Pulsed acoustic wave dermal clearing systems and methods

Abstract

To provide methods and systems for the methods for acoustic treatment of tissue to disperse vacuoles within the tissue.SOLUTION: Some of the present methods and systems include directing pulsed acoustic waves from an acoustic wave generator into the tissue containing the vacuoles. Some of the present methods include identifying the location of the tissue containing the vacuoles, and / or coupling (e.g., acoustically) an acoustic wave generator to the tissue containing the vacuoles. In one embodiment, the methods further include treating skin containing vacuoles with a laser after directing pulsed acoustic waves from the acoustic wave generator into the tissue containing the vacuoles.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] (Citation of Related Application) This application claims priority to U.S. Provisional Patent Application No. 62 / 312,372, filed March 23, 2016, which is incorporated by reference in its entirety.

[0002] FIELD OF THE INVENTION Embodiments of the present invention relate generally to the therapeutic use of shock waves. More specifically, but not by way of limitation, embodiments of the present invention relate to devices for generating therapeutic shock waves (shock waves with therapeutic uses) for use in skin clearing systems and applications thereof. [Background technology]

[0003] Shock waves have been used in certain medical and aesthetic treatments. "Shock waves" or shock waves are generally used to refer to acoustic phenomena (e.g., resulting from an explosion or lightning) that produce sudden and rapid changes in pressure. These rapid pressure changes can generate intense energy waves that can travel through elastic media such as air, water, human soft tissue, or certain solid materials such as bone and / or induce inelastic responses in such elastic media. Methods for generating shock waves for therapeutic use include (1) electrohydraulic or spark gap (EH), (2) electromagnetic or EMSE, and (3) piezoelectric. Each is based on its own unique physical principle.

[0004] A. Devices and Systems for Shock Wave Generation U.S. Patent Application No. 13 / 574,228 (a national stage application of PCT / US2011 / 021692, published as International Publication No. WO2011 / 091020) by one of the present inventors discloses a device for generating shock waves at a high pulse rate using a transducer. The device includes an acoustic wave generator configured to emit acoustic waves having at least one frequency between 1 MHz and 1000 MHz, a shock wave housing coupled to the acoustic wave generator, and a shock wave medium disposed within the shock wave housing. The device is configured such that when the acoustic wave generator emits acoustic waves, at least a portion of the acoustic waves will travel through the shock wave medium to form shock waves. The device can be activated to form shock waves configured to disrupt one or more cells of the patient into particles within the patient, and the shock waves can be directed toward the patient's cells so that the shock waves disrupt one or more of the cells into particles. The present acoustic transducer device is capable of generating high power shock waves at high frequencies or pulse rates.

[0005] Other systems for generating shock waves can include electrohydraulic (EH) wave generators. EH systems can generally deliver similar levels of energy as other methods, but can be configured to deliver that energy over a wider area and therefore deliver a greater amount of shock wave energy to the target tissue over a shorter period of time. EH systems generally incorporate an electrode (i.e., a spark plug) to initiate the shock wave. In EH systems, high-energy shock waves are generated when electricity is applied to an electrode immersed in treated water contained in an enclosure. When an electric charge is fired, a small amount of water is vaporized at the tip of the electrode, and the rapid, near-instantaneous expansion of the vaporized water generates shock waves that propagate outward through the liquid water. In some embodiments, the water is contained in an ellipsoidal enclosure. In these embodiments, the shock waves can bounce off the sides of the ellipsoidal enclosure and converge to a focal point coincident with the location of the area to be treated.

[0006] For example, U.S. Patent No. 7,189,209 (the '209 patent) describes a method for treating pathological conditions associated with bone and musculoskeletal environments and soft tissues by applying acoustic shock waves. The '209 patent explains that the shock waves induce localized trauma and cellular apoptosis therein, including microfractures, as well as promote the formation of bone, cartilage, tendon, fascia, and soft tissue morphogen and growth factor molecules to induce osteogenic responses such as cell recruitment and induce angiogenesis. The '209 patent claims several specific implementations of its method. For example, the '209 patent claims a method for treating diabetic foot ulcers or pressure sores, including locating a site or suspected site of a diabetic foot ulcer or pressure sore in a human patient, generating acoustic shock waves, focusing the acoustic shock waves throughout the identified site, and applying 500 to more than about 2,500 shock waves per treatment to the identified site to induce microdamage and increased vascularization, thereby inducing or accelerating healing. The '209 patent discloses a frequency range of about 0.5 Hz to 4 Hz and the application of about 300 to 2,500 or about 500 to 8,000 shock waves per treatment site, which can result in treatment durations per treatment site and / or "total time per treatment" for all sites that are inconveniently long. For example, the '209 patent discloses total time per treatment for different embodiments ranging from about 20 minutes to 3 hours.

[0007] U.S. Patent No. 5,529,572 (the '572 patent) includes another example of the use of electrohydraulic generated shock waves to produce a therapeutic effect in tissue. The '572 patent describes a method for increasing bone density and strength (such as to treat osteoporosis) that includes subjecting bone to substantially planar, parallel compressive shock waves having a substantially constant intensity as a function of distance from a shock wave source, the parallel shock waves being applied to the bone at an intensity of 50 to 500 atmospheres. The '572 patent describes the application of unfocused shock waves to generate dynamic, cyclic loading to the bone to increase average bone density, thereby strengthening the bone against fracture. As explained in the '572 patent, "the unfocused shock waves are preferably applied over a distance of, for example, 10 cm." 2 ~150cm 2 The shock waves are applied over a relatively large surface of the bone to be treated, covering an area of ​​approximately 1000 m. The intensity of the shock waves may be 50-500 atmospheres. Each shock wave is of a few microseconds duration, as in conventional lithotriptors, and is preferably applied at a frequency of 1-10 shock waves per second for 5-30 minutes per treatment. The number of treatments depends on the particular patient.

[0008] U.S. Patent Application No. 10 / 415,293 (the '293 Application), also published as US2004 / 0006288 (Patent Document 4), discloses another embodiment of the use of EH-generated shock waves to provide a therapeutic effect to tissue. The '293 Application discloses devices, systems, and methods for the generation of therapeutic acoustic shock waves to at least partially detach deposits from vascular structures. The '293 Application discloses that the device is capable of delivering shock waves up to 1 cm 2 It is described that shock waves can be generated at pulse rates of about 50 to about 500 pulses per minute (i.e., 0.83 Hz to 8.33 Hz) using pulse numbers of about 100 to about 5,000 per treatment area (per length of vascular unit being treated).

[0009] (B. Shock wave speed) Prior art literature indicates that faster pulse rates used with EH systems to deliver shock waves can lead to tissue damage. For example, one study (Delius, Jordan, & et al., 1988) [2] examined the effects of shock waves on normal canine kidneys in groups of dogs whose kidneys were exposed to 3,000 shock waves. The groups differed only in the shock wave delivery rate, which ranged from 100 Hz to 1 Hz, respectively. Necropsies were performed 24 to 30 hours later. Grossly and histologically, significantly more bleeding occurred in the renal parenchyma when shock waves were delivered at a rate of 100 Hz (vs. 1 Hz). Results indicated that renal damage was dependent on the shock wave delivery rate.

[0010] In another study (Madbouly & et al., 2005) [7], slower shock wave lithotripsy rates (SWL) were associated with significantly higher success rates with fewer total shock waves compared to faster shock wave lithotripsy rates. In this paper, the authors discussed how human studies also demonstrated a reduced incidence of SWL-induced renal injury or the need for anesthesia when slower test SWL rates were used.

[0011] Yet another study (Gillitzer et al., 2009) [5] showed that reducing the delivery rate from 60 to 30 shock waves per minute also provided significant protection to the integrity of the real vasculature in a porcine model. These findings support the potential strategy of reduced pulse rate frequency to improve the safety and efficacy of extracorporeal shock wave lithotripsy.

[0012] Soft tissue can transition from elastic to viscous behavior for pulse rates (PR) between 1 Hz and 10 Hz. As a result, potential tissue damage from shock waves at pulse rates between 1 Hz and 10 Hz is unpredictable when typical lithotripsy power levels are used. Perhaps as a result, the prior art teaches slower pulse rates and long total times per treatment (TTPT). For example, currently known EH shockwave systems generally deliver pulse rates below 10 Hz and require long total times per treatment (TTPT) (e.g., TTPT cycles of minutes or even hours even for a single treatment site). When treatment requires device repositioning at multiple treatment sites, as may be typical, TTPT becomes large and potentially impractical for many patients and treatment needs.

[0013] While long treatment times may be acceptable for extracorporeal shock wave lithotripsy, the use of shock waves to provide non-lithotripsy therapeutic effects to tissue in medical institutions is suboptimal, if not impractical. For example, the cost of treatment often increases with the time required to administer the treatment (e.g., due to labor, equipment, and other resources allocated to administering the treatment). Furthermore, in addition to the cost, at some point the duration of providing the treatment to a patient becomes unbearable for the patient receiving the treatment and the medical staff providing the treatment.

[0014] (C. Tissue as a viscoelastic substance) One reason for the sensitivity to pulse rate found in prior art techniques may be due in part to the relaxation time of the tissue. Cells possess both elastic and viscous properties and are therefore viscoelastic materials. Unlike most conventional materials, cells exhibit highly nonlinear changes in their elastic modulus depending on the degree of applied or internal stress (Kasza, 2007) [6]. One study (Fernandez (2006) [3]) suggests that fibroblasts can be modeled as a gel with a cross-linked actin network that exhibits a transition from the linear regime to power-law strain hardening.

[0015] Another paper's authors (Freund, Colonius, & Evan, 2007) [4] hypothesized that the cumulative shear force of many impacts causes damage, and that the mechanism may depend on whether there is sufficient time between impacts for the tissue to relax to an unstrained state. Their viscous fluid model suggested that any deformation recovery that occurs would be nearly complete by the first 0.15 seconds after impact. As a result, their model of the mechanism for cell damage would be independent of impact velocity for impact rates slower than approximately 6 Hz. However, the actual viscoelasticity of the interstitial material, with its relaxation time of approximately 1 second, would be expected to introduce its sensitivity to impact delivery rate. Assuming that the interstitial material has a relaxation time of approximately 1 second, the authors would expect a significant decrease in damage for delivery rates slower than approximately 1 Hz. Conversely, damage should increase for faster delivery rates. An implication of their model is that both a slowing delivery rate and a widening focal zone should reduce damage.

[0016] D. Laser-Based Skin Treatments In other areas of therapeutic medicine, the use of laser-based skin treatments has been used in tattoo removal, laser skin resurfacing, laser removal of birthmarks, laser removal of skin lesions, laser hair transplantation or hair removal, laser scar removal, and many other various procedures. The body's natural response to each of these treatments poses challenges to the effectiveness of the treatment.

[0017] For example, in the context of tattoo removal, exposure of a tattooed area to laser power currently produces a "blanching" condition within the treatment area, which tends to reduce the effectiveness of subsequent laser exposures. During tattoo treatment, a "blanching" reaction typically occurs when the laser wavelength and power are appropriate to affect the tattoo. The immediate blanching reaction is the result of the development of vacuoles due to the rapid heating or energy transfer associated with laser exposure to tattoo pigment particles. The skin vacuoles associated with blanching result in attenuation or scattering of laser light, resulting in a loss of laser effectiveness after the initial treatment. Furthermore, the skin vacuoles remain in the skin for a period of time, limiting the effectiveness of subsequent laser exposures in the same session.

[0018] Laser-generated skin vacuoles are generally located at the epidermal-dermal junction and around individual pigment particle clusters.

[0019] Vacuoles located at the epidermal-dermal junction are thought to be generated by localized heating from laser light absorption by melanin in the epidermis. Vacuoles located around pigment particle aggregates are thought to be a direct result of rapid heating from laser light absorption by pigment particle aggregates in the dermis.

[0020] The post-laser whitening reaction may subside for about 20 minutes or more after the final laser exposure, as evidenced by the resolution of superficial vacuoles caused by the dissipation and absorption of gas-containing vacuolar contents over time.

[0021] Blanching is a problem, at least in part, because the presence of skin vacuoles in the treatment area caused by the first laser pass can attenuate or weaken the delivery of light in one or more subsequent laser passes. For example, light impinging on vacuoles can scatter in multiple directions, including away from the treatment area. Thus, the presence of vacuoles reduces the effectiveness of laser treatment.

[0022] Currently, the primary approach to tattoo removal is through the use of lasers. However, after a single laser treatment of the tattooed area, the laser is no longer effective for the reasons mentioned above. As a result, multiple sessions over a period of many months are required to remove a tattoo using a laser.

[0023] There is a strong desire to accelerate the tattoo removal process. To do so, repeated laser treatments of the tattooed site within the same day have been pursued. One approach, called the R20 method, treats the tattooed site with a laser, with the laser treatments separated by at least 20 exposures to allow the vacuoles to resorb at the site (see, e.g., Kossida et al., Optical tattoo removal in a single laser session based on the method of repeated exposures, J. Am. Acad. Dermatology 2012 Feb. 66 (2): 271-7). Due to busy practices, this approach is impractical because it requires the patient to be in the office for long periods of time.

[0024] More recently, to overcome this problem, U.S. Patent Application No. 13 / 753,816 (the '816 application), also published as U.S. Patent Application No. US2013 / 0165839 (Patent Document 5), discloses the use of perfluorodecalin (PFD) to prevent or reduce the whitening caused by laser tattoo treatment. The '816 application discloses that by using a PFD on the affected skin, the laser can be applied in rapid succession without waiting 20 minutes.

[0025] PFDs are colorless, inert liquids with low surface tension that are insoluble in blood and water. Unfortunately, PFDs have very poor skin penetration. As a result, they are widely used in cosmetics. As a result, PFDs are excellent at reducing whitening caused by superficially located vacuoles (e.g., at the epidermal-dermal junction). However, due to their poor skin penetration, vacuoles surrounding and occluding previously treated intradermal pigment particles are unaffected. Therefore, while PFDs offer benefits in reducing the appearance of whitening, they offer only limited benefit in improving the effectiveness of repeated laser treatments at tattoo sites. [Prior art documents] [Patent documents]

[0026] [Patent Document 1] International Publication No. 2011 / 091020 [Patent Document 2] U.S. Patent No. 7,189,209 [Patent Document 3] U.S. Patent No. 5,529,572 [Patent Document 4] US Patent Publication No. 2004 / 0006288 [Patent Document 5] US Patent Publication No. 2013 / 0165839 Summary of the Invention [Means for solving the problem]

[0027] Embodiments of the present methods, devices, and systems can be configured to provide skin clearing by dispersing and / or eliminating skin vacuoles located superficially and / or deeper in the dermis (e.g., adjacent to pigment particle agglomerations), as well as vacuoles within the epidermis. The present methods, devices, and systems can thereby enable more effective repeated laser treatments over the same treatment area in rapid succession.

[0028] Some embodiments of the present methods (e.g., for acoustic treatment of tissue to disperse vacuoles within the tissue) include identifying a location of tissue containing vacuoles, coupling an acoustic wave generator to the tissue containing vacuoles, and directing pulsed acoustic waves from the acoustic wave generator into the tissue containing vacuoles.

[0029] In some embodiments of the method, the tissue containing the vacuoles has been previously treated with a laser.

[0030] Some embodiments of the method further include treating the vacuole-containing tissue with a laser after directing pulsed acoustic waves from the acoustic wave generator into the vacuole-containing tissue. In some embodiments, the skin is treated with the acoustic wave generator for about 0.1 minutes to about 10 minutes. In some embodiments, the laser treatment includes applying a laser to the target skin with a pulse duration of about 1 nanosecond to about 1 microsecond. In some embodiments, the laser comprises a Q-switched laser or a picosecond laser.

[0031] In some embodiments of the method, the laser treatment comprises tattoo removal, laser skin resurfacing, laser removal of birthmarks, laser removal of skin lesions, laser hair transplantation, laser scar removal, laser assisted hair reduction, laser removal of vascular lesions, laser lip whitening, and / or laser treatment of melasma.

[0032] Some embodiments of the method further include directing pulsed acoustic waves from the acoustic wave generator into tissue containing the vacuoles, followed by treating the skin containing the vacuoles with a laser, and repeating the directing and treating steps in an alternating manner for at least two repetitions in a single treatment session. In some embodiments, treating the skin containing the vacuoles with a laser is performed within 10 minutes of the directing pulsed acoustic waves. In some embodiments of the method, at least two subsequent repetitions of the directing pulsed acoustic waves are performed within 10 minutes or less.

[0033] Some embodiments of the present systems (e.g., skin clearing systems) include a pulsed acoustic wave generator configured to generate pulsed acoustic waves and direct the generated waves toward the skin to clear the epidermis and intradermal vacuoles.

[0034] In some embodiments of the system, the generated acoustic waves have a frequency between about 700 KHz and about 100 Mhz.

[0035] In some embodiments of the system, the generated acoustic waves have a pulse duration of about 1 nanosecond to about 1 microsecond.

[0036] In some embodiments of the system, the generated acoustic waves have a pulse rate of about 10 Hz to about 1 KHz.

[0037] In some embodiments of the system, the mechanical index MI of the generated waves is between about 0.15 and about 1.9.

[0038] In some embodiments of the system, the pulsed acoustic wave generator includes a high-velocity pulsed electric-hydraulic shock wave generator including a housing defining a chamber and a shock wave outlet, a medium disposed within the chamber, a plurality of electrodes and capacitors disposed within the chamber and configured to define one or more spark gaps, and a pulse-generation system configured to apply voltage pulses to the plurality of electrodes and capacitors within the chamber.

[0039] In some embodiments of the system, the pulsed acoustic wave generator is configured to generate acoustic waves in pulses at a rate between about 10 Hz and about 5 MHz.

[0040] In some embodiments of the system, the pulsed acoustic wave generator includes a megasonic wave generator. In some embodiments, the megasonic wave generator is configured to generate pulsed acoustic waves with a frequency of about 700 KHz to about 20 MHz. In some embodiments, the megasonic wave generator is configured to generate pulsed acoustic waves with a pulse duration of about 1 nanosecond to about 1 microsecond. In some embodiments, the megasonic wave generator is configured to generate pulsed acoustic waves with a pulse rate of about 10 Hz to about 1 KHz. In some embodiments, the power of the megasonic wave generator is set so that the mechanical index (MI) is about 0.15 to 1.8.

[0041] In some embodiments of the system, the high-speed pulse electrohydraulic generator is configured to have a peak pressure output of about 0.8 MPa to 20 MPa.

[0042] The term "coupled" is defined as "connected," although not necessarily directly, and not necessarily mechanically; two items that are "coupled" may be integral with one another. The terms "a" and "an" are defined as one or more than one, unless this disclosure expressly requires otherwise. The term "substantially" is defined as "for the most part," although not necessarily entirely, what is defined, as would be understood by one of ordinary skill in the art (and includes what is defined, e.g., substantially 90 degrees includes 90 degrees, and substantially parallel includes parallel). In any disclosed embodiment, the terms "substantially," "approximately," and "about" may be substituted for "within [a percentage]" of what is defined, including percentages of 0.1, 1, 5, and 10 percent.

[0043] "Comprise" (and any form of comprise, such as "comprises" and "comprising"), "have" (and any form of have, such as "has" and "having"), "include" (and any form of include, such as "includes" and "including"), and "contain" (and any form of contain, such as "contains" and "containing") are open-ended linking verbs. Consequently, a system or device that "comprises," "has," "includes," or "contains" one or more elements may possess, but is not limited to possessing only those elements. Similarly, a method that "comprises," "has," "includes," or "contains" one or more steps may possess, but is not limited to possessing only those steps.

[0044] Furthermore, a structure (eg, a component of a device) that is configured in a certain way is configured in at least that way, but may also be configured in ways other than those specifically described.

[0045] Any embodiment of any of the present systems, apparatuses, and methods can consist of, or consist essentially of, any of the described steps, elements, and / or features. Thus, in any of the claims, the terms "consisting of" or "consisting essentially of" can be substituted for any of the open-ended linking verbs listed above to modify the scope of a given claim from that which would otherwise be written using the open-ended linking verb.

[0046] Details associated with the above-described embodiments and others are presented below.

[0047] The following drawings are illustrated by way of example, and not by way of limitation. For simplicity and clarity, not every feature of a given structure is always labeled in every figure in which that structure appears. The same reference number does not necessarily refer to the same structure. Rather, the same reference number may be used to indicate a similar feature or a feature with similar functionality, which may not be the same reference number. The figures are drawn to scale (unless otherwise noted), and sizes of depicted elements are meant to be accurate relative to each other, at least for the embodiments depicted in the figures. [Brief explanation of the drawings]

[0048] [Figure 1] FIG. 1 depicts a block diagram of a first embodiment of the present electrohydraulic (EH) shock wave generation system.

[0049] [Figure 2] FIG. 2 depicts a cross-sectional side view of a handheld probe for some embodiments of the present EH shockwave generation system.

[0050] [Figure 2A] FIG. 2A depicts a cross-sectional side view of a first embodiment of a removable spark head usable with embodiments of the present handheld probe, such as the probe of FIG. 2.

[0051] [Figure 2B] FIG. 2B depicts a cutaway side view of a second embodiment of a removable spark head that can be used with embodiments of the present handheld probe, such as the probe of FIG. 2.

[0052] [Figure 2C] FIG. 2C depicts a cutaway side view of a third embodiment of a removable spark head that can be used with embodiments of the present handheld probe, such as the probe of FIG. 2.

[0053] [Figure 3]3A-3B depict timing diagrams of one embodiment of the timed application of energy cycles or voltage pulses in the system of FIG. 1 and / or the handheld probe of FIG.

[0054] [Figure 4] FIG. 4 depicts waveforms that may be emitted by the system of FIG. 1 and / or the handheld probe system of FIG. 2 into target tissue.

[0055] [Figure 5] FIG. 5 depicts a schematic diagram of one embodiment of a multi-gap pulse generation system for use in or with some embodiments of the present system.

[0056] [Figure 6] FIG. 6 depicts a block diagram of an embodiment of a radio frequency (RF) powered acoustic ablation system.

[0057] [Figure 7A] FIG. 7A depicts a perspective view and a cross-sectional view of a first prototype spark chamber housing. [Figure 7B] FIG. 7B depicts a perspective view and a cross-sectional view of the first prototype spark chamber housing.

[0058] [Figure 8] FIG. 8 depicts a cross-sectional view of a second prototype embodiment of the spark chamber housing.

[0059] [Figure 9] FIG. 9 depicts a schematic diagram of the electronic circuitry for the prototype pulse generation system.

[0060] [Figure 10] FIG. 10 depicts a conceptual flow chart of one embodiment of the method.

[0061] [Figure 11]FIG. 11 depicts an exploded perspective view of a further prototype embodiment of the present probe with a spark head or module.

[0062] [Figure 12A] FIG. 12A depicts parts of the assembly of the probe of FIG. [Figure 12B] FIG. 12B depicts parts of the assembly of the probe of FIG.

[0063] [Figure 13A] FIG. 13A depicts a perspective view and a side cross-sectional view of the probe of FIG. [Figure 13B] FIG. 13B depicts a perspective view and a side cross-sectional view of the probe of FIG.

[0064] [Figure 13C] FIG. 13C depicts an enlarged side cross-sectional view of the spark gap of the probe of FIG.

[0065] [Figure 14] FIG. 14 depicts a schematic diagram of a second embodiment of the electronic circuitry for the prototype pulse generation system.

[0066] [Figure 15] FIG. 15 depicts a cross-sectional view of an ultrasonic generator probe.

[0067] [Figure 16] FIG. 16 depicts a histology image of skin containing blue tattoo pigment that underwent a single laser treatment.

[0068] [Figure 17] FIG. 17 depicts a histology image of skin containing black tattoo pigment that underwent three laser treatments (three applications of the laser).

[0069] [Figure 18]FIG. 18 depicts a histological image of skin containing black tattoo pigment treated with three applications of laser treatment followed by fast pulse shock waves.

[0070] [Figure 19] FIG. 19 depicts a histological image of the skin illustrating the size of the intradermal vacuoles. DETAILED DESCRIPTION OF THE INVENTION

[0071] It should be understood that the drawings are not necessarily drawn to scale, and that the disclosed embodiments are, at times, illustrated diagrammatically and in partial views. In some instances, details that are not necessary for an understanding of the disclosed methods and apparatuses or that obscure other details may have been omitted. Of course, it should be understood that the present disclosure is not limited to the particular embodiments illustrated herein.

[0072] Certain embodiments of the present systems and devices are configured to generate high-frequency shock waves in a predictable and consistent manner. In some embodiments, the generated EH shock waves can be used in medical and / or aesthetic treatment applications (e.g., when directed and / or delivered to a patient's target tissue). Examples of medical and / or aesthetic treatment applications in which the present systems can be used are disclosed in (1) U.S. Patent Application No. 13 / 574,228, published as U.S. 2013 / 0046207; (2) U.S. Patent Application No. 13 / 547,995, published as U.S. 2013 / 0018287; (3) U.S. Patent Application No. 13 / 798,710, published as U.S. 2014 / 0257144; and (4) PCT / US2014 / 021746, all of which are incorporated herein in their entireties. The EH shock waves generated by the present system can be configured to impart sufficient mechanical stress to rupture cells in the target tissue (eg, through membrane-degrading damage).

[0073] When target cells (cells of a target tissue) are exposed to the generated PR shock waves, they experience a steep gradient of mechanical stress due to spatial heterogeneity parameters of the cell, such as the density and shear modulus of different cell components. For example, dense and / or inelastic components inside the cell experience greater mechanical stress when exposed to the shock waves compared to lighter components. In particular, the acceleration of higher-density particles or components within the cellular structure exposed to the impact surface is typically very large. At the same time, impacts on lower-density biological structures that make up the cellular structure are significantly reduced because the elasticity of the lower-density biological structures generally behaves as a low-compliance material when exposed to such a large pressure gradient. The difference in mechanical stress results in the movement of dense and / or inelastic components within the cell.

[0074] When cells are exposed to repeated shock waves at certain frequencies and energy levels, dense and / or inelastic components are repeatedly displaced until they disrupt the cells, thereby causing cell rupture. In particular, the property mismatch of the cellular structure and the ability of cells to undergo deformation when exposed to an impact surface leads to the described cell rupture. One possible theory for explaining the phenomenon of rupture of the cellular structure can be found in (Burov, VA, 2002) [1], which is incorporated herein by reference in its entirety.

[0075] As discussed by Burov [1], while cells may oscillate as an integral unit when impacted by these pressure surfaces, steep gradients of mechanical stress may be generated inside the cells as a result of spatial heterogeneity parameters (i.e., density and shear elasticity tensile stress). The concept is based on the masses m1 and m2, the densities of the balls differing slightly (by ρ1 and ρ2, respectively), and the velocity μ o This can be illustrated by modeling the biological structure as two connected balls, with the density of the liquid (ρ) oscillating around the balls at (t). If only the resistance to potential flow is considered, the force applied to the connection is calculated as shown in equation (1).

number

[0076] Additional discussion of equation (1) and its variables is provided in [1]. For example, if the ball radius (R) is approximately 10 μm and the difference between the densities of the balls is 0.1ρ, then 10 9 dyne / cm 2 Stress F / (πR 2 )m, which is sufficient to rupture the cell membrane. Embodiments of the present device generate shock waves that can be used to cause targeted damage to certain cells in a controlled manner, with medical and / or cosmetic therapeutic applications, discussed further below.

[0077] Another possible theory to explain the phenomenon of cell rupture is the accumulated shear stress in the denser material within the cellular structure. In heterogeneous media, such as cells with particles (e.g., pigment particles), shock waves disrupt cell membranes by a progressive (i.e., accumulated) shear mechanism. On the other hand, in homogeneous media, shock wave compression causes minimal, if any, damage to the membrane. As the shock wave passes through a heterogeneous medium, microscopic focusing and defocusing can locally strengthen or weaken the shock wave, resulting in increased local shear. Relative shear motion of the cell membrane occurs depending on the scale of heterogeneity in the cellular structure. When a shock wave strikes a heterogeneous region (e.g., a cell containing particles), particle motion out of phase with the incident wave is thought to generate cell-disrupting energy transfer (e.g., shear stress). Out-of-phase motion (eg, shear stress) can cause microscopic damage to the cell membrane, which can progressively increase to cell membrane collapse with additional successive accumulations of shear stress.

[0078] The progressive shear mechanism of repeated exposure to shock waves can be considered dynamic fatigue of cell membranes. Damage from dynamic fatigue depends on three factors: (1) the applied stress or strain, (2) the rate at which the strain is applied, and (3) the accumulated number of strain cycles. These three factors can be manipulated to cause heterogeneous cells to suffer catastrophic cell membrane disruption compared to relatively more homogeneous cells at a specific applied strain, strain rate, and strain cycles.

[0079] Factor manipulation can be achieved by providing EH shock waves with certain characteristics, such as the number of shock waves, the amount of time between each shock wave, and the intensity of the applied shock waves. As discussed above, if there is too much time between shock waves for the tissue to relax to its unstrained state, the cells will become more resistant to collapse. Therefore, in embodiments of the EH system, shock waves at pulse rates greater than 5 Hz, greater than 100 Hz, and greater than 1 MHz are delivered to the target cellular structure to achieve dynamic fatigue of the tissue and not allow the tissue time to relax.

[0080] A third possible theory is that EH shock waves induce a combination of direct movement of particles contained within the cellular structure and the effects of dynamic fatigue to rupture the cells. While particle-containing cells are an obvious example of a cellular structure exhibiting heterogeneity, that description is not intended to limit the scope of the present disclosure. Instead, the embodiments disclosed herein can be used to rupture or cause damage to other cellular structures exhibiting heterogeneity, such as cellular structures having regions of different effective densities. Parameters of shock waves generated according to the disclosed aspects can be adjusted based on regions of different effective densities (i.e., heterogeneity) to cause cellular damage as described at least herein. The heterogeneity can be regions within a single cell, regions of different types of cells, or a combination of both. In certain embodiments, regions of heterogeneity within a cell include regions having an effective density greater than the effective density of the cell. In one specific example, the effective density of fibroblasts is about 1.09 g / cm. 3and the region of intracellular heterogeneity has a density of 2.25 g / cm 3 graphite, etc., with 1.09 g / cm 2 In some embodiments, the regions of cellular heterogeneity between cells include regions with different types of cells, each cell type having a different effective density, such as fibroblasts and adipocytes or hair follicles. The present disclosure provides further examples of cellular structures that include heterogeneity below.

[0081] Referring now to the drawings, and more particularly to FIG. 1 , a block diagram of one example of a present device or system for electrohydraulic generation of shock waves in a controlled manner is shown therein and designated by reference numeral 10. In some embodiments, such as the one shown, system 10 includes a handheld probe (e.g., with a first housing as in FIG. 2 ) and a separate controller or pulse generation system (e.g., in or with a second housing coupled to the handheld probe via a flexible cable or the like). In other embodiments, the present system includes a single handheld device disposed within a single housing.

[0082] In the embodiment shown, apparatus 10 includes a housing 14 defining a chamber 18 and a shockwave outlet 20, a liquid (54) disposed within chamber 18, a plurality of electrodes (e.g., in spark head or module 22) disposed within the chamber and configured to define one or more spark gaps, and a pulse-generation system 26 configured to apply voltage pulses to the electrodes at a rate between 10 Hz and 5 MHz. In this embodiment, capacitive / inductive coil system 26 is configured to apply voltage pulses to the electrodes such that a portion of the liquid is vaporized, propagating shockwaves through the liquid and the shockwave outlet.

[0083] In the illustrated embodiment, pulse-generation system 26 is configured for use with an AC power source (e.g., a wall outlet). For example, in this embodiment, pulse-generation system 26 includes a plug 30 configured to be inserted into a 110V wall outlet. In the illustrated embodiment, pulse-generation system 26 includes a capacitive / inductive coil system, an example of which is described below with reference to FIG. 6. In other embodiments, pulse-generation system 26 can include any suitable structure or components configured to periodically apply a high voltage to electrodes to generate electric sparks of sufficient power to vaporize liquid in individual spark gaps, as described in this disclosure.

[0084] In the embodiment shown, pulse-generation system 26 is (e.g., removably) coupled to electrodes in spark head or module 22 via high-voltage cable 34, which may, for example, include two or more conductors and / or may be heavily shielded with rubber or other types of electrically insulating material to prevent shock. In some embodiments, high-voltage cable 34 is a composite tether or cable that further includes one or more (e.g., two) fluid lumens through which chamber 18 can be filled with fluid and / or through which fluid can be circulated through chamber 18 (e.g., via composite connection 36). In the embodiment shown, device 10 includes a handheld probe or handpiece 38, with cable 34 removably coupled to probe 38 via high-voltage connector 42, which is coupled to spark head or module 22 via two or more electrical conductors 44. In the embodiment shown, the probe 38 includes a head 46 and a handle 50, which may include a polymer or other electrically insulating material to allow a practitioner to grasp the handle 50 and position the probe 38 during surgery. For example, the handle 50 may be molded from plastic and / or coated with an electrically insulating material such as rubber.

[0085] In the embodiment shown, liquid 54 (e.g., a dielectric liquid such as distilled water) is disposed in chamber 18 (e.g., substantially fills chamber 18). In this embodiment, spark head 22 is positioned in chamber 18 and surrounded by liquid such that electrodes can receive voltage pulses from pulse-generation system 26 (e.g., at a rate of 10 Hz to 5 MHz) such that a portion of the liquid is vaporized, propagating shock waves through the liquid and shock wave outlet 20. In the embodiment shown, probe 38 includes an acoustic delay chamber 58 between chamber 18 and outlet 20. In this embodiment, the acoustic delay chamber is substantially filled with liquid 62 (e.g., of the same type as liquid 54) and has a length 66 sufficient to allow shock waves to form and / or be directed toward outlet 20. In some embodiments, length 66 may be between 2 millimeters (mm) and 25 millimeters (mm). In the embodiment shown, chamber 18 and acoustic delay chamber 58 are separated by a layer of anechoic (acoustically permeable or transparent) material that allows sound waves and / or shock waves to travel from chamber 18 into acoustic delay chamber 58. In other embodiments, liquid 62 may be different from liquid 54 (e.g., liquid 62 may include air bubbles, water, oil, mineral oil, and / or the like). Certain features, such as air bubbles, may introduce and / or enhance nonlinearity in the acoustic behavior of liquid 54 to increase shock wave formation. In further embodiments, chamber 18 and acoustic delay chamber 54 may be integral (i.e., comprise a single chamber). In further embodiments, acoustic delay chamber 54 may be replaced with a solid member (e.g., a solid cylinder of an elastomeric material such as polyurethane). In the embodiment shown, probe 38 further includes an outlet member 70 that is removably coupled to the housing at the distal end of the acoustic delay chamber, as shown. Member 70 is configured to contact tissue 74 and can either be removed and sterilized or replaced between patients. Member 70 comprises a polymer or other material (e.g., low-density polyethylene or silicone rubber) that is acoustically permeable to allow shock waves to exit acoustic delay chamber 58 via outlet 20.Tissue 74 may be, for example, human skin tissue to be treated with device 10 and may include, for example, a tattoo, a blemish, a subcutaneous lesion, or a basal cell abnormality. In some embodiments, an acoustic coupling gel (not shown) may be disposed between member 70 and tissue 74 to lubricate and provide additional acoustic transmission into tissue 74.

[0086] In the embodiment shown, probe 38 includes acoustic mirror 78, which comprises a material (e.g., glass) and is configured to reflect a majority of sound waves and / or shock waves incident on the acoustic mirror. As shown, acoustic mirror 58 can be angled to reflect sound waves and / or shock waves (e.g., originating from spark head 22) toward outlet 20 (through an acoustic delay chamber). In the embodiment shown, housing 14 can include a translucent or transparent window 82 configured to allow a user to view (through window 82, chamber 18, chamber 58, and member 70) a region of the patient comprising target cells (e.g., tissue 74) (e.g., during or prior to application of shock waves to position outlet 20 at the target tissue). In the embodiment shown, window 82 comprises an acoustically reflective material (e.g., glass) configured to reflect a majority of sound waves and / or shock waves incident on the window. For example, window 82 can include transparent glass of sufficient thickness and strength to withstand the high-energy acoustic pulses generated by spark head 22 (e.g., tempered thick plate glass having a thickness of about 2 mm and an optical transmission efficiency of greater than 50%).

[0087] While FIG. 1 shows a user with a human eye 86 viewing the target tissue through window 82, it should be understood that the target tissue can be “viewed” through window 82 via a camera (e.g., a digital still and / or video camera). Acoustic energy can be positioned, applied, and repositioned by direct or indirect observation, according to the target tissue, such as an existing tattoo, and by adaptation of the acoustic energy, such as a change in tissue color. However, if spark head 22 is positioned in a location where the user can view it, the brightness of the resulting sparks from spark head 22 may be too bright for the user to comfortably view; in the embodiment shown, probe 38 is configured so that the multiple electrodes are not visible to a user viewing the area (e.g., the target tissue) through window 82 and outlet 20. For example, in the embodiment shown, probe 38 includes an optical shield 90 positioned between spark head 22 and window 82. Shield 90 can have a width and / or length that is smaller than the corresponding width and / or length of window 82, for example, so that shield 90 is large enough to substantially block light from spark head 22 traveling directly to the user's eyes, but does not interfere with the field of view through window 82 and outlet 20 more than necessary to block that light. Shield 90 can comprise, for example, a thin sheet of metal such as stainless steel or other opaque material, or it can comprise welding glass (e.g., an LCD darkened by a photocell or other photosensitive material) that is optically activated and darkened by the brightness of the spark at the spark gap. To maintain the effect of a point light source from spark head 22 and the resulting desired planar waveform, the acoustic effect of shielding the resulting spark from the spark gap head must be considered. If shield 90 includes an acoustically reflective material to prevent pulse broadening, the distance between the shield and the spark gap between the electrodes in spark head 22 can be selected to minimize (e.g., at least destructive) interference between acoustic and / or shock waves reflected from the shield and those emanating from spark head 22 (e.g., so that cross waves do not generate excessive echoes or reverberation).With the speed of sound waves in a medium such as distilled water at approximately 1,500 m / sec, the distance between the spark head and the shield can be calculated to be between 1 / 2 and 3 / 4 wavelengths from the source.

[0088] Spark head 22 (e.g., electrodes in spark head 22) may have a limited lifespan that can be extended by limiting the duration of activation. In the embodiment shown, device 10 includes a switch or trigger 94 that is coupled to pulse-generation system 26 via a switch wire or other connection 98 through connector 42, such that switch 94 can be actuated to apply a voltage pulse to the electrodes in spark head 22.

[0089] FIG. 2 depicts a cross-sectional side view of a second embodiment 38a of the present handheld probe or handpiece for use with some embodiments of the present EH shockwave generation systems and devices. Probe 38a is substantially similar in some respects to probe 38, and therefore, the differences will primarily be described here. For example, probe 38a is also configured so that multiple electrodes of spark head or module 22a are not visible to a user viewing an area (e.g., of target tissue) through window 82a and outlet 20a. However, rather than including an optical shield, probe 38a is configured so that spark head 22a (and its electrodes) are offset from the optical path extending through window 82a and outlet 20a. In this embodiment, acoustic mirror 78a is positioned between spark head 22a and outlet 20a, as shown, to define the boundary of chamber 18a and to direct acoustic and / or shock waves from spark head 22a to outlet 20a. In the embodiment shown, an acoustic mirror 78a is disposed between the window 82a and the chamber 18a, and because sound waves and / or shock waves are not directly incident on the window 82a (i.e., because the sound waves and / or shock waves are primarily reflected by the acoustic mirror 78a), the window 82a may comprise a polymer or other acoustically permeable or transparent material.

[0090] In the illustrated embodiment, spark head 22a includes multiple electrodes 100 that define multiple spark gaps. The use of multiple spark gaps can be advantageous because it can double the number of pulses that can be delivered in a given period. For example, after a pulse vaporizes a certain amount of liquid in the spark gap, the vapor must either return to its liquid state or be displaced by a different portion of the liquid that is still in a liquid state. In addition to the time required for the spark gap to refill with water before a subsequent pulse can vaporize additional liquid, the spark also heats the electrodes. Therefore, for a given spark rate, increasing the number of spark gaps reduces the rate at which each spark gap must be fired, thereby extending electrode life. Thus, ten spark gaps potentially increases the possible pulse rate and / or electrode life by ten times.

[0091] As mentioned above, high pulse rates can generate a large amount of heat, which can increase wear on the electrodes and / or increase the time required for the vapor to return to a liquid state after being evaporated. In some embodiments, this heat can be managed by circulating a liquid around the spark head. For example, in the embodiment of FIG. 2, probe 38 includes conduits 104 and 108 extending from chamber 18a to respective connectors 112 and 116, as shown. In this embodiment, connectors 112 and 116 can be coupled to a pump to circulate the liquid through chamber 18a (e.g., and through a heat exchanger). For example, in some embodiments, pulse-generation system 26 (FIG. 1) can include a pump and a heat exchanger configured in series and coupled to connectors 112 and 116 via conduits or the like. In some embodiments, a filter can be included in probe 38a within the spark-generation system (e.g., 26) and / or between the probe and the spark-generation system to filter the liquid circulated through the chamber.

[0092] Additionally, due to the limited lifespan of electrode 100 at high pulse rates, some embodiments of the present probes may be disposable. Alternatively, some embodiments are configured to allow the user to replace the electrode. For example, in the embodiment of FIG. 2, spark head 22a is configured to be removable from probe 38a. For example, spark head 22a may be removable through handle 50a, or handle 50a may be removably coupled to head 46a (e.g., via threads or the like) such that spark head 22a can be removed from head 46a and replaced upon removal of handle 50a from head 46a.

[0093] 2, each shock wave application to the target tissue includes a waveform 118 that propagates from the outlet 20a and progresses outward through the tissue 74. As shown, the waveform 74 is curved as it travels outward, following its expansion and in part following the shape of the outer surface of the outlet member 70a that contacts the tissue 74. In other embodiments, such as the embodiment of FIG. 1, the outer shape of the contact member may be planar or otherwise shaped to affect certain properties of the waveform as it passes through the outlet 20a and propagates through the target tissue.

[0094] FIG. 2A depicts an enlarged cross-sectional view of a first embodiment of a removable spark head or module 22a. In the embodiment shown, spark head 22a includes a sidewall 120 defining a spark chamber 124 and multiple electrodes 100a, 100b, 100c disposed within the spark chamber. In the embodiment shown, spark chamber 124 is filled with a liquid 128, which may be similar to liquid 54 (FIG. 1). At least a portion of sidewall 120 includes an acoustically permeable or transparent material (e.g., a polymer such as polyurethane) configured to allow sound waves and / or shock waves generated at the electrodes to travel through sidewall 120 and through chamber 18a. For example, in the embodiment shown, spark head 22a includes a cup-shaped member 132, which may be configured to be an acoustically reflective and acoustically permeable cap member 136. In this embodiment, cap member 136 is dome-shaped to approximate the curved shape of the expanding waveforms emanating from the electrodes and to compress the skin when moderate pressure is applied. Cap member 136 can be coupled to cup-shaped member 132 with an O-ring or gasket 140 and a retaining collar 144. In the embodiment shown, cup-shaped member 132 has a cylindrical shape with a circular cross-section (e.g., with a diameter of 2 inches or less). In this embodiment, the cup-shaped member includes bayonet-style pins 148, 152 configured to align with corresponding grooves in head 46a of probe 38a (FIG. 2) to lock the position of spark head 22a relative to the probe.

[0095] In the embodiment shown, electrode core 156 has conductors 160a, 160b, 160c that extend through opening 164, with the interface between opening 164 and electrode core 156 sealed with grommet 168. In the embodiment shown, center conductor 160a extends through the center of core 156 and serves as a ground to the corresponding center electrode 100a. Peripheral conductors 160b, 160c communicate with peripheral electrodes 100b, 100c to generate sparks across the spark gaps between electrodes 100a, 100b, and between electrodes 100a, 100c. While two spark gaps are shown, it should be understood that any number of spark gaps may be used and may be limited only by the spacing and size of the spark gaps. For example, other embodiments include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark gaps.

[0096] FIG. 2B depicts an enlarged side view of a second embodiment of removable spark head or module 22b. In the embodiment shown, spark head or module 22b includes a sidewall 120a defining a spark chamber 124a and multiple electrodes 100d-1, 100d-2, 100, 100f disposed within the spark chamber. In the embodiment shown, spark chamber 124a is filled with a liquid 128a, which may be similar to liquids 128 and / or 54. At least a portion of sidewall 120a includes an acoustically permeable or transparent material (e.g., a polymer such as polyurethane) configured to allow sound waves and / or shock waves generated at the electrodes to travel through sidewall 120a and through chamber 18a ( FIG. 2 ). For example, in the embodiment shown, spark head 22b includes a cup-shaped member 132a, which may be configured to be an acoustically reflective and acoustically permeable cap member 136a. In this embodiment, cap member 136a is dome-shaped to approximate the curved shape of the expanding waveforms resulting from the electrodes and to compress the skin when moderate pressure is applied. Cap member 136a can be coupled to cup-shaped member 132a with an O-ring or gasket (not shown, but similar to 140) and a retaining collar 144a. In the embodiment shown, cup-shaped member 132a has a cylindrical shape with a circular cross-section (e.g., with a diameter of 2 inches or less). In some embodiments, the cup-shaped member can also include a bayonet-style pin (not shown, but similar to 148, 152) configured to align with a corresponding groove in head 46a of probe 38a to lock the position of spark head 22b relative to the probe.

[0097] In the illustrated embodiment, conductors 160d, 160e, and 160f extend through the rear portion of sidewall 132a (opposite outlet cap member 136a) as shown. In this embodiment, center conductor 160b and peripheral conductors 160a and 160c can be molded into sidewall 120a so that grommets and the like are not required to seal the interface between the sidewall and the conductors. In the illustrated embodiment, center conductor 160d serves as a ground to corresponding center electrodes 100d-1 and 100d-2, which are also in electrical communication with each other. Peripheral conductors 160e and 160f communicate with peripheral electrodes 100e and 100f to generate sparks across the spark gaps between electrodes 100d-1 and 100e and between electrodes 100d-2 and 100f. Although two spark gaps are shown, it should be understood that any number of spark gaps may be used and may be limited only by the spacing and size of the spark gaps. For example, other embodiments include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark gaps.

[0098] In the embodiment shown, center electrodes 100d-1 and 100d-2 may be carried by, and integral with, an elongated member 172 that extends from sidewall 120a toward cap member 136a and into chamber 124a. In this embodiment, member 172 is mounted on a hinge 176 (fixed relative to sidewall 120a) to allow a distal end of the member adjacent electrodes 100d-1, 100d-2 to pivot back and forth between electrodes 100e and 100f, as indicated by arrow 180. In the embodiment shown, the distal portion of member 172 is biased toward electrode 100e by a spring arm 184. In this embodiment, spring arm 184 is configured to position electrode 100d-1 at an initial spark gap distance from electrode 100e. In response to application of an electric potential across electrodes 100d-1 and 100e (e.g., via a pulse-generation system as described elsewhere in this disclosure), a spark will arc between the two electrodes, emitting an electric pulse and vaporizing liquid between the two electrodes. The expansion of the vapor between the two electrodes drives member 172 and electrode 100d-2 downward toward electrode 100f. During a cycle in which member 172 travels downward, when the distance between electrodes 100d-2 and 100f becomes small enough, the pulse-generation system can recharge and apply an electric potential between electrodes 100d-2 and 100f, such that a spark will arc between the two electrodes, emitting an electric pulse and vaporizing liquid between the two electrodes. The expansion of the vapor between electrodes 100d-2 and 100f then drives member 172 and electrode 100d-1 upward toward electrode 100e. During the upward travel cycle of member 172, the pulse-generating system can recharge and apply a potential between electrodes 100d-1 and 100e such that when the distance between electrodes 100d-1 and 100e becomes small enough, a spark arcs between the two electrodes, releasing an electrical pulse to vaporize the liquid between the two electrodes and start the cycle again. In this manner, member 172 oscillates between electrodes 100e and 100f until no potential is applied to the electrodes.

[0099] Exposure to high-velocity and high-energy electrical pulses, especially in liquids, subjects the electrodes to rapid oxidation, erosion, and / or other degradation that can vary the spark gap distance between the electrodes if they are held in a fixed position (e.g., requiring them to be replaced and / or adjusted). However, in the embodiment of FIG. 2B , the pivoting of member 172 between electrodes 100e and 100f and electrodes 100d-1, 100d-2 effectively adjusts the spark gap for each spark. Specifically, the distance between the electrodes at which current arcs between them is a function of the electrode material and potential. Thus, a spark is generated between the electrodes when the nearest surfaces of adjacent electrodes (e.g., 100d-1 and 100e) reach the spark gap distance for a given embodiment (even if eroded). Thus, member 172 is configured to self-adjust the respective spark gaps between electrodes 100d-1 and 100e and between electrodes 100d-2 and 100f.

[0100] As another example of the advantages of the present movable electrode as shown in FIG. 2B, as long as the electrodes are positioned such that only a pair of electrodes are within the arc discharge distance at any given time, no multiple coils are required, and such a single coil or coil system is configured to recharge in less time than required for member 172 to pivot from one electrode to the next. For example, in the embodiment of FIG. 2B, a potential may be applied simultaneously to electrodes 100e and 100f, with electrodes 100d-1 and 100d-2 serving as a common ground, and the potential is such that (in the orientation shown) when member 172 is pivoted upward relative to horizontal, a spark arcs only between electrodes 100d-1 and 100e, and when member 172 is pivoted downward relative to horizontal, a spark arcs only between electrodes 100d-2 and 100f. Thus, as member 172 pivots upward and downward as described above, a single coil or coil system can be connected to both of the surrounding electrodes 100e, 100f and discharged alternately through each of the surrounding electrodes. In such an embodiment, the pulse rate can be adjusted by selecting the physical properties of member 172 and spring arm 184. For example, the properties of member 172 (e.g., mass, stiffness, cross-sectional shape and area, length, and / or the equivalent), and the properties of spring arm 184 (e.g., spring constant, shape, length, and / or the equivalent) can be varied to adjust the resonant frequency of the system and thereby the pulse rate of spark head or module 22b. Similarly, the viscosity of liquid 128a can be selected or adjusted (e.g., increased to reduce the travel speed of arm 172 or decreased to increase the travel speed of arm 172).

[0101] As another example of the benefits of the present movable electrode, such as in FIG. 2B, the properties of the electrode (e.g., shape, cross-sectional area, depth, and the like) can be configured to achieve a known effective or useful life of the spark head (e.g., one 30-minute treatment) so that the spark head 22b is inoperable or of limited effectiveness after the specified useful life. Such a feature can be useful, for example, to ensure that the spark head is discarded after a single treatment, such as to ensure that a new, sterile spark head is used for each patient or area treated to minimize potential cross-contamination between treated patients or areas.

[0102] 2C depicts an enlarged cutaway side view of a third embodiment of removable spark head or module 22c. Spark head 22c is substantially similar to spark head 22b, except as described below, and therefore like reference numerals are used to designate structures of spark head 22c that are similar to corresponding structures of spark head 22b. The primary difference relative to spark head 22b is that spark head 22c includes unhinged beam 172a, such that flexure of the beam itself provides movement of electrodes 100d-1 and 100d-2 in the up or down direction indicated by arrow 180, as described above with respect to spark head 22b. In this embodiment, the resonant frequency of spark head 22c depends, among other things, on the physical properties (e.g., mass, stiffness, cross-sectional shape and area, length, and / or the like) of beam 172a. As described with respect to spring arm 184 of spark head 22b, beam 172a is configured to be biased toward electrode 100e so that electrode 100d-1 is initially positioned at an initial spark gap distance from electrode 100e. The function of spark head 22c is similar to that of spark head 22b, except that beam 172a itself flexes to provide some resistance to movement, such that hinge 176 and spring arm 184 are unnecessary.

[0103] In the embodiment shown, spark head 22b also includes liquid connectors or ports 188, 192 through which liquid can be circulated through spark chamber 124b. In the embodiment shown, proximal end 196 of spark head 22b serves as a compound connection with two lumens for liquid (connectors or ports 188, 192) and two or more (e.g., three as shown) electrical conductors (connectors 160d, 160e, 160f). In such an embodiment, the compound connection at proximal end 196 can be coupled (directly or via a probe or handpiece) to a compound tether or cable having two liquid lumens (corresponding to connectors or ports 188, 192) and two or more electrical conductors (e.g., a first electrical conductor for connecting to connector 160d and a second electrical conductor for connecting to both peripheral connectors 160e, 160f). Such a composite tether or cable can couple the spark head (and, e.g., a probe or handpiece to which the spark head is coupled) to a pulse-generation system having a liquid reservoir and pump, such that the pump can circulate liquid between the reservoir and the spark chamber. In some embodiments, cap member 136a is omitted, such that connectors or ports 188, 192 can allow liquid to be circulated through a larger chamber (e.g., 18a) of the handpiece to which the spark head is coupled. Similarly, a probe or handpiece to which spark head 22a is configured to be coupled can include electrical and liquid connectors that correspond to the spark head's respective electrical connectors (160d, 160e, 160f) and liquid connectors (188, 192) such that when the spark module is coupled to the handpiece (e.g., via crimping the spark head and probe together and / or twisting or rotating the spark head relative to the probe), the spark head's electrical and liquid connectors are simultaneously connected to the probe's or handpiece's respective electrical and liquid connectors.

[0104] In this embodiment, pulse rates from a few Hz to many KHz (e.g., up to 5 MHz) can be employed. Because fatigue events produced by multiple pulses or shock waves are generally cumulative at higher pulse rates, treatment times can be significantly reduced by using moderate-power shock waves in rapid succession, rather than several high-power shock waves separated by long periods of quiescence. As noted above, at least some of the present embodiments (e.g., embodiments with multiple spark gaps) enable electrohydraulic generation of shock waves at higher rates. For example, FIG. 3A depicts a timing diagram expanded to show only two sequences of voltage pulses applied to the electrodes of this embodiment, while FIG. 3B depicts a timing diagram showing a larger number of voltage pulses applied to the electrodes of this embodiment.

[0105] In additional embodiments similar to any of spark modules 22a, 22b, 22c, portions of the individual sidewalls (120, 120a, 120b) may be omitted, such that the individual spark chambers (124, 124a, 124b) are also omitted, or may be left open so that liquid in a larger chamber (e.g., 18 or 18a) of the corresponding handpiece may be freely circulated between the electrodes. In such embodiments, the spark chambers (e.g., sidewalls 120, 120a, 120b) may include liquid connectors, or liquid may be circulated through fluid ports that are separate from the spark chambers (e.g., as depicted in FIG. 2).

[0106] The portion of the pulse train or sequence 200 shown in FIG. 3A includes pulse groups 204 and 208 timed with a delay period 212 between them. A burst or group (e.g., 204, 208) can include as few as one or two pulses or as many as thousands of pulses. Generally, each group 204, 208 can include several voltage pulses applied to the electrodes to trigger an event (i.e., a spark across the spark gap). The duration of the delay period 212 can be set to allow cooling of the electrodes across each spark gap and to allow recharging of the electronics. As used in the embodiments of the present disclosure, pulse rate refers to the rate at which voltage pulse groups (each having one or more pulses) are applied to the electrodes, meaning that individual pulses within a pulse group having two or more pulses are applied at a greater frequency, as illustrated in FIGS. 3A-3B. Each of these pulse groups can be configured to generate one or multiple shock waves.

[0107] The train of events (sparks) initiated by multiple bursts or groups 204 and 208 delivered using the present system and device can have a higher pulse rate (PR), which can shorten treatment time relative to lower pulse rates that may need to be applied over many minutes. Tattoos, for example, may encompass large areas and therefore take time to treat unless rapid cell destruction is achieved (e.g., with the higher pulse rates of the present disclosure). In contrast to the prior art systems described above, the present embodiment can be configured to deliver shock waves at a relatively high pulse rate 216 of 10 to 5,000 or more pulses per second (e.g., greater than or between any one of 10 Hz, 30 Hz, 50 Hz, 1,000 Hz, 10,000 Hz, 1,000,000 Hz, 500,000 Hz, and / or 5,000,000 Hz).

[0108] 4 depicts a waveform that can be delivered into a volume of tissue by either probe 38 or 38a, a configuration that can be useful for tattoo removal. Pulse 300 is a relatively high-voltage pulse that is typical of the impulses generated by the present EH spark head. For example, pulse 300 has a rapid rise time, short duration, and ring-down period. Vertical axis V a The units of σ are arbitrary, as may be displayed on an oscilloscope. Actual acoustic pulse amplitudes can be as low as 50 μPa and as high as several MPa in various embodiments, at least as cumulative energy delivery can be effective as discussed above. Individual time periods 304 may each be 100 nanoseconds, corresponding to short pulse lengths referred to in the art as "shock wave" pulses due to their sharpness and short rise and fall times. For example, rise times of <30 nanoseconds are considered shock waves for purposes of this disclosure, velocities that are particularly effective for generating relatively large pressure-time gradients across small, cellular-scale structures within tissue (e.g., the dermis). Rapid compression and decompression of dermal structures containing tattoo "ink," which is actually a particulate content, over time leads to the fatigue and destruction of pigment-bearing cells and is believed to be one underlying mechanism of the present method as described above. For example, tissue agitation using such shock waves has been shown to be effective when applied at a high pulse rate within a relatively short period of time and at an energy level sufficient to rupture pigmented cells, resulting in the release of trapped particulate matter and the subsequent dispersion of pigment particles into the body, thereby reducing the appearance of the tattoo. It is believed necessary to have a short pulse waveform 300 that can be applied multiple times, preferably hundreds to millions of times, to the area being treated to generate the fatigue required for tattoo "ink" removal.

[0109] FIG. 5 depicts a schematic diagram of one embodiment 400 of a pulse generation system for use in or with some embodiments of the present system. In the embodiment shown, circuit 400 includes multiple charge storage / discharge circuits, each with a magnetic storage or inductive coil 404a, 404b, 404c (e.g., similar to those used in automotive ignition systems). As shown, each of coils 404a, 404b, 404c can be grounded via resistors 408a, 408b, 408c to limit the current allowed to flow through each coil, similar to certain aspects of automotive ignition systems. Each of resistors 408a, 408b, 408c can include a dedicated resistor, or the length and properties of the coil itself can be selected to provide the desired level of resistance. The use of components of the type used in automotive ignition systems can reduce costs and improve safety over custom components. In the illustrated embodiment, circuit 400 includes spark head 22b similar to spark head 22a, except that spark head 22b includes three spark gaps 412a, 412b, 412c instead of two, and each of the three spark gaps is defined by a separate pair of electrodes rather than a common electrode (e.g., 100a) cooperating with multiple peripheral electrodes. It should be understood that this circuit could be coupled to peripheral electrodes 100b, 100c of spark head 22a to generate a spark across the spark gap defined by common electrode 22a, as shown in FIG. 2A. In the illustrated embodiment, each circuit is configured to function similarly. For example, coil 404a is configured to collect and store current for a short duration such that when the circuit is broken with switch 420a, the coil's magnetic field collapses, generating a so-called electromotive force, or EMF, across spark gap 412a, resulting in the rapid discharge of capacitor 424a.

[0110] The RL or resistor-inductance time constant of the coil 404a, which can be affected by factors such as the size and inductive reactance of the coil, the resistance of the coil windings, and other factors, generally corresponds to the time it takes to overcome the resistance of the coil wire and the time for the coil's magnetic field to build up, after which the magnetic field collapses and energy is released through the circuit, followed by discharge, again controlled by the time it takes to overcome the circuit's resistance. This RL time constant generally determines the coil's maximum charge-discharge cycle rate. If the charge-discharge cycle rate is too fast, the available current in the coil may be too low and the resulting spark impulse may be weak. The use of multiple coils can overcome this limitation by firing multiple coils per pulse group (e.g., 204, 208 as illustrated in FIG. 3A) in rapid succession. For example, two coils can double the practical charge-discharge rate by doubling the (combined) current and the resulting spark impulse, and three coils (as shown) can effectively triple the effective charge-discharge rate. When using multiple spark gaps, timing can be critical to the proper generation of the spark impulse and the resulting liquid vaporization and shock wave. Accordingly, a controller (e.g., a microcontroller, processor, FPGA, and / or the like) can be coupled to each of control points 428a, 428b, 428c to control the timing of the opening of switches 420a, 420b, 420c and the resulting discharge of capacitors 424a, 424b, 424c and the generation of the shock wave.

[0111] 6 depicts a block diagram of an embodiment 500 of a radio frequency (RF)-powered acoustic shock wave generation system. In the embodiment shown, the system 500 comprises a nonlinear medium 504 (e.g., such as the acoustic delay chamber 58 described above or a nonlinear member) that provides an acoustic path from a transducer 512 to a target tissue 508 to generate useful harmonic or acoustic energy (e.g., shock waves). In the embodiment shown, the transducer 512 is powered and controlled through a bandpass filter and tuner 516, an RF power amplifier 520, and a control switch 524. The system is configured such that actuation of the switch 524 activates a pulse generator 528 to generate timed RF pulses that drive the amplifier 520 in a predetermined manner. A typical drive waveform may comprise, for example, a sine wave burst (e.g., multiple sine waves in rapid succession). For example, in some embodiments, a typical burst may have a burst length of 10 milliseconds and comprise a sine wave having a period duration of 0.1 microseconds (at a frequency of 100 MHz) to over 2 microseconds (at a frequency of 50 kHz).

[0112] Embodiments of the method include positioning an embodiment of the device (e.g., 10, 38, 38a, 500) adjacent to a region of a patient comprising target cells (e.g., tissue 74) and activating a spark-generating (e.g., capacitive / inductive coil) system (e.g., 26, 400) to propagate shock waves to the target cells. In some embodiments, the region is viewed through a window (e.g., 82, 82a) while positioning the device and / or while shock waves are generated and delivered to the region. Some embodiments further include coupling a removable spark head or module (e.g., 22a, 22b) to the housing of the device prior to activating the pulse-generating system.

[0113] Still other embodiments of the method eliminate intradermal vacuoles formed when skin is treated with a laser. Such methods may include treating tissue debris with a laser, which causes intradermal vacuoles to form, and treating vacuole-containing tissue with an acoustic wave generator, in which the acoustic wave generator applies fast-pulsed acoustic waves to the skin at a frequency, pulse rate, and intensity that disrupts and disperses the intradermal vacuoles. These described embodiments of the system and method for skin clearing of intradermal vacuoles utilize an acousto-mechanical effect to induce vacuole fragmentation and absorption into the surrounding tissue. One embodiment of the method may include one or more of the following steps: coupling an acoustic wave generator to the vacuole-containing tissue; and directing pulsed acoustic waves from the acoustic wave generator into the vacuole-containing tissue. Directing pulsed acoustic waves into the vacuole-containing tissue will initiate an acousto-mechanical effect on the vacuole, resulting in vacuole fragmentation and absorption of the vacuole contents into the surrounding tissue. This vacuole fragmentation and absorption leads to skin clearing.

[0114] In some embodiments of the present methods and systems, the acoustic wave generator may comprise an ultrasound generator or a shock wave generator. In some embodiments, the acoustic wave generator may be configured to generate pulsed acoustic waves with a frequency of about 700 KHz to about 100 MHz, including 750 KHz, 800 KHz, 850 KHz, 900 KHz, 950 KHz, 1 MHz, 2 MHz, 5 MHz, 10 MHz, 20 MHz, 30 MHz, 40 MHz, 50 MHz, 60 MHz, 70 MHz, 80 MHz, or 90 MHz.

[0115] In some embodiments, the acoustic wave generator can be configured to generate pulsed acoustic waves with a pulse duration of about 1 nanosecond to 1 microsecond, including 0.1 microsecond, 0.2 microsecond, 0.3 microsecond, 0.4 microsecond, 0.5 microsecond, 0.6 microsecond, 0.7 microsecond, 0.8 microsecond, or 0.9 microsecond.

[0116] In some embodiments, the acoustic wave generator can be configured to generate pulsed acoustic waves with a pulse rate of about 10 Hz to 1 KHz, including 50 Hz, 100 Hz, 200 Hz, 300 Hz, 400 Hz, 500 Hz, 600 Hz, 700 Hz, 800 Hz, or 900 Hz.

[0117] In some embodiments, the power of the described systems is set so that the Mechanical Index is between about 0.15 and 1.9, including 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, or 1.8. MI is calculated as shown in equation (2).

number

[0118] where P [MPA] is the amplitude of the acoustic wave pressure and f [MHz] is the ultrasound frequency. In some embodiments, the power output of the described systems is set so that the peak pressure output is between 0.8 MPa and 20 MPa.

[0119] In embodiments, the acoustic waves are generated from a high-velocity pulse electrohydraulic (EH) shock wave generator or a megasonic wave generator. In some embodiments, a disclosed system for electrohydraulic generation of shock waves includes a housing defining a chamber and a shock wave outlet, a liquid disposed within the chamber, a plurality of electrodes (e.g., in a spark head or module) disposed within the chamber and configured to define one or more spark gaps, and a pulse-generation system configured to apply voltage pulses to the electrodes at a rate of about 10 Hz to about 5 MHz. In one embodiment, the pulse-generation system is configured to apply the voltage pulses directly to the electrodes.

[0120] In one embodiment, the megasonic wave generator is configured to generate pulsed acoustic waves with a frequency of 1.0-9.0 MHz, a pulse duration of 1 nanosecond to 1 microsecond, a pulse rate of 50 Hz to 500 Hz, and a power set such that the mechanical index (MI) is 0.15 to 1.9.

[0121] Other embodiments of the present methods for high-speed laser-based tattoo removal include treating tattooed skin with a laser and then treating the tattooed site with an acoustic wave generator that applies fast-pulsed acoustic waves to the skin at a frequency, pulse rate, and intensity that disrupts and disperses intradermal vacuoles. These embodiments enable and enable repeated laser treatments over the same treatment area in rapid succession, something not possible with prior art methods.

[0122] In some embodiments, the laser used by the described pulsed acoustic laser post-skin clearing systems and methods may be any high-powered skin laser system. More specifically, in some embodiments, the laser is a Q-switched (QS) laser and / or a picosecond laser system.

[0123] Other embodiments use pulsed acoustic wave skin clearing systems and methods in conjunction with topical and intradermal skin clearing agents such as perfluorodecalin, glycerol, and the like.

[0124] (Experimental results) Experiments were conducted in Gottingen minipigs to observe the effects of high-speed pulsed acoustic waves generated by an acoustic wave generator on laser-treated skin, with the aim of eliminating intradermal vacuoles. Studies were conducted to demonstrate the elimination of "whitening" caused by intradermal vacuoles as a result of laser treatment using a high-speed pulsed electrohydraulic (EH) shock wave generator.

[0125] While the high frequency shock waves generated by certain embodiments of the present disclosure and the controlled and predictable manner in which they are generated have many uses, certain embodiments of the present disclosure and the shock waves generated are particularly useful in therapeutic applications, particularly in eliminating skin vacuoles in patients that form from laser skin treatments.

[0126] 7A-7B and 8 depict two different prototype spark chamber housings. The embodiment in FIGS. 7A-7B depicts a first embodiment 600 of a spark chamber housing used in the described experiments. Housing 600 is similar in some respects to the portion of housing 14a that defines head 46a of probe 38a. For example, housing 600 includes fittings 604, 608 to allow liquid to be circulated through spark chamber 612. In the embodiment shown, housing 600 includes electrode supports 616 and 620 through which electrode 624 can be inserted to define spark gap 628 (e.g., of 0.127 millimeters or 0.005 inches in the experiments described below). However, housing 600 has an elliptical inner surface that is shaped to initially reflect shock waves traveling backward from the spark gap into the wall. Doing so has the advantage that for each shock wave generated in the spark gap, a first or primary shock wave is produced that propagates from the spark gap to the outlet 640, followed by a secondary shock wave that first propagates to the inner elliptical wall and then is reflected back to the outlet 640.

[0127] In this embodiment, supports 616 and 620 are not aligned with (and are rotated approximately 30 degrees relative to) the fittings 604, 608 around the chamber 612. In the embodiment shown, the housing 600 has a hemispherical shape, and the electrode 624 is positioned such that the angle 632 between a central axis 636 passing through the center of the shock wave outlet 640 and the perimeter 644 of the chamber 612 is approximately 57 degrees. Other embodiments can be configured to limit this angular sweep, thereby directing the acoustic and / or shock waves through a smaller outlet. For example, FIG. 8 depicts a cross-sectional view of a second embodiment 600a of a spark chamber housing. The housing 600a is similar to the housing 600 except that the fittings 604a, 608a are rotated 90 degrees relative to the supports 616a, 620a. The housing 600a also differs in that the chamber 612a includes a hemispherical rear or proximal portion and a frustoconical front or distal portion. In this embodiment, the electrode 624a is positioned such that the angle 632a between the central axis 636a passing through the center of the shock wave outlet 640a and the perimeter 644a of the chamber 612a is approximately 19 degrees.

[0128] Figure 9 depicts a schematic diagram of the electronics for a prototype pulse-generation system used with the spark chamber housing of Figures 7A-7B in this experimental procedure. The schematic includes symbols known in the art and is configured to achieve pulse-generation functionality similar to that described above. The depicted circuit is capable of operating in a relaxed discharge mode using embodiments of the present shockwave heads (e.g., 46, 46a, etc.). As shown, the circuit includes a 110V alternating current (AC) power supply, an on-off switch, a timer ("control block"), and a step-up voltage converter with a secondary voltage of 3 kV or 3,000 V. The secondary AC voltage is rectified by a pair of high-voltage rectifiers in a full-wave configuration. These rectifiers charge a pair of oppositely polarized 25 mF capacitors, each protected by a pair of parallel resistors (100 kΩ and 25 kΩ), which together temporarily store the high-voltage energy. When the impedance of the shock wave chamber is low and the voltage charge is high, a discharge is initiated with the aid of an ionization switch, a large spark gap that conducts when a threshold voltage is reached. Because positive and negative voltages flow to each of the electrodes, the potential between the electrodes can be up to approximately 6 kV or 6,000 V. The resulting spark between the electrodes causes a portion of the liquid to evaporate into a rapidly expanding gas bubble, which generates a shock wave. During the spark, the capacitor discharges, ready for recharging by the transformer and rectifier. In the experiments described below, the discharge was approximately 30 Hz and was regulated solely by the natural charge and discharge rate (hence the term "relaxation oscillation"). In other embodiments, the discharge rate can be higher (e.g., as high as 100 Hz, such as for the multi-gap configuration of FIG. 5).

[0129] Further embodiments of the present EH shockwave generation systems and devices are depicted in Figures 11-13C. Probe 38b is similar in some respects to probes 38 and 38a, and therefore the differences will primarily be described here. In this embodiment, probe 38b includes a housing 14b defining a chamber 18b and a shockwave outlet 20b, a liquid (54) disposed within chamber 18b, and a plurality of electrodes (e.g., in spark head or module 22d) disposed within the chamber and configured to define one or more spark intervals, and is configured to be coupled to a pulse-generation system 26 configured to apply voltage pulses to the electrodes at a rate between 10 Hz and 5 MHz.

[0130] In the embodiment shown, spark head 22d includes a sidewall or body 120d and a plurality of electrodes 100g that define a spark gap. In this embodiment, probe 38b is configured to allow liquid to be circulated through chamber 18b via liquid connectors or ports 112b and 116b, one of which is coupled to spark head 22d and the other of which is coupled to housing 14b, as shown. In this embodiment, housing 14b is configured to receive spark head 22d, as shown, such that housing 14b and housing 120d cooperate to define chamber 18b (e.g., so that spark head 22d and housing 14b include complementary parabolic surfaces that cooperate to define the chamber). In this embodiment, housing 14b and spark head 22d include acoustically reflective liners 700, 704 covering their respective surfaces that cooperate to define chamber 18b. In this embodiment, housing 120d of spark head 22d includes channel 188b (e.g., along a central longitudinal axis of spark head 22d) that extends between liquid connector 112b and chamber 18b and is aligned with the spark gap between electrodes 100g so that circulating water will flow in close proximity and / or through the spark gap. In the embodiment shown, housing 14b includes channel 192b that extends between connection 116b and chamber 18b. In this embodiment, housing 120d includes groove 708 configured to receive elastomeric gasket or O-ring 140a to seal the interface between spark head 22d and housing 14b, and housing 14b includes groove 712 configured to receive elastomeric gasket or O-ring 140b to seal the interface between housing 14b and cap member 136b when cap member 136b is secured to housing 14b by ring and retaining collar 144b.

[0131] In the embodiment shown, electrodes 100g each include a flat rod portion 724 and a vertical cylindrical portion 728 (e.g., comprising tungsten for durability) in electrical communication with (e.g., integral with) rod portion 724 such that cylindrical portion 728 can extend into chamber 18b through a corresponding opening 732 in spark head 22d, as shown. In some embodiments, a portion of the side of cylindrical portion 728 can be covered with an electrically insulating and / or resilient material (e.g., shrink wrap), such as to seal the interface between portion 728 and housing 120b. In this embodiment, housing 120b also includes a longitudinal groove 732 configured to receive rod portion 724 of electrode 100g. In the embodiment shown, housing 38g also includes set screw 736 that is positioned in alignment with cylindrical portion 732 of electrode 100g when spark head 22d is placed in housing 38g such that set screw 736 can be tightened to press cylindrical portion 736 inward to adjust the spark gap between the cylindrical portions of electrode 100g. In some embodiments, spark head 22d is permanently adhered to housing 38b; however, in other embodiments, spark head 22d may be removable from housing 38b, such as to enable replacement of electrode 100g, individually or as part of a new or replacement spark head 22d.

[0132] Figure 14 depicts a schematic diagram of a second embodiment of an electrical circuit for a prototype pulse generation system. The circuit of Figure 14 is substantially similar to the circuit of Figure 9, primarily except that the circuit of Figure 14 includes an array of triggered spark gaps instead of ionization switches and includes certain components with different properties than corresponding components in the circuit of Figure 9 (e.g., 200 kΩ resistors instead of 100 kΩ resistors). In the circuit of Figure 14, block "1" corresponds to the primary controller (e.g., processor) and block "2" corresponds to a voltage timer controller (e.g., oscillator), both of which may, in some embodiments, be incorporated into a single unit.

[0133] 15 depicts a cross-sectional view of an embodiment of an ultrasound generator probe. In one embodiment, a power cable 1507 is attached to the proximal end of a metal outer casing 1501. The casing 1501 may include a sound insulator 1506, a backing block 1502, a piezoelectric crystal 1504, and an electrode 1503 that applies an AC potential difference to the crystal 1504. In an embodiment, the distal end of the casing 1501 is capped by a plastic "nose" 1505.

[0134] (A. Tattoo) Tattoos are essentially phagocytic cells, such as fibroblasts, macrophages, and the like, that contain aggregates of ink particles. Because the trapped ink particles are denser than the biological structure of the cells, tattoos or cells containing ink particles have large differences in elasticity within their structure. When exposed to shock waves, cells containing ink particles experience greater mechanical strain than other cells that do not contain dense particles. Shock waves can be delivered at optimal frequencies and amplitudes sufficient to accelerate ink particles and rupture specific cells while leaving intact fibroblasts that do not have the specific elasticity differences. Details of the biological process of tattoos and removal of particles released from cells are discussed further below.

[0135] Tattoo inks and dyes have historically been derived from substances found in nature and generally comprise a heterogeneous suspension of colored particles and other impurities. One example is India ink, which comprises a suspension of carbon particles in a liquid such as water. Tattoos are generally achieved by applying tattoo ink into the dermis, where the ink generally remains substantially permanent. This technique involves driving a pigment suspension through the skin by alternating pressure-suction action caused by the skin's elasticity, combined with the up-and-down movement of a tattoo needle. Water and other carriers for the pigment introduced into the skin diffuse and are absorbed through the tissue. In most cases, 20% to 50% of the pigment is dispersed internally. However, the remaining portion of insoluble pigment particles is deposited within the dermis where it resides. In tattooed skin, pigment particles are generally phagocytosed by cells, resulting in pigment aggregates within the cell's cytoplasm (i.e., in membrane-bound structures known as secondary lysosomes). The resulting pigment aggregates ("particle aggregates") can range in diameter from several micrometers. As the skin heals, the pigment particles remain within the interstitial spaces of the skin tissue within the cells. Tattoo ink is generally difficult to eliminate due to the immobility of the cells caused by the relatively large amount of insoluble pigment particles in the cells. Tattoos may fade over time, but will generally remain throughout the life of the person receiving the tattoo.

[0136] Tattoo inks are typically composed of aluminum (87% of the pigment), oxygen (73% of the pigment), titanium (67% of the pigment), and carbon (67% of the pigment). The relative contributions of the elements to the tattoo ink composition have varied widely among different compounds. At least one study has determined the particle size of three commercially available tattoo inks, as shown in Table 1. [Table 1]

[0137] (B. Tattoo Removal) In traditional tattooing (decorative, cosmetic, and reconstructive), as previously mentioned, a pigment or dye is administered into the dermis to form a tattoo, which generally remains in place permanently.

[0138] Despite the general permanence of tattoos, individuals may change their mind and desire tattoo removal for a variety of reasons. For example, over time, people may change their mind (or reconsider) and desire to remove or alter the design of their decorative tattoo. As another example, individuals with cosmetic tattoos, such as eyeliner, eyebrow, or lip coloring, may desire to change the color or area of ​​the tattoo as fashions change. Unfortunately, no simple and successful method for tattoo removal currently exists. Currently, methods for removing traditional tattoos (e.g., pigmented skin) include salt abrasion, cryosurgery, surgical excision, and CO2 lasers. These methods require invasive procedures associated with potential complications, such as infection, and can usually result in significant scarring. More recently, the use of Q-switched lasers has gained widespread acceptance for tattoo removal. By limiting the pulse duration, ink particles generally reach extremely high temperatures, resulting in the destruction of tattoo ink pigment-containing cells with relatively minimal damage to adjacent normal skin. This significantly reduces the scarring that often occurs after non-selective tattoo removal methods, such as dermabrasion or carbon dioxide laser treatment. The mechanism of tattoo removal by Q-switched laser radiation may still be largely unknown. It is believed that Q-switched lasers allow for more specific tattoo removal through mechanisms of selective photothermolysis and thermodynamic selectivity. Specifically, it is believed that pigment particles within cells can absorb laser light, causing heating of the particles and resulting in thermal destruction of the cells containing the particles. The destruction of these cells results in the release of the particles, which can then be removed from the tissue, usually through an absorption process.

[0139] Q-switched lasers may be superior to some alternatives for tattoo removal, but they are not perfect. Some tattoos resist all laser therapy despite the predicted high particle temperatures achieved through selective photothermolysis. For clarity, reasons cited for the breakdown of some tattoos include pigment absorption spectra, pigment depth, and the structural characteristics of some inks. Adverse events following laser tattoo treatment with Q-switched ruby ​​lasers may include skin texture changes, scarring, and / or pigmentary changes. Transient hypopigmentation and skin texture changes have been reported in up to 50% and 12%, respectively, of patients treated with Q-switched alexandrite lasers. Hyperpigmentation and skin texture changes are rare adverse events with Q-switched Nd:YAG lasers, and the incidence of hypopigmentation changes is generally lower than with ruby ​​lasers. Local and systemic allergic reactions are also a formidable (albeit rare) complication of tattoo removal with Q-switched ruby ​​and Nd:YAG lasers. Additionally, laser treatment can be painful, so much so that local injections of lidocaine or the use of topical anesthetic creams are typically used prior to laser treatment. Finally, laser removal generally requires multiple treatment sessions (e.g., 5-20) and can require expensive equipment for maximum removal. Because multiple wavelengths are typically required to treat multicolor tattoos, a single laser system cannot be used to remove all available inks and ink combinations. Even with multiple treatments, laser therapy can only remove 50-70% of the tattoo pigment, which can result in residual staining.

[0140] In investigating the effectiveness of conventional laser tattoo removal, experiments showed that initial QS laser treatment of both control and test black tattoo sites resulted in a sharp snapping sound when the tattoo site was pulsed with the laser. In addition, each laser pulse on the untreated tattooed area resulted in an immediate "whitening" of the black tattoo site.

[0141] A pre-tattooed Gottingen miniature pig weighing approximately 30 kg was anesthetized. The control and test sites, consisting of a black tattoo, were treated with a QS laser (1054 wavelength, 5 Hz, 5 mm spot size, 1.1 W output). Immediately after laser treatment, the test sites were treated with a rapid-pulse electrohydraulic shock wave generator (as described in US 2014 / 021746) for 2 minutes. The EH shock wave generator generated plane shock waves with peak pressures of 2 MPa to 3.5 MPa at a pulse rate of 50 Hz. After the rapid-pulse EH shock wave treatment, the control and test sites were treated once more with the QS laser. The test sites were then treated again with the rapid-pulse EH shock wave generator. This treatment protocol was repeated once more so that the control and test sites were treated a total of three times with the QS laser. At the test sites, each QS laser treatment was followed by rapid-pulse EH shock wave treatment. After all treatments, each tattoo was biopsied for histological examination.

[0142] (method) Applying EH shockwave treatment to the test site for two minutes resulted in a return of the tattoo color and loss of "whitening." No dissipation of the "whitening" was observed in the control site during this time period. Furthermore, when a second laser pulse was applied to the test site treated with the EH generator, the laser pulse again resulted in a sharp snap and immediate and substantial "whitening" of the black tattoo site. Applying a second laser pulse to the already "whitened" control site resulted in a dull sound with only slight additional "whitening." The results of the third laser treatment using EH shockwaves were similar to the first two.

[0143] Visual and auditory findings provide evidence that acoustic waves were able to eliminate intradermal vacuoles. This provided the ability to repeat laser treatment at the tattoo site. Visually, the elimination of skin "whitening" with color return at the black tattoo site indicates the elimination of intradermal vacuoles that lead to ineffective repeated laser treatment.

[0144] For the EH-treated site, laser pulsing to the pre-treated test tattoo site once again resulted in the generation of a sharp snap, indicating that the laser light was once again able to reach the black tattoo pigment, resulting in a snap caused by a microexplosion from the superheated pigment. In contrast, laser pulsing to the pre-treated control tattoo site resulted in only a dull sound, indicating that the laser light was limited in its ability to reach the black tattoo pigment due to laser attenuation resulting from light scattering by skin vacuoles, thereby limiting the laser's ability to cause the desired pigment microexplosions.

[0145] Examples of laser skin treatments that generate epidermal and / or intradermal vacuoles include laser tattoo removal, laser skin resurfacing, laser removal of birthmarks, laser removal of skin lesions, laser hair transplantation, laser scar removal, laser-assisted hair reduction, laser removal of vascular lesions, laser lip whitening, or laser treatment of melasma. These are merely non-limiting exemplary treatments that can be complemented or supported by the rupture or destruction of vacuoles caused by laser skin treatment. In some embodiments, the destruction or dispersion of vacuoles caused by laser skin treatment may be caused by non-thermal cell membrane degradation of specific cells secondary to nonlinear processes accompanying the propagation of high-frequency shock waves, as discussed above.

[0146] Some general embodiments of the present method include delivering (e.g., via one or more of the present devices) a plurality of generated shock waves to at least one skin vacuole comprising at least one region of heterogeneity until at least one skin vacuole ruptures or disperses. In some embodiments, the shock waves are delivered for no more than 30 minutes in a 24-hour cycle. In some embodiments, the shock waves are delivered for no more than 20 minutes in a 24-hour cycle. In some embodiments, 200 to 5,000 shock waves are delivered at each of multiple locations of the shock wave outlet for 30 seconds to 20 minutes.

[0147] 16 provides a histology image of skin containing blue tattoo pigment that has undergone a single laser treatment. As can be seen from the image, there is significant vacuolation 1602 at the epidermal-dermal junction and adjacent to tattoo pigment particle agglomerations 1601.

[0148] Figures 17 and 18 provide histological images of biopsies taken from the control and test sites, respectively, after completion of the study. More specifically, Figure 17 depicts a control black tattoo site that was treated three times using laser treatment alone. As can be seen from Figure 17, the control site had a significant amount of microbubbles both at the epidermal-dermal junction and around the black tattoo pigment clusters. Based on current understanding, vacuoles at the epidermal-dermal junction 1701 are the primary cause of the visual "whitening" seen after laser treatment. However, more importantly, vacuoles surrounding pigment particles 1702 within the dermis are likely another cause of laser ineffectiveness with repeated laser treatments.

[0149] FIG. 18 depicts a test black tattoo site that was treated three times using laser treatment with accompanying rapid pulse shock wave treatment. FIG. 18 shows that there is significant evidence of depigmented pigment 1801, indicating that the black pigment particles were successfully treated with the laser. In addition, FIG. 18 depicts a portion of the tissue containing minimal vacuoles 1802 compared to the corresponding tissue from the control site in FIG. 17. The present results provide solid evidence that "whitening" from laser-treated tattoo sites can be minimized, allowing for repeated treatment of tattoo sites in a single session.

[0150] FIG. 10 illustrates one embodiment of a method 700 for directing shock waves toward target tissue using the device 10. In the embodiment shown, the method 700 includes step 704, in which target cells 708 in a patient's tissue 712 are identified for treatment. For example, the tissue 712 can include skin tissue, and / or the target cells 708 can include cells containing tattoo pigment and / or vacuoles in or near the skin tissue. In the embodiment shown, the method 700 also includes step 716, in which a probe or handpiece 38 is positioned within the adjacent tissue 712 so that shock waves generated in the probe 38 can be directed toward the target cells 708. In the embodiment shown, the method 700 also includes step 720, in which a pulse-generating system 26 is coupled to the probe 38. In the embodiment shown, the method 700 also includes step 724, in which the pulse-generating system 26 is activated to generate sparks across electrodes in the probe 38, generating shock waves in the probe 38 for delivery to the target cells 708, as shown. In the embodiment shown, method 700 also includes optional step 728, in which pulse-generation system 26 is decoupled from probe 38 and probe 38 is removed from or moved relative to tissue 712. In the embodiment shown, target cells 708 are omitted from step 728, representing their destruction. Other embodiments of the method may include some or all of the steps illustrated in FIG.

[0151] (C. Use of acoustic waves on intradermal vacuoles) Acoustic waves have previously been used to destroy contrast microbubbles used in medical imaging and drug delivery (as shown in Chatterjee D., et al., Ultrasound-medicated destruction of contrast microbubbles used for medical imaging and drug delivery, Physics of Fluid 17, 100603 (2005)). The destruction of these bubbles is typically the result of rupturing the encapsulating membrane, which allows the gas to diffuse into the body.

[0152] These contrast agent microbubbles, as well as others in the prior art, are typically less than 2 micrometers in diameter and are formed by encapsulating a liquid or gas within a stabilizing layer of surfactant. As disclosed in the prior art, smaller bubbles with a larger surface-to-volume ratio are believed to be less stable due to stronger diffusion. Despite the small size of contrast agent microbubbles, significant bubble destruction takes 4 to 10 minutes, depending on the acoustic pressure used.

[0153] As shown in Figure 19, the intradermal vacuoles caused by laser-treated skin range in size from <2 micrometers to >100 micrometers. These intradermal vacuoles are not encapsulated like the contrast agent microbubbles found in prior art. Unlike superficial dermal vacuoles, which begin to dissipate after 20 minutes, these deep dermal vacuoles are relatively stable. Histological analysis 2 hours after laser treatment shows a significant number of deep vacuoles present around tattoo pigment particle agglomerates. Even 48 hours later, these deep vacuoles are still present, indicating that, unlike air bubbles, the vacuoles are relatively stable. However, by this time, they have filled with fluid or fibrin material. This provides evidence that the vacuoles are not air bubbles similar to those seen in prior art.

[0154] Given the size of deep skin vacuoles, unexpected results were achieved when pulsed acoustic waves were successfully used to rapidly clear these vacuoles, despite their high stability.

[0155] D. Methods of Treating Additional Diseases and Conditions In addition to tattoo removal, embodiments of the present method may include the application of high-frequency shock waves to complement and / or support various laser-based skin treatments that result in epidermal and intradermal vacuoles, as discussed above. Some embodiments of the present system and method may be used to support any laser procedure that results in the immediate formation of superficial and deep vacuoles. As with tattoo removal, the formation of epidermal and intradermal vacuoles limits the ability to perform repeated effective laser treatments due to the obstruction or blocking of subsequent laser pulses by the vacuoles. As a result, repeated laser treatments typically cannot be administered without long-duration rest periods.

[0156] For example, such additional laser-based treatments that would benefit from embodiments of the present systems and methods may include laser skin resurfacing, laser removal of birthmarks, laser removal of skin lesions, laser hair transplantation, laser scar removal, laser-assisted hair reduction, laser removal of vascular lesions, laser lip whitening, and / or laser treatment of melasma.

[0157] Some embodiments in which the present method or system may be implemented include a system or method using a laser to treat pigmented epidermal and / or dermal lesions on a patient. Such treatment may include the use of a 532 nm (frequency-doubled Nd:YAG) laser or a 1,064 nm laser, and may include the treatment of lentigines, cafe au lait spots, freckles, and / or dermal pigmented lesions.

[0158] In other embodiments, the methods and systems may be used during laser skin resurfacing, including mid-depth non-ablative skin resurfacing and / or non-ablative skin resurfacing of wrinkles and acne scars. Such embodiments may use a frequency-doubled 532 nm Q-switched laser or a Q-switched Nd:YAG 1,064 nm laser.

[0159] Additional embodiments include implementing the methods and systems in the laser treatment of melasma. Such embodiments may include the use of a 694 nm Q-switched ruby ​​laser, a 755 nm Q-switched alexandrite laser, a 532 nm frequency-doubled Q-switched Nd:YAG laser, and / or a 1,064 nm Q-switched Nd:YAG laser. Additional embodiments include laser-assisted hair reduction using a Q-switched laser, such as the Medlite from Hoya ConBio. TM Implementing the method and system in laser treatment of vascular lesions using a laser or laser lip whitening using a Q-switched 532 nm laser.

[0160] The above specification and examples provide a description of the structure and use of exemplary embodiments. While certain embodiments have been described above in some detail, or with reference to one or more individual embodiments, those skilled in the art may make numerous modifications to the disclosed embodiments without departing from the scope of the present invention. Therefore, the various illustrative embodiments of the device are not intended to be limited to the particular forms disclosed. Rather, they include all modifications and alternatives that fall within the scope of the claims, and embodiments other than those shown may include some or all of the features of the depicted embodiments. For example, components may be combined into a single structure. Furthermore, where appropriate, any aspect of the above-described examples may be combined with any aspect of other described examples to form additional examples having similar or different properties and addressing the same or different problems. Similarly, it will be understood that the benefits and advantages described above may relate to one embodiment or to several embodiments.

[0161] The claims are not intended to, and should not be construed as, including means-plus or step-plus-function limitations unless such limitations are expressly recited in a given claim using the phrase "means for" or "step for," respectively.

[0162] [Embodiment 1-1] 1. A skin clearing system, comprising: a pulsed acoustic wave generator configured to generate a plurality of pulsed acoustic waves and direct the generated waves toward skin, the pulsed acoustic wave generator operable with a laser light source configured to emit laser light before the pulsed acoustic wave generator generates the plurality of pulsed acoustic waves; a controller coupled to the pulsed acoustic wave generator, the controller configured to enable generation of the pulsed acoustic waves for a second time period based on expiration of a first time period during which generation of the pulsed acoustic waves is disabled and laser light is applied to the skin by the laser light source; and Equipped with the pulsed acoustic waves delivered to the skin during the second time period clear at least a portion of the epidermis and intradermal vacuoles generated as a result of the laser light source during the first time period; A skin-clearing system wherein the second time period is greater than or equal to 30 seconds, and the first time period and the second time period are each less than or equal to 10 minutes. [Embodiment 1-2] The skin clearing system of embodiment 1-1, wherein the generated acoustic waves have a frequency of 700 KHz to 100 Mhz, and the controller is configured to enable generation of the pulsed acoustic waves for a fourth time period based on expiration of a third time period during which generation of the pulsed acoustic waves is disabled and laser light is applied to the skin by the laser light source. [Embodiment 1-3] 3. The skin clearing system of claim 1, wherein the controller is configured to generate the pulsed acoustic waves with a pulse duration of 1 nanosecond to 1 microsecond, and the controller is configured to direct the pulsed acoustic waves in the fourth time period within 10 minutes of directing the pulsed acoustic waves in the second time period. [Embodiments 1-4] 2. The skin clearing system of claim 1, wherein the controller is configured to generate the pulsed acoustic waves at a pulse rate of 10 Hz to 1 KHz. [Embodiments 1-5] 2. The skin clearing system of embodiment 1-1, wherein the controller is configured to generate pulsed acoustic waves having a mechanical index MI of 0.15 to 1.9. [Embodiments 1-6] The pulsed acoustic wave generator includes a high-speed pulsed electric hydraulic shock wave generator, the high-speed pulsed electric hydraulic shock wave generator comprising: a housing defining a chamber and a shock wave outlet; a medium disposed within the chamber; and a plurality of electrodes and capacitors disposed within the chamber and configured to define one or more spark gaps; a pulse generation system configured to apply voltage pulses to the plurality of electrodes and capacitors in the chamber; A skin clearing system as described in embodiment 1-1, comprising: [Embodiment 1-7] 2. The skin clearing system of claim 1, wherein the controller is configured to generate the acoustic waves in pulses at a rate of 10 Hz to 5 MHz. [Embodiment 1-8] the pulsed acoustic wave generator includes a megasonic wave generator; The megasonic wave generator comprises: Frequencies between 700KHz and 20Mhz or 10Hz and 1KHz, and / or Pulse durations from 1 nanosecond to 1 microsecond 2. A skin clearing system as described in embodiment 1-1, configured to generate pulsed acoustic waves with: [Embodiments 1-9] the pulsed acoustic wave generator includes a megasonic wave generator; 2. The skin clearing system of embodiment 1-1, wherein the power of the megasonic wave generator is set so that the mechanical index (MI) is 0.15 to 1.8. [Embodiments 1-10] 7. The skin clearing system of any one of claims 1-6, wherein the high-speed pulse electric water pressure generator is set to have a peak pressure output of 0.8 MPa to 5 MPa. [Embodiments 1-11] The skin clearing system of embodiment 1-1, wherein the second time period is between 30 seconds and 2 minutes. [Embodiments 1-12] The controller Disabling generation of the pulsed acoustic wave during the first time period corresponding to operation of the laser light source; Disabling generation of the pulsed acoustic wave during a third time period corresponding to operation of the laser light source; enabling generation of the pulsed acoustic wave for a fourth time period based on expiration of the third time period during which laser light is applied to the skin; disabling generation of the pulsed acoustic wave during a fifth time period corresponding to operation of the laser light source; enabling generation of the pulsed acoustic wave during a sixth time period based on expiration of the fifth time period during which laser light is applied to the skin; and further configured to: the pulsed acoustic waves delivered to the skin during the fourth time period and the sixth time period clear at least a portion of the epidermis and intradermal vacuoles generated by the laser light source; 2. The skin clearing system of claim 1, wherein directing the pulsed acoustic waves during the second time period, the fourth time period, and the sixth time period is performed within 10 minutes of each other. [Embodiments 1-13] the first time period, the third time period, and the fifth time period occur within a 24-hour period; at least some of the cleared epidermal and intradermal vacuoles are not deep dermal vacuoles; and / or 13. The skin clearing system of claim 1-12, wherein the pulsed acoustic wave generator is configured to treat the skin during the second time period, the fourth time period, and / or the sixth time period for 0.1 minutes to 10 minutes. [Embodiments 1-14] further comprising a skin laser system including the laser light source, the skin laser system configured to generate laser light during the first time period, the third time period, and the fifth time period; the laser light source comprises a Q-switched laser or a picosecond laser; A skin clearing system as described in embodiments 1-12, wherein the skin laser system is configured to apply the laser to the target skin with a pulse duration of 1 nanosecond to 1 microsecond. [Embodiment 1-15] The skin clearing system of embodiment 1-1, wherein the laser treatment provided by the laser light source comprises a treatment selected from the group including tattoo removal, laser skin resurfacing, laser removal of birthmarks, laser removal of skin lesions, laser hair transplantation, laser scar removal, laser-assisted hair reduction, laser removal of vascular lesions, laser lip whitening, and laser treatment of melasma. [Embodiment 2-1] 1. A skin clearing system, comprising: a laser light source configured to emit laser light and direct the emitted laser light toward the skin during a first period of time; a pulsed acoustic wave generator configured to generate a plurality of pulsed acoustic waves and direct the generated pulsed acoustic waves toward the skin to clear non-encapsulated intradermal vacuoles generated as a result of the laser light source, the pulsed acoustic waves being emitted sequentially after the laser light source configured to emit laser light; a controller coupled to the pulsed acoustic wave generator and configured to enable generation of the pulsed acoustic waves for a second time period based on expiration of the first time period during which generation of the pulsed acoustic waves is disabled and laser light is applied to the skin by the laser light source; Equipped with the second time period is greater than or equal to 30 seconds, and each of the first time period and the second time period is less than or equal to 10 minutes; the pulsed acoustic waves delivered to the skin during the second time period clear at least a portion of the non-encapsulated intradermal vacuoles generated as a result of the laser light source during the first time period; A skin-clearing system, wherein the non-encapsulated intradermal vacuoles are free of tattoo pigment particle agglomerates. [Embodiment 2-2] The skin clearing system of embodiment 2-1, wherein the second time period is 10 minutes or less. [Embodiment 2-3] 3. The skin clearing system of embodiment 2-2, wherein the first time period is within 10 minutes of the second time period. [Embodiment 2-4] The controller Disabling generation of the pulsed acoustic wave during the first time period corresponding to operation of the laser light source; Disabling generation of the pulsed acoustic wave during a third time period corresponding to operation of the laser light source; The skin clearing system of embodiment 2-1, further configured to: [Embodiment 2-5] The controller enabling generation of the pulsed acoustic wave for a fourth time period based on expiration of the third time period during which laser light is applied to the skin; disabling generation of the pulsed acoustic wave during a fifth time period corresponding to operation of the laser light source; enabling generation of the pulsed acoustic wave for a sixth time period based on expiration of the fifth time period during which laser light is applied to the skin; and further configured to: A skin clearing system as described in embodiments 2-4, wherein the pulsed acoustic waves delivered to the skin during the fourth time period and the sixth time period clear at least a portion of the non-encapsulated intradermal vacuoles generated by the laser light source. [Embodiment 2-6] the first time period, the third time period, and the fifth time period occur within a 24-hour period; At least some of the cleared non-encapsulated intradermal vacuoles are not deep dermal vacuoles; the pulsed acoustic wave generator is configured to treat the skin during the second time period, the fourth time period, or the sixth time period for a period of between 0.1 minutes and 10 minutes; Or a combination thereof, the skin clearing system according to any one of embodiments 2-5. [Embodiment 2-7] a skin laser system including the laser light source, the skin laser system configured to generate laser light during one or more of the time periods; the laser light source comprises a Q-switched laser or a picosecond laser; A skin clearing system as described in embodiments 2-5, wherein the skin laser system is configured to apply the Q-switched laser or picosecond laser with a pulse duration of 1 nanosecond to 1 microsecond to the skin. [Embodiment 2-8] The skin clearing system of embodiment 2-1, wherein the laser treatment provided by the laser light source comprises a treatment selected from the group including tattoo removal, laser skin resurfacing, laser removal of birthmarks, laser removal of skin lesions, laser hair transplantation, laser scar removal, laser-assisted hair reduction, laser removal of vascular lesions, laser lip whitening, and laser treatment of melasma. [Embodiment 2-9] The skin clearing system of embodiment 2-1, wherein the non-encapsulated intradermal vacuoles are formed by treating tissue with laser light. [Embodiment 2-10] The skin clearing system of embodiment 2-1, wherein the non-encapsulated intradermal vacuoles are laser-generated. [Embodiment 2-11] The skin clearing system of embodiment 2-1, wherein the non-encapsulated intradermal vacuoles are generated as a result of rapid heating and / or energy transfer by the laser light source.

Claims

1. 1. A method for acoustic treatment of tissue to disperse vacuoles within the tissue, the method comprising: Identifying the location of tissue containing vacuoles; coupling an acoustic wave generator to the tissue containing the vacuole; directing pulsed acoustic waves from the acoustic wave generator into the tissue containing the vacuole.

2. The method of claim 1 , wherein the tissue containing the vacuoles has been previously treated with a laser.

3. 3. The method of claim 2, further comprising treating skin containing the vacuoles with a laser after directing pulsed acoustic waves from the acoustic wave generator into the tissue containing the vacuoles.

4. 4. The method of claim 3, wherein the skin is treated with the acoustic wave generator for about 0.1 minutes to about 10 minutes.

5. The method of claim 3 , wherein the laser treatment comprises applying a laser to the target skin with a pulse duration of about 1 nanosecond to about 1 microsecond.

6. The method of claim 3 , wherein the laser comprises a Q-switched laser or a picosecond laser.

7. The method of claim 3 , wherein the laser treatment comprises tattoo removal.

8. The method of claim 3 , wherein the laser treatment comprises laser skin resurfacing.

9. The method of claim 3 , wherein the laser treatment comprises laser removal of a birthmark.

10. The method of claim 3 , wherein the laser treatment comprises laser removal of a skin lesion.

11. The method of claim 3 , wherein the laser treatment comprises laser hair transplantation.

12. The method of claim 3 , wherein the laser treatment comprises laser scar removal.

13. The method of claim 3 , wherein the laser treatment comprises laser-assisted hair reduction.

14. The method of claim 3 , wherein the laser treatment comprises laser ablation of a vascular lesion.

15. The method of claim 3 , wherein the laser treatment comprises laser lip whitening.

16. The method of claim 3 , wherein the laser treatment comprises laser treatment for melasma.

17. treating the skin containing the vacuoles with a laser after directing pulsed acoustic waves from the acoustic wave generator into the tissue containing the vacuoles; Repeating the directing and treating in an alternating manner for at least two repetitions in a single treatment session; The method of claim 3 further comprising:

18. 18. The method of claim 17, wherein treating the skin containing vacuoles with a laser is performed within 10 minutes of directing the pulsed acoustic waves.

19. 20. The method of claim 18, wherein the at least two subsequent repetitions of directing the pulsed acoustic waves are performed within 10 minutes or less.

20. 1. A skin clearing system comprising a pulsed acoustic wave generator configured to generate pulsed acoustic waves and direct the generated waves toward the skin to clear the epidermis and intradermal vacuoles.

21. 21. The skin-clearing system of claim 20, wherein the generated acoustic waves have a frequency of about 700 KHz to about 100 Mhz.

22. 21. The skin-clearing system of claim 20, wherein the generated acoustic waves have a pulse duration of about 1 nanosecond to about 1 microsecond.

23. 21. The skin clearing system of claim 20, wherein the generated acoustic waves have a pulse rate of about 10 Hz to about 1 KHz.

24. 21. The skin clearing system of claim 20, wherein the generated waves have a mechanical index MI of about 0.15 to about 1.

9.

25. The pulsed acoustic wave generator includes a high-speed pulsed electric hydraulic shock wave generator, the high-speed pulsed electric hydraulic shock wave generator comprising: a housing defining a chamber and a shock wave outlet; a medium disposed within the chamber; and a plurality of electrodes and capacitors disposed within the chamber and configured to define one or more spark gaps; a pulse generation system configured to apply voltage pulses to the plurality of electrodes and capacitors in the chamber; 21. The skin clearing system of claim 20, comprising:

26. 21. The skin-clearing system of claim 20, wherein the pulsed acoustic wave generator is configured to generate the acoustic waves in pulses at a rate of about 10 Hz to about 5 MHz.

27. 21. The skin-clearing system of claim 20, wherein the pulsed acoustic wave generator comprises a megasonic wave generator.

28. 28. The skin clearing system of claim 27, wherein the megasonic wave generator is configured to generate pulsed acoustic waves with a frequency of about 700 KHz to about 20 Mhz.

29. 28. The skin clearing system of claim 27, wherein the megasonic wave generator is configured to generate pulsed acoustic waves with a pulse duration of about 1 nanosecond to about 1 microsecond.

30. 28. The skin clearing system of claim 27, wherein the megasonic wave generator is configured to generate pulsed acoustic waves with a pulse rate of about 10 Hz to about 1 KHz.

31. 28. The skin clearing system of claim 27, wherein the power of the megasonic wave generator is set so that the mechanical index (MI) is between about 0.15 and 1.

8.

32. 28. The skin clearing system of claim 27, wherein the high-speed pulsed electric-hydraulic generator is configured to have a peak pressure output of about 0.8 MPa to 20 MPa.

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