Pulse Acoustic Wave Skin Clearing System and Method

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 Applications) This application claims priority to U.S. Provisional Patent Application No. 62 / 312,372, filed on March 23, 2016, which is hereby incorporated by reference in its entirety.

[0002] (Field of the Invention) Embodiments of the present invention generally relate to the therapeutic use of shock waves. More specifically, but not limited to, embodiments of the present invention relate to a dermal clearing system and an apparatus for generating a therapeutic shock wave (a shock wave with therapeutic use) for use in the system.

Background Art

[0003] Shock waves have been used in certain medical and aesthetic treatments. "Shock wave" or shock wave is generally used to refer to an acoustic phenomenon that causes a sudden and rapid change in pressure (e.g., due to an explosion or lightning strike). These rapid pressure changes can travel through elastic media such as air, water, human soft tissue, etc., and / or a solid material such as bone, and can generate strong energy waves that can induce an inelastic response 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) The U.S. patent application Ser. No. 13 / 574,228 (national stage application of PCT / US2011 / 021692, published as International Publication No. WO2011 / 091020 (Patent Document 1)) by one of the inventors of the present invention discloses a device for generating shock waves using a transducer. The device includes an acoustic wave generator configured to emit acoustic waves having at least one frequency from 1 MHz to 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 an acoustic wave, at least a portion of the acoustic wave will travel through the shock wave medium and form a shock wave. The device can be operated to form a shock wave configured to disrupt one or more cells of a patient's cells in particles, and the shock wave can be directed toward the patient's cells such that the shock wave disrupts one or more of the cells in the particles. The present acoustic transducer device can generate high-power shock waves at a high frequency or pulse rate.

[0005] Other systems for generating shock waves can include an electrohydraulic (EH) wave generator. EH systems can generally deliver a similar level of energy as other methods, but deliver that energy over a larger area and thus can be configured to deliver a greater amount of shock wave energy to a target tissue over a shorter period. EH systems generally incorporate an electrode (i.e., a spark plug) to initiate the shock wave. In an EH system, a high-energy shock wave is generated when an electric charge is applied to an electrode immersed in treated water contained within an enclosure. When the charge is emitted, a small amount of water is vaporized at the tip of the electrode, and the rapid and nearly instantaneous expansion of the vaporized water generates a shock wave that propagates outwardly through the liquid water. In some embodiments, the water is contained within an ellipsoidal enclosure. In these embodiments, the shock wave can bounce off the sides of the ellipsoidal enclosure and converge at a focus that coincides with the location of the area to be treated.

[0006] For example, U.S. Patent No. 7,189,209 ('209 Patent) (Patent Document 2) describes a method for treating pathological conditions associated with bone and musculoskeletal environment as well as soft tissues by applying acoustic shock waves. The '209 Patent explains that the shock waves induce local trauma and cell apoptosis, including microdamage, and promote the formation of molecular bone, cartilage, tendon, fascia, and soft tissue morphogens and growth factors to induce an osteogenic response such as cell mobilization and induce angiogenesis. The '209 Patent claims several specific implementations of the method. For example, the '209 Patent includes steps of identifying the location of a diabetic foot ulcer or decubitus ulcer site or suspected site in a human patient, generating acoustic shock waves, focusing the acoustic shock waves throughout the identified location, and applying 500 to more than about 2,500 acoustic shock waves per treatment to the identified site to induce an increase in microdamage and angiogenesis, thereby inducing or accelerating healing, and claims a method for treating a diabetic foot ulcer or decubitus ulcer. 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 acoustic shock waves per treatment site, which can result in a treatment duration per treatment site and / or a "total time per treatment" for all sites that are inconveniently large. For example, the '209 Patent discloses a 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 electrohydraulically generated shock waves to produce a therapeutic effect in tissue. The '572 patent describes a method of increasing bone density and strength (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 50-500 atmospheres. The '572 patent describes the application of unfocused shock waves to generate dynamic, repetitive 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 at a frequency 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 ​​​​100 mm. The intensity of the shock waves may be 50-500 atmospheres. Each shock wave is of a duration of a few microseconds, as in conventional lithotriptors, and is preferably applied at a frequency of 1-10 shock waves per second for 5-30 minutes in each treatment. The number of treatments depends on the particular patient.

[0008] U.S. Patent Application Serial No. 10 / 415,293 (the '293 Application), also published as US 2004 / 0006288, 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 a pulse rate of about 100 to about 5,000 pulses per treatment area (per length of vascular unit being treated).

[0009] (B.Shock wave speed) Prior art literature has shown that higher pulse rates, which use an EH system to provide shock waves, can lead to tissue damage. For example, in one study (Delius, Jordan, & others, 1988)[2], the effects of shock waves on normal canine kidneys were examined in a group of dogs whose kidneys were exposed to 3,000 shock waves. The groups differed only in the shock wave delivery rate, which was 100 Hz to 1 Hz, respectively. Autopsies were performed 24 - 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 (compared to 1 Hz). The results showed that kidney damage is dependent on the shock wave delivery rate.

[0010] In another study (Madbouly & others, 2005)[7], a slower shock wave lithotripsy (SWL) rate was associated with a significantly higher success rate with a smaller number of total shock waves compared to a faster SWL rate. In this paper, the authors discussed how human experiments have shown a decrease in the incidence of SWL-induced kidney injury or the need for anesthesia when a slower test SWL rate was used.

[0011] In yet another study (Gillitzer & others, 2009)[5], reducing the shock wave delivery rate from 60 to 30 shocks per minute also provides a significant protective effect on the integrity of the actual vasculature in a porcine model. These findings support a potential strategy of reduced pulse rate frequency to improve the safety and effectiveness of extracorporeal shock wave lithotripsy.

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

[0013] Long treatment times may be acceptable for extracorporeal shock wave lithotripsy, but the use of shock waves to provide non-lithotripsy treatment effects to tissue in a medical institution is sub-optimal 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 resource resources allocated to the administration of the treatment). In addition to cost, at some point, the duration of providing treatment to a patient becomes intolerable for the patient receiving the treatment and the medical staff providing the treatment.

[0014] (C. Tissue as a viscoelastic material) One reason for the sensitivity to pulse rates found in the prior art may be due in part to the relaxation time of the tissue. Cells have both elastic and viscous properties and are therefore viscoelastic materials. Unlike most conventional materials, cells are highly non-linear with their elastic modulus depending on the magnitude of the applied stress or internal stress (Kasza, 2007)[6]. One study (Fernandez (2006)[3] suggests that fibroblasts can be modeled as gels with cross-linked actin networks that show a transition from the linear region to power-law strain hardening.

[0015] The authors of another paper (Freund, Colonius, & Evan, 2007)[4] hypothesized that the cumulative shear force of many impacts damages and that the mechanism may depend on whether there is sufficient time between impacts for the tissue to relax to an unstressed state. Their viscous fluid models suggested that any deformation recovery that would occur would be almost complete by the first 0.15 seconds after impact. As a result, their models of the mechanism for cell damage would be independent of impact velocity for impact velocities slower than about 6 Hz. However, the actual viscoelasticity of the interstitial material would be expected to introduce its sensitivity to the impact delivery velocity, along with a relaxation time of about 1 second. Assuming that the interstitial material has a relaxation time of about 1 second, the authors would expect a significant decrease in damage for delivery velocities slower than about 1 Hz. Conversely, damage should increase for faster delivery velocities. As an implication of their models, both a decreasing delivery velocity and an expanding focus zone should decrease damage.

[0016] (D. Laser-based skin treatment) In another area of therapeutic medicine, the use of laser-based skin treatment has been used in tattoo removal, laser skin resurfacing, laser removal of moles, laser removal of skin lesions, laser hair implantation or removal, laser scar removal, and a number of other various procedures. The natural reaction of the body to each of these treatments poses challenges to the effectiveness of the treatment.

[0017] For example, in the context of tattoo removal, exposure of the tattooed area to laser output currently tends to reduce the effectiveness of subsequent laser exposures and results in a "whitening" condition within the treatment area. The "whitening" reaction typically occurs when the laser wavelength and output are appropriate to affect the tattoo. The immediate whitening reaction is the result of the generation of cavities due to rapid heating or energy transfer associated with laser exposure to the tattoo pigment particles. The skin cavities associated with whitening result in attenuation or scattering of the laser light, which leads to a loss of laser effectiveness after the initial treatment. Furthermore, the skin cavities remain in the skin over a period of time and limit the effectiveness of subsequent laser exposures in the same session.

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

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

[0020] The post-laser whitening reaction can subside after about 20 minutes or more after the last laser exposure. Such subsidence can be evidenced by the resolution of the superficial cavities, which is caused by the dissipation and absorption of the gas-containing cavity contents over time.

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

[0022] Currently, the main approach for tattoo removal is through the use of lasers. However, after a single laser treatment of the tattooed area, the laser becomes ineffective for the reasons described above. As a result, multiple sessions over several months are required to remove the tattoo using lasers.

[0023] There is a strong desire to accelerate the tattoo removal process. To do so, repeated laser treatments of the tattooed area on the same day have been pursued. One approach, called the R20 method, uses a laser to treat the tattooed area, and the laser treatments are separated by at least 20 minutes to allow the cavitation to be reabsorbed at the site (see, for example, 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 schedules, this approach is not practical as it requires the patient to be in the examination room for extended periods.

[0024] More recently, to overcome this problem, U.S. Patent Application No. 13 / 753,816 (the '816 application), also published as U.S. Patent No. 2013 / 0165839 (Patent Document 5), discloses the use of perfluorodecalin (PFD) to prevent or reduce the whitening caused by laser treatment of tattoos. The '816 application discloses that by using PFD on the affected skin, the lasers can be applied rapidly and continuously without waiting for 20 minutes.

[0025] PFD is a liquid, a colorless, inert compound with low surface tension and insoluble in blood and water. Unfortunately, PFD has very poor skin penetration. As a result, it is widely used in cosmetics. As a result, PFD is excellent at reducing depigmentation caused by vacuoles located superficially (e.g., at the epidermis-dermis boundary). However, due to its poor skin penetration, vacuoles that surround and shield previously treated intradermal pigment particles are not affected. Thus, PFD provides a benefit in reducing the appearance of depigmentation, but only a limited benefit in improving the effectiveness of repeated laser treatment of tattoo sites.

Prior Art Documents

Patent Documents

[0026]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Means for Solving the Problems

[0027] Embodiments of the method, apparatus, and system 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 aggregation), as well as vacuoles within the epidermis. The method, apparatus, and system can thereby enable more effective repeated laser treatment over a rapidly contiguous same treatment area.

[0028] Some embodiments of the present method (e.g., for acoustic therapy of tissue that disperses vacuoles within the tissue) include the steps of identifying the location of the tissue containing the vacuoles, coupling an acoustic wave generator to the tissue containing the vacuoles, and directing pulsed acoustic waves from the acoustic wave generator into the tissue containing the vacuoles.

[0029] In some embodiments of the present method, the tissue containing the vacuoles has been pre-treated using a laser.

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

[0031] In some embodiments of the present method, the laser treatment includes tattoo removal, laser skin resurfacing, laser removal of moles, 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 present method further include the step of treating the skin containing the vacuoles using a laser after directing pulsed acoustic waves from the acoustic wave generator into the tissue containing the vacuoles, and repeating the steps of directing and treating in an alternating manner for at least two repetitions in a single treatment session. In some embodiments, the step of treating the skin containing the vacuoles using a laser is performed within 10 minutes of the step of directing the pulsed acoustic waves. In some embodiments of the present method, at least two subsequent repetitions of the step of directing the pulsed acoustic waves are performed within 10 minutes or less.

[0033] Some embodiments of the system (e.g., a skin clearing system) include a pulsed acoustic wave generator configured to generate pulsed acoustic waves, direct the generated waves toward the skin, and clear epidermal and dermal cavities.

[0034] In some embodiments of the system, the generated acoustic waves have a frequency of from about 700 KHz to about 100 MHz.

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

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

[0037] In some embodiments of the system, the mechanical index MI of the generated wave is from about 0.15 to about 1.9.

[0038] In some embodiments of the system, the pulsed acoustic wave generator includes a high-speed pulsed electrohydraulic shock wave generator comprising 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 of from about 10 Hz to about 5 MHz.

[0040] In some embodiments of the present 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 such that the mechanical index (MI) is about 0.15 to 1.8.

[0041] In some embodiments of the present system, the high-speed pulsed electrohydraulic generator is set 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, and two items that are "coupled" can be integral with each other. The terms "a" and "an" are defined as one or more, unless the present disclosure explicitly requires otherwise. The term "substantially" is defined as "mostly" (and includes what is defined, e.g., substantially 90 degrees includes 90 degrees, and substantially parallel includes parallel), although not necessarily completely as understood by one of ordinary skill in the art. In any of the disclosed embodiments, the terms "substantially," "approximately," and "about" can be substituted with "within [a percentage]" of what is defined, including percentages of 0.1, 1, 5, and 10.

[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 conjunctive verbs. As a result, a system or apparatus that "comprises", "has", "includes", or "contains" one or more elements holds those one or more elements, but is not limited to holding only those elements. Similarly, a method that "comprises", "has", "includes", or "contains" one or more steps holds those one or more steps, but is not limited to holding only those one or more steps.

[0044] Furthermore, a structure (e.g., a component of an apparatus) configured in a certain way is at least configured in that way, but can also be configured in ways other than those specifically described.

[0045] Any embodiment of any of the systems, apparatuses, and methods herein need not comprise, include, contain, or have any of the steps, elements, and / or features described, but can instead consist of or consist essentially of them. Thus, in any of the claims, the terms "consisting of" or "consisting essentially of" can be substituted for any of the open-ended conjunctive verbs described above to change the scope of a given claim from what would otherwise be described using an open-ended conjunctive verb without limitation.

[0046] The embodiments described above and other related details are presented below.

[0047] The following drawings are illustrated by way of example, not limitation. For the sake of brevity and clarity, not all features of a given structure are always labeled in every drawing in which that structure appears. The same reference numerals do not necessarily refer to the same structure. Rather, the same reference numerals may be used to indicate features with similar characteristics or features with similar functionality that may be different reference numerals. The drawings are drawn to scale (unless otherwise noted), meaning that the sizes of the depicted elements are accurate relative to each other, at least for the embodiments depicted in the figures.

Brief Description of the Drawings

[0048]

Figure 1

[0049]

Figure 2

[0050]

Figure 2A

[0051]

Figure 2B

[0052]

Figure 2C

[0053]

Figure 3

[0054]

Figure 4

[0055]

Figure 5

[0056]

Figure 6

[0057]

Figure 7A

Figure 7B

[0058]

Figure 8

[0059]

Figure 9

[0060]

Figure 10

[0061]

Figure 11

[0062]

Figure 12A

Figure 12B

[0063]

Figure 13A

Figure 13B

[0064]

Figure 13C

[0065]

Figure 14

[0066]

Figure 15

[0067]

Figure 16

[0068]

Figure 17

[0069]

Figure 18

[0070]

Figure 19

DETAILED DESCRIPTION OF THE INVENTION

[0071] It should be understood that the drawings are not necessarily drawn to scale and that the disclosed embodiments may sometimes be illustrated schematically and in part views. In some instances, details that are not necessary for an understanding of the disclosed methods and apparatuses or that render other details less perceptible may be 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 system and apparatus 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 system can be used are incorporated herein in their entirety: (1) U.S. Patent Application No. 13 / 574,228, published as US 2013 / 0046207; (2) U.S. Patent Application No. 13 / 547,995, published as US 2013 / 0018287; (3) U.S. Patent Application No. 13 / 798,710, published as US 2014 / 0257144; and (4) disclosed in PCT / US2014 / 021746. The EH shock waves generated by the present system can be configured to impart sufficient mechanical stress to rupture the cells of the target tissue (e.g., through membrane degradation damage).

[0073] When a target cell (a cell of a target tissue) is exposed to the generated PR shock wave, the cell undergoes a steep gradient of mechanical stress due to spatial heterogeneity parameters of the cell such as the density and shear elastic modulus of different components of the cell. For example, the dense and / or inelastic components inside the cell are subjected to greater mechanical stress when exposed to the shock wave compared to the lighter components. In particular, the acceleration of higher density particles or components within the cell structure exposed to the collision surface is typically very large. At the same time, the collision of the shock wave with the lower density biological structures that make up the cell structure, when exposed to such a large gradient of pressure, significantly reduces the elasticity of the lower density biological structures as their elasticity generally causes them to act as low compliance materials. The difference in mechanical stress results in the movement of the dense and / or inelastic components within the cell.

[0074] When a cell is exposed to repetitive shock waves at a certain frequency and energy level, the dense and / or inelastic components are repeatedly moved until they break the cell and thereby cause the cell to rupture. In particular, the ability of the cell to experience property mismatches and deformations in the cell structure, when exposed to the collision surface, leads to cell destruction as described. One of the theories considered as a possibility to explain the phenomenon of cell structure rupture can be found in (Burov, V.A., 2002) [1], which is hereby incorporated by reference in its entirety.

[0075] As discussed by Burov [1], when a cell is collided by these pressure fronts, a steep gradient of mechanical stress can occur inside the cell as a result of the spatial heterogeneity parameters (i.e., density and shear elastic tensile stress) while the cell can oscillate as an integrated unit. This concept can be illustrated by modeling the biological structure as two connected balls with masses m1 and m2 and a density of the liquid oscillating around the balls at velocity μ o (t) that is slightly different from the density of the balls (ρ1 and ρ2 respectively). When only the resistance to the potential flow is considered, the force applied to the connection is calculated as shown in Equation (1).

Number

[0076] Equation (1) and additional discussion of its variables are further provided in [1]. For example, when the ball radius (R) is about 10 μm and the difference in the density of the ball is 0.1ρ0, 10 9 dyne / cm 2 of stress F / (πR 2 )m results. This is sufficient to rupture the cell membrane. Embodiments of the present device can be used to generate shock waves that, in a controlled manner, cause target damage to certain cells for medical and / or aesthetic treatment applications, which are further discussed below.

[0077] Another theory that can be considered as a possibility to explain the phenomenon of cell rupture is the accumulated shear stress in denser materials within the cell structure. In heterogeneous media such as cells with particles (e.g., pigment particles), shock waves disrupt the cell membrane by a progressive (i.e., accumulated) shearing mechanism. On the other hand, in homogeneous media, compression by shock waves causes minimal damage to the membrane, if any. As the shock wave passes through the heterogeneous medium, microscopically focusing and defocusing the shock wave can result in local enhancement or weakening of the shock wave, which leads to an increase in local shear. The relative shearing motion of the cell membrane occurs depending on the scale of heterogeneity of the cell structure. When the shock wave impinges on a region of heterogeneity (e.g., a cell containing particles), it is thought that the particle motion out of phase with the incident wave generates cell-destroying energy transfer (e.g., shear stress). The out-of-phase motion (e.g., shear stress) causes microscopic damage to the cell membrane and can progressively increase towards cell membrane rupture with the additional continuous accumulation of shear stress.

[0078] The progressive shearing mechanism of repeated exposure to shock waves can be regarded as the 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 in cells with heterogeneity to cause catastrophic cell membrane disintegration in specific applied strains, strain rates, and strain cycles, as compared to relatively more homogeneity.

[0079] Factor manipulation can be done by providing EH shock waves of 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 the tissue has too much time between shock waves to relax to its non-strained state, the cells will become resistant to disintegration. Thus, 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 cell structure so as to achieve the dynamic fatigue of the tissue and not give the tissue a relaxation time.

[0080] A third possible theory is that EH shock waves cause a combination of the direct movement of particles contained within the cell structure and the effect of dynamic fatigue that fractures the cell. Particle-containing cells are an obvious example of a cell structure with heterogeneity, but its description is not intended to limit the scope of the present disclosure. Instead, the embodiments disclosed herein can be used to fracture or cause damage to other cell structures with heterogeneity, such as cell structures having different effective density regions. The parameters of the shock waves generated in accordance with the disclosed aspects can be adjusted based on regions of different effective densities (i.e., heterogeneity) that cause cell damage at least as described herein. Heterogeneity can be a region within a single cell, a region of different types of cells, or a combination of both. In one embodiment, the region of heterogeneity within the cell includes a region having an effective density that exceeds 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 contains particles within the cell having an effective density greater than that of, for example, graphite with a density of 2.25 g / cm 3 and greater than 1.09 g / cm 2 In certain embodiments, the regions of intercellular heterogeneity will include regions with different types of cells, each cell type having a different effective density, such as fibroblasts and adipocytes or hair follicles. Further examples of cell structures containing heterogeneity are provided below in the present disclosure.

[0081] Referring now to the drawings, and more particularly to FIG. 1, a block diagram of one embodiment of the apparatus or system for generating shock waves electrohydraulically in a controlled manner is shown therein and designated by reference numeral 10. In some embodiments, such as those shown, system 10 includes a handheld probe (e.g., with a first housing as shown in FIG. 2) and a separate controller or pulse generation system (e.g., within or with a second housing coupled to the handheld probe via a flexible cable or equivalent). In other embodiments, the 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 shock wave outlet 20, a liquid (54) disposed within chamber 18, a plurality of electrodes (e.g., within a 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 of 10 Hz to 5 MHz. In this embodiment, the capacitance / inductive coil system 26 is configured to apply voltage pulses to the electrodes such that a portion of the liquid is vaporized and the shock wave propagates through the liquid and out the shock wave outlet.

[0083] In the illustrated embodiment, the pulse generation system 26 is configured for use with an alternating current power source (e.g., a wall outlet). For example, in this embodiment, the pulse generation system 26 includes a plug 30 configured to be inserted into a 110V wall outlet. In the illustrated embodiment, the pulse generation system 26 includes a capacitance / inductance coil system, an example of which is described below with reference to FIG. 6. In other embodiments, the pulse generation system 26 may include any suitable structure or component configured to periodically apply a high voltage to an electrode to generate an electrical spark of sufficient power to evaporate a liquid in an individual spark gap, as described in this disclosure.

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

[0085] In the illustrated embodiment, a liquid 54 (e.g., a dielectric liquid such as distilled water) is disposed within chamber 18 (e.g., substantially filling chamber 18). In this embodiment, the spark head 22 is positioned within chamber 18 and surrounded by the liquid such that the electrodes can receive voltage pulses from the pulse generation system 26 (e.g., at a rate of 10 Hz to 5 MHz) so that a portion of the liquid is vaporized and the shock wave propagates through the liquid and out through the shock wave outlet 20. In the illustrated embodiment, the 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 a liquid 62 (e.g., of the same type as liquid 54) and has a length 66 sufficient to allow the shock wave to form and / or be directed toward outlet 20. In some embodiments, the length 66 may be from 2 millimeters (mm) to 25 millimeters (mm). In the illustrated embodiment, chamber 18 and acoustic delay chamber 58 are separated by a layer of anechoic (acoustically permeable or transmissive) 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 the non-linearity of the acoustic behavior of liquid 54 to increase the formation of the shock wave. In further embodiments, chamber 18 and acoustic delay chamber 54 may be integral (i.e., may 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 illustrated embodiment, the probe 38 further includes an outlet member 70 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 be removed, sterilized, or exchanged between patients. Member 70 includes a polymer or other material (e.g., low density polyethylene or silicone rubber) that is acoustically permeable to allow the shock wave to exit acoustic delay chamber 58 through outlet 20.The tissue 74 can be, for example, human skin tissue to be treated by the apparatus 10 and can include, for example, tattoos, stains, subcutaneous lesions, or basal cell abnormalities. In some embodiments, an acoustic coupling gel (not shown) can be disposed between the member 70 and the tissue 74 so as to lubricate and provide additional acoustic transmission into the tissue 74.

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

[0087] In FIG. 1, a human eye 86 is shown for a user visually recognizing a target tissue through a window 82, but it should be understood that the target tissue can be "visually recognized" through the window 82 via a camera (e.g., a digital still and / or video camera). By direct or indirect observation, according to the target tissue such as existing tattoos, etc., and by adapting the acoustic energy such as a change in the color of the tissue, the acoustic energy can be positioned, applied, and repositioned. However, when the spark head 22 is placed where the user can view the spark head 22, the resulting spark luminance from the spark head 22 may be too bright for the user to view comfortably. In the illustrated embodiment, the probe 38 is configured such that a plurality of electrodes are not visible to a user visually recognizing an area (e.g., the target tissue) through the window 82 and the outlet 20. For example, in the illustrated embodiment, the probe 38 includes an optical shield 90 disposed between the spark head 22 and the window 82. The shield 90 is large enough to substantially block the light from the spark head 22 that travels directly to the user's eye, but does not interfere with the field of view through the window 82 and the outlet 20 more than necessary to block that light. The shield 90 can have, for example, a width and / or length smaller than the corresponding width and / or length of the window 82. The shield 90 can include, for example, a thin sheet of metal such as stainless steel or other opaque material, or a welding glass (e.g., an LCD darkened by a photocell or other photosensitive material) that is optically activated and darkened by the spark luminance in the spark gap. To maintain the point source from the spark head 22 and the resulting desired planar waveform effect, the acoustic effect of shielding the spark resulting from the spark gap head must be considered. If the shield 90 includes an acoustic reflective material to prevent pulse spreading, the distance between the shield and the spark gap between the electrodes in the spark head 22 is selected to minimize (e.g., at least destructive) interference between the sound waves and / or shock waves reflected from the shield and the spark head 22 resulting from the spark from the spark head 22.At the speed of sound waves in a medium such as distilled water of about 1,500 m / s, the distance between the spark head and the shield can be calculated to be at 1 / 2 and 3 / 4 wavelengths from the source of generation.

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

[0089] FIG. 2 depicts a cross-sectional side view of a second embodiment 38a of the handheld probe or handpiece for use with some embodiments of the present EH shock wave generation system and apparatus. The probe 38a is substantially similar to the probe 38 in some respects and thus the differences will mainly be described here. For example, the probe 38a is also configured such that the plurality of electrodes of the spark head or module 22a are not visible to the user viewing the area (e.g., of the target tissue) through the window 82a and the outlet 20a. However, rather than including an optical shield, the probe 38a is configured such that the spark head 22a (and the electrodes of the spark head) is offset from the optical path extending through the window 82a and the outlet 20a. In the present embodiment, an acoustic mirror 78a is positioned between the spark head 22a and the outlet 20a as shown so as to define the boundary of the chamber 18a and direct acoustic waves and / or shock waves from the spark head 22a to the outlet 20a. In the illustrated embodiment, the acoustic mirror 78a is disposed between the window 82a and the chamber 18a such that the window 82a can include a polymer or other acoustically permeable or transmissive material since acoustic waves and / or shock waves do not impinge directly on the window 82a (i.e., since acoustic waves and / or shock waves are mainly reflected by the acoustic mirror 78a).

[0090] In the embodiment shown, the spark head 22a includes a plurality of electrodes 100 that define a plurality of spark gaps. The use of a plurality of 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 has evaporated an amount of liquid within a spark gap, the vapor must either return to its liquid state or be displaced by a different portion of the liquid that remains in the liquid state. In addition to the time required for the spark gap to be refilled with water before a subsequent pulse can evaporate additional liquid, the spark also heats the electrodes. Thus, for a given spark rate, increasing the number of spark gaps reduces the rate at which each spark gap must be fired, thereby extending the life of the electrodes. Thus, ten spark gaps potentially increase the possible pulse rate and / or electrode life tenfold.

[0091] As described above, a high pulse rate can generate a large amount of heat that can increase fatigue on the electrodes and / or increase the time required for the vapor to return to the 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, the probe 38 includes conduits 104 and 108 that extend from the chamber 18a to individual connectors 112 and 116, as shown. In this embodiment, the connectors 112 and 116 can be coupled to a pump to circulate a liquid through the chamber 18a (e.g., and through a heat exchanger). For example, in some embodiments, the pulse generation system 26 (FIG. 1) can include a pump and a heat exchanger that are in series and configured to be coupled to the connectors 112 and 116 via conduits or the like. In some embodiments, a filter can be included within the 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] In addition, due to the limited lifespan of the electrode 100 at high pulse rates, some embodiments of this probe may be disposable. Alternatively, some embodiments are configured to allow the user to replace the electrode. For example, in the embodiment of FIG. 2, the spark head 22a is configured to be removable from the probe 38a. For example, the spark head 22a may be removable through the handle 50a, or the handle 50a may be removably coupled to the head 46a (e.g., via threads or the like) such that the spark head 22a can be removed from and replaced with the head 46a in response to the removal of the handle 50a from the head 46.

[0093] As shown in FIG. 2, the application of each shock wave to the target tissue includes a waveform 118 that propagates from the outlet 20a and travels outwardly through the tissue 74. As shown, the waveform 74 is curved as it moves outwardly, in accordance with its expansion, and in part in accordance with 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 so as to affect the nature of the waveform as it passes through the outlet 20a and propagates through the target tissue.

[0094] Figure 2A depicts an enlarged cross-sectional view of a first embodiment of a removable spark head or module 22a. In the embodiment shown, the spark head 22a includes sidewalls 120 that define a spark chamber 124 and a plurality of electrodes 100a, 100b, 100c disposed within the spark chamber. In the embodiment shown, the spark chamber 124 is filled with a liquid 128 that may be similar to the liquid 54 (FIG. 1). At least a portion of the sidewalls 120 comprises an acoustically permeable or transmissive material (e.g., a polymer such as polyurethane) configured to allow sound waves and / or shock waves generated by the electrodes to travel through the sidewalls 120 and through the chamber 18a. For example, in the embodiment shown, the spark head 22a may include a cup-shaped member 132 configured to be an acoustically reflective and acoustically permeable cap member 136. In this embodiment, the cap member 136 is dome-shaped so as to approximate the curved shape of the expanding waveform generated from the electrodes and to compress the skin when a moderate pressure is applied. The cap member 136 can be coupled to the cup-shaped member 132 using an O-ring or gasket 140 and a retaining collar 144. In the embodiment shown, the 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-type pins 148, 152 configured to lock the position of the spark head 22a relative to the probe in alignment with corresponding grooves within the head 46a of the probe 38a (FIG. 2).

[0095] In the illustrated embodiment, the electrode core 156 has conductors 160a, 160b, 160c, extends through the opening 164, and involves an interface between the opening 164 sealed by the grommet 168 and the electrode core 156. In the illustrated embodiment, the central conductor 160a extends through the center of the core 156 and serves as a ground to the corresponding central electrode 100a. The peripheral conductors 160b, 160c communicate with the surrounding electrodes 100b, 100c so as to generate a spark across the spark gaps between the electrodes 100a and 100b and between the electrodes 100a and 100c. Although two spark gaps are shown, it should be understood that any number of spark gaps can be used and can 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] Figure 2B depicts an enlarged side view of a second embodiment of a removable spark head or module 22b. In the embodiment shown, the spark head or module 22b includes sidewalls 120a that define a spark chamber 124a and a plurality of electrodes 100d-1, 100d-2, 100, 100f disposed within the spark chamber. In the embodiment shown, the spark chamber 124a is filled with a liquid 128a that may be similar to liquid 128 and / or 54. At least a portion of the sidewalls 120a includes an acoustically permeable or transmissive material (e.g., a polymer such as polyurethane) configured to allow sound waves and / or shock waves generated by the electrodes to travel through the sidewalls 120a and through the chamber 18a (FIG. 2). For example, in the embodiment shown, the spark head 22b may include a cup-shaped member 132a configured to be an acoustically reflective and acoustically permeable cap member 136a. In this embodiment, the cap member 136a is dome-shaped to approximate the curved shape of the expanding waveform generated by the electrodes and to compress the skin when a moderate pressure is applied. The cap member 136a can be coupled to the cup-shaped member 132a using an O-ring or gasket (not shown but similar to 140) and a retaining collar 144a. In the embodiment shown, the 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 may also include bionet-type pins (not shown but similar to 148, 152) configured to lock the position of the spark head 22b relative to the probe in alignment with corresponding grooves within the head 46a of the probe 38a.

[0097] In the embodiment shown, conductors 160d, 160e, 160f extend through the rear portion of side wall 132a (opposite the outlet cap member 136a) as shown. In this embodiment, the center conductor 160b and the peripheral conductors 160a, 160c can be molded into the side wall 120a such that grommets and the like are not necessary to seal the interface between the side wall and the conductors. In the embodiment shown, the center conductor 160d serves as a ground to the corresponding center electrodes 100d-1 and 100d-2, which are also in electrical communication with each other. The peripheral conductors 160e, 160f are in communication with the surrounding electrodes 100e, 100f so as to generate a spark across the spark gaps between the electrodes 100d-1 and 100e and between the electrodes 100d-2 and 100f. Although two spark gaps are shown, it should be understood that any number of spark gaps can be used and can 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 illustrated embodiment, the central electrodes 100d-1 and 100d-2 can be carried by and integral with an extension member 172 that extends into the chamber 124a from the sidewall 120a toward the cap member 136a. In this embodiment, the member 172 is mounted to a hinge 176 (fixed to the sidewall 120a) such that the distal ends of the members adjacent to the electrodes 100d-1, 100d-2 can pivot back and forth between the electrodes 100e and 100f as indicated by the arrow 180. In the illustrated embodiment, the distal portion of the member 172 is biased toward the electrode 100e by a spring arm 184. In this embodiment, the spring arm 184 is configured to position the electrode 100d-1 at an initial spark gap distance from the electrode 100e. In response to the application of a potential (e.g., via a pulse generation system as described elsewhere in this disclosure) across the electrodes 100d-1 and 100e, a spark will arc between these two electrodes to emit an electrical pulse to vaporize the liquid between these two electrodes. The expansion of the vapor between these two electrodes drives the member 172 and the electrode 100d-2 downward toward the electrode 100f. When the distance between the electrodes 100d-2 and 100f becomes small enough during the period that the member 172 travels downward, a spark arcs between these two electrodes, and the pulse generation system can recharge and apply a potential between the electrodes 100d-2 and 100f to emit an electrical pulse to vaporize the liquid between these two electrodes. The expansion of the vapor between the electrodes 100d-2 and 100f then drives the member 172 and the electrode 100d-1 upward toward the electrode 100e. When the distance between the electrodes 100d-1 and 100e becomes small enough during the period that the member 172 travels upward, a spark arcs between these two electrodes, and the pulse generation system can recharge and apply a potential between the electrodes 100d-1 and 100e to emit an electrical pulse to vaporize the liquid between these two electrodes and restart the cycle. In this way, the member 172 oscillates between the electrodes 100e and 100f until the potential is no longer applied to the electrodes.

[0099] Exposure to high-speed and high-energy electrical pulses, especially in a liquid, subjects the electrodes to rapid oxidation, erosion, and / or other degradation that can vary the spark gap distance between the electrodes when the electrodes are held in a fixed position (e.g., requiring the electrodes to be exchanged and / or adjusted). However, in the embodiment of FIG. 2B, the pivoting of the members 172 between the electrodes 100e and 100f and the electrodes 100d-1, 100d-2 effectively adjusts the spark gap for each spark. Specifically, the distance between the electrodes across which current arcs is a function of the electrode material and potential. Thus, when the closest surfaces of adjacent electrodes (e.g., 100d-1 and 100e) reach the spark gap distance of a given embodiment (even if eroded), a spark is caused to occur between the electrodes. Accordingly, the member 172 is configured to self-regulate the respective spark gaps between the electrodes 100d-1 and 100e and between the 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, multiple coils are not 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 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 like), and the properties of spring arm 184 (e.g., spring constant, shape, length, and / or the like) 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 advantages of such a movable electrode as shown in FIG. 2B, the properties of the electrode (e.g., shape, cross-sectional area, depth, and the like) can be configured so that the spark head 22b becomes inoperable or has limited effectiveness after a specified useful life, such as achieving a known effective or useful life of the spark head (e.g., one 30-minute treatment). Such features can be useful, for example, to ensure that a new sterilized spark head is used for each patient or area being treated, such as to minimize potential secondary contamination between patients or areas being treated, etc., to ensure that the spark head is discarded after a single treatment.

[0102] FIG. 2C depicts an enlarged cutaway side view of a third embodiment of a removable spark head or module 22c. The spark head 22c is substantially similar to the spark head 22b except as described below, and thus like reference numerals are used to designate the structure of the spark head 22c that is similar to the corresponding structure of the spark head 22b. The main difference with respect to the spark head 22b is that the spark head 22c includes a beam 172a that does not have a hinge so that the deflection of the beam itself provides upward or downward movement of the electrodes 100d-1 and 100d-2 as indicated by the arrow 180, as described above with respect to the spark head 22b. In this embodiment, the resonant frequency of the spark head 22c depends in particular on the physical properties of the beam 172a (e.g., mass, stiffness, cross-sectional shape and area, length, and / or the like). The beam 172a is configured to be biased toward the electrode 100e so that the electrode 100d-1 is initially positioned at an initial spark gap distance from the electrode 100e, as described with respect to the spring arm 184 of the spark head 22b. The function of the spark head 22c is similar to that of the spark head 22b except that the beam 172a itself bends to provide some resistance to movement so that the hinge 176 and spring arm 184 are not necessary.

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

[0104] In this embodiment, pulse rates from several Hz to several KHz (e.g., up to 5 MHz) can be employed. Since fatigue events generated by multiple pulses or shock waves are generally cumulative at higher pulse rates, rather than using several high-power shock waves separated by long durations of rest, the treatment time can be significantly reduced by using shock waves of moderate output that are rapidly consecutive. As described above, at least some of the embodiments of the present disclosure (e.g., embodiments with multiple spark gaps) enable faster electrohydraulic generation of shock waves. For example, FIG. 3A depicts an enlarged timing diagram showing only two sequences of voltage pulses applied to the electrodes of this embodiment, and 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, a portion of the individual sidewalls (120, 120a, 120b) may be omitted or left open such that liquid in a larger chamber of the corresponding handpiece (e.g., 18 or 18a) can freely circulate between the electrodes, also omitting the individual spark chambers (124, 124a, 124b). In such embodiments, the spark chambers (e.g., sidewalls 120, 120a, 120b) can include liquid connectors, or the liquid can circulate through fluid ports independent of 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 that are timed with the intervening delay period 212. A burst or group (e.g., 204, 208) can include as few as one or two, or as many as thousands of pulses. Generally, each group 204, 208 can include several voltage pulses that are applied to the electrodes to trigger an event (i.e., a spark that traverses 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 recharge of the electronics. As used in embodiments of the present disclosure, the pulse rate refers to the rate at which groups of voltage pulses (each having one or more pulses) are applied to the electrodes, and individual pulses within a pulse group having two or more pulses are applied at a higher frequency, as illustrated in FIGS. 3A - 3B. Each of these pulse groups can be configured to generate one shock wave or a plurality of shock waves.

[0107] A series of events (sparks) initiated by the plurality of bursts or groups 204 and 208 delivered using the present system and apparatus can have a higher pulse rate (PR) that can shorten the treatment time for a lower pulse rate that may need to be applied over several minutes. Tattooing, for example, can cover a large area and thus takes time to treat unless rapid cell destruction (e.g., at the higher pulse rates of the present disclosure) is achieved. 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 over 5,000 pulses per second (e.g., greater than 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, or between any two of them).

[0108] Figure 4 depicts a waveform that can be emitted into a volume of tissue by either probe 38 or 38a and may be useful for tattoo removal. Pulse 300 is of a typical shape for an impulse, generated by this EH spark head with a relatively high voltage pulse. For example, pulse 300 has a rapid rise time, a short duration, and a ringdown period. The unit of the vertical axis V a is arbitrary so as to be displayable on an oscilloscope. The actual acoustic pulse amplitude can be as low as about 50 μPa and as high as several MPa in various embodiments of the present invention, since at least the cumulative energy delivery can be effective as discussed above. Each of the individual time periods 304 may correspond to a short pulse length, which in the art is referred to as a "shock wave" pulse, due to their sharpness and short rise and fall times, and may be 100 nanoseconds. For example, a rise time of <30 nanoseconds is considered a shock wave for the purposes of the present disclosure and the velocity is particularly effective for generating a relatively large pressure - time pressure gradient across small cell - scale structures within tissue (e.g., the dermis). In practice, the rapid compression and decompression of the dermal structure containing the tattoo "ink", which is actually particulate content, results in the fatigue and destruction of pigment - containing cells over time and is considered one of the fundamental mechanisms of the present method as described above. For example, agitation of tissue using such shock waves has been shown to be effective when applied at a high pulse rate within a relatively short time period and at an energy level sufficient to break 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 that a short pulse waveform 300 having a plurality of applications, preferably hundreds to millions of times, is necessary to generate the fatigue required for tattoo "ink" removal over the area being treated.

[0109] Figure 5 depicts a schematic view 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 a plurality of 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 that is allowed to flow through each coil, similar to an aspect of an automotive ignition system. Each of resistors 408a, 408b, 408c can comprise a dedicated resistor or the length and nature 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 against custom components. In the embodiment shown, circuit 400 includes a 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) that cooperates with a plurality of surrounding electrodes. It should be understood that this circuit can be coupled to surrounding 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 embodiment shown, each circuit is configured to function similarly. For example, coil 404a is configured to collect and store current over a short duration such that when the circuit is interrupted by switch 420a, the magnetic field of the coil collapses, generating a so-called electromotive force or EMF that results in a rapid discharge of capacitor 424a across spark gap 412a.

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

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

[0112] Embodiments of the method include positioning an embodiment of the device (e.g., 10, 38, 38a, 500) adjacent to an area of a patient that includes target cells (e.g., tissue 74), and activating a spark generation (e.g., capacitive / inductive coil) system (e.g., 26, 400) to propagate shock waves to the target cells. In some embodiments, the area is visible through a window (e.g., 82, 82a) while the device is being positioned and / or while shock waves are being generated and delivered to the area. 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 generation system.

[0113] Still other embodiments of the present method eliminate the dermal cavities formed when the skin is treated using a laser. Such a method may include treating a tissue piece using a laser that forms dermal cavities, and treating the cavity-containing tissue using an acoustic wave generator that applies high-speed pulsed acoustic waves to the skin at a frequency, pulse rate, and intensity that destroys and disperses the dermal cavities. These embodiments of the described systems and methods for skin clearing of dermal cavities utilize acoustic mechanical effects to induce fragmentation of the cavities 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 cavity-containing tissue; and directing pulsed acoustic waves from the acoustic wave generator into the cavity-containing tissue. Directing pulsed acoustic waves into the cavity-containing tissue will initiate an acoustic mechanical effect on the cavities that results in fragmentation of the cavities and absorption of the cavity contents into the surrounding tissue. This cavity fragmentation and absorption leads to skin clearing.

[0114] In some embodiments of the method and system, the acoustic wave generator may comprise an ultrasonic generator or a shock wave generator. In some embodiments, the acoustic wave generator can be configured to generate pulsed acoustic waves with a frequency of from 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 from 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 system described is set such that the mechanical index is about 0.15 to 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. The 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 ultrasonic frequency. In some embodiments, the output of the system described is set such that the peak pressure output is 0.8 MPa to 20 MPa.

[0119] In an embodiment, the acoustic wave is generated from a high-speed pulsed electrohydraulic (EH) shock wave generator or a megasonic wave generator. In some embodiments, the disclosed system for electrohydraulic generation of shock waves includes a housing that defines a chamber and a shock wave outlet, a liquid disposed within the chamber, a plurality of electrodes (e.g., within 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 to 9.0 MHz, a pulse duration of 1 nanosecond to 1 microsecond, a pulse rate of 50 Hz to 500 Hz, and a power such that the mechanical index (MI) is 0.15 to 1.9.

[0121] Other embodiments of the present method for high-speed laser-based tattoo removal include treating tattooed skin with a laser and then treating the tattoo site with an acoustic wave generator. The acoustic wave generator applies high-speed pulsed acoustic waves to the skin at a frequency, pulse rate, and intensity that disrupt and disperse intracutaneous cavities. These embodiments enable and are effective in performing repeated laser treatments rapidly and continuously over the same treatment area, which was not possible with prior art methods.

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

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

[0124] (Experimental results) Experiments were conducted on Göttingen minipigs to observe the effect of high-speed pulsed acoustic waves generated by an acoustic wave generator on laser-treated skin, which was intended to eliminate intracutaneous cavities. The study was conducted to demonstrate the elimination of "whitening" caused by intracutaneous cavities as a result of laser treatment using a high-speed pulsed electrohydraulic (EH) shock wave generator.

[0125] The high-frequency shock waves generated by certain embodiments of the present disclosure and the controlled, predictable manner in which they are generated have many applications, but certain embodiments of the present disclosure and the generated shock waves are particularly useful in therapeutic applications. Specifically, they are useful in eliminating skin cavities of a patient formed from laser skin treatment.

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

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

[0128] FIG. 9 depicts a schematic of an electronic circuit for a prototype pulse generation system used with the spark chamber housing of FIGS. 7A - 7B in the present 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 relaxation discharge mode using embodiments of the present shock wave head (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 transformer having 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 are each protected by a pair of parallel resistors (100 kΩ and 25 kΩ) that together temporarily store high - voltage energy and charge a pair of 25 mF capacitors polarized in opposite directions. When the impedance of the shock wave chamber is low and the voltage charge is high, discharge is initiated with the aid of an ionization switch, which is a large spark gap that conducts when a threshold voltage is achieved. Since positive and negative voltages flow to each of the electrodes, the potential between the electrodes can be up to about 6 kV or 6,000 V. The resulting spark between the electrodes causes partial evaporation of the liquid into a rapidly expanding bubble, which generates a shock wave. During the spark, the capacitor discharges and prepares for re - charging by the transformer and rectifier. In the experiments described below, the discharge is at about 30 Hz and is adjusted only by the natural charging and discharging rates (hence the term “relaxation oscillation”). In other embodiments, the discharge rate can be higher (e.g., up to about 100 Hz for the multi - gap configuration of FIG. 5, etc.).

[0129] Further embodiments of the present EH shock wave generation system and apparatus are depicted in FIGS. 11-13C. Probe 38b is similar to probes 38 and 38a in several respects, and thus the differences will mainly be described here. In this embodiment, probe 38b comprises a housing 14b that defines a chamber 18b and a shock wave outlet 20b, a liquid (54) disposed within chamber 18b, and a plurality of electrodes disposed within the chamber and configured to define one or more spark gaps (e.g., within a spark head or module 22d), and is configured to be coupled to a pulse generation system 26 configured to apply voltage pulses to the electrodes at a rate of 10 Hz to 5 MHz.

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

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

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

[0133] FIG. 15 depicts a cross-sectional view of an embodiment of an ultrasonic generator probe. In one embodiment, the power cable 1507 is attached to the proximal end of the metal outer casing 1501. The casing 1501 may include a sound insulation material 1506, a backing block 1502, a piezoelectric crystal 1504, and an electrode 1503 that applies an alternating 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 equivalents that contain aggregates of ink particles. Since the captured ink particles are denser than the biological structure of the cells, the tattoo or the cells containing the ink particles have a large difference in elasticity in their structure. When exposed to shock waves, the cells containing the ink particles undergo greater mechanical strain compared to other cells that do not contain the dense particles. The shock waves can be delivered at an optimal frequency and amplitude sufficient to rupture specific cells while leaving intact fibroblasts that do not have a specific elastic difference, and configured to accelerate the ink particles. The details of the biological process of removing the particles released from the tattoo and the cells are further discussed below.

[0135] Tattooin inks and dyes have historically been derived from substances found in nature and generally contain a heterogeneous suspension of colored particles and other impurities. One example is ink that contains a suspension of carbon particles in a liquid such as water. Tattoos are generally brought about by applying tattoo ink into the dermis, and the ink generally remains substantially permanently. This technique, in combination with the up-and-down movement of the tattoo needle, introduces the pigment suspension through the skin by the alternating pressure-suction action caused by the elasticity of the skin. Water and other carriers for the pigments introduced into the skin diffuse through and are absorbed by the tissue. In most cases, 20% to 50% of the pigment is dispersed into the body. However, the remaining portion of the insoluble pigment particles is deposited in the dermis where it is left. In tattooed skin, the pigment particles are generally phagocytosed by cells, resulting in pigment aggregates in the cytoplasm of the cells (i.e., within membrane-bound structures known as secondary lysosomes). The resulting pigment aggregates (“particle aggregates”) can reach diameters of up to several micrometers. When the skin heals, the pigment particles remain in the interstitial cavity of the skin tissue within the cells. Tattoo ink is generally difficult to eliminate due to the immobility of cells caused by a relatively large amount of insoluble pigment particles in the cells. Tattoos can fade over time but generally will remain for the lifetime of the tattooed person.

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

Table 1

[0137] (B. Tattoo Removal) In traditional tattoos (for decoration, beauty, and reconstruction), as described above, the pigment or dye is administered into the dermis and, once the tattoo is formed, the pigment or dye generally remains permanently in place.

[0138] Despite the general permanence of tattoos, an individual may change their mind and desire tattoo removal for various reasons. For example, over time, people's moods may change (or they may reevaluate), and they may desire to remove or modify the design of a decorative tattoo. As another example, an individual with cosmetic tattoos such as eyeliner, eyebrows, or lip coloring may desire to change the tattooed color or area as fashion changes. Unfortunately, currently, there is no simple and successful method for removing tattoos. Currently, methods for removing traditional tattoos (e.g., pigment-containing skin) may include salt abrasion, cryosurgery, surgical excision, and CO2-lasers. These methods require invasive procedures associated with potential complications such as infections and can usually result in significant scarring. More recently, the use of Q-switched lasers has been widely accepted for tattoo removal. By limiting the pulse duration, the 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 results after non-selective tattoo removal methods such as dermabrasion or treatment with a carbon dioxide laser. The mechanism of tattoo removal by Q-switched laser irradiation may still have many unknowns. The Q-switched laser is thought to enable more specific removal of tattoos through mechanisms of selective photothermolysis and thermodynamic selectivity. Specifically, it is thought that pigment particles within the cells can absorb the laser light, causing heating of the particles and potentially 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 through normal absorption processes.

[0139] Q - switched lasers may be superior to some alternatives for tattoo removal but are not perfect. Some tattoos resist all laser therapies, despite the predicted high particle temperatures achieved through selective photo - thermolysis. To be clear, reasons cited for the breakdown of some tattoos include the pigment absorption spectrum, pigment depth, and the structural properties of some inks. Adverse events following laser tattoo treatment with Q - switched ruby lasers can include skin texture changes, scarring, and / or pigmentary alterations. Transient hypopigmentation and skin texture changes have been reported in up to 50 and 12% of patients treated with Q - switched alexandrite lasers, respectively. 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 when using ruby lasers. The onset of local and systemic allergic reactions is also an intractable (albeit rare) complication of tattoo removal with Q - switched ruby and Nd:YAG lasers. In addition, laser treatment can be painful, such that the use of local injection with lidocaine or topical anesthetic creams is typically required prior to laser treatment. Finally, laser removal generally requires multiple treatment sessions (e.g., 5 - 20), and expensive equipment for maximal clearance may be required. Typically, since multiple wavelengths are needed to treat multicolored tattoos, no single laser system can be used to remove all available inks and ink combinations. Even with multiple treatments, laser therapy can only remove 50 - 70% of tattoo pigments and can result in residual staining.

[0140] When investigating the effect of conventional laser tattoo removal, experiments showed that initial QS laser treatment to both control and test black tattoo sites produced a sharp snapping sound when the tattoo sites were pulsed with the laser. In addition, each laser pulse to the untreated tattoo area produced immediate “whitening” on the black tattoo site.

[0141] A Göttingen minipig, having a mass of approximately 30 Kg and pre - tattooed, was anesthetized. The control and test sites consisting of black tattoo were treated using a QS laser (1,054 wavelength, 5 Hz, 5 mm spot size, 1.1 W output). Immediately after the laser treatment, the test site was treated using a high - speed pulsed electrohydraulic shock wave generator (as described in US2014 / 021746) for 2 minutes. The EH shock wave generator produced planar shock waves with peak pressures of 2 MPa - 3.5 MPa at a pulse rate of 50 Hz. After the high - speed pulsed EH shock wave treatment, the control and test sites were treated again using the QS laser. The test site was then treated again using the high - speed pulsed EH shock wave generator. This treatment protocol was repeated once more so that the control and test sites were treated a total of 3 times using the QS laser. In the test site, high - speed pulsed EH shock wave treatment followed each QS laser treatment. After all the treatments, each tattoo was biopsied for histological examination.

[0142] (Method) Regarding the test site, the step of applying EH shock wave treatment for 2 minutes resulted in the return of the tattoo color and the loss of "whitening". During this time period, no dissipation of "whitening" in the control site was observed. Further, when the second laser pulse was applied to the test site treated with the EH generator, the laser pulse again produced a sharp snapping sound and an immediate and substantial "whitening" of the black tattoo site. The step of applying the second laser pulse to the already "whitened" control site resulted in a dull sound along with only a slight additional "whitening". The results of the third laser treatment using the EH shock wave were similar to the first two times.

[0143] Visual and auditory findings provided evidence that the acoustic waves were able to eliminate dermal cavities. This provided the ability to repeat laser treatment at the tattoo site. Visually, the elimination of skin "whitening" accompanied by the return of color at the black tattoo site indicated that the dermal cavities that resulted in ineffective repeated laser performance were eliminated.

[0144] Regarding the site treated with EH, the laser pulse to the pre-treated test tattoo site again resulted in a sharp snapping sound. This indicates that the laser light was able to reach the black tattoo pigment again, resulting in a snapping sound caused by micro-explosions from overheated pigment. In contrast, the laser pulse to the pre-treated control tattoo site resulted in only a dull sound. This indicates 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 micro-explosions.

[0145] Examples of laser skin treatments that produce 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 assisted 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 can be caused by non-thermal cell membrane degradation of specific cells, following a non-linear process associated with the propagation of high-frequency shock waves, as discussed above.

[0146] Some general embodiments of the method include delivering a plurality of generated shock waves (e.g., via one or more of the devices of the present apparatus) to at least one skin vacuole having at least one region of inhomogeneity until at least one skin vacuole ruptures or disperses. In some embodiments, the shock waves are delivered for only 30 minutes over a 24-hour period. In some embodiments, the shock waves are delivered for only 20 minutes over a 24-hour period. In some embodiments, 200 to 5,000 shock waves are delivered at each of a plurality of positions of the shock wave outlet in 30 seconds to 20 minutes.

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

[0148] FIGS. 17 and 18 provide tissue images of biopsies taken from the control site and the test site, respectively, after completion of the study. More specifically, FIG. 17 depicts a control black tattoo site treated three times using only laser treatment. As can be seen from FIG. 17, the control site had a significant amount of microbubbles both at the epidermal-dermal junction and around the black tattoo pigment population. Under current understanding, the vacuoles at the epidermal-dermal junction 1701 are, visually, the main cause of the "whitening" seen after laser treatment. However, more importantly, the vacuoles around the pigment particles 1702 in the dermis are probably another cause of laser ineffectiveness due to repeated laser treatment.

[0149] FIG. 18 depicts a test black tattoo site treated three times using laser treatment along with an accompanying high-speed pulsed shock wave treatment. FIG. 18 shows significant evidence of decolorized pigment 1801, indicating that the black pigment particles were successfully treated by the laser. In addition, FIG. 18 depicts a portion of the tissue that contains minimal vacuoles 1802 as compared to the corresponding tissue from the control site in FIG. 17. This result provides conclusive evidence that "whitening" from laser-treated tattoo sites can be minimized, enabling repeated treatment of tattoo sites in a single session.

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

[0151] (C. Use of Acoustic Waves on Intradermal Vacuoles) Acoustic waves have been previously used for the destruction of contrast agent 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 deliver, Physics of Fluid 17, 100603 (2005)). The destruction of these bubbles is typically the result of rupturing the encapsulating membrane, which allows for the diffusion of gas into the body.

[0152] These contrast agent microbubbles and 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 thought to be less stable due to stronger diffusion. Despite the small size of the contrast agent microbubbles, significant destruction of the bubbles takes 4 to 10 minutes depending on the acoustic pressure used.

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

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

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

[0156] For example, such additional laser-based treatments that would benefit from embodiments of the system and method may include laser skin resurfacing, laser removal of moles, 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 method or system may be implemented include a system or method that uses 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 freckles, café-au-lait spots, lentigines, and / or dermal pigmented lesions.

[0158] In other embodiments, the method and system may be used during laser skin resurfacing, including medium-depth non-ablative skin resurfacing and / or wrinkle and acne scar non-ablative skin resurfacing. 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 method and system 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 removal using a Q-switched laser, laser treatment of vascular lesions using a Medlite TM laser from Hoya ConBio, or implementing the method and system in laser lip whitening using a Q-switched 532 nm laser.

[0160] The above specifications and examples provide an explanation of the structure and use of exemplary embodiments. Although one embodiment has been described above in a certain degree of detail or with reference to one or more individual embodiments, those skilled in the art can make numerous changes to the disclosed embodiments without departing from the scope of the invention. Accordingly, the various illustrative embodiments of the device are not intended to be limited to the specific forms disclosed. Rather, they include any modifications and alternatives within the scope of the claims, and embodiments other than those shown may include some or all of the features of the described embodiments. For example, components may be combined as an integral structure. Further, where appropriate, any aspect of the examples described above may be combined with any aspect of the other examples described to form additional examples having equivalent 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 to, include means-plus or step-plus function limitations, such that such limitations are not explicitly recited in a given claim using the phrase "means for" or "step for" respectively.

[0162] [Embodiment 1] A skin clearing system, wherein the skin clearing system comprises: A pulsed acoustic wave generator configured to generate a plurality of pulsed acoustic waves and direct the generated waves towards the skin, the pulsed acoustic wave generator being 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 pulsed acoustic wave generator; A controller coupled to the pulsed acoustic wave generator, the controller being configured to enable the generation of the pulsed acoustic waves during a second time period based on the expiration of a first time period during which the generation of the pulsed acoustic waves is disabled and laser light is applied to the skin by the laser light source, a controller Comprising The pulsed acoustic waves delivered to the skin during the second time period clear at least a portion of the epidermal and dermal vacuoles generated as a result of the laser light source during the first time period; 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, a skin clearing system. [Embodiment 2] The generated acoustic waves have a frequency of 700 KHz to 100 MHz, and the controller is configured to enable the generation of the pulsed acoustic waves during a fourth time period based on the expiration of a third time period during which the generation of the pulsed acoustic waves is disabled and laser light is applied to the skin by the laser light source, the skin clearing system according to Embodiment 1. [Embodiment 3] 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 during the fourth time period within 10 minutes of directing the pulsed acoustic waves during the second time period, the skin clearing system according to Embodiment 2. [Embodiment 4] The skin clearing system according to Embodiment 1, wherein the controller is configured to generate the pulsed acoustic wave at a pulse rate of 10 Hz to 1 KHz. [Embodiment 5] The skin clearing system according to Embodiment 1, wherein the controller is configured to generate a pulsed acoustic wave having a mechanical index MI of 0.15 to 1.9. [Embodiment 6] The pulsed acoustic wave generator includes a high-speed pulsed electrohydraulic shock wave generator, and the high-speed pulsed electrohydraulic shock wave generator a housing defining a chamber and a shock wave outlet, a medium disposed in the chamber, a plurality of electrodes and capacitors disposed in the chamber and configured to define one or more spark gaps, a pulse generation system configured to apply a voltage pulse to the plurality of electrodes and capacitors in the chamber and is provided with the skin clearing system according to Embodiment 1. [Embodiment 7] The skin clearing system according to Embodiment 1, wherein the controller is configured to generate the acoustic wave with a pulse at a rate of 10 Hz to 5 MHz. [Embodiment 8] The pulsed acoustic wave generator includes a megasonic wave generator, and the megasonic wave generator has a frequency of 700 KHz to 20 MHz or 10 Hz to 1 KHz, and / or a pulse duration of 1 nanosecond to 1 microsecond and is configured to generate a pulsed acoustic wave accompanied by the skin clearing system according to Embodiment 1. [Embodiment 9] The pulsed acoustic wave generator includes a megasonic wave generator, The power of the megasonic wave generator is set such that the mechanical index (MI) is 0.15 to 1.8, the skin clearing system according to Embodiment 1. [Embodiment 10] The high-speed pulsed electrohydraulic generator is set such that the peak pressure output is 0.8 MPa to 5 MPa, the skin clearing system according to Embodiment 6. [Embodiment 11] The second time period is 30 seconds to 2 minutes, the skin clearing system according to Embodiment 1. [Embodiment 12] The controller is During the first time period corresponding to the operation of the laser light source, to disable the generation of the pulsed acoustic wave, During the third time period corresponding to the operation of the laser light source, to disable the generation of the pulsed acoustic wave, Based on the end of the third time period when the laser light is applied to the skin, to enable the generation of the pulsed acoustic wave during the fourth time period, During the fifth time period corresponding to the operation of the laser light source, to disable the generation of the pulsed acoustic wave, Based on the end of the fifth time period when the laser light is applied to the skin, to enable the generation of the pulsed acoustic wave during the sixth time period and is further configured to perform The pulsed acoustic wave delivered to the skin during the fourth time period and the sixth time period clears at least a part of the epidermis and the intracutaneous vacuoles generated by the laser light source, Directing the pulsed acoustic wave during the second time period, during the fourth time period, and during the sixth time period is performed within 10 minutes of each other, the skin clearing system according to Embodiment 1. [Embodiment 13] The first time period, the third time period, and the fifth time period occur within a 24-hour period, At least a portion of the cleared epidermal and dermal vacuoles is not a deep skin vacuole and / or The pulsed acoustic wave generator is configured to treat the skin for between 0.1 minute and 10 minutes during the second time period, during the fourth time period, and / or during the sixth time period, of the skin clearing system of embodiment 12. [Embodiment 14] The skin clearing system further comprises a skin laser system comprising the laser light source, the skin laser system being configured to generate laser light during the first time period, during the third time period, and during the fifth time period, The laser light source comprises a Q-switched laser or a picosecond laser, The skin laser system is configured to apply the laser with a pulse duration of 1 nanosecond to 1 microsecond to the target skin, of the skin clearing system of embodiment 12. [Embodiment 15] The laser treatment provided by the laser light source includes a treatment selected from the group including tattoo removal, laser skin resurfacing, laser removal of moles, laser removal of skin lesions, laser hair implantation, laser scar removal, laser-assisted hair reduction, laser removal of vascular lesions, laser lip whitening, and laser treatment of melasma, of the skin clearing system of embodiment 1.

Claims

1. A skin clearing system, wherein the skin clearing system comprises: A laser light source configured to emit laser light and direct the emitted laser light towards the skin during a first time period; A pulse acoustic wave generator configured to generate a plurality of pulse acoustic waves, direct the generated plurality of pulse acoustic waves towards the skin, and clear non-encapsulated intradermal cavities generated as a result of the laser light source, and sequentially emit the pulse acoustic waves after the laser light source configured to emit laser light; A controller coupled to the pulse acoustic wave generator and configured to enable the generation of the pulse acoustic waves during a second time period based on the expiration of the first time period during which the generation of the pulse acoustic waves is disabled and the laser light is applied to the skin by the laser light source; comprising 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 pulse acoustic waves delivered to the skin during the second time period clear at least a portion of the non-encapsulated intradermal cavities generated as a result of the laser light source during the first time period. The non-encapsulated intradermal cavities are configured without containing tattoo pigment particle aggregates, a skin clearing system.

2. The skin clearing system according to claim 1, wherein the second time period is 10 minutes or less.

3. The skin clearing system according to claim 2, wherein the first time period is within 10 minutes of the second time period.

4. The controller Disabling the generation of the pulse acoustic waves during the first time period corresponding to the operation of the laser light source; During a third time period corresponding to the operation of the laser light source, disabling the generation of the pulsed acoustic wave; The skin clearing system according to claim 1, further configured to perform **Claim 5** The controller is Based on the expiration of the third time period during which the laser light is applied to the skin, enabling the generation of the pulsed acoustic wave during a fourth time period; During a fifth time period corresponding to the operation of the laser light source, disabling the generation of the pulsed acoustic wave; Based on the expiration of the fifth time period during which the laser light is applied to the skin, enabling the generation of the pulsed acoustic wave during a sixth time period; And is further configured to perform The pulsed acoustic wave delivered to the skin during the fourth time period and the sixth time period clears at least a portion of the non-encapsulated intradermal cavities generated by the laser light source. The skin clearing system according to claim 4. **Claim 6** The first time period, the third time period, and the fifth time period occur within a 24-hour period; At least a portion of the non-encapsulated intradermal cavities that have been cleared are not deep skin cavities; The pulsed acoustic wave generator is configured to treat the skin for between 0.1 minute and 10 minutes during the second time period, the fourth time period, or the sixth time period; Or a combination thereof. The skin clearing system according to claim 5. **Claim 7** Further comprising a skin laser system comprising the laser light source, the skin laser system being 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, The skin clearing system according to claim 5, wherein the skin laser system is configured to apply the Q-switched laser or picosecond laser having a pulse duration of 1 nanosecond to 1 microsecond to the skin.

8. The laser treatment provided by the laser light source includes a treatment selected from the group consisting of tattoo removal, laser skin resurfacing, laser removal of moles, laser removal of skin lesions, laser hair implantation, laser scar removal, laser-assisted hair reduction, laser removal of vascular lesions, laser lip whitening, and laser treatment of melasma. The skin clearing system according to claim 1.

9. The skin clearing system according to claim 1, wherein the non-encapsulated intradermal cavity is formed by treating tissue with laser light.

10. The skin clearing system according to claim 1, wherein the non-encapsulated intradermal cavity is generated by the laser.

11. The skin clearing system according to claim 1, wherein the non-encapsulated intradermal cavity is generated as a result of rapid heating and / or energy transfer by the laser light source.

Images