Method and device 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] The present disclosure is generally directed to a method and laser system for treating stones in a human or animal body that controls the temporal structure of the laser power to speed up stone treatment following various surgical procedures. In particular, the present invention relates to a method and laser system for treating stones with laser pulses having an improved temporal structure through modulation of pulse energy, peak power and repetition rate as well as pulse shape. [Background technology]

[0002] Pulsed laser sources may be used in lithotripsy to eliminate stones in humans and animals. Concretions (also referred to herein as stones) are concretions of material that may occur in organs or ducts of the body. Urinary stones include kidney stones (also referred to as intrakidney stones or renal stones) as well as bladder stones (also referred to as intravesical stones or bladder stones) and may have any one of a variety of compositions, including mixed compositions. The main compositions often include calcium oxalate, calcium phosphate, magnesium ammonium phosphate, diammonium calcium phosphate, magnesium phosphate, cysteine, uric acid or urate salts, and xanthine. Stones in the gallbladder and bile ducts are called gallstones and are primarily generated from bile salts and cholesterol derivatives. Concretions may also occur 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 stone destruction through various mechanisms. An optical fiber traveling along the long axis of a rigid or flexible or angled endoscope typically transmits a laser beam for lithotripsy. Stones can be broken down (fragmented) into particles between 1 and 3 to 4 mm in size and subsequently removed through the working channel of a rigid instrument using a basket or similar instrument. Alternatively, stones can be broken down into small particles (<1 mm in size) in a process called dusting. A subclassification of dusting known as fine dusting (particles <0.25 to 0.5 mm, depending on the stone composition and shape of the dust particles) results in fragments small enough to be removed by urine flow or by standard irrigation delivered by a water / saline bag suspended at a height of about 40 cm. Vaporization down to molecular levels is also possible. The efficiency of ablation depends on the conditions at the treatment site and can be substantially lower for larger stones or when treating multiple stones with a single surgical procedure. This problem is more typical for the treatment of large and multiple kidney stones with a flexible ureteroscope when the aim is to complete stone dusting in contact and non-contact modes during surgery.

[0004] Another problem is the movement of stones during treatment due to back-out. Back-out is caused by the following phenomenon: the light energy absorbed by the water in the gap between the fiber and the stone generates a hydraulic wave that pushes the stone away from the tip of the fiber. When the laser energy is absorbed by the stone and ablation of the stone occurs, the recoil momentum of the ablation also displaces the stone away from the fiber. Back-out prolongs the operation time and makes it difficult for the surgeon to complete the fragmentation or dusting of the stone to achieve a result without residual stone particles. Compensating for a low ablation rate by increasing the laser average power and the time of treatment may be limited by increasing the risk of soft tissue damage.

[0005] Several surgical techniques are known for performing laser lithotripsy, e.g. based on the mutual position and relative displacement of the fiber tip and the stone to be treated. These techniques generally fall into one of the following categories: contact fragmentation, quasi-contact scanning (dancing) and non-contact (popcorn) techniques. When using a fragmentation technique, the fiber tip is positioned in contact with the stone center and laser power is delivered to the stone until macro-fracture and fragmentation of the stone occurs. In a fragmentation technique, the laser power is applied to one small area for a relatively long time. Such a mode of operation results in relatively deep drill holes and thermo-mechanical stresses that induce macro-fracture of the stone.

[0006] In the scanning technique, the fiber moves continuously across the stone surface in quasi-contact with the stone (distance 0-1 mm). Every pass across the stone surface results in the removal (ablation) of a thin layer of the stone. This technique is preferred for ablating (dusting) the stone into small fragments. A non-contact technique is used for the treatment of small stone fragments (typically less than 3 mm in size) if retraction does not allow the possibility to operate in contact or quasi-contact mode. In the non-contact technique, the fiber is positioned at a fixed location close to the location of the targeted stone fragment and the laser is irradiated in a non-contact manner. Water vaporization and bubble implosion result in water flow, which causes the small stone fragments to move. If 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, on the operating parameters of the laser (e.g. wavelength, radiation energy, peak power, pulse width and repetition frequency), on the thickness of the intermediate layer between the end of the fiber delivering the radiation and the surface of the stone, as well as on the optical properties (transparency) of the material in this intermediate layer. Various physical processes and mechanisms of ablation are involved in the above mentioned stone destruction surgical procedures and include photomechanical, photothermal and / or photochemical mechanisms.

[0008] The opto-mechanical mechanism, typical for laser pulses shorter than a few microseconds, posits that ablation is initiated when the laser-induced tensile stress exceeds the ultimate tensile strength of the target. 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 effective strength of the material, fracture and material ejection can occur (a process called spallation). In addition, transient tensile stress in liquids can rupture the medium, causing a phenomenon known as cavitation. Cavitation involves the growth and collapse of cavities in the liquid and can cause damage to the surrounding solid material. Laser energy can also lead to plasma formation on the object. Plasma formation is achieved through fast object ionization with optical breakdown, which is a nonlinear effect created 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 caused by direct or plasma-mediated absorption. This absorption gives rise to a growing vapor bubble. Although the growing vapor bubble may not reach the stone, energy from the pulse is further absorbed by the liquid. Thus, a bipolar pressure pulse (i.e., a shock wave) is formed in front of the growing bubble, inducing stone fracture. Cavitation processes involving the bubble further contribute to shock wave growth. Thus, focusing the laser energy on the target material damages the material by plasma formation, shock wave generation, and induction of negative pressure during bubble cavitation, with a series of optical breakdowns.

[0009] Photothermal mechanisms are typical for lasers with pulses longer than about 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 that facilitates the conversion of laser energy into heat and thermomechanical energy that contributes to stone fracturing in the infrared spectrum transmitted through the silica fiber.

[0010] The photothermal mechanism can be carried out in two modes. The first mode is stone dusting, which is initially caused by high pressure caused by expansion or evaporation water (about 10% of stone weight / weight) trapped in the stone between the stone crystallites in the stone pores, crevices, initial microcracks and other micro spaces. Heating and subsequent boiling are caused by selective absorption of water surrounded by mineral and organic components of the stone, which themselves show low absorption of light of about 2 μm wavelength. This mechanism leads to the separation of fragments whose size ranges from the characteristic dimensions of the elementary crystallites (up to hundreds of microns, mainly submicrons to tens of microns) or their aggregates / areas with characteristic dimensions up to 0.5 mm (fine dusting) or 1 mm (dusting). The second mode is stone fragmentation (to fragments >1 mm), which is mainly due to thermal stresses in the stone volume around the area heated by the laser and dominates 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 dominates in scanning and popcorning surgical procedures. The second mode is appropriate for very high pulse energies and for fragmentation 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. The photochemical mechanism may play a role in increasing the absorption of the stone by carbonization of organic molecules in the stone structure or by thermochemical reactions in the mineral matrix. The surgical techniques such as fine dusting, dusting and spalling, the ablation efficiency and the retreat effect can be controlled by the laser parameters such as pulse width, energy per pulse, pulse repetition rate and average power. In addition, the method of energy delivery, e.g., fiber parameters such as core diameter, numerical aperture, distal tip condition and the distance between the distal end of the fiber and the stone, also play an important role. Finally, drilling, scanning or non-contact application all contribute to the outcome of the laser-stone interaction.

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

[0013] Other lasers besides Ho:YAG that are used for laser lithotripsy and operate at wavelengths near the water absorption peak of about 1.94 μm include, but are not limited to, diode-pumped thulium Tm:YAG lasers and diode-pumped Tm fiber lasers (TFL). In particular, diode-pumped Tm fiber lasers have many advantageous properties. These lasers can operate over a wide pulse energy range (0.001-20 J) and at high and low pulse rates (1-1 million Hz). Comparative studies of TFL and Ho:YAG configurations have been conducted (see, e.g., Blackmon et al., Journal of Biomedical Optics, 16(7):071403, July 2011). In addition, the effect of laser pulse operating parameters such as power settings on or reducing recession has been 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 tuned 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 about 20-30 °C and 1.908 μm for water at about 90-100 °C). The TFL ablation thresholds for various stone compositions are much lower (about 5 times) than those of Ho:YAG lithotripsy systems, meaning lower pulse energies for the same ablation rate or equivalent pulse energies but more efficient stone ablation than Ho:YAG systems.

[0014] The beam profile of fiber lasers, including TFL, is thus more uniform and symmetrical than the multimode beams of Ho:YAG lasers or other solid-state lasers, which cannot be coupled into small-core fibers due to unavoidable damage to the fiber. For example, single-mode (SM) thulium fiber lasers are capable of focusing the laser beam down to about 25 microns. The small fiber diameter provided by TFL allows for focusing of higher power densities than holmium lasers, and also reduces back-out. The small fiber diameter increases the radiation exposure or irradiance on the stone surface, which means that lower laser pulse energy can be used during the laser ablation process. When fibers are used in flexible ureteroscopes with small working channels, a small fiber diameter is important to improve irrigation and not to compromise 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, which means 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 through focusing the laser energy between clusters (areas) of crystallites and into cracks and crevices 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 are capable of operating at a greater variety of laser operating parameters than conventional flash lamp 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 possibility of overheating and causing thermal damage to the laser rod. The white light from the flash lamp is mostly wasted in the form of heat with only a small portion contributing to the actual operation of the laser, and these systems typically have wall plug efficiencies of <1-2%. Large, bulky cooling devices (e.g., water cooling) are therefore required for these systems to dissipate this heat and prevent damage to the laser rod. In contrast, diode-pumped fiber laser systems have wall plug efficiencies 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 powers than holmium-based systems, yet still be able to use 110-120V electrical outlets.

[0016] Other advantages of diode-pumped Tm fiber lasers include their ability to generate a variety of temporal structures, including a wide range of pulse shapes, which can also be implemented with other diode-pumped lasers emitting in the 1.85-2.2 μm range. For example, diode-laser-pumped Tm:YAG lasers have this capability. The above-mentioned 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 duration of action, which is associated with the stone ablation rate, the path (velocity) of fragment travel (e.g., reducing regression), as well as the products of destruction. This challenge can be significantly improved by optimizing the temporal structure of the laser emission, a capability offered by diode-pumped fiber or solid-state lasers.

[0018] All lasers used for laser lithotripsy are operated at preset energy per pulse (E = 0.025-6 J), repetition rate (ν = 1-2500 Hz), pulse width and average power P = E × ν (2-120 W). The laser parameters (E, ν and P) are preselected to achieve the desired result: fragmentation, dusting or popcorning, and to provide a safety margin that should minimize the risk of organ wall perforation or water overheating and thermal cauterization of the mucosa. However, stones, as mentioned above, have various compositions, shapes and sizes. Although a fixed set of the aforementioned parameters may effectively fragment one particular stone, it may be ineffective for another.

[0019] To achieve minimal back-off with high ablation efficiency, it has been proposed to broaden the pulse width (long pulse mode) or to use a special double-pulse regime. US Patent No. 5,321,715 proposes a method of irradiating a target (stone as an 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 made transparent in two steps: (1) generating a first laser pulse with sufficient energy to form a vapor bubble in the liquid medium at the delivery end of the fiber, 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 an amount sufficient to displace a substantial portion of the liquid medium from the space between the delivery end of the fiber 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. In this way, the first pulse creates a vapor channel between the fiber end and the target (the Moses effect), and the second pulse propagates to the target with minimal loss and interaction with the liquid. However, the solution taught by this patent has only been partially successful.

[0020] Therefore, a need exists for shaped pulsed 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 times and costs. [Prior art documents] [Patent documents]

[0021] [Patent Document 1] U.S. Patent No. 5,321,715 [Non-patent literature]

[0022] [Non-Patent Document 1] Blackmon et al., Journal of Biomedical Optics, 16(7):071403, July 2011 [Non-Patent Document 2] White et al., Journal of Endourology, 12(2):183-186, March 2009 [Non-Patent Document 3] Andreeva V et al., World journal of urology, May 4, 2019: 1-7 [Non-Patent Document 4] 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 Summary of the Invention [Problem to be solved by the invention]

[0023] This objective is met by the laser system and method for treating stones in a human or animal body according to the present invention. Broadly speaking, there are two aspects 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. Creation and maintenance of optimal pulse shape. Each of the aspects is described in the context of a laser system for treating stones and a method for treating stones. As will be readily apparent to those skilled in the art of laser and urological technology, the aspects are complementary to each other, and the below-described structural features of one of the aspects can be used in the other aspect. [Means for solving the problem]

[0024] Each embodiment of the method provides multi-component size 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 a diode-pumped solid-state laser operating in the 1.85-2.2 μm wavelength range at a specific range of laser power densities. Particles less than 500 μm, preferably less than 250 μm, can be easily removed by irrigation through a ureteroscope configured with a pressure that is safe for the kidney (<40 cm water column height).

[0025] The method according to the first aspect relates to the modulation of the pulse energy E and / or the pulse peak power Pp, referred to as Amplitude Modulation (AM), as well as the modulation of the pulse frequency (i.e. the pulse repetition rate) v, defined as Frequency Modulation (FM). Finally, the method relates to simultaneous amplitude and frequency modulation - Amplitude Frequency Modulation (AFM).

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

[0027] A method for an AFM emitting a sequence of laser pulses provides for periodically varying at least one of pulse peak power or pulse energy, or pulse peak power and energy, with a modulation period Na equal to the number of pulses in a set of amplitude periods, and periodically varying the PRF with a frequency modulation period Np equal to the number of pulses in a set of frequency periods.

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

[0029] The second aspect of the invention was directed to the formation of an optimal pulse shape which was formed according to the following two embodiments.

[0030] In particular, in one embodiment, a method for treating stones in a human or animal body includes 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 of first and second sub-pulses spaced in time from each other. The energy of the first sub-pulse 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 sub-pulses are spaced in time at intervals varying in the range of 50 to 900 μs, with the preferred range being 100 to 500 μs. The energy of the second sub-pulse varies in the range of 0.1 to 10 J beyond that of the first sub-pulse, while its peak power varies in the range of 300 to 20000 W beyond the peak power of the first sub-pulse.

[0031] Another embodiment relates to a method for treating stones in a human or animal body, comprising 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, 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 a power level of the subsequent section, the minimum power level varying between 0 and 200 W. The duration of the initial section varies between 0.1 and 10 ms, while the energy of the initial pulse section constitutes 10 to 70% of the total energy of the pulse. The subsequent section varies in power between 400 and 20000 W, and the duration of the subsequent section varies between 0.5 and 20 ms.

[0032] According to one of the above-mentioned aspects of the present invention, the laser system for treating stones according to the present invention provides a cluster-type mechanism of laser ablation of multi-component solids by configuring a pulse-repetitive laser. In particular, the laser is configured with modulated laser emission and controlled shaping of the laser pulses to simultaneously (i) control the size of the ablation products, (ii) improve the ablation rate, and (iii) reduce stone recession. Modulated laser emission and controlled shaping of the laser pulses can also be used in spallation mode to improve the ablation rate and reduce recession.

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

[0034] According to another feature, the laser system according to the invention includes a laser capable of operating in an amplitude frequency modulation mode (AFMR), characterized in that the laser emits a sequence of laser pulses with a periodically changed pulse peak power or pulses or both with a modulation period Na equal to the number of pulses in one amplitude period group of pulses. The AMPR mode further comprises a sequence of pulses emitted with a periodically changed PRF with a frequency modulation period Np equal to the number of pulses in one frequency period group of pulses.

[0035] The types of lasers utilized in any of the inventive laser systems of the above characterization preferably include diode-pumped solid-state lasers and diode-pumped fiber lasers such as pumped solid-state lasers. In particular, diode-pumped lasers are 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 utilized in the inventive laser system. Furthermore, the use of direct diode lasers is not excluded from the scope of the present invention.

[0036] The modulation period Na of the periodically varied peak power, pulse energy or both ranges from 2 to 100 laser pulses and is applicable to both features of the laser system. The modulation period of at least one of the peak power or pulse energy or both in the AMR ranges from 2 to 1000 laser pulses. The period Np of the periodically varied PF in the AFMR ranges from 2 to 1000 laser pulses.

[0037] The lasers utilized in constructing both aspects of the laser system of the present invention emit laser pulses in the 1.85 to 2.2 μm wavelength range, and preferably in the 1.908 to 1.96 μm wavelength range. Operation at these wavelengths allows for the predominant absorption of laser radiation by water, which is highly beneficial for any of the above mentioned surgical procedures.

[0038] The above mentioned lasers used in the construction of both features can be operated in free-running mode and Q-switched with the difference being that they are a type of modulator. Modulators utilized in the free-running mode include diode lasers while the Q-switched mode is associated with acousto-optic or electro-optic modulators (AOM and EOM respectively).

[0039] In free running mode, any of the disclosed lasers output a sequence of laser pulses at a PRF ranging between 2 and 5000 Hz, each laser pulse having the following characteristics: laser pulse energy in the range of 0.001 J to 10 J, laser pulse peak power in the range of 100 to 20000 W, preferably 250 to 3000 W, and laser pulse duration in the range of 25 μs to 50 ms, preferably in the range of 100 μs to 15 ms.

[0040] The laser operating in 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 invention for both laser configurations includes a controller that outputs a control signal containing information regarding the desired peak power or pulse energy in the AMR or the desired peak power or pulse energy in the AFMR and the desired PRF, the signal being coupled to a driver for any of the modulators mentioned above.

[0042] According to another aspect, the laser system according to the invention is configured with a controller that outputs a control signal that includes information regarding a desired laser pulse shape. The laser is operatively coupled to the controller such that each laser pulse has a desired laser pulse shape in response to the control signal. The shaped laser pulse is formed of first and second sub-pulses that are spaced apart in time from each other. The energy of the first sub-pulse 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 sub-pulse varies in the range of 50 to 500 W (preferably 100 to 250 W). The interval between the first and second sub-pulses varies in the range of 50 to 900 μs, with a preferred range of 100 to 500 μs. The second sub-pulse varies in energy in the range of 0.1 to 10 J, exceeding the energy of the first sub-pulse, and in peak power in the range of 300 to 20000 W, exceeding the peak power of the first sub-pulse.

[0043] In yet another configuration of the inventive laser system according to this aspect, a controller is configured to output a control signal including information regarding a desired laser pulse shape. The laser is operatively coupled to the controller such that the desired laser pulse shape is formed for each laser pulse, and emits a sequence of laser pulses in response to the control signal. The shaped laser pulses are formed in an initial and a subsequent section, with the subsequent section having a higher power than that of the initial section.

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

[0045] Further aspects, structural details and advantages of the present invention will be detailed in the following specific description. Moreover, it should be understood that the above information as well as the following detailed description 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. As can be easily understood, 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 laser and urology.

[0046] Aspects of the present invention are further described below with reference to the accompanying figures, which are not intended to be drawn to scale. The figures are included to provide an illustration and further understanding of various structural features, and are incorporated into and constitute a part of this specification, but are not intended as a definition of the scope of any particular embodiment. The drawings, together with the remainder of the specification, serve to explain the principles and operation of the described and claimed aspects and embodiments. In the figures, each identical or nearly identical component illustrated in the various figures is represented by a like numeral. For purposes of clarity, not every component is labeled in every figure. [Brief description of the drawings]

[0047] [Figure 1] 1 is an illustrative diagram of a laser system and delivery system for lithotripsy in accordance with the present invention; [Figure 2A] FIG. 1 illustrates a sequence of laser pulses of constant peak power and uniform pulse period currently used in known prior art laser lithotripsy. [Figure 2B] FIG. 2 illustrates pulse shapes of diode-pumped fiber or solid-state lasers as known in the art. [Figure 2C] FIG. 2 illustrates an example pulse shape of a flashlamp-pumped solid-state laser as known in the art. [Figure 2D] FIG. 2 illustrates a spiked flashlamp-pumped solid-state laser pulse shape as known in the art. [Figure 2E] FIG. 2 illustrates the pulse shape of a multi-head flashlamp pumped solid-state laser as known in the art. [Figure 2F] FIG. 2 illustrates a specially constructed pulse shape of a flashlamp-pumped solid-state laser designed to minimize energy loss in water between the distal end of the fiber and the target, as known in the art. [Diagram 3] 1 illustrates an exemplary sequence of laser pulses emitted by a laser system according to the present invention operating in an amplitude frequency modulation regime (AFMR) characterized by a periodically varied peak power Pp or energy E with a modulation period Na equal to the number of laser pulses, and a periodically varied pulse frequency with a modulation period Np corresponding to the number of pulses in the frequency periodic pulse group. [Figure 4A] FIG. 1 illustrates examples of laser pulse sequences used in dusting, fragmentation and non-contact experiments in a normal manner as known in the art. [Figure 4B] FIG. 1 illustrates examples of laser pulse sequences used in dusting, fragmentation and non-contact experiments in a normal manner as known in the art. [Figure 4C] FIG. 1 illustrates an example of a group of laser pulses emitted by a system according to the invention operating in amplitude frequency modulation mode (AFMR) and used in dusting experiments. [Figure 4D] FIG. 1 illustrates an example of a group of laser pulses emitted by a system according to the invention operating in amplitude frequency modulation mode (AFMR) and used in dusting experiments. [Figure 4E] FIG. 1 illustrates an example of a group of laser pulses emitted by a system according to the invention operating in amplitude frequency modulation mode (AFMR) and used in dusting experiments. [Diagram 5] FIG. 1 is a diagram of an example of an amplitude modulation format (AMR). [Figure 6A] FIG. 13 is an example of an amplitude periodic group of laser pulses in AMR characterized by different amplitude modulation periods Na and used in contact mode experiments. [Figure 6B] FIG. 13 is an example of an amplitude periodic group of laser pulses in AMR characterized by different amplitude modulation periods Na and used in contact mode experiments. [Figure 6C] FIG. 13 is an example of an amplitude periodic group of laser pulses in AMR characterized by different amplitude modulation periods Na and used in contact mode experiments. [Figure 6D] FIG. 13 is an example of an amplitude periodic group of laser pulses in AMR characterized by different amplitude modulation periods Na and used in contact mode experiments. [Figure 6E] FIG. 13 is an example of an amplitude periodic group of laser pulses in AMR characterized by different amplitude modulation periods Na and used in contact mode experiments. [Figure 6F] FIG. 13 is an example of an amplitude periodic group of laser pulses in AMR characterized by different amplitude modulation periods Na and used in contact mode experiments. [Figure 6G] FIG. 13 is an example of an amplitude periodic group of laser pulses in AMR characterized by different amplitude modulation periods Na and used in contact mode experiments. [Figure 7A] FIG. 13 illustrates further examples of amplitude periodic groups of laser pulses having a modulation period Na according to AMR and used in non-contact mode experiments. [Figure 7B] FIG. 13 illustrates further examples of amplitude periodic groups of laser pulses having a modulation period Na according to AMR and used in non-contact mode experiments. [Figure 7C] FIG. 13 illustrates further examples of amplitude periodic groups of laser pulses having a modulation period Na according to AMR and used in non-contact mode experiments. [Figure 8] FIG. 1 is a diagram of an example of a frequency modulation format (FMR). [Figure 9] 1 is an example of a single laser pulse shaped into two temporally spaced sub-pulses with different peak powers. [Figure 10] FIG. 2 is an example of a single laser pulse that is shaped in two adjacent sections. [Figure 11A] FIG. 14 is a diagram of different laser pulse shapes used in the spallation experiments. [Figure 11B] FIG. 14 is a diagram of different laser pulse shapes used in the spallation experiments. [Figure 11C] FIG. 14 is a diagram of different laser pulse shapes used in the spallation experiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0048] Reference will now be made in detail to the embodiments of the present invention. Wherever possible, the same or similar reference numerals or letters are used in the drawings and the description to refer to the same or similar parts or steps. The drawings are in simplified form and are not to scale. For convenience and clarity only, directional (up / down, etc.) or motional (front / back, etc.) terms may be used on the drawings. The term "couple" and similar terms do not necessarily imply 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 providing high ablation rates by increasing the ablation efficiency while minimizing the setback effect, which is realized by (a) modulation (periodic variation) of the pulse energy E(n) or peak power Pp(n) or both, defined as AM, (b) modulation of the pulse frequency (repetition rate) v(n) with the 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] The first aspect of the present invention - modulation of pulse peak power and / or energy - can be better understood in view of the following explanation: In the present laser system for treating stones in a human or animal body, the temporal structure of the laser power is a periodic pulse sequence that can be described by the following equation: P(t)=Pp*f(tT*n, n=0,1,2,..., (1) where 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, which is 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) where 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) The individual pulse shape (profile) f(t) is characterized by a pulse duration τ. For laser systems for lithotripsy, the pulse duration is much shorter than the sequence period: τ< <Tまたはτ<0.1T。

[0052] Traditional stone treatment techniques are based on a modality 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 are switchable 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 the known prior art, amplitude modulation is defined here as a regime having constant period T and frequency v and periodic variation of 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) where Pp(n)=Pp(n-Na) or E(n)=E(n-Na) or τ(n)=τ(n-Na) or combinations thereof, Na being a positive integer referred to as the period of amplitude modulation. In the AM mode (AMR) of the laser according to the invention, all laser pulse sequences can be presented as a periodic sequence of a group of Na pulses (amplitude modulated periodic pulse group) with variable amplitude within the group.

[0054] 6A-6G and 7A-7C illustrate sequences of laser pulses with different modulation periods Na emitted from a laser system according to the invention operating in AMR, these figures being described in detail below.

[0055] Frequency Modulation (FM) according to the present invention In contrast to known prior art, frequency modulation as used in this application is defined as a regime having a constant peak power Pp or energy E and a periodic variation of 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) where T(n)=T(n-Np), Np is a positive integer called the period of frequency modulation. Frequency modulation refers to frequency modulation because ν(n)=1 / T(n)=ν(n-Np). In FM regime (FMR), any laser pulse sequence can be presented as a periodic sequence of a group of Np pulses (frequency modulated periodic pulse group) with a variable period between pulses in the group.

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

[0057] Amplitude Frequency Modulation (AFM) according to the present invention: Based on the AM and FM defined according to the present invention, Amplitude Frequency Modulation is defined as a modality having a simultaneous periodic variation of peak power Pp (or energy E) and frequency v (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) where Pp(n)=Pp(n-Na) or E(n)=E(n-Na) or τ(n)=τ(n-Na) and T(n)=T(n-Np).

[0058] 3 and 4A-4C illustrate a system according to the present invention operating with an AFMR and are described in more detail below.

[0059] Turning to FIG. 1 illustrating a schematic diagram of an exemplary laser system 100 according to the invention, the skilled person will immediately recognize that structurally this system is relevant to the discussion of both aspects according to the invention and can be embodied using various types of laser technologies. However, the preferred embodiment is based on a specific classification of laser technologies, specifically pulsed laser technology, including a pulsed laser 104 operating in either free-running or Q-switched mode. Regardless of the laser type in either mode of laser operation, the laser system 100 according to the invention comprises a pump 103 for exciting the laser 104. Typically, the pump 104 comprises one or more diode lasers. In the most preferred embodiment, the pulsed laser technology implies the use of an energy storage device (e.g., an electrical capacitor, an inductor, or a combination thereof).

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

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

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

[0063] For purposes of the present invention, the following terms are defined: A 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. A sequence of laser pulses is the output of the laser system generated by multiple direct single modulation or a single charge / discharge cycle of the energy storage device 102.

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

[0065] Based on the above equations 4-9, which mathematically describe the AM and combined AM and FM according to the present invention, the laser system 100 operating according to the first aspect by controlling the temporal structure of the laser emission is controlled through: a) Modulating the peak power Pp or pulse energy E relative to the number of pulses in a sequence of pulses, Pp(n)=Pp(n-Na), where Na is the period of the amplitude modulation; b) modulating the period T (and, respectively, the frequency v) of the pulse sequence relative to the number of pulses, T(n)=T(n-Np), where Np is the period of the frequency modulation; c) Combining the modulation modalities described in a), b) and c) above, for example simultaneous amplitude and frequency modulation (amplitude frequency modulation).

[0066] All three types of modulation (amplitude, frequency and amplitude frequency) as well as tailoring of individual pulse shapes are used in various embodiments of the invention. Diode-pumped fiber (preferred) and solid-state lasers can be modulated by controlling the current in the pump diode, and allowing the laser parameters to be changed by varying the current on the pump diode. Preferably, the diode current is modulated above the threshold current I for diode-pumped laser generation. th and a certain maximum current that is below the saturation level Ist of the laser power as a function of the diode current. In this range, the laser power is approximately linearly dependent on the diode current, and various laser temporal structures can be generated by programming the excitation current of the laser driver.

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

[0068] In the case of contact dusting, the desired end result is the fragmentation of the stone 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 modality requires continuous movement of the fiber across the stone surface using a 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 keeping the average power Pa = E * ν within a safe limit to avoid thermal damage of the soft tissue due to the hot water in the urinary tract. This safe 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 a high ablation rate with equal average power through laser pulse shaping and / or through modulating the sequence of laser pulses while reducing or at least keeping the recession at the same level. Ablation efficiency and recession 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. Beam diameter depends on fiber core diameter 3. Distance between fiber end and stone 4. The speed of fiber movement. This factor is related to the number of effective pulses applied to one 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 efficiency of ablation decreases with increasing K due to the increasing distance between the fiber end and the bottom of the laser crater, the shadowing effect from the products of ablation, water damage at the bottom of the laser crater, and other factors. 5. Fiber vibration induced by laser pulsing. The fiber can vibrate at a range of amplitudes. These vibrations are induced by forces from laser-induced bubble formation in water, electrostrictive effects, and other mechanisms. Fiber vibration can effectively reduce the number of pulses applied to a single point K, increasing the ablation efficiency. 6. Stone size and shape

[0069] Pulse modulation works in combination with all listed factors, but can lead to different effects. For example, lasing with constant energy at one point at the same frequency and average power and fiber moving speed can compensate for the decrease in ablation efficiency while cyclic increase of laser energy from minimum to maximum. Provided below is an experimental comparison of stone ablation and retreating speed using constant pulse energy and peak power and frequency with different amplitude modes (normal mode, representing the current mode of the treated stone), proving the advantages of the proposed modes of amplitude and amplitude frequency modulation over contact and non-contact modes.

[0070] Characterization of the time profile of laser lithotripsy The overarching objectives of optimizing laser lithotripsy are to speed up the procedure, ensure stone breakage 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 regression effect. For the purpose of comparing the various time modalities of laser firing, we use the following metrics: 1) Efficiency of stone ablation, Ka, defined as Va / Et, where Va is the total ablation volume and Et is the total laser energy [mm 3 / J]; 2) the critical recession velocity Vr, defined as the velocity of recession in the first instance of laser treatment [mm / s]; 3) the absolute quality of the time regime Qa, which increases with the ablation efficiency and decreases with recession Ka / Vr [mm 2 / W]; 4) relative quality of time regime Qr, defined as (Qa) / (Qa)ref, where the subscript ref refers to the reference normal regime [dimensionless]; 5) time of stone breaking, defined as the time to break the stone in the crushing mode.

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

[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 Miro M310 manufactured by Phantom Vision Research) 5) Fiber holder 6) Mechanical surface gauge (Contracer (registered trademark), made by Mitutoyo Corporation, Kawasaki, Japan)

[0073] material and method: All experiments were performed on an artificial stone phantom. Stones were produced using BegoStone powder (Bego GmbH, Bremen, Germany) in a 5:1 water ratio. Samples were cut into slabs with dimensions of 60 x 40 x 8 mm. Stones were immersed in water for 24 h before laser exposure.

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

[0075] First, the stone was placed in a container with water (two bubble levels were used for adequate positioning of the equipment). The fiber holder was mounted on a 2-D motorized stage. A 30 mm long linear crater was created using a 1-D horizontal fiber movement at a speed of 6 mm / s, representing a typical clinical scanning speed. The laser parameters were modified according to the table below. Measurements of the cross-sectional area, depth and width of the crater were made using a mechanical profilometer. 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. The distance between the fiber end and the flat stone surface was kept approximately 0.2 + / - 0.1 mm during the scan.

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

[0077] Bubble characterization experiments 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. A high-speed camera was used to record video bubble formation with a single pulse 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 lighting system was used to illuminate the scene. The recorded videos were used to evaluate bubble growth times up to 1 mm, up to 2.5 mm, and up to the maximum bubble dimension. Bubble lengths were 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 equipment included a specially constructed inner cuvette with a diameter of 13 mm and a 0.25 mm hole drilled in the wall at a height of 40 mm. Laser treatment was performed through a flexible endoscope. The water flow through the flexible endoscope was 10 ml / min. The inner cuvette was placed into an outer cuvette, which collected the effluent with suspended dust particles smaller than 0.25 mm, which were expelled by the water flow through the side hole during lithotripsy. BegaStone spheres with a radius of 2 mm were used in this study as stone phantoms. Five spheres were used for each laser parameter. Lithotripsy was performed for a period of 2 minutes 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 between the dust mass and the duration of treatment.

[0081] Perforations and cracks 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 experiments were performed on an artificial stone phantom. Stones were produced using BegoStone powder (Bego GmbH, Bremen, Germany) in a 5:1 water ratio. The stones were sized 5 × 2.5 × 2.5 mm. The stones were soaked in water for 24 h before laser exposure. The stone samples were placed in a glass cuvette filled with water. The stones were perforated with different parameters of the laser radiation in such a way that the fiber was always in contact with the stone in the center of the 5 × 2.5 mm side, mimicking a spallation style treatment. During the experiment, a stopwatch was used to record the fracture time at which the stone sample broke into two fragments. Afterwards, the 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 calculated for each set point, mean and standard deviation.

[0084] Amplitude Frequency Modulation (AFM) A general case of laser pulse sequences currently used in current laser lithotripsy is illustrated by Fig. 2, where the sequence is characterized by a constant magnitude (peak power) Pp, a constant pulse energy E and a constant period T of each single pulse (Fig. 2A). The single pulse (201) shape can vary between a simple quasi-rectangular pulse 202 (Fig. 2B), typical for diode-pumped lasers, a pulse shape 203 (Fig. 2C), with a steep rising edge and a long tail, typical of flashlamp-pumped lasers, a pulse shape 204 (Fig. 2D), also typical for flashlamp-pumped solid-state lasers, where the smooth general shape is modulated by irregular micropulses or spikes due to relaxation oscillations of the laser, or a complex pulse shape 205 (Fig. 2E), found in multi-head flashlamp solid-state laser systems. Other pulse shapes are known in the art, such as, for example, pockets 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 sub-pulses 206 (FIG. 2F) with a forward, low-energy sub-pulse followed by a high-energy backward sub-pulse 206 spaced 100 to 200 μs apart [U.S. Pat. No. 5,321,715].

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

[0086]

number

[0087] where Ng is the number of pulses in the period group and Ti is the period of the ith pulse.

[0088] AFM is useful for both contact and non-contact treatment modes. Preferred AFM parameters are: 1. Scanning Mode Preferred parameters: Wavelength: 1.81 to 2.2 μm, more preferably 1.908 to 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=5-3000Hz / period T=0.00033-0.2s, more preferably 50-1000Hz, 0.001-0.02s Na = 2 to 10 Np=1~100 These settings are illustrated by Figure 4 and Table 1. All experiments were performed at the same average power of 30 W to provide the same soft tissue safety profile.

[0089] [Table 1]

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

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

[0092] Amplitude Modulation Amplitude modulation is a particular case of AFM, where the pulse period remains constant. A typical case of amplitude modulation (AM) is illustrated in Figure 5, where the magnitude (Pp or E) varies 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 periodic pulse group.

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

[0094] [Table 2]

[0095] These data suggest that amplitude modulation can increase modality quality by more than three-fold. 2. Contact / Crush Mode Preferred parameters: Wavelength: 1.81 to 2.2 μm, more preferably 1.908 to 1.98 μm Peak power Pa = 100 to 20,000 W, preferably 250 to 3,000 W Energy per pulse: 0.2-20 J, more preferably 0.5-10 J Pulse repetition rate ν=1~500Hz / period T=0.002~1s Na = 2 to 10 3. Non-contact (Popcorning) Mode Preferred parameters: Wavelength: 1.81 to 2.2 μm, more preferably 1.908 to 1.98 μm Peak power Pa = 500 to 3000W, more preferably 500 to 2000W Energy per pulse: 0.05-1 J, more preferably 0.05-0.5 J Pulse repetition rate ν=10~3000Hz / period T=0.0003~0.1s Na = 2 to 100 These settings are illustrated by FIG. 7 and Table 3.

[0096] [Table 3]

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

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

[0099] Many variations of FM pulse groups are possible.

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

[0101] Pulse Shape Laser energy emanating from the fiber end and traveling through the liquid (water) medium in the gap between the fiber end and the stone or tissue surface towards the target stone or tissue will be absorbed, but the absorption may be less than expected, which has been attributed to the "Moses effect", where a first component of the emitted energy is absorbed by the liquid, creating a vapor bubble in the liquid medium, resulting in the remaining energy passing through a less restrictive or absorbing gas / vapor medium characterized by low optical attenuation. The laser-induced vapor bubble created during the initial pulse acts to "part 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 delivering a short, low-energy pulse that creates a vapor bubble, followed by a longer, more energetic treatment pulse (see U.S. Pat. No. 5,321,715).

[0102] In the present invention, controlling the temporal structure of the laser power is used to minimize the backlash effect. Water bubble formation between the stone and the distal fiber end can generate pressure and forces that move the stone away from the fiber. This effect can be minimized by reducing the laser power and energy during bubble formation. The collapse of the bubble between pulses generates negative pressure and forces on the stone, and during stone ablation, bubble growth and recoil movement can compensate for the stone movement (absorption effect). These effects can be controlled by varying the individual pulse shape f(t), pulse energy E, and the interval between pulses T.

[0103] Laser ablation usually requires a combination of high ablation efficiency and low back-off effect. To compare different temporal laser configurations, we define the laser ablation efficiency η, defined as the volume of the ablation product divided by the total laser energy expended to ablate this volume and the velocity V of stone displacement due to back-off at the very beginning of laser pulsing. abl The value of V can be determined by impact of a single pulse for low repetition rates, or by impact of several pulses for about 0.1 s for high repetition rate laser systems. In particular, the ratio η abl / V can characterize the actual (composite) efficiency or speed of treatment.

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

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

[0106] When treating stones in contact mode, the objective is to increase the efficiency of stone ablation to reduce the total time required to fragment the stone. This can be achieved through adjusting the shape of the pulse by applying a low intensity to the first part of the pulse to establish a Moses channel with minimal energy loss, but at the same time minimizing the backlash effect of such a pulse, followed by applying a high intensity to the second part of the pulse to maximize the thermal or thermomechanical effect on the stone. The water absorption loss of the second part of the pulse will be greatly reduced by the Moses channel established by the first part of the pulse. However, Moses vaporization bubbles or channels are growing between the fiber end and the stone, generating pressure and forces on the stone, thus creating the backlash effect. In the present invention, it is proposed to minimize the laser pulse peak power and energy to reduce the backlash effect. In the experimental setup, the bubble dynamics were measured at the end of the 0.2 mm fiber using a high-speed video camera with a frame rate of 120000 frames per second. The displacement effect of the single pulse exposure on the stone sample was measured. See the description of the experimental equipment above.

[0107] [Table 4]

[0108] Table 4 summarizes the experimental data for a TFL with a wavelength of 1940 nm and a fiber core of 0.2 mm. The results show that the bubble length and stone displacement, which are proportional to the bubble pressure, increase with the laser pulse peak power and energy. The distance between the fiber end and the stone under clinical contact setting ranges between 0 and 1 mm, but during treatment it can exceed 2.5 mm for short periods. In order to utilize the Moses (vaporization) channel for ablation efficiency but minimize the retraction effect, it is proposed to use laser parameters of the first sub-pulse that gives rise to a bubble with a length that is at most 2.5 mm at the lowest pressure. Based on the measured peak power data of the first laser sub-pulse, which gives rise to the Moses (vapor) channel, the peak power should be in the range 50-500 W, preferably 100-300 W, and the energy per pulse should be 0.02-0.15 J, preferably 0.05-0.1 J. The interval between the first and second sub-pulse for efficient ablation should be defined based on the following criteria: 1) The second sub-pulse should be initiated after the vapor channel front has reached the stone, i.e. when the bubble has grown to 2.5 mm, preferably 1 mm; 2) To generate the stone absorption effect, the pressure on the bubble has dropped or become negative.

[0109] [Table 5]

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

[0111] In another embodiment of the present invention, we propose a pulse shape with the power delivered continuously during the pulse. This shape is most effective for the spallation mode when the operator uses the drilling procedure while providing a close contact between the laser fiber end and the stone during the entire treatment cycle. In this case, the water layer between the fiber end and the stone can be very minimal (less than 0.5 mm) or not at all. Lasers currently used for lithotripsy have uniform rectangular or flat-topped pulses, which are typical for diode-pumped fiber and solid-state lasers 202 (Fig. 2). Flash-pumped solid-state lasers such as Ho:YAG have asymmetric shapes with high power at the beginning of the pulse and a slow relaxation of power at the back tail 203 or 204 (Fig. 2). These shapes of pulses are not optimal for stones to crack during drilling. To increase the efficiency of ablation during drilling and spallation, in this invention we propose to use a pulse with two parts, the first part is used for removing the residual moisture between the fiber and the stone, and for ablation of the stone, and preheating of the stone around the ablation crater (Fig. 10). The preheating by the first part of the pulse with low power will result in an increase in the thermal stress around the laser crater and an increase in the absorption coefficient of the stone matrix due to heating above 100-250 °C. The second part of the pulse with high power will be absorbed more effectively by the stone material and will result in better absorption than the first pulse part and more efficient mechanical damage due to the high peak power of the second part, as well as an initial mechanical stress of the stone around the laser crater. As a result, the probability of the stone cracking into large pieces will increase. At the same time, the recoil effect of such pulsing will be reduced due to a more effective conversion of the laser energy into cracks rather than due to the ablation of small particles with high recoil moment. This is illustrated by Figure 10, where τ1 is the duration of the first part of the pulse and τ2 is the duration of the second part of the pulse. The power profile f1(t) of the first part of the pulse is at the level P min or P min From P maxcan 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 dependences of the brightness are possible and will be apparent to those skilled in the art. The duration of the first part of the pulse can be determined from considering the minimum energy required to establish the Moses channel and can result in ablation of the stone with substantial heating of the stone matrix around the laser crater, increasing the 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 signal the establishment of the Moses channel and / or the stone crater temperature and can be based on optical, acoustic or other techniques. For example, the stone temperature can be detected by measuring the thermal radiation emitted by the stone through the same fiber used for the laser power delivery. For a TFL with a wavelength of 1.94 μm, we assume that the laser power of the first part of the pulse is in the range P min It was experimentally found that 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, while the energy of the first part should be 10-70% of the total energy of the pulse, and 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 rock drilling and crushing 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 decrease in the break time, but also increases the backlash effect, while the resulting mode quality remains approximately the same. In contrast, the pulse shaping proposed in the present invention reduces both the break time and the backlash effect, thus leading to the desired increase in mode quality.

[0115] The above description and examples have been set forth merely to illustrate the present disclosure and are not intended to be limiting. Accordingly, the present disclosure should be broadly construed to include all modifications within the scope of the appended claims. [Explanation of symbols]

[0116] 100 Laser System 101 Power supply 102 Energy storage device 103 Laser driver 104 Pump 105 Laser Cavity 106 Optical Coupler 107 Delivery System 108 Control Module 201~205 Pulse 206 Subpulse 501 Pulse 801 Pulse

Claims

1. A laser system for treating calculi in a living body, comprising: a laser for emitting radiation in a wavelength range; an optical fiber for delivering the radiation from the laser to the calculus; a power source for providing a current for driving the laser; a control signal provided to the power source such that the laser emits a waveform having a first sub-pulse and a second sub-pulse; wherein the first sub-pulse promotes the formation of a Morse vaporization channel with reduced recoil between the optical fiber and the calculus, and the second sub-pulse excises the calculus.

2. The laser system according to claim 1, wherein the wavelength range is between 1.81 micrometers and 2.2 micrometers.

3. The laser system according to claim 1, wherein the first sub-pulse has an energy in the range from 0.02 joules to 0.15 joules and a peak power in the range from 50 W to 500 W.

4. The laser system according to claim 3, wherein the first sub-pulse has an energy in the range from about 0.05 joules to about 0.1 joules and a peak power in the range from 50 W to about 300 W.

5. The laser system according to claim 1, wherein the second sub-pulse has an energy in the range from about 0.1 joules to about 10 joules and a peak power in the range from about 300 W to about 20,000 W.

6. The laser system according to claim 1, wherein the laser is selected from the group consisting of 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.

7. The laser system according to claim 1, wherein the second sub-pulse starts when the pressure inside the Morse vaporization bubble decreases or becomes negative, generating a stone absorption effect.

8. The laser system according to claim 7, wherein the time interval between the first sub-pulse and the second sub-pulse varies in the range from about 50 microseconds to about 900 microseconds.

9. A laser system for treating calculi in a living body, comprising: a laser for emitting radiation in a wavelength range; an optical fiber for delivering the radiation from the laser to the calculus; A power supply for providing a current to drive the laser; A control signal provided to the power supply so that the laser emits a pulse having a first portion and a second portion; Comprising A laser system, wherein the first portion reduces water between the laser fiber and the calculus, heats the calculus, and the second portion reduces the size of the calculus. **Claim 10**: The laser system according to claim 9, wherein the first portion of the pulse has a power between 50 W and 200 W and a duration between about 0.1 millisecond and about 10 milliseconds. **Claim 11**: The laser system according to claim 9, 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 millisecond and about 20 milliseconds. **Claim 12**: The laser system according to claim 9, wherein the first portion of the pulse comprises between 10% and 70% of the total energy of the pulse. **Claim 13**: The laser system according to claim 9, wherein the power of the first portion of the pulse is selected from the group comprising a function that does not monotonically decrease, a function that increases from a minimum level to a maximum level, a constant function, and combinations thereof. **Claim 14**: The laser system according to claim 9, wherein the laser is selected from the group comprising 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. **Claim 15**: The laser system according to claim 9, further comprising a controller for generating the control signal, the controller determining the duration of the first portion of the laser pulse based on thermal radiation from the calculus. **Claim 16**: The laser system according to claim 15, wherein the optical fiber acquires thermal radiation from the calculus for use by the controller. **Claim 17**: A laser system for treating calculus in a living body, A controller that outputs an electrical signal indicating a desired laser pulse shape including a first sub-pulse and a second sub-pulse; A power supply that provides variable power delivery in response to receiving the control signal; A laser connected to the power supply for emitting radiation according to the desired laser pulse shape; Comprising The second sub-pulse has a total energy greater than the total energy of the first sub-pulse. A laser system, wherein the duration of the second sub-pulse is variable and is determined by the controller.

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

19. The laser system according to claim 17, wherein the desired laser pulse shape includes the peak power of the second sub-pulse, which is an input to the controller for determining the duration of the second sub-pulse.

20. The laser system according to claim 17, wherein the duration of the first sub-pulse is predetermined.

21. The laser system according to claim 17, wherein the first sub-pulse vaporizes the fluid above the calculus.

22. The laser system according to claim 17, wherein the first sub-pulse heats the calculus.

23. The laser system according to claim 17, wherein the first sub-pulse prepares for reducing the size of the calculus with low total energy and reduces the movement of the calculus.

24. The laser system according to claim 17, wherein the second sub-pulse excises the calculus.

25. The laser system according to claim 17, wherein the second sub-pulse cracks the calculus.

26. The laser system according to claim 17, wherein the power supply further includes an energy storage device, and at least the second sub-pulse is at least partially powered by the discharge from the energy storage device.

27. The laser system according to claim 17, wherein the power supply further includes an energy storage device, and the length of the pause time is at least partially determined by the charging time of the energy storage device.

28. The laser system according to claim 17, wherein the laser further includes at least one diode.

29. The laser system according to claim 17, including a temperature sensor coupled to the controller for modifying the laser pulse shape.

30. The laser system according to claim 17, further including an optical fiber coupled to the laser, and the optical fiber returns temperature data to the controller for determining the duration of the first sub-pulse to vaporize moisture without overly moving the calculus.

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