivery, sub-millisecond and millisecond lasers with wavelengths close to the water absorption peak at 1940 nm (1.85 to 2.1 μm range) are preferred. Water is the single most important initial chromophore in the stone, facilitating the conversion of laser energy into thermal and thermomechanical energy that contributes to fracturing the stone in the infrared spectrum transmitted through the silica fiber.

[0010] The photothermal mechanism can be performed in two modes. The first mode is stone dusting, which is initially caused by high pressure resulting from expansion or evaporated water (about 10% of the stone's weight) trapped in the stone's pores, cracks, initial microcracks, and other microspaces between the stone's microcrystals. Heating and subsequent boiling are triggered by the selective absorption of water surrounded by the mineral and organic components of the stone, which themselves exhibit low absorption of light at a wavelength of about 2 μm. This mechanism leads to the separation of fragments ranging in size from the characteristic dimensions of the basic microcrystals (up to several hundred microns, mainly from submicrons to tens of microns) or aggregates / regions of those with characteristic dimensions up to 0.5 mm (fine dusting) or 1 mm (dusting). The second mode is stone crushing (fragments > 1 mm), which is mainly due to thermal stress within the volume of the stone around the area heated by the laser, and prevails over dusting when the laser power is applied to a single point on the stone (stone drilling). The first mode is virtually always present regardless of the surgical procedure, but it is superior in scanning and pop-corning surgical procedures. The second mode is appropriate for very high pulse energies and for lithotripsy procedures.

[0011] The photochemical mechanism of ablation is based on the absorption of high-energy photons leading to the direct dissociation of molecular bonds in the material. This photochemical mechanism can play a role in increasing absorption by the rock due to carbonization of organic molecules within the rock structure or thermochemical reactions within the mineral matrix. Surgical methods such as microdusting, dusting, and fracturing, as well as ablation efficiency and receding effects, can be controlled by laser parameters such as pulse width, energy per pulse, pulse repetition rate, and average power. In addition, fiber parameters such as the energy delivery method, e.g., core diameter, numerical aperture, distal tip conditions, and the distance between the distal end of the fiber and the rock, also play an important role. Finally, drilling, scanning, or non-contact application all contribute to the outcome of the laser-rock interaction.

[0012] Several types of lasers can be used in laser lithotripsy, and they are selected based on various criteria. For example, holmium:YAG (Ho:YAG) flashlamp-pumped laser lithotripters typically operate at high pulse energies (0.1-6 J), but are limited to low pulse rates (5-100 Hz) during lithotripsy. Control of other properties such as pulse shape and temporal properties is very limited for this laser due to flashlamp excitation.

[0013] Other lasers used in laser lithotripsy that operate at wavelengths close to the absorption peak of approximately 1.94 μm include, but are not limited to, diode-pumped thulium-Tm:YAG lasers and diode-pumped Tm fiber lasers (TFLs). Diode-pumped Tm fiber lasers, in particular, possess many advantageous characteristics. These lasers can operate over a wide pulse energy range (0.001 to 20 J) and at high and low pulse rates (1 to 1,000,000 Hz). Comparative studies of TFL and Ho:YAG configurations have been conducted (see, for example, Blackmon et al., Journal of Biomedical Optics, 16(7):071403, July 2011). In addition, the effects of laser pulse operation parameters such as power settings, or on reducing receding, were investigated (see, for example, White et al., Journal of Endourology, 12(2):183-186, March 2009, and Andreeva V et al., World Journal of Urology, May 4, 2019:1-7). The TFL emission line can be adjusted in the range between 1.85 and 2.2 μm and very close to the water absorption peak around 1.94 μm (1.94 μm for water at approximately 20-30°C and 1.908 μm for water at approximately 90-100°C). The TFL ablation threshold for various rock compositions is significantly lower (about 5 times lower) than that of the Ho:YAG lithotripsy system, meaning that rock ablation is more efficient than the Ho:YAG system at lower pulse energies or equivalent pulse energies for the same ablation rate.

[0014] The beam profiles of fiber lasers, including TFLs, are thus more uniform and symmetrical than the multimode beams of Ho:YAG lasers or other solid-state lasers, which cannot be coupled to small core fibers due to inevitable damage to the fiber. For example, single-mode (SM) thulium fiber lasers can focus their laser beams to approximately 25 microns. The small fiber diameter provided by TFLs allows for higher power density focusing than with holmium lasers, while also reducing recoil. Although the small fiber diameter increases radiant exposure or irradiance on the stone surface, this means that lower laser pulse energies can be used during the laser ablation process. When fibers are used in flexible ureteroscopes with small working channels, the small fiber diameter is important both to improve perfusion and to avoid compromising the deflection angle of the ureteroscope. The improved spatial beam profile provided by thulium fiber lasers reduces laser-induced damage to the proximal fiber tip surface, resulting in a longer operating life than holmium-based systems. The use of small-diameter fibers (less than 150 microns (μm), preferably between 50 and 125 μm) can increase the efficiency of fine dusting by focusing laser energy between microcrystalline clusters (regions) and into cracks and fissures on the stone surface. Holmium laser systems also generate heat, which can contribute to beam misalignment and subsequently cause fiber damage.

[0015] As a group, diode-pumped fiber lasers can operate with a wider range of laser operating parameters than conventional flashlamp-pumped solid-state lasers such as Ho:YAG systems. For example, single-laser-head Ho:YAG systems are typically limited to pulse rates of <30 Hz due to the potential for overheating and thermal damage to the laser rod. The white light from the flashlamp is largely wasted in the form of heat, with only a small portion contributing to the actual operation of the laser, and these systems typically have a wall-plug efficiency of <1-2%. These systems therefore require large and bulky cooling devices (e.g., water cooling) to dissipate this heat and prevent damage to the laser rod. In contrast, diode-pumped fiber laser systems have a wall-plug efficiency of about 10-50%, which means that very small cooling devices (e.g., air cooling) can be used. The increased wall-plug efficiency also allows fiber-based systems to operate at higher average power than holmium-based systems, but still to use 110-120V electrical outlets.

[0016] Other advantages of diode-pumped Tm fiber lasers include their ability to generate a wide range of temporal structures, including a broad pulse shape, which can also be implemented with other diode-pumped lasers emitting in the 1.85–2.2 μm range. For example, diode-pumped Tm:YAG lasers possess this capability. The aforementioned advantages of diode-pumped solid-state and fiber lasers are incorporated into the present invention and will be described in this application.

[0017] Challenges associated with the development of laser lithotripsy include reducing the time required for the procedure, which is related to the ablation rate of the stone, the path (velocity) of the fragments (e.g., reducing recession), and the products of the fracture. This challenge can be significantly improved by optimizing the temporal structure of the laser emission, a capability provided by diode-pumped fibers or solid-state lasers.

[0018] All lasers used for laser lithotripsy operate with a preset pulse-per-pulse energy (E=0.025~6J), repetition rate (ν=1~2500Hz), pulse width, and average power P=E×ν (2~120W). The laser parameters (E, ν, and P) are pre-selected to achieve the desired result: fragmentation, dusting, or pop coning, while providing a safety margin that should minimize the risk of organ wall perforation or hydrothermal and mucosal cauterization. However, stones, as mentioned above, come in a variety of compositions, shapes, and sizes. While a fixed set of parameters described above may be effective for one particular stone, it may be ineffective for another.

[0019] To achieve high ablation efficiency and minimal recession, it has been proposed to widen the pulse width (long pulse mode) or to use a special dual-pulse mode. U.S. Patent No. 5,321,715 proposes a method of irradiating a target (a stone, for example) in which the space between the target and the fiber end, which is normally occupied by a liquid medium that absorbs laser radiation, is cleared in two steps: (1) generating a first laser pulse with sufficient energy to form a vapor bubble in the liquid medium at the fiber exit end, and (2) generating a second laser pulse at a predetermined time interval after the first pulse, the predetermined time interval being selected to allow the vapor bubble to expand by a sufficient amount to displace a substantial portion of the liquid medium from the space between the fiber exit end and the target, so that the second laser pulse can be delivered to the target through the vapor bubble, thereby minimizing the laser radiation absorbed by the liquid medium and maximizing the laser radiation that reaches the target. Thus, the first pulse creates a vapor channel between the fiber end and the target (Moses effect), and the second pulse propagates to the target with minimal loss and interaction with the liquid. However, the solution taught in this patent has only been partially successful.

[0020] Therefore, there is a need for shaped pulse laser lithotripsy performed by a laser system that operates to modulate pulse energy, peak power, pulse repetition frequency, and pulse shape to provide optimal conditions for laser - stone interaction leading to reduced treatment time and cost.

Prior Art Documents

Patent Documents

[0021]

Patent Document 1

Non - Patent Documents

[0022]

Non - Patent Document 1

Non - Patent Document 2

Non - Patent Document 3

Non - Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0023] This objective is fulfilled by the laser system and method for treating litholiths in the human or animal body according to the present invention. Generally, there are two embodiments of the inventive concept that provide a high-efficiency ablation rate while minimizing the undesirable effects of recession: 1. modulation or periodic variation of pulse energy, peak power, and pulse frequency, and 2. formation and maintenance of an optimal pulse shape. Each embodiment is described in view of the laser system and method for treating litholiths. As will be readily apparent to those skilled in the art of laser and urological technology, the embodiments are complementary to each other, and structural features described later in one embodiment can be used in the other embodiment. [Means for solving the problem]

[0024] Each embodiment of the method provides multi-component sized particles in the range of less than 1 mm, preferably less than 0.5 mm, and most preferably less than 0.25 mm, by using a diode-pumped fiber laser or diode-pumped solid-state laser operating in the wavelength range of 1.85 to 2.2 μm at a specific range of laser power densities. Particles less than 500 μm, preferably less than 250 μm, can be readily removed by perfusion through a ureteroscope configured at a pressure (<40 cm water column height) that is safe for the kidney.

[0025] The first aspect of the method relates to the modulation of pulse energy E and / or pulse peak power Pp, and to the modulation of pulse frequency (i.e., pulse repetition rate) ν, which is defined as frequency modulation (FM) in addition to amplitude modulation (AM). Finally, the method relates to simultaneous amplitude and frequency modulation—amplitude-frequency modulation (AFM).

[0026] In particular, the first embodiment of a method for treating stones in the human or animal body relates to AM and includes the step of emitting a sequence of laser pulses from a laser at a constant pulse repetition frequency (PRF) and with periodically changing peak power or pulse energy or peak power and pulse energy with amplitude modulation period Na ≥ 2.

[0027] Methods for dealing with AFMs that emit a sequence of laser pulses include periodically varying at least one of the pulse peak power or pulse energy, or both, with a modulation period Na equal to the number of pulses in a pulse of one amplitude period group, and periodically varying the PRF with a frequency modulation period Np equal to the number of pulses in a pulse of one frequency period group.

[0028] In both of the above methods of the first embodiment, a modulation period Na ranging from 2 to 1000 laser pulses, preferably 2 to 100 laser pulses, and most preferably 2 to 10 laser pulses is implemented, and the modulation period Np of the PRF changes to 2 to 1000 laser pulses, preferably 2 to 100 laser pulses, and most preferably 2 to 10 laser pulses. In both methods, the laser pulses are emitted in the wavelength range of 1.85 to 2.2 μm, preferably 1.91 to 1.96 μm.

[0029] A second aspect of the present invention relates to the formation of an optimal pulse shape, which is formed according to the following two embodiments.

[0030] In particular, in one embodiment, a method for treating gallstones in the human or animal body includes the step of outputting a control signal containing information about a desired laser pulse shape. In response to the control signal, a sequence of laser pulses is emitted such that each laser pulse has a desired laser shape formed by first and second subpulses that are temporally separated from each other. The energy of the first subpulse varies in the range of 0.02 to 0.15 J (preferably 0.05 to 0.1 J), and its peak power ranges from 50 to 500 W (preferably 100 to 300 W). The subpulses are spaced temporally at intervals that vary in the range of 50 to 900 μs, preferably in the range of 100 to 500 μs. The energy of the second subpulse varies in the range of 0.1 to 10 J, exceeding that of the first subpulse, while its peak power varies in the range of 300 to 20000 W, exceeding the peak power of the first subpulse.

[0031] Another embodiment relates to a method for treating gallstones in the human or animal body, and includes the step of outputting a control signal containing information about a desired laser pulse shape. In response to the control signal, a sequence of laser pulses is emitted such that the desired laser pulse shape has an initial and a subsequent section, with the subsequent section having a higher power level than the initial section. The power of the initial section is monotonically increased from a minimum power level to the power level of the subsequent section, with the minimum power level varying between 0 and 200 W. The energy of the initial pulse section constitutes 10 to 70% of the total energy of the pulse, while the duration of the initial section varies in the range of 0.1 to 10 ms. The power of the subsequent section varies between 400 and 20000 W, and the duration of the subsequent section varies in the range of 0.5 to 20 ms.

[0032] According to one aspect of the present invention described above, the laser system for treating gallstones according to the present invention provides a cluster-type mechanism for laser ablation of multicomponent solids by configuring a pulsed repetition laser. In particular, the laser is configured with modulated laser emission and laser pulse control shapes to simultaneously (i) control the size of the ablation product, (ii) improve the ablation rate, and (iii) reduce gallstone recession. Modulated laser emission and laser pulse control shapes can also be used in fragmentation mode to improve the ablation rate and reduce recession.

[0033] In accordance with one feature of this embodiment, the laser system according to the present invention comprises a laser that emits a sequence of laser pulses and is capable of operating in AM mode (AMR). In this mode, the laser emits laser pulses with at least one of a constant pulse repetition frequency (PRF) and a periodically varying peak power and pulse energy with an amplitude modulation period Na equal to the number of laser pulses in a pulse of one amplitude period group.

[0034] In accordance with another feature, the laser system according to the present invention includes a laser capable of operating in amplitude-frequency modulation (AFMR). This mode is characterized by the laser emitting a sequence of laser pulses with periodically varying pulse peak power or pulses, or both, with a modulation period Na equal to the number of pulses in a pulse of one amplitude period group. The AMPR mode further comprises a sequence of pulses emitted with periodically varying PRF with a frequency modulation period Np equal to the number of pulses in a pulse of one frequency period group.

[0035] The types of lasers used in any of the laser systems according to the present invention with the above-described features preferably include diode-pumped solid-state lasers and diode-pumped fiber lasers such as excitation solid-state lasers. In particular, diode-pumped lasers include Tm:YAG, Tm:YLF, Tm:YAP, Tm:LuAG, Tm:LuLF, Tm:LuAP, and Tm fiber lasers. However, flashlamp-pumped solid-state lasers such as Ho:YAG can be used in the laser systems according to the present invention. Furthermore, the use of direct diode lasers is not excluded from the scope of the present invention.

[0036] The periodically changing peak power, pulse energy, or both modulation period Na ranges from 2 to 100 laser pulses and is applicable to laser systems with both characteristics. In AMR, the modulation period of at least one or both of the peak power or pulse energy ranges from 2 to 1000 laser pulses. In AFMR, the periodically changing period Np of PF varies from 2 to 1000 laser pulses.

[0037] The laser used in the configuration of both features of the laser system according to the present invention emits laser pulses in the wavelength range of 1.85 to 2.2 μm, preferably in the wavelength range of 1.908 to 1.96 μm. Operation at these wavelengths allows for the dominant absorption of laser radiation by water, which is extremely beneficial for any of the surgical procedures described above.

[0038] The lasers used in the configuration of both features, as described above, can operate in free-running mode and Q-switched mode, where the structural difference between them is a type of modulator. Modulators used in the free-running mode include diode lasers, while the Q-switched mode is associated with acousto-optical or electro-optical modulators (AOM and EOM, respectively).

[0039] In free-running mode, any of the disclosed lasers outputs a sequence of laser pulses with a PRF (Pressure Frequency Range) between 2 and 5000 Hz. Each laser pulse has the following characteristics: a laser pulse energy in the range of 0.001 J to 10 J, a laser pulse peak power in the range of 100 to 20000 W, preferably in the range of 250 to 3000 W, and a laser pulse duration in the range of 25 μs to 50 ms, preferably in the range of 100 μs to 15 ms.

[0040] A laser operating in a Q-switched mode with modulated resonator quality outputs laser pulses characterized by the following pulse characteristics: energy varying between 0.1 and 10 mJ, peak power ranging between 200 and 1,000,000 W, and PF ranging between 500 and 500,000 Hz.

[0041] The system according to the present invention, with laser configurations having both features, includes a controller that outputs a control signal containing information about a desired peak power or pulse energy in the AMR or a desired peak power or pulse energy in the AFMR and a desired PRF. The signal is coupled to either of the above-described modulator drivers.

[0042] In another embodiment, the laser system according to the present invention is configured to include a controller that outputs a control signal containing information about a desired laser pulse shape. The laser is operationally coupled to the controller so that each laser pulse has a desired laser pulse shape in response to the control signal. The shaped laser pulse is formed by first and second subpulses spaced apart in time from each other. The energy of the first subpulse varies in the range of 0.02 to 0.15 J (preferably 0.05 to 0.1 J), and the peak power of the first subpulse varies in the range of 50 to 500 W (preferably 100 to 250 W). The interval between the first and second subpulses varies in the range of 50 to 900 μs, preferably in the range of 100 to 500 μs. The second subpulse has an energy exceeding the energy of the first subpulse, varying in the range of 0.1 to 10 J, and a peak power exceeding the peak power of the first subpulse, varying in the range of 300 to 20000 W.

[0043] In yet another configuration of the laser system according to this embodiment, a controller is constructed that outputs a control signal containing information about a desired laser pulse shape. The laser is operationally coupled to the controller such that a desired laser pulse shape is formed in each laser pulse, and emits a sequence of laser pulses in response to the control signal. Shaped laser pulses are formed in initial and subsequent sections, with the subsequent section having higher power than the initial section.

[0044] The initial interval has power that monotonically increases from a minimum power level varying between 0 and 200W to a power level varying between 400 and 20000W in the subsequent interval. The duration of the initial interval varies in the range of 0.1 to 10 ms, and the energy of the initial interval is 10-70% of the total pulse energy, while the duration of the subsequent interval varies in the range of 0.5 to 20 ms. The power of the initial interval increases according to one of the following: linear, polynomial, or exponential.

[0045] Further aspects, structural details, and advantages of the present invention are described in detail below in specific descriptions. Furthermore, it should be understood that the information above and the detailed descriptions below are merely illustrative examples of various aspects and embodiments and are intended to provide an overview or framework for understanding the essence and characteristics of the claimed aspects and embodiments. To make it easily understandable, all of the structural details disclosed above and below of the present invention can be combined in any reasonable combination that is easily understood by those skilled in the art of lasers and urology.

[0046] Aspects of the present invention will be described further later with reference to accompanying drawings, which are not intended to be drawn to a specific scale. The drawings are included to illustrate and further understand various structural features and are incorporated into and form part of this specification, but are not intended to define the scope of any particular embodiment. The drawings, together with the rest of this specification, serve to illustrate the principles and operation of the described and claimed aspects and embodiments. In the drawings, each identical or substantially identical component illustrated in various drawings is represented by similar numbers. For the purposes of clarity, not every component is labeled in every drawing. [Brief explanation of the drawing]

[0047] [Figure 1] This is an illustrative diagram of a laser system and delivery system for lithotripsy according to the present invention. [Figure 2A] This figure illustrates a sequence of laser pulses with constant peak power and uniform pulse period, currently used in known prior art laser lithotripsy. [Figure 2B] This figure illustrates the pulse shape of a diode-excited fiber or solid-state laser, which is known in the present technology. [Figure 2C] This figure illustrates the pulse shape of a flash lamp-pumped solid-state laser, which is known in this technology. [Figure 2D] This figure illustrates the pulse shape of a flash lamp-pumped solid-state laser with spikes, which is known in the present technology. [Figure 2E] This figure illustrates the pulse shape of a multi-head flash lamp-pumped solid-state laser, which is known in this technology. [Figure 2F] This figure illustrates a specially constructed pulse shape for a flashlamp-pumped solid-state laser, known in the art, designed to minimize energy loss in water between the distal end of the fiber and the target. [Figure 3] This figure illustrates an illustrative sequence of laser pulses emitted by a laser system according to the present invention, which operates an amplitude-frequency modulation (AFMR) mode characterized by a periodically changing peak power Pp or energy E with a modulation period Na equal to the number of laser pulses. In the amplitude-period pulse group, the pulse frequency is periodically changed with a modulation period Np corresponding to the number of pulses in the frequency-period pulse group. [Figure 4A] This figure illustrates an example of a laser pulse sequence known in the art and used as a normal mode for dusting, crushing, and non-contact experiments. [Figure 4B] This figure illustrates an example of a laser pulse sequence known in the art and used as a normal mode for dusting, crushing, and non-contact experiments. [Figure 4C] This figure illustrates an example of a group of laser pulses emitted by the system according to the present invention, operating in amplitude-frequency modulation (AFMR), and used in dusting experiments. [Figure 4D] This figure illustrates an example of a group of laser pulses emitted by the system according to the present invention, operating in amplitude-frequency modulation (AFMR), and used in dusting experiments. [Figure 4E] This figure illustrates an example of a group of laser pulses emitted by the system according to the present invention, operating in amplitude-frequency modulation (AFMR), and used in dusting experiments. [Figure 5] This is a diagram illustrating an example of amplitude modulation (AMR). [Figure 6A] This figure shows examples of laser pulses with amplitude periods in an AMR, characterized by various amplitude modulation periods Na and used in contact mode experiments. [Figure 6B] This figure shows examples of laser pulses with amplitude periods in an AMR, characterized by various amplitude modulation periods Na and used in contact mode experiments. [Figure 6C] This figure shows examples of laser pulses with amplitude periods in an AMR, characterized by various amplitude modulation periods Na and used in contact mode experiments. [Figure 6D] This figure shows examples of laser pulses with amplitude periods in an AMR, characterized by various amplitude modulation periods Na and used in contact mode experiments. [Figure 6E] This figure shows examples of laser pulses with amplitude periods in an AMR, characterized by various amplitude modulation periods Na and used in contact mode experiments. [Figure 6F] This figure shows examples of laser pulses with amplitude periods in an AMR, characterized by various amplitude modulation periods Na and used in contact mode experiments. [Figure 6G] This figure shows examples of laser pulses with amplitude periods in an AMR, characterized by various amplitude modulation periods Na and used in contact mode experiments. [Figure 7A] This figure illustrates further examples of laser pulses with amplitude period groups that have a modulation period Na following AMR and are used in non-contact mode experiments. [Figure 7B] This figure illustrates further examples of laser pulses with amplitude period groups that have a modulation period Na following AMR and are used in non-contact mode experiments. [Figure 7C] This figure illustrates further examples of laser pulses with amplitude period groups that have a modulation period Na following AMR and are used in non-contact mode experiments. [Figure 8] This is a diagram illustrating an example of frequency modulation (FMR). [Figure 9] This is an example of a single laser pulse shaped by two temporally separated subpulses with different peak powers. [Figure 10] This is a diagram illustrating an example of a single laser pulse shaped by two adjacent segments. [Figure 11A] This is a diagram showing different laser pulse shapes used in the crushing experiment. [Figure 11B] This is a diagram showing different laser pulse shapes used in the crushing experiment. [Figure 11C] This is a diagram showing different laser pulse shapes used in the crushing experiment. [Modes for carrying out the invention]

[0048] Detailed references to embodiments of the present invention are provided hereby. Wherever possible, the same or similar reference numerals or letters are used in the drawings and description to refer to the same or similar parts or steps. The drawings are simplified and not to exact scale. For convenience and clarity only, terms indicating direction (up / down, etc.) or motion (forward / backward, etc.) may be used in the drawings. The terms “join” and similar terms do not necessarily mean a direct and immediate connection, but also include connections through intermediate elements or devices.

[0049] The inventive concept of the present invention is based on minimizing the recession effect while providing a high ablation rate by increasing ablation efficiency. This concept is realized by (a) modulation (periodic variation) of pulse energy E(n) or peak power Pp(n) or both, defined as AM; (b) modulation of pulse frequency (repetition rate) ν(n) with pulse period T(n), defined as FM; (c) simultaneous amplitude and frequency modulation referred to as AFM; and (d) configuration of a specific pulse shape.

[0050] A first aspect of the present invention—modulation of pulse peak power and / or energy—can be better understood by considering the following description. In this laser system for treating gallstones in the human or animal body, the temporal structure of the laser power is a periodic pulse sequence (sequence) that can be described by the following equation: P(t)=Pp*f(tT*n, n=0,1,2,..., (1) In the equation, P(t) is the instantaneous laser power, Pp is the peak power, f(t) is the individual pulse shape (profile), and T is the sequence period, inversely proportional to the pulse frequency: T = 1 / ν. The energy per pulse is the integral of the power: E=INT(P(t),0,T)=Pp*τ, (2) In the formula, τ is the effective pulse width.

[0051] A periodic pulse sequence can also be described by the following equation: P(t)=(E / τ)*f(tT*n), (3) Each pulse shape (profile) f(t) is characterized by the pulse width τ. For laser systems used in lithotripsy, the pulse width is much shorter than the sequence period: τ< <Tまたはτ<0.1T。

[0052] Conventional laser therapy techniques are based on a system where Pp, T, ν, and E are set before treatment and kept constant during treatment. Some laser systems can be configured with dual-pedal treatment parameters that can be switched between two sets of parameters with constant peak power, frequency, and energy per pulse: Pp1, T1, ν1, E1 and Pp2, T2, ν2, E2.

[0053] Amplitude modulation (AM) according to the present invention: In contrast to known prior art, amplitude modulation is defined here as a mode having a periodic change in period T and frequency ν, as well as a peak power Pp: P(t)=Pp(n)*f(tT*n), n=0,1,2,... (4) or energy P(t)=E(n) / τ(n)*f(tT*n), (5) In the formula, Pp(n) = Pp(n-Na), E(n) = E(n-Na), or τ(n) = τ(n-Na), or a combination thereof, where Na is a positive integer referred to as the amplitude modulation period. In the AM style (AMR) of the laser according to the present invention, all laser pulse sequences can be presented as periodic sequences of a group of Na pulses (amplitude-modulated period pulse groups) with variable amplitude within the group.

[0054] Figures 6A–6G and 7A–7C illustrate sequences of laser pulses with various modulation periods Na emitted from the laser system according to the present invention operating in an AMR. These figures are described in detail below.

[0055] Frequency modulation (FM) according to the present invention In contrast to known prior art, the frequency modulation used in this application is defined as having a periodic variation of a constant peak power Pp or energy E and a frequency ν or pulse period T: P(t)=Pp*f(tT(n)*n), n=0,1,2,... (6) or P(t)=E / τ*f(tT(n)*n), (7) In the equation, T(n) = T(n-Np), where Np is a positive integer called the period of frequency modulation. Frequency modulation means frequency modulation because ν(n) = 1 / T(n) = ν(n-Np). In FM style (FMR), all laser pulse sequences can be presented as a periodic sequence of a group of Np pulses (a group of frequency-modulated periodic pulses) with a variable period between pulses within the group.

[0056] Figure 8 illustrates a laser system according to the present invention operating in FMR mode.

[0057] Amplitude-frequency modulation (AFM) according to the present invention: Based on AM and FM as defined in this invention, amplitude-frequency modulation is defined as a mode having simultaneous periodic changes in peak power Pp (or energy E) and frequency ν (and period T): P(t)=Pp(n)*f(tT(n)*n), n=0,1,2,... (8) or energy P(t)=E(n) / τ(n)*f(tT(n)*n), (9) In the formula, Pp(n)=Pp(n-Na) or E(n)=E(n-Na) or τ(n)=τ(n-Na) and T(n)=T(n-Np).

[0058] Figures 3 and 4A to 4C illustrate the system according to the present invention operating with AFMR, which are described in detail below.

[0059] Focusing on Figure 1, which illustrates a schematic and illustrative laser system 100 according to the present invention, those skilled in the art will immediately recognize that structurally this system is relevant to the consideration of both embodiments of the present invention and can be embodied using various types of laser technology. However, preferred embodiments are based on a specific classification of laser technology, in particular on pulsed laser technology, including a pulsed laser 104 operating in either free-running mode or Q-switched mode. Regardless of the laser type and mode of laser operation, the laser system 100 according to the present invention comprises a pump 103 for exciting the laser 104. Typically, the pump 104 consists of one or more diode lasers. In the optimal embodiment, pulsed laser technology implies the use of an energy storage device (e.g., an electrical capacitor, an inductor, or a combination thereof).

[0060] Power supply 101 provides power to the system, and optionally, energy storage device 102 stores a sufficient amount of energy to form laser pulses. The laser driver 103 of pump 104 forms electrical pulses of specified characteristics in response to control signals from control module 108. The electrical pulses are received by one or more diodes of pump 104, which form optical pulses necessary to excite the laser medium in the laser cavity 105. The output of the laser medium is coupled to a delivery system 107, which is considered external to the laser system, through an optical coupler 106.

[0061] The entire system is controlled by the control module CM(108), which provides a contained calibration curve or table (determining the characteristics of the electrical pulses required to achieve the desired optical output), control signals, timing, and safety functions. Instead of an excitation diode, other devices, such as a flash lamp, can be used as the excitation light source.

[0062] Alternatively, the laser medium itself can be used as an energy storage device. In this configuration, pulse formation is achieved through the application of a cavity loss internal optical modulator as a Q modulation device, such as an acoustic-optical, electro-optical, or passive modulator.

[0063] For the purposes of this invention, the following terms are defined: The laser pulse is the output of the laser system 100 according to the present invention, generated by direct modulation of the diode current by the laser driver 103 or by a single charge-discharge cycle of the energy storage device 102. The sequence of laser pulses is the output of the laser system, generated by a number of direct single modulations or single charge-discharge cycles of the energy storage device 102.

[0064] Thus, in one aspect of the present invention, the modulation of the pulse sequence is achieved by the control module 108 setting a desired peak power Pp or pulse energy E for AM, or an interval T between two consecutive pulses for FM. In the other aspect of the present invention, pulse shaping is achieved by the laser driver 103 forming a desired temporal structure of the pulse.

[0065] A laser system 100 operating according to the first embodiment by controlling the temporal structure of laser emission based on equations 4-9 above, which mathematically describe AM and combined AM and FM according to the present invention, is controlled as follows: a) Modulate the peak power Pp or pulse energy E with respect to the number of pulses in a pulse sequence, Pp(n) = Pp(n-Na), where Na is the period of amplitude modulation. b) Modulate the period T of the pulse sequence (and frequency ν, respectively) with respect to the number of pulses, given by T(n) = T(n-Np), where Np is the period of frequency modulation. c) Combining the modulation modalities described in a), b), and c) above, for example, simultaneous modulation of amplitude and frequency (amplitude-frequency modulation).

[0066] In addition to all three types of modulation (amplitude, frequency, and amplitude-frequency), adjusting the individual pulse shapes is used in various aspects of the present invention. Diode-excited fibers (preferred) and solid-state lasers can be modulated by controlling the current of the excitation diode, and the laser parameters can be changed by changing the current on the excitation diode. Preferably, the diode current is the threshold current I of the diode-excited laser generation. th The current should vary within a range between a certain maximum current and a saturation level Ist of the laser power as a function of the diode current. Within this range, the laser power depends almost linearly on the diode current, and various laser temporal structures can be generated by programming the excitation current of the laser driver.

[0067] The primary proposal of the present invention is to increase the rate of stone dusting or crushing without compromising or (preferably) increasing the safety profile. This can be achieved by appropriate pulse shaping or by modulating the pulse sequence (with one or more of the modulation modalities described above). Such modulation should be optimal for each mode of treatment, such as contact dusting or crushing, and for non-contact dusting.

[0068] In contact dusting, the desired final result is the fragmentation of stones into small particles less than 1 mm, preferably less than 0.5 mm, and most preferably less than 0.25 mm. In current laser systems, this method requires continuous movement of a fiber across the stone surface using relatively low energy per pulse (0.025–0.3 J). To compensate for the low ablation volume per pulse due to the low energy per pulse, the repetition rate should be as high as possible, while the average power Pa = E*ν should be kept within a safety limit to avoid thermal damage to soft tissue from the warm water in the urinary tract. This safety limit of Pa max depends on the irrigation rate and the total treatment time. The temporal structure of the laser output can be optimized to achieve high ablation rates with equal average power through laser pulse shaping and / or modulation of the laser pulse sequence, while simultaneously reducing or maintaining at least the same level of retreat. Ablation efficiency and retreat effect are the result of a combination of many factors, including but not limited to: 1. Pulse energy, pulse peak power or pulse width, repetition rate 2. Depends on beam diameter and fiber core diameter. 3. Distance between the fiber end and the stone 4. Fiber movement speed. This factor is related to the number of effective pulses applied to a single point. This number can be estimated by the formula K = (d / 2v)*ν, where d is the beam diameter on the stone surface and v is the fiber movement speed. The ablation efficiency decreases with increasing K due to increasing distance between the fiber end and the bottom of the laser crater, shading effect from ablation products, water loss at the bottom of the laser crater, and other factors. 5. Fiber vibrations induced by laser pulsing. Fibers can vibrate within a certain amplitude range. These vibrations are induced by forces from laser-induced bubble formation in water, electrostrictive effects, and other mechanisms. Fiber vibrations can effectively reduce the number of pulses applied to a single point K, thereby increasing ablation efficiency. 6. Stone size and shape

[0069] Pulse modulation, while acting in combination with all the listed factors, can lead to a variety of effects. For example, periodic increase of laser energy from minimum to maximum can compensate for the decrease in ablation efficiency, while the same frequency, average power, and fiber travel speed result in laser treatment at a constant energy at a single point. Provided below are experimental comparisons of stone ablation and retraction velocity using constant pulse energy, peak power, and frequency with various amplitude modes (representing normal mode and current mode of treatment stones), demonstrating the advantages of the proposed modes of amplitude and amplitude-frequency modulation over contact and non-contact modes.

[0070] Characterization of the time mode of laser lithotripsy The overarching objectives for optimizing laser lithotripsy are to expedite the procedure, ensure stone fragmentation into fragments of the desired size, and minimize the incidence of side effects. Among the parameters relevant to this objective, the two most important are the efficiency of stone ablation and the magnitude of the retraction effect. To compare various time modes of laser emission, we use the following metrics: 1) Efficiency of stone ablation, defined as Ka, Va / Et, where Va is the total excision volume and Et is the total laser energy [mm²]. 3 1) Critical retreat velocity Vr [mm / s], defined as the rate of retreat in the first case of laser treatment, and 2) Absolute quality in time mode Qa, which increases with ablation efficiency and decreases with retreat [mm / s]. 2 4) Relative quality Qr in time mode, defined as (Qa) / (Qa)ref, where the subscript ref in the formula refers to the reference normal mode [dimensionless], 5) Time of stone splitting, defined as the time it takes to split the stone in fracturing mode.

[0071] The following experimental techniques were used to characterize and compare various time modes:

[0072] Scanning experiment device: 1) Tm fiber laser with a wavelength of 1.94 μm and a maximum peak power of 1000 W 2) Delivery fiber with a core diameter of 200 μm 3) 2D Motor Stage 4) High-speed camera (Phantom Vision Research Phantom Miro M310) 5) Fiber holder 6) Mechanical surface roughness gauge (Mitutoyo Corporation, Kawasaki, Japan-made Contracer® registered trademark)

[0073] material and method: All experiments were conducted on an artificial stone phantom. Stone was produced using BegoStone powder (Bego GmbH, Bremen, Germany) in a 5:1 water-to-stone ratio. The sample was cut into a slab with dimensions of 60 × 40 × 8 mm. The stone was immersed in water for 24 hours before laser exposure.

[0074] Ablation efficiency and regression effect were measured using two different instruments.

[0075] First, a stone was placed in a container filled with water (two bubble levels were used for proper positioning of the equipment). A fiber holder was mounted on a 2-D motor stage. A 30 mm long linear crater was created using 1-D horizontal fiber movement at a speed of 6 mm / s, representing a typical clinical scanning speed. Laser parameters were modified according to the table below. The cross-sectional area, depth, and width of the crater were measured using a mechanical surface roughener. The ablation rate and efficiency were calculated using the cross-section of the profile, multiplied by the scanning speed, and divided by the average laser power. During scanning, the distance between the fiber end and the flat stone surface was maintained at approximately 0.2 ± 0.1 mm.

[0076] Secondly, the receding effect was measured for the same laser parameters. To measure the magnitude of the stone displacement, two straight rulers were mounted along the long sides to form a 90° groove. The groove was immersed in a water tank. Two bubble levels were used for proper positioning of the equipment. A stone sample (5×5×5 mm cube) was placed in the groove. A fiber was introduced through a holder provided in a hole on the side of the equipment. The tip of the fiber was brought into contact with the center of the stone. A high-speed (1000 frames per second) camera (Phantom MIRO M310, Phantom Vision Research, USA) was used to acquire the stone movement. The stone movement was analyzed during the first 0.5 seconds of exposure. Using image software, the stone movement as a function of time was quantified, and the velocity of the stone movement at the initial moment of laser processing was calculated as the slope of such a function at the start of laser processing.

[0077] Bubble Characterization Experiment device: 1) Tm fiber laser with a wavelength of 1.94 μm and a maximum peak power of 1000 W 2) Fiber with a core diameter of 200 μm 3) Quartz cuvette 4) Experiment stand 5) Halogen lighting system 6) High-speed camera Phantom Miro M310

[0078] material and method: A fiber holder was mounted on a laboratory stand. The fiber was placed in a quartz cuvette filled with water. Using a high-speed camera, single-pulse video bubble formation was recorded for various laser parameters (energy and peak power lasers ranging from 0.025 mJ to 0.4 J and 100 to 500 W, respectively). The camera frame rate was 120,000 frames per second, and the exposure time was 7 μs. A halogen illumination system was used to illuminate the scene. The recorded video was used to evaluate bubble growth time up to 1 mm, up to 2.5 mm, and up to the maximum bubble size. Bubble length was quantified using ImageJ software.

[0079] Contactless mode device: 1) Tm fiber laser with a wavelength of 1.94 μm and a maximum peak power of 1000 W 2) Fiber with a core diameter of 200 μm 3) Flexible endoscope 4) Two glass cuvettes

[0080] material and method: The experimental apparatus included a specially constructed inner cuvette with a diameter of 13 mm and a 0.25 mm hole perforated in the wall at a height of 40 mm. Laser treatment was performed via a flexible endoscope. The water flow through the flexible endoscope was 10 ml / min. The inner cuvette was placed inside the outer cuvette, which collected the wastewater containing suspended dust particles smaller than 0.25 mm that were discharged by the water flow through the side hole during lithotripsy. BegaStone spheres with a radius of 2 mm were used as stone phantoms in this study. Five spheres were used for each laser parameter. Lithotripsy was performed for a period of 2 minutes and 40 seconds. After lithotripsy, the fragments remaining in the inner cuvette were weighed. The dust mass was determined as the difference between the initial mass of the sphere and that of the residual fragments. The ablation rate was defined as the ratio of the dust mass to the duration of treatment.

[0081] Perforation and cracking device: 1) Tm fiber laser with a wavelength of 1.94 μm and a maximum peak power of 1000 W 2) Fiber with a core diameter of 200 μm 3) Fiber holder 4) Glass cuvette 5) Stopwatch

[0082] material and method: The experiment was conducted on an artificial stone phantom. Stones were produced using BegoStone powder (Bego GmbH, Bremen, Germany) in a 5:1 water-to-stone ratio. The stones were sized at 5 × 2.5 × 2.5 mm. The stones were immersed in water for 24 hours before laser exposure. The stone samples were placed in glass cuvettes filled with water. The stones were perforated with various parameters of laser radiation in a manner that mimicked a fracture-type treatment, with the fiber always in contact with the stone at the center of the 5 × 2.5 mm side. During the experiment, a stopwatch was used to record the fracture time at which the stone sample broke into two fragments. Subsequently, recession was evaluated with the same laser parameters using the equipment described in the scanning experiment section above.

[0083] All measurements were repeated three times, and calculations were performed for each setpoint, mean, and standard deviation.

[0084] Amplitude-frequency modulation (AFM) A typical case of laser pulse sequences currently used in laser lithotripsy is illustrated in Figure 2. Here, the sequence is characterized by a constant magnitude (peak power) Pp, constant pulse energy E, and constant period T of each single pulse (Figure 2A). The shape of the single pulse (201) can vary between a simple quasi-rectangular pulse 202 (Figure 2B), which is typical for diode-pumped lasers, a pulse shape 203 (Figure 2C), which is characteristic of flashlamp-pumped lasers with a steep rise edge and a long tail, a pulse shape 204 (Figure 2D), which is also common for flashlamp-pumped solid-state lasers, where the smooth general shape is modulated by irregular micropulses or spikes due to the relaxation oscillations of the laser, or a composite pulse shape 205 (Figure 2E), which is found in multi-head flashlamp solid-state laser systems. For example, other pulse shapes are known in this art, such as a pocket of regular micropulses [Blackmon RL, Fried NM, Irby PB, Enhanced thulium fiber laser lithotripsy using micro-pulse train modulation, Journal of biomedical optics, February 2012, 17(2):028002], or a pulse consisting of two subpulses 206 (Figure 2F), with a forward low-energy subpulse followed by a high-energy backward subpulse 206 at an interval of 100 to 200 μs [U.S. Patent No. 5321715].

[0085] In contrast, the present invention highlights the various advantages and benefits that can be obtained by varying one or more of the quantities Pp, E, and T according to formulas (4-9). Amplitude-frequency modulation is the most common type of modulation encompassed by the present invention. An example of AFM is illustrated in Figure 3, where the amplitude modulation period Na is equal to the frequency modulation Np and equal to 4. The AFM may be characterized by the mean group period Tav, which is defined below:

[0086]

number

[0087] In the formula, Ng is the number of pulses in the period group, and Ti is the period of the i-th pulse.

[0088] AFM is beneficial for both contact and non-contact treatment modes. Preferred AFM parameters are as follows: 1. Scanning Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 250-5000W, more preferably 400-1000W Energy per pulse: 0.01-2 J, more preferably 0.05-0.5 J Pulse repetition rate ν = 5 to 3000 Hz / Period T = 0.00033 to 0.2 s, more preferably 50 to 1000 Hz, 0.001 to 0.02 s Na = 2~10 Np = 1 to 100 These settings are illustrated by Figure 4 and Table 1. All experiments were conducted at the same average power of 30W, providing the same soft tissue safety profile.

[0089] [Table 1]

[0090] The table shows that the AFM method significantly increases ablation efficiency (up to 3.1 times) and ablation depth compared to the normal (unmodulated) method at 500W and 1000W peak power without increasing recession.

[0091] Contact / Crushing Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 100-2000W, more preferably 250-1000W Energy per pulse: 0.2 to 10 J, more preferably 0.5 to 5 J Pulse repetition rate ν = 1 to 300 Hz / Period T = 0.0033 to 1 s Na = 2~10 Np = 1 to 100 2. Contactless (Pop Corning) Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 500-3000W, more preferably 500-2000W Energy per pulse: 0.05 to 1 J, more preferably 0.05 to 0.5 J Pulse repetition rate ν = 10 to 1000 Hz / Period T = 0.001 to 0.1 s Na = 2 to 100 Np = 1 to 100

[0092] Amplitude modulation Amplitude modulation is a specific case of AFM where the pulse period remains constant. A typical case of amplitude modulation (AM) is illustrated in Figure 5. Here, the magnitude (Pp or E) changes with a period Na=3, while the period T between individual pulses remains constant. A group of pulses 501 within a time interval T*Na is called an amplitude-modulated period pulse group.

[0093] Many variations of the pulse group are possible. Some are illustrated in Figure 6(ag). As can be seen from Figure 6, both Pp and E can be varied within the AM framework. AM can be beneficial for both primary modes of laser lithotripsy (i.e., contact and non-contact). Preferred forms and illustrations are summarized below: 1. Contact / Scanning Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 250-3000W, more preferably 400-1000W Energy per pulse: 0.02 to 2 J, more preferably 0.05 to 0.5 J Pulse repetition rate ν = 5 to 3000 Hz / Period T = 0.00033 to 0.2 s, more preferably 50 to 1000 Hz, 0.001 to 0.02 s Na = 2~10 These settings are illustrated by Figure 6 and Table 2.

[0094] [Table 2]

[0095] These data suggest that amplitude modulation can increase style quality by more than three times. 2. Contact / Crushing Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 100-20000W, more preferably 250-3000W Energy per pulse: 0.2 to 20 J, more preferably 0.5 to 10 J Pulse repetition rate ν = 1 to 500 Hz / Period T = 0.002 to 1 s Na = 2~10 3. Contactless (Pop Corning) Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 500-3000W, more preferably 500-2000W Energy per pulse: 0.05 to 1 J, more preferably 0.05 to 0.5 J Pulse repetition rate ν = 10 to 3000 Hz / Period T = 0.0003 to 0.1 s Na = 2 to 100 These settings are illustrated by Figure 7 and Table 3.

[0096] [Table 3]

[0097] These data suggest that amplitude modulation significantly reduces (up to 60%) the time required to complete the non-contact dusting method while maintaining a constant average laser power.

[0098] Frequency modulation (FM) Frequency modulation is a specific case of FM, where the pulse period changes while the pulse energy and peak power remain constant. A typical case of frequency modulation is illustrated in Figure 8. Here, the magnitude (Pp and E) remains constant, while the pulse period changes with a period Np = 5. As AFM, FM is characterized by the mean pulse period Tav. A group of pulses 801 within a time interval Tav * Np forms a group of periodic pulses.

[0099] Many variations of the FM pulse group are possible.

[0100] FM can be beneficial for both primary modes of laser lithotripsy (i.e., contact and non-contact). The preferred mode is summarized below: 1. Contact / Scanning Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 250-3000W, more preferably 400-1000W Energy per pulse: 0.02 to 2 J, more preferably 0.05 to 0.5 J Pulse repetition rate ν = 5 to 3000 Hz / Period T = 0.00033 to 0.2 s, more preferably 50 to 1000 Hz, 0.001 to 0.02 s Np = 10 to 100 2. Contact / Crushing Mode Preferred parameters: Wavelength 1.81–2.2 μm, more preferably 1.908–1.98 μm Peak power Pa = 100-3000W, more preferably 400-1000W Energy per pulse: 0.2 to 20 J, more preferably 0.5 to 5 J Pulse repetition rate ν = 1 to 300 Hz / Period T = 0.0033 to 1 s Np = 10 to 100 3. Contactless (Pop Corning) Mode Preferred parameters: Wavelength 1.81-2.2, more preferably 1.908-1.98 Peak power Pa = 250-5000W, more preferably 250-1000W Energy per pulse: 0.02 to 1 J, more preferably 0.05 to 0.5 J Pulse repetition rate ν = 10 to 1000 Hz / Period T = 0.001 to 0.1 s Np = 10 to 100

[0101] pulse shape Laser energy emitted from the fiber end and traveling through the liquid (water) medium in the gap between the fiber end and the surface of the target stone or tissue will be absorbed, however, absorption may be less than expected. This is attributed to the "Moses effect," where the first component of the emitted energy is absorbed by the liquid, creating vapor bubbles in the liquid medium, and the remaining energy passes through a low-restriction or absorbent gas / vapor medium characterized by low light attenuation. The laser-induced vapor bubbles created during the initial pulse act like "separating the water," allowing subsequent pulses to be delivered to the stone more efficiently. This phenomenon has been proposed to be used to increase the efficiency of stone ablation using two pulses: first a short, low-energy pulse to create vapor bubbles, followed by a longer, higher-energy therapeutic pulse (see U.S. Patent No. 5,321,715).

[0102] In this invention, controlling the temporal structure of the laser power is used to minimize the receding effect. The formation of water bubbles between the rock and the distal fiber end can generate pressure and force that moves the rock away from the fiber. This effect can be minimized by reducing the laser power and energy during bubble formation. The collapse of bubbles between pulses generates negative pressure and force on the rock, and during rock ablation, the rock movement can be compensated for by bubble growth and rebound movement (absorption effect). These effects can be controlled by changing the individual pulse shape f(t), pulse energy E, and the interval T between pulses.

[0103] Laser ablation typically requires a combination of high ablation efficiency and low receding effect. To compare different temporal laser structures, laser ablation efficiency η is defined as the volume of ablation product divided by the total laser energy spent to remove this volume and the velocity V of stone displacement due to receding at the very beginning of laser pulsing. abl The following can be used. The value of V is determined by a single pulse shock for low repetition rates, or by several pulse shocks over a period of approximately 0.1 s for high repetition rate laser systems. In detail, the ratio η abl / V can characterize the practical (combined) efficiency or speed of treatment.

[0104] The pulse shape for solid-state lasers configured with flashlamp pumping typically has an irregular spike structure and can be controlled by current through flashlamp pumping in a very limited manner. In contrast, diode-pumped fiber and solid-state lasers allow for precise control of pulse shape within a wide range of parameters, thereby increasing the speed of treatment.

[0105] In this invention, in addition to AM and AFM, the temporal structure of the laser emission is controlled by modulating the individual pulse shapes f(t) to provide optimal conditions for stone ablation with maximum efficiency and reduced recession.

[0106] When treating stones in contact mode, the objective is to increase the efficiency of stone ablation in order to reduce the total time required to break up the stone. This can be achieved by adjusting the shape of the pulse by applying low brightness to the first part of the pulse to establish a Moses channel with minimal energy loss while simultaneously minimizing the recession effect of such a pulse, and then applying high brightness to the second part of the pulse to maximize the thermal or thermomechanical effect on the stone. The water absorption loss in the second part of the pulse will be greatly reduced by the Moses channel established by the first part of the pulse. However, the Moses vaporization bubble or channel grows between the fiber end and the stone, generating pressure and force on the stone and thus producing a recession effect. In this invention, it is proposed to reduce the recession effect by minimizing the laser pulse peak power and energy. In the experimental setup, bubble dynamics were measured at the end of a 0.2 mm fiber using a high-speed video camera with a frame rate of 120,000 frames per second. The displacement effect of a stone sample with single-pulse exposure was measured. See the description of the experimental equipment above.

[0107] [Table 4]

[0108] Table 4 summarizes experimental data for TFLs with a wavelength of 1940 nm and a fiber core of 0.2 mm. The results show that bubble length and stone displacement, which are proportional to bubble pressure, increase with laser pulse peak power and energy. The distance between the fiber end and the stone under clinical contact setting is in the range of 0 and 1 mm, however it can exceed 2.5 mm for short periods during treatment. This is to utilize the Moses (vaporization) channel for ablation efficiency, but to minimize the receding effect, it is proposed to use laser parameters for a first subpulse that produce bubbles with a length of no more than 2.5 mm at the lowest pressure. Based on the measured peak power data of the first laser subpulse that produces the Moses (vaporization) channel, the peak power should be in the range of 50 to 500 W, preferably 100 to 300 W, and the energy per pulse should be 0.02 to 0.15 J, preferably 0.05 to 0.1 J. The interval between the first and second subpulses for efficient ablation should be defined based on the following criteria: 1) The second subpulse should begin after the vapor channel front has reached the stone, i.e., when the bubble has grown to 2.5 mm, preferably 1 mm. 2) The pressure on the bubble has decreased or become negative in order to produce a stone absorption effect.

[0109] [Table 5]

[0110] Table 5 shows the time for bubble growth up to 1 mm and 3 mm as a function of laser peak power and energy from the proposed range. Therefore, the interval between subpulses should be in the range of 50 to 900 μs, preferably 100 to 500 μs. The energy of the second subpulse should be in the range of 0.1 to 10 J. Such pulse shapes are illustrated by Figure 9.

[0111] In another embodiment of the present invention, we propose a pulse shape with power continuously delivered between pulses. This shape is most effective for the fragmentation mode when the operator uses a drilling technique while providing close contact between the laser fiber end and the stone throughout the entire treatment cycle. In this case, the water layer between the fiber end and the stone is extremely minimal (less than 0.5 mm) or cannot exist at all. Lasers currently used for lithotripsy have uniform rectangular or flat-topped pulses, which are typical for diode-pumped fibers and solid-state lasers 202 (Figure 2). Flash-pumped solid-state lasers such as Ho:YAG have an asymmetric shape with high power at the beginning of the pulse and a slow relaxation of power at the back tail 203 or 204 (Figure 2). These pulse shapes are not optimal for stones that break during drilling. To increase the efficiency of ablation during drilling and fragmentation, in the present invention we propose using a pulse having two parts, the first part used for removing residual moisture between the fiber and the stone, and for stone ablation and preheating of the stone around the ablation crater (Figure 10). The preheating by the first portion of the low-power pulse will result in increased thermal stress around the laser crater and an increased absorption coefficient of the lithoplasm due to heating above 100-250°C. The second portion of the high-power pulse will be more effectively absorbed by the lithoplasm and will result in better absorption than the first portion, more efficient mechanical damage due to the high peak power of the second portion, and initial mechanical stress on the lith around the laser crater. As a result, the probability of the lith fracturing into larger pieces will increase. At the same time, the recession effect of such pulsing will be reduced by a more effective conversion of laser energy to fracture rather than by ablation of small particles with high recoil moments. This is illustrated by Figure 10, where τ1 is the duration of the first portion of the pulse and τ2 is the duration of the second portion of the pulse. The power profile f1(t) of the first portion of the pulse is at level P min It is constant at P min From P maxIt can be a monotonic function such as a linear, exponential, or polynomial function that increases to P max is the peak power of the second part of the pulse. Other time dependencies of the luminance are possible and will be apparent to those skilled in the art. The duration of the first part of the pulse can be determined considering the minimum energy required to establish the Mose channel and causing ablation of the stone by substantial heating of the stone matrix around the laser crater, increasing stone matrix absorption and enhancing the stone macro cracking effect. In an alternative embodiment, the duration of the first part can be determined in real time using a feedback mechanism. The feedback mechanism will send signals for the establishment of the Mose channel and / or the stone crater temperature and can be based on optical, acoustic, or other technologies. For example, the stone temperature can be detected by measuring the thermal radiation emitted by the stone through the same fiber used for laser power delivery. For a TFL with a wavelength of 1.94 μm, we have found experimentally that the laser power of the first part of the pulse should be in the range P min = 50 - 200 W, the pulse duration τ1 should be in the range 0.1 to 10 ms, the energy of the first part is 10 - 70% of the total energy of the pulse, while the power of the second part of the pulse should be in the range 400 to 20000 W and its duration should be in the range 0.5 to 20 ms.

[0112] Examples of pulse shapes optimized for stone drilling and fracturing are given in FIG. 11 and Table 6.

[0113]

Table 6

[0114] Table 6 shows that increasing the peak power in the normal mode leads to a reduction in the cracking time, but also increases the retreat effect, and the resulting pattern quality remains approximately the same. In contrast, the pulse shaping proposed in the present invention reduces both the cracking time and the retreat effect, thus leading to the desired increase in pattern quality.

[0115] The above descriptions and examples are provided solely to illustrate the present disclosure and are not intended to be limiting. Therefore, this disclosure should be broadly interpreted to include all variations within the scope of the appended claims. [Explanation of symbols]

[0116] 100 Laser Systems 101 Power supply 102 Energy storage devices 103 Laser Driver 104 Pump 105 Laser Cavity 106 Optical Coupler 107 Delivery System 108 Control Modules 201-205 pulses 206 Subpulse 501 pulse 801 pulse

Claims

1. A laser system for treating kidney stones in living organisms, A laser for emitting radiation in a wavelength range, wherein the wavelength range is between 1.908 micrometers and 1.96 micrometers; An optical fiber for transmitting radiation from the laser to the calculus; A power supply that provides current to drive the laser; A control signal is provided to the power supply such that the laser emits a waveform having a first subpulse and a second subpulse; Equipped with, A laser system in which the first subpulse promotes the formation of vapor bubbles between the optical fiber and the calculus, thereby reducing the retraction of the calculus, and the second subpulse excises the calculus.

2. The laser system according to claim 1, wherein the first subpulse has an energy in the range of 0.02 joules to 0.15 joules and a peak power in the range of 50 W to 500 W.

3. The laser system according to claim 2, wherein the first subpulse has an energy in the range of about 0.05 joules to about 0.1 joules and a peak power in the range of 50 W to about 300 W.

4. The laser system according to claim 1, wherein the second subpulse has an energy in the range of about 0.1 joules to about 10 joules and a peak power in the range of about 300 W to about 20,000 W.

5. The laser system according to claim 1, wherein the laser is selected from the group including Tm: fiber laser, Tm: YAG laser, Tm: YAP laser, Tm: LuAG laser, Tm: LuF laser, Tm: LuAP laser, and combinations thereof.

6. The laser system according to claim 1, wherein the second subpulse is initiated when the pressure inside the vapor bubble decreases or becomes negative, thereby generating a stone absorption effect.

7. The laser system according to claim 6, wherein the time interval between the first subpulse and the second subpulse varies in the range between about 50 microseconds and about 900 microseconds.

8. A laser system for treating kidney stones in living organisms, A laser for emitting radiation in a wavelength range, wherein the wavelength range is between 1.908 micrometers and 1.96 micrometers; An optical fiber for transmitting radiation from the laser to the calculus; A power supply that provides current to drive the laser; A control signal is provided to the power supply so that the laser emits pulses having a first part and a second part; Equipped with, A laser system in which the first part reduces water between the optical fiber and the calculus by forming steam bubbles, heats the calculus, and reduces the retraction of the calculus, and the second part reduces the size of the calculus.

9. The laser system according to claim 8, wherein the first portion of the pulse has a power between 50 W and 200 W and a duration between about 0.1 milliseconds and about 10 milliseconds.

10. The laser system according to claim 8, wherein the first portion of the pulse has a laser power between 400 W and 20,000 W and a duration between about 0.5 milliseconds and about 20 milliseconds.

11. The laser system according to claim 8, wherein the first portion of the pulse includes between 10% and 70% of the total energy of the pulse.

12. The laser system according to claim 8, wherein the power of the first portion of the pulse is selected from the group including a function that does not decrease monotonically, a function that increases from a minimum level to a maximum level, a constant function, and combinations thereof.

13. The laser system according to claim 8, wherein the laser is selected from the group including a Tm fiber laser, a Tm:YAG laser, a Tm:YAP laser, a Tm:LuAG laser, a Tm:LuF laser, a Tm:LuAP laser, and combinations thereof.

14. The laser system according to claim 8, further comprising a controller for generating the control signal, wherein the controller determines the duration of the first portion of the laser pulse based on thermal radiation from the calculus.

15. The laser system according to claim 14, wherein the optical fiber acquires thermal radiation from the calculus for use by the controller.

16. A laser system for treating kidney stones in living organisms, A controller that outputs a control signal indicating a desired laser pulse shape including a first subpulse and a second subpulse; A power supply that provides variable power output in response to the reception of the aforementioned control signal; A laser connected to the power supply for emitting radiation according to the desired laser pulse shape, the laser having a wavelength range between 1.908 micrometers and 1.96 micrometers; Equipped with, The second subpulse has a total energy greater than the total energy of the first subpulse, The duration of the second subpulse is variable and determined by the controller. A laser system in which the first subpulse promotes the formation of vapor bubbles between the laser and the stone, thereby reducing the retreat of the stone, and the second subpulse excises the stone.

17. The laser system according to claim 16, wherein the desired laser pulse shape is repeatedly applied to the calculus with a pause in between.

18. The laser system according to claim 16, wherein the desired laser pulse shape includes the peak power of the second subpulse, which is an input to the controller for determining the duration of the second subpulse.

19. The laser system according to claim 16, wherein the duration of the first subpulse is predetermined.

20. The laser system according to claim 16, wherein the first subpulse vaporizes the fluid on the calculus.

21. The laser system according to claim 16, wherein the first subpulse heats the calculus.

22. The laser system according to claim 16, wherein the first subpulse prepares for a reduction in the size of the gallstone with a low total energy, thereby reducing the movement of the gallstone.

23. The laser system according to claim 16, wherein the second subpulse excises the gallstone.

24. The laser system according to claim 16, wherein the second subpulse breaks the calculus.

25. The laser system according to claim 16, wherein the power supply further comprises an energy storage device, and at least the second subpulse is at least partially powered by a discharge from the energy storage device.

26. The laser system according to claim 16, wherein the power supply further comprises an energy storage device, and the length of the downtime is at least partially determined by the charging time of the energy storage device.

27. The laser system according to claim 16, wherein the laser further comprises at least one diode.

28. The laser system according to claim 16, further comprising a temperature sensor coupled to the controller for modifying the laser pulse shape.

29. The laser system according to claim 16, further comprising an optical fiber coupled to the laser, wherein the optical fiber returns temperature data to the controller in order to determine the duration of the first subpulse in order to vaporize the water without excessively moving the calculus.

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