Patent Publication Number: US-2022211573-A1

Title: Methods of treating cellulite and subcutaneous adipose tissue

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. Ser. No. 15/573,353, filed Nov. 10, 2017, which is a national phase under 35 U.S.C. § 371 of International Application PCT/US2016/032069, filed May 12, 2016, which claims priority to U.S. Provisional Patent Application No. 62/160,147, filed May 12, 2015; and U.S. Provisional Patent Application No. 62/277,796, filed Jan. 12, 2016; the entire contents of each of which are incorporated by reference in their respective entireties. 
    
    
     BACKGROUND 
     1. Field of the Invention 
     The present invention relates generally to methods of treatment for reducing adipose tissue using pressure waves. More particularly, but not by way of limitation, the present invention relates to methods of treatment for reducing subcutaneous adipose tissue using shockwaves. 
     2. Description of Related Art 
     Treating Celuite 
     Excess body fat, localized adiposity, and cellulite represent important social problems. To date, techniques using radiofrequencies, ultrasound, and carbon dioxide have been studied as treatments for noninvasive body contouring. 
     Two high intensity ultrasound medical devices products that have been developed for treatment of excess body fat include Ultrashape and LipoSonix. Ultrashape&#39;s technology, as disclosed in U.S. Pat. No. 7,347,855 describes “[a] methodology and system for lysing adipose tissue including directing ultrasonic energy at a multiplicity of target volumes within the region, which target volumes contain adipose tissue, thereby to selectively lyse the adipose tissue in the target volumes and generally not lyse non-adipose tissue in the target volumes and computerized tracking of the multiplicity of target volumes notwithstanding movement of the body.” “In accordance with a preferred embodiment of the present invention, the modulating provides between 2 and 1000 sequential cycles at an amplitude above a cavitation threshold, more preferably between 25 and 500 sequential cycles at an amplitude above a cavitation threshold and most preferably between 100 and 300 sequential cycles at an amplitude above a cavitation threshold.” 
     Liposonix&#39;s technology, as disclosed in U.S. Pat. No. 7,258,674, describes “a system for the destruction of adipose tissue utilizing high intensity focused ultrasound (HIFU) within a patient&#39;s body.” Liposonix&#39;s high intensity focused ultrasound technology can cause thermal damage of the adipose tissue at focused spots within the adipose tissue. 
     While both technologies result in adipose tissue destruction, the application of these technologies is likely to have potential safety issues because of the cavitation or thermal affects. These cavitation or thermal affects may even cause damage to non-adipose cells and tissues. Given these safety issues, great care must be taken in treating a patient using these technologies. 
     An approach to fat tissue volume reduction, that minimizes the safety issues related to these high intensity ultrasound technologies, is cryolipolysis. As the name implies, cryolipolysis is a medical treatment to reshape body contours that relies on controlled cooling of the patient&#39;s tissue to cause a non-invasive local reduction of fat deposits. This technology has been commercialized by Zeltiq under the name CoolSculpting and is described in U.S. Pat. No. 8,840,608, entitled, “Methods and devices for selective disruption of fatty tissue by controlled cooling” As described in this patent, the “invention relates to methods for use in the selective disruption of lipid-rich cells by controlled cooling.” 
     While the process is not fully understood, it appears fatty tissue that is cooled below body temperature, but above freezing, undergoes localized cell death followed by a local adipose inflammatory response. This inflammation, over the course of several months, results in a reduction of the fatty tissue layer. See Manstein et al. Specifically, as discussed by Krueger N, et al.: “cryolipolysis exploits the premise that adipocytes are more susceptible to cooling than other skin cells.” “Precise application of cold temperatures triggers the death of adipocytes that are subsequently engulfed and digested by macrophages.” “An inflammatory process stimulated by apoptosis of adipocytes, as reflected by an influx of inflammatory cells, can be seen within 3 days after treatment and peaks at approximately 14 days thereafter as adipocytes become surrounded by his histiocytes, neutrophils, lymphocytes, and other mononuclear cells.” 
     In terms of efficacy, cryolipolysis has demonstrated reducing adipose tissue by 20-30% in published studies. More importantly, compared to ultrasound technologies based on cavitation or thermal mechanism of action to reduce adipose volume, cryolipolysis is relatively safe. According to Zelteq&#39;s company website. “the controlled cooling of the CoolSculpting procedure targets and eliminates only fat cells. Other treatment modalities, such as lasers, radiofrequency and focused ultrasound, affect fat cells and may affect other adjacent tissue in a way that is not comparable to the CoolSculpting method of Cryolipolysis®.” While side effects such as transient local redness, bruising and numbness of the skin are common following the cryolipolysis treatment, the company claims the these side effects typically subside over time. 
     While the use of cryolipolysis to induce an inflammatory response that results in an adipose tissue volume reduction is an improvement over prior art approaches, it is still less than ideal. 
     One problem with using cryolipolysis to induce inflammation is the time it takes to administer the cryolipolysis treatment (i.e., cooling the adipose tissue). Typically, the cryolipolysis procedure (e.g. using Coolsculpting) lasts approximately 1-2 hours for each treatment site (e.g., right or left love handle). If a patient seeking to have fat volume reduction in an extensive area, the patient would be required to have multiple 1-2 hour cryolipolysis treatments that could require multiple doctor visits. Another problem, during these long cryolipolysis treatments, the patient is limited on making any movements, which makes the treatment unpleasant. Additionally, a major problem for the physician or spa owner who is treating the patient, the required long treatments limits the throughput of patients that can be seen which has a real impact on the practice revenues. 
     Approaches to improve cryolipolysis, by use of ultrasound, have been reported. US Patent Application No. 2013/0190744 by Anderson R R, one on the primary inventors of cryolipolysis, discloses, “cooling of the lipid-rich tissue can be accompanied by mechanical or other disruption of the fatty tissue. e.g., through application of acoustic fields that may be either constant or oscillating in time. For example, one or more transducers may be introduced into the region of tissue being cooled through the catheter, and signals provided to them to produce mechanical oscillations and disruption of the fatty tissue.” “Alternatively, ultrasound energy can be provided from one or more sources of such energy, e.g., piezoelectric transducers, provided in contact with an outer surface of the subject&#39;s body during the cooling procedure. Such ultrasound energy can optionally be focused to the approximate depth of the fatty tissue being cooled to further disrupt the tissue.” 
     Another group, lead by Ferraro GA, studied synergistic effects of cryolipolysis and shockwaves for noninvasive body contouring. This technology developed by the Promoitalia Group SP and called Ice-Shock Lipolysis, “is a new noninvasive procedure for reducing subcutaneous fat volume and fibrous cellulite in areas that normally would be treated by liposuction.” Ice-Shock Lipolysis “uses a combination of acoustic waves and cryolipolysis. Shockwaves are focused on the collagen structure of cellulite-afflicted skin. When used on the skin and underlying fat, they cause a remodeling of the collagen fibers, improving the orange-peel appearance typical of the condition. Cryolipolysis, on the other hand, is a noninvasive method used for the localized destruction of subcutaneous adipocytes, with no effects on lipid or liver marker levels in the bloodstream. The combination of the two procedures causes the programmed death and slow resorption of destroyed adipocytes.” 
     The combination of cryolipolysis and acoustic waves promises to improve the outcome of the cryolipolysis procedure. As discussed in the prior art, the use of the acoustic waves are to either aid in the direct disruption of the adipose cell or to provide better appearance outcomes by remodeling the collagen fibers. However, the principal method of inducing inflammation, which leads to the adipose tissue volume reduction, is from the cooling of the adipose tissue. As a result, the fundamental problems, as discussed above, related to the cryolipolysis treatment has not changed. 
     SUMMARY 
     Embodiments of the present disclosure are directed to methods of inducing therapeutic adipose tissue inflammation using high frequency pressure waves (e.g. high frequency shockwaves) wherein the inflammation results in a reduction in the volume of subcutaneous adipose tissue. In some embodiments, the high frequency pressure waves (e.g., in the form of shockwaves) are applied to the skin so as to induce lipid nucleation, which can cause crystallization and eventually, adipocyte apoptosis. Adipocyte apoptosis can result in a reduction in the appearance of the cellulite on the skin (e.g., smoother skin) overlying the treated adipocyte tissue. In some embodiments, the applied pressure waves are applied at a rate and magnitude such that minimal to no cavitation occurs in the tissue. In some embodiments, the methods of treatment can reduce undesired side effects and the total times per treatment (TTPT) relative to known systems. Moreover, the present pressure wave therapies can be used to induce inflammation across a given area of adipose tissue such that a practical total time per treatment (TTPT) can be obtained. 
     Present embodiments include methods that comprise: generating a plurality of pressure waves at sub-cavitation levels and delivering at least a portion of the plurality of pressure waves to an adipose tissue thereby inducing inflammation in the adipose tissue. It is noted that throughout the application, pressure waves are understood to include shockwaves. 
     Some embodiments include methods that comprise: generating a plurality of pressure waves at a pulse rate of at least 10 Hz and delivering to an adipose tissue at least a portion of the plurality of pressure waves. 
     Some embodiments include methods of applying electrohydraulic generated shockwaves to induce inflammation in an adipose tissue. The EH-shockwave systems utilized can be configured to deliver shockwaves to tissues to induce inflammation on the treated tissue, such as by delivering shockwaves at higher frequencies (e.g., greater than ˜10 Hz). 
     Still other embodiments also include methods of generating pressure wave energy of at least 0.5 mJ per mm 2  at the pressure wave outlet window and delivering to an adipose tissue at least a portion of the plurality of pressure waves. In further embodiments, the pressure wave energy of at least 0.5 mJ per mm 2  at the pressure wave outlet window is applied to at least a 20 mm 2  area. In some embodiments, at least a portion of the generated pressure waves are planar or unfocused. 
     Some embodiments include a method of treating a patient to reduce subcutaneous fat in a treatment area. The fat comprises fat cells having intracellular fat and interstitial space between the fat cells. The method can comprise directing a pressure wave generating probe to expose an external area of the patient to a series of pressure waves, where the pressure wave generating probe comprises a pressure wave outlet window, where the pressure wave generating probe emits at least 0.5 mJ per mm 2  at the pressure wave outlet window, and where the pressure waves are not focused prior to entering into the treatment area of the patient. 
     Some embodiments include a method of inducing inflammation of subcutaneous adipose tissue. The method can comprise directing a pressure wave generating probe to expose an external area of the patient to a series of pressure waves, where the pressure wave generating probe comprises a pressure wave outlet window and where the pressure wave generating probe emits at least 0.5 mJ per mm 2  of the pressure wave outlet window. 
     Some embodiments include a method of applying pressure wave energy to an adipose tissue. The method can comprise directing a pressure wave generating probe to expose an external area of the patient to a series of pressure waves, where the pressure wave generating probe comprises a pressure wave outlet window and where the pressure wave generating probe emits at least 0.5 mJ per mm 2  of the pressure wave outlet window. 
     Some embodiments include a method of treating a patient to reduce the appearance of cellulite in a treatment area. The method can comprise directing a pressure wave generating probe to expose an external area of the patient to a series of pressure waves, where the pressure wave generating probe comprises a pressure wave outlet window and where the pressure wave generating probe emits at least 0.5 mJ per mm 2  of the pressure wave outlet window. 
     Some embodiments include a method of inducing inflammation in subcutaneous adipose tissue. The method can comprise directing a pressure wave generating probe to expose an external area of the patient to a series of pressure waves, where the pressure wave generating probe comprises a pressure wave outlet window and where the probe is emits a series of pressure waves that would not induce transient cavitation bubbles in an aqueous solution. 
     Some embodiments include a method where the probe emits a series of pressure waves that would induce minimal to no adipose cell damage while treating an external treatment area of a subject, e.g., a patient or animal model. For example, in some embodiments, the probe emits a series of pressure waves that would increase the amount of lipid crystals within an adipose tissue within the treatment area of the subject as compared with an adipose tissue sample outside of the treatment area of the subject. In some embodiments, the probe can emit a series of pressure waves that would cause a comparable increase of a luminosity value of an adipose tissue sample from the treated area relative to that of an adipose tissue sample from an untreated area of the subject. In still other embodiments, the probe emits a series of pressure waves that would cause a comparable volume loss of a treatment area relative to an untreated area of the subject. 
     The term “coupled” is defined as connected, although not necessarily directly, and not necessarily mechanically; two items that are “coupled” may be unitary with each other. The terms “a” and “an” are defined as one or more unless this disclosure explicitly requires otherwise. The term “substantially” is defined as largely but not necessarily wholly what is specified (and includes what is specified; e.g., substantially 90 degrees includes 90 degrees and substantially parallel includes parallel), as understood by a person of ordinary skill in the art. In any disclosed embodiment, the terms “substantially,” “approximately,” and “about” may be substituted with “within [a percentage] of” what is specified, where the percentage includes 0.1, 1, 5, and 10 percent. 
     The terms “comprise” (and any form of comprise, such as “comprises” and “comprising”), “have” (and any form of have, such as “has” and “having”), “include” (and any form of include, such as “includes” and “including”) and “contain” (and any form of contain, such as “contains” and “containing”) are open-ended linking verbs. As a result, a system or apparatus that “comprises,” “has,” “includes” or “contains” one or more elements possesses those one or more elements, but is not limited to possessing only those elements. Likewise, a method that “comprises,” “has,” “includes” or “contains” one or more steps possesses those one or more steps, but is not limited to possessing only those one or more steps. 
     Any embodiment of any of the present systems, apparatuses, and methods can consist of or consist essentially of—rather than comprise/include/contain/have—any of the described steps, elements, and/or features. Thus, in any of the claims, the term “consisting of” or “consisting essentially of” can be substituted for any of the open-ended linking verbs recited above, in order to change the scope of a given claim from what it would otherwise be using the open-ended linking verb. 
     Further, a structure (e.g., a component of an apparatus) that is configured in a certain way is configured in at least that way, but it can also be configured in other ways than those specifically described. 
     Details associated with the embodiments described above and others are presented below. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The following drawings illustrate by way of example and not limitation. For the sake of brevity and clarity, every feature of a given structure is not always labeled in every figure in which that structure appears. Identical reference numbers do not necessarily indicate an identical structure. Rather, the same reference number may be used to indicate a similar feature or a feature with similar functionality, as may non-identical reference numbers. The figures are drawn to scale (unless otherwise noted), meaning the sizes of the depicted elements are accurate relative to each other for at least the embodiment depicted in the figures. 
         FIG. 1  depicts a waveform that can be emitted by system of  FIG. 3  and/or the handheld probe of  FIG. 4  into target tissue. 
         FIG. 2  depicts a conceptual flowchart of one embodiment of the present methods. 
         FIG. 3  depicts a block diagram of a first embodiment of the present electro-hydraulic (EH) shockwave generating systems. 
         FIG. 4  depicts a cross-sectional side view of a handheld probe for some embodiments of the present EH shockwave generating systems. 
         FIG. 4A  depicts a cross-sectional side view of a first embodiment of a removable spark head usable with embodiments of the present handheld probes, such as the one of  FIG. 4 . 
         FIG. 4B  depicts a cutaway side view of a second embodiment of a removable spark head usable with embodiments of the present handheld probes, such as the one of  FIG. 4 . 
         FIG. 4C  depicts a cutaway side view of a third embodiment of a removable spark head usable with embodiments of the present handheld probes, such as the one of  FIG. 4 . 
         FIGS. 5A-5B  depict a timing diagrams of one example of the timed application of energy cycles or voltage pulses in the system of  FIG. 3  and/or the handheld probe of  FIG. 4 . 
         FIG. 6  depicts a schematic diagram of one embodiment of a multi-gap pulse-generation system for use in or with some embodiments of the present systems. 
         FIG. 7  depicts a block diagram of an embodiment of a radio-frequency (RF) powered acoustic ablation system. 
         FIGS. 8A-8B  depict perspective and cross-sectional views of a first embodiment of a spark chamber housing. 
         FIG. 9  depicts a cross-sectional view of a second embodiment of spark chamber housing. 
         FIG. 10  depicts a schematic diagram of an electric circuit for a pulse-generation system. 
         FIG. 11  depicts an exploded perspective view of a further embodiment of the present probes having a spark head or module. 
         FIGS. 12A and 12B  depict parts of the assembly of the probe of  FIG. 11 . 
         FIGS. 13A and 13B  depict perspective and side cross-sectional views, respectively, of the probe of  FIG. 11 . 
         FIG. 13C  depicts an enlarged side cross-sectional view of a spark gap of the probe of  FIG. 11 . 
         FIG. 14  depicts a schematic diagram of a second embodiment of an electric circuit for a prototyped pulse-generation system. 
     
    
    
     DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS 
     Embodiments of the present disclosure are directed to inducing inflammation in a tissue and particularly a tissue near the surface of the skin such as a subcutaneous adipose tissue, by applying a plurality of shockwaves to the tissue. The induced inflammation will lead to eventual apoptosis to a portion of the cells in the treated area. While the shockwave treatments induce inflammation, the shockwaves are at a strength, frequency, and duration that are not likely to cause cavitation or thermal degradation in the treated tissue. As such, cell rupturing, would not be likely to occur. Rather, apoptosis would be caused by the inflammatory response of the body. 
     When the cell is exposed to repeated pressure waves within a certain frequency and energy level, sub-lytic injury occurs that induces inflammation. More particularly, the repeated high frequency, pressure wave energy applied to cells with lipid reserves can cause sub-lytic injury to the lipid containing vacuoles, triggering an inflammatory response. The ability to induce inflammation is dependent on four factors: (1) applied intensity (Pa), (2) the rate of wave pulses (Hz), (3) wave form shape (e.g., wave front rise time (ns) and wave length (ns)), or (4) duration of exposure. One or more of these factors can be manipulated to cause a tissue with a high amount of stored lipids to have increased inflammation as compared to a non-treated area of similar character. The inflammation will eventually result in apoptosis and a reduction in the number of cells in the treated area. 
     A possible theory to explain the phenomenon of the induced inflammations is the formation of lipid crystals in a sub-cellular structure. In a liquid lipid media, such as in adipose cells, a series of pressure waves at a high frequency may induce nucleation of lipid crystals leading to the formation of crystals sufficiently large to cause injury to cellular organelles, such as a bilayer membrane. This injury initiates an inflammatory response that will eventually lead to apoptosis and necrosis. Nearby cells that are also exposed but not lipid rich like adipocyte cells, such as cells in the epidermis layer, are less likely to be damaged in the process. 
     In some embodiments, a method of treating a patient to reduce subcutaneous fat in a treatment area can comprise: directing a pressure wave generating probe (such as probe  38  or  38   a  described below) to expose an external area of the patient to a series of pressure waves, where the pressure wave generating probe comprises a pressure wave outlet window, where the pressure wave generating probe is configured to generate at least 0.5 mJ per mm 2  or at least 2 mJ per mm 2  at the pressure wave outlet window. For example, the pressure waves can have 0.5, 0.6, 0.8, 0.9, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.4, 3.8, 4, 4.4, 4.8, 5, 5.5, 6, 6.5, 7 mJ per mm 2 , or any value or range therebetween. In some embodiments, the pressure wave generating probe is configured to generate or generates between 0.5 mJ per mm 2  to 5 mJ per mm 2 . In some embodiments, the pressure wave outlet window has an area of 0.5 cm 2  to 20 cm 2 . For example, the outlet window can have an area of at least 0.5, 0.8, 1, 2, 3, 4, 5, 6, 7. 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 cm 2 , or any value or range therebetween. 
     In some embodiment, the pressure waves are unfocused or substantially planar prior to entering into the treatment area of the patient. Other embodiments of the present methods comprise focusing the one or more pressure waves to a treatment area. In some embodiments the adipose tissue at which the one or more pressure waves is focused is the depth at which there is adipose tissue. Focusing the shockwaves may result in higher pressures at targeted cells than unfocused or planar waves. 
     In some embodiments, the treatment area is a portion of butt, thigh, stomach, waist, and/or upper arm area. In some embodiments, the treatment area of subcutaneous fat is within a depth of 0-6 cm from the external area, such as 1, 2, 3, 4, 5, 6 cm, or any value or range therebetween. In some embodiments, the treatment area is at a depth of 1-4 cm. 
     In some embodiments, the pressure wave directed to the treatment area is a shockwave.  FIG. 1  depicts a waveform of a shockwave that can be emitted from a probe and into a volume of tissue. The depicted form can be useful for inducing inflammation without causing cell rupturing. Pulse  300  is of a typical shape for an impulse generated by the described electrohydraulic (EH) spark heads described below. For example, pulse  300  has a rapid rise time (or wave front rise time), a short duration, and a ring down period. The units of vertical axis V a  are arbitrary as may be displayed on an oscilloscope. 
     In some embodiments, the pressure wave generating probe can emit a shockwave comprising the following waveform characteristics in a transmitting medium. A transmitting medium can be a gas (e.g., air), a tissue (e.g., an adipose tissue) or an aqueous solution (e.g., a saline solution, such as one at 0.5-10% concentration). In some embodiments, a shockwave emitted at the outlet window of the probe and/or delivered to the treatment area can have a shockwave front rise time of less than 20 ns, less than 18 ns, less than 15 ns, or less than 12 ns as measured in a transmitting medium. In some embodiments, the actual acoustic pulse amplitude emitted may be 0.5 to 50 MPa. In some embodiments, the individual time periods  304  may be 0.5 to 50 micro-seconds each in a transmitting medium. In some embodiments, the probe emits a pressure wave at a pulse rate of at least 10 Hz. For example, the probe emits a pressure wave at a pulse rate of between 10 Hz and 1000 Hz., such as 20, 30, 40, 50, 60, 70, 80 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Hz, or any value or range therebetween. In some embodiments, the probe emits a pressure wave at a pulse rate of between 10 Hz and 100 Hz. In some embodiments, the probe emits a pressure wave at a pulse rate of between 20 Hz and 75 Hz. In some embodiments, the probe emits a pressure wave at a pulse rate of between 100 Hz and 500 Hz. In some embodiments, the probe emits a pressure wave at a pulse rate of between 500 Hz and 1000 Hz. In some embodiments, the emitted waves are configured according to the characteristics above to induce minimal to no detectable transient cavitation in a transmitting medium. 
     In some embodiments, the method of treatment induces lipid crystallization, induces inflammation in the treated adipose tissue, reduces the amount of subcutaneous fat in the treatment area, and/or reduces the appearance of cellulite (e.g., resulting in a smoother appearance in the skin overlying the treatment area). In some embodiments, subcutaneous fat comprises fat cells having intracellular fat and interstitial space between the fat cells. A reduction in the amount of fat (e.g., a reduction in volume) can be determined by a histological evaluation or 3-D camera. Example 2 describes a method for detecting a change in adipose tissue volume. In some embodiments, the amount of fat is reduced about 1-14 days after one or more treatments, such as after 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 days after the last treatment, or any value or range therebetween. In some embodiments, an inflammation increase is indicated by an increase of one or more cytokines, such as one or more of leptin, IL-6, and TNF-α, in the patient&#39;s blood serum, or in the treatment area after treatment. In some embodiments, an inflammation increase is indicated by an increase in inflammatory cells in the treatment area after treatment. In some embodiments, even with an inflammation increase, the series of pressure waves would induce minimal to no adipose cell rupturing immediately after treatment, such as when treating an external treatment area of an animal model. Cell rupturing can be detected histologically, such as under 200× to 1000× magnification. In some embodiments, inducing lipid crystallization is indicated by relatively higher tissue luminosity value under cross-polarized microscopy as compared with a control sample. Example 3 describes a method for detecting a comparable increase in lipid crystallization. Because of the recognized difficulty of performing such evaluations on a human patient, in some embodiments, the result of a treatment on a human can be estimated to correspond to the result of a treatment protocol on an animal model, such as a minipig. 
     Inducing crystallization of lipids using the methods of this invention can occur in relatively short treatment times. As a result, the long treatment times seen with the prior art, along with the problems associated with these long treatment times (e.g., office space, costs, discomfort, etc.) can be avoided using this invention. For example, in some embodiments, a treatment session can be 1 to 30 minutes within a 24 hour period. A treatment session can be 1, 2, 4, 5, 8, 10, 12, 15, 18, 20, 22, 24, 26, 28, 30 minutes or any value or within any range therebetween. A treatment session can be performed daily, every other day, every three days, weekly, bi-weekly, monthly, bi-monthly, and quarterly. A treatment plan can comprise 1 to 20 sessions within a one-year period, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 sessions or any value therebetween. In some embodiments, a treatment plan comprises a session at least once per two weeks for at least 6 weeks. 
       FIG. 2  illustrates one embodiment of a method  700  to direct shockwaves to target tissue. In the embodiment shown, method  700  comprises a step  704  in which a treatment area  712  is identified. For example, treatment area  712  can comprise skin affected with cellulite or having an unwanted accumulation of subcutaneous fat. In the embodiment shown, method  700  also comprises a step  716  in which a probe or handpiece  38  is disposed toward treatment area  712 , such that shockwaves originating in probe  38  can be directed toward the adipose tissue in the treatment area. In the embodiment shown, method  700  also comprises a step  720  in which a pulse-generation system  26  is coupled to probe  38 . In the embodiment shown, method  700  also comprises a step  724  in which pulse-generation system  26  is activated to generate sparks across electrodes within probe  38  to generate shockwaves in probe  38  for delivery to adipose tissue underlying treatment area  712 , as shown. 
     Shockwave Generator 
     The above-described modalities may employ a shockwave generator. The generator can be configured to deliver focused, defocused, or planar waves with the above-described characteristics. In some embodiments, EH waves are generated. For example, the systems and apparatus described in U.S. Patent Publication No. 2014/0257144 can be configured to apply EH shockwaves at the described rate, energy level, and duration. In particular, the shockwave generating apparatus can be configured to generate a planar or defocused pressure wavefront. 
     With reference to  FIG. 3 , such a system can include a handheld probe (e.g., with a first housing, such as in  FIG. 4 ) and a separate controller or pulse-generation system (e.g., in or with a second housing coupled to the handheld probe via a flexible cable or the like). In the embodiment shown, apparatus  10  comprises: a housing  14  defining a chamber  18  and a shockwave outlet  20 ; a liquid ( 54 ) disposed in chamber  18 ; a plurality of electrodes (e.g., in spark head or module  22 ) configured to be disposed in the chamber 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 between 10 Hz and 1000 Hz, such as between 10 Hz and 100 Hz, 100 Hz and 500 Hz, or 500 Hz and 1000 Hz. In this embodiment, the pulse-generation system  26  is configured to apply the voltage pulses to the electrodes such that portions of the liquid are vaporized to propagate shockwaves through the liquid and the shockwave outlet window. 
     In the embodiment shown, pulse-generation system  26  is configured for use with an alternating current power source (e.g., a wall plug). For example, in this embodiment, pulse-generation system  26  comprises a plug  30  configured to be inserted into a 110V wall plug. In the embodiment shown, pulse-generation system  26  comprises a capacitive/inductive coil system, on example of which is described below with reference to  FIG. 7 . In the embodiment shown, pulse-generation system  26  is (e.g., removably) coupled to the electrodes in spark head or module  22  via a high-voltage cable  34 , which may, for example, include two or more electrical conductors and/or be heavily shielded with rubber or other type of electrically insulating material to prevent shock. In some embodiments, high-voltage cable  34  is a combined tether or cable that further includes one or more (e.g., two) liquid lumens through which chamber  18  can be filled with liquid and/or via which liquid can be circulated through chamber  18  (e.g., via combined connection  36 ). In the embodiment shown, apparatus  10  comprises a handheld probe or handpiece  38  and cable  34  is removably coupled to probe  38  via a high-voltage connector  42 , which is coupled to spark head or module  22  via two or more electrical conductors  44 . In the embodiment shown, probe  38  comprises a head  46  and a handle  50 , and probe  38  can comprise a polymer or other electrically insulating material to enable an operator to grasp handle  50  to position probe  38  during operation. For example, handle  50  can be molded with plastic and/or can be coated with an electrically insulating material such as rubber. 
     In the embodiment shown, a liquid  54  (e.g., a dielectric liquid such as distilled water) is disposed in (e.g., and substantially fills) chamber  18 . In this embodiment, spark head  22  is positioned in chamber  18  and surrounded by the liquid such that the electrodes can receive voltage pulses from pulse-generation system  26  (e.g., at a rate of between 10 Hz and 1000 Hz, 10 Hz and 100 Hz, 100 Hz and 500 Hz, or 500 Hz and 1000 Hz) such that portions of the liquid are vaporized to propagate shockwaves through the liquid and shockwave outlet  20 . In the embodiment shown, probe  38  includes an acoustic delay chamber  58  between chamber  18  and outlet  20 . In this embodiment, acoustic delay chamber is substantially filled with a liquid  62  (e.g., of the same type as liquid  54 ) and has a length  66  that is sufficient to permit shockwaves to form and/or be directed toward outlet  20 . In some embodiments, length  66  may be between 2 millimeters (mm) and 25 millimeters (mm). In the embodiment shown, chamber  18  and acoustic-delay chamber  58  are separated by a layer of sonolucent (acoustically permeable or transmissive) material that permits pressure waves or, more particularly, shockwaves to travel from chamber  18  into acoustic-delay chamber  58 . In other embodiments, liquid  62  may be different than liquid  54  (e.g., liquid  62  may comprise bubbles, water, oil, mineral oil, and/or the like). Certain features such as bubbles may introduce and/or improve a nonlinearity in the acoustic behavior of liquid  54  to increase the formation of shockwaves. In further embodiments, chamber  18  and acoustic-delay chamber  58  may be unitary (i.e., may comprise a single chamber). In further embodiments, acoustic-delay chamber  58  may be replaced with a solid member (e.g., a solid cylinder of elastomeric material such as polyurethane). In the embodiment shown, probe  38  further includes an outlet member  70  removably coupled to the housing at a distal end of the acoustic delay chamber, as shown. Member  70  is configured to contact an external area located above tissue  74 , and can be removed and either sterilized or replaced between patients. Member  70  comprises a polymer or other material (e.g., low-density polyethylene or silicone rubber) that is acoustically permeable to permit shockwaves to exit acoustic-delay chamber  58  via outlet  20 . In some embodiments, an acoustic coupling gel (not shown) may be disposed between member  70  and tissue  74  to lubricate and provide additional acoustic transmission into tissue  74 . 
     In the embodiment shown, probe  38  includes an acoustic mirror  78  that comprises a material (e.g., glass) and is configured to reflect a majority of sound waves and/or shockwaves that are incident on the acoustic mirror. As shown, acoustic mirror  78  can be angled to reflect sound waves and/or shockwaves (e.g., that originate at spark head  22 ) toward outlet  20  (via acoustic-delay chamber) in a defocused manner. In the embodiment shown, housing  14  can comprise a translucent or transparent window  82  that is configured to permit a user to view (through window  82 , chamber  18 , chamber  58 , and member  70 ) a region of a patient (e.g., tissue  74 ) comprising target cells (e.g., during application of shockwaves or prior to application of shockwaves to position outlet  20  at the target tissue). In the embodiment shown, window  82  comprises an acoustically reflective material (e.g., glass) that is configured to reflect a majority of sound waves and/or shockwaves that are incident on the window. For example, window  82  can comprise clear glass of sufficient thickness and strength to withstand the high-energy acoustic pulses produced at spark head  22  (e.g., tempered plate glass having a thickness of about 2 mm and an optical transmission efficiency of greater than 50%). 
     In  FIG. 3 , a human eye  86  indicates a user viewing the target tissue through window  82 , but it should be understood that target tissue may be “viewed” through window  82  via a camera (e.g., a digital still and/or video camera). By direct or indirect observation, acoustic energy can be positioned, applied, and repositioned according to target tissues, such as a region of cellulite, and by indications of acoustic energy, such as a change in the color of the tissue. 
       FIG. 4  depicts a cross-sectional side view of a second embodiment  38   a  of the present handheld probes or handpiece for use with some embodiments of the present EH shockwave generating systems and apparatuses. Probe  38   a  is substantially similar in some respects to probe  38 , and the differences are therefore primarily described here. For example, probe  38   a  is also configured such that the plurality of electrodes of spark head  22   a  are not visible to a user viewing a region (e.g., of target tissue) through window  82   a  and outlet  20   a . However, rather than including an optical shield, probe  38   a  is configured such that spark head  22   a  (and the electrodes of the spark head) are offset from an optical path extending through window  82   a  and outlet  20   a . In this embodiment, acoustic mirror  78   a  is positioned between spark head  22   a  and outlet  20   a , as shown, to define a boundary of chamber  18   a  and to direct acoustic waves and/or shockwaves from spark head  22   a  to outlet  20   a . In the embodiment shown, window  82   a  can comprise a polymer or other acoustically permeable or transmissive material because acoustic mirror  78   a  is disposed between window  82   a  and chamber  18   a  and sound waves and/or shockwaves are not directly incident on window  82   a  (i.e., because the sound waves and/or shockwaves are primarily reflected by acoustic mirror  78   a ). 
     In the embodiment shown, spark head  22   a  includes a plurality of electrodes  100  that define a plurality of spark gaps. The use of multiple spark gaps can be advantageous because it can double the number of pulses that can be delivered in a given period of time. For example, after a pulse vaporizes an amount of liquid in a spark gap the vapor must either return to its liquid state or must be displaced by a different portion of the liquid that is still in a liquid state. In addition to the time required for the spark gap to be re-filled with water before a subsequent pulse can vaporize additional liquid, sparks also heat the electrodes. As such, for a given spark rate, increasing the number of spark gaps reduces the rate at which each spark gap must be fired and thereby extends the life of the electrodes. Thus, ten spark gaps potentially increases the possible pulse rate and/or electrode life by a factor of ten. 
     As noted above, high pulse rates can generate large amounts of heat that may increase fatigue on the electrodes and/or increase the time necessary for vapor to return to the liquid state after it is vaporized. In some embodiments, this heat can be managed by circulating liquid around the spark head. For example, in the embodiment of  FIG. 4 , probe  38  includes conduits  104  and  108  extending from chamber  18   a  to respective connectors  112  and  116 , as shown. In this embodiment, connectors  112  and  116  can be coupled to a pump to circulate liquid through chamber  18   a  (e.g., and through a heat exchanger. For example, in some embodiments, pulse-generation system  26  ( FIG. 3 ) can comprise a pump and a heat exchanger in series and configured to be coupled to connectors  112  and  116  via conduits or the like. In some embodiments, a filter can be included in probe  38   a , in a spark generation system (e.g.,  26 ), and/or between the probe and the spark generation system to filter liquid that is circulated through the chamber 
     As illustrated in  FIG. 4 , application of each shockwave to a target tissue includes a wave front  118  propagating from outlet  20   a  and traveling outward through tissue  74 . As shown, wave front  118  is curved according to its expansion as it moves outwardly and partially according to the shape of the outer surface of outlet member  70   a  that contacts tissue  74 . In other embodiments, such as that of  FIG. 3 , the outer shape of the contact member can be planar. 
       FIG. 4A  depicts an enlarged cross-sectional view of first embodiment of a removable spark head, shown as module  22   a . In the embodiment shown, spark head  22   a  comprises a sidewall  120  defining a spark chamber  124 , and a plurality of electrodes  100   a ,  100   b ,  100   c  disposed in the spark chamber. In the embodiment shown, spark chamber  124  is filled with liquid  128  which may be similar to liquid  54  ( FIG. 3 ). At least a portion of sidewall  120  comprises an acoustically permeable or transmissive material (e.g., a polymer such as polyethylene) configured to permit sound waves and/or shockwaves generated at the electrodes to travel through sidewall  120  and through chamber  18   a  ( FIG. 4 ). For example, in the embodiment shown, spark head  22   a  includes a cup-shaped member  132  that may be configured to be acoustically reflective and includes an acoustically permeable cap member  136 . In this embodiment, cap member  136  is dome shaped to approximate the curved shape of an expanding wavefront that originates at the electrodes and to compress the skin when applied with moderate pressure. Cap member  136  can be coupled to cup-shaped member  132  with an O-ring or gasket  140  and a retaining collar  144 . In the embodiment shown, cup-shaped member  132  has a cylindrical shape with a circular cross-section (e.g., with a diameter of 2 inches or less). In this embodiment, cup-shaped member includes bayonet-style pins  148 ,  152  configured to align with corresponding grooves in head  46   a  of probe  38   a  ( FIG. 4 ) to lock the position of spark head  22   a  relative to the probe. 
     In the embodiment shown, an electrode core  156  having conductors  160   a ,  160   b ,  160   c  and extending through aperture  164 , with the interface between aperture  164  and electrode core  156  sealed with a grommet  168 . In the embodiment shown, a central conductor  160   a  extends through the center of core  156  and serves as a ground to corresponding center electrode  100   a . Peripheral conductors  160   b ,  160   c  are in communication with peripheral electrodes  100   b ,  100   c  to generate sparks across the spark gap between electrodes  100   a  and  100   b , and between electrodes  100   a  and  100   c . It should be understood that while two spark gaps are shown, any number of spark gaps may be used, and may be limited only by the spacing and size of the spark gaps. For example, other embodiments include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark gaps. 
       FIG. 4B  depicts an enlarged cutaway side view of a second embodiment of a removable spark head or module  22   b . In the embodiment shown, spark head or module  22   b  comprises a sidewall  120   a  defining a spark chamber  124   a , and a plurality of electrodes  100   d - 1 ,  100   d - 2 ,  100 ,  100   f  disposed in the spark chamber. In the embodiment shown, spark chamber  124   a  is filled with liquid  128   a  which may be similar to liquid  128  and/or  54 . At least a portion of sidewall  120   a  comprises an acoustically permeable or transmissive material (e.g., a polymer such as polyethylene) configured to permit sound waves and/or shockwaves generated at the electrodes to travel through sidewall  120   a  and through chamber  18   a  ( FIG. 4 ). For example, in the embodiment shown, spark head  22   b  includes a cup-shaped member  132   a  that may be configured to be acoustically reflective and an acoustically permeable cap member  136   a . In this embodiment, cap member  136   a  is dome shaped to approximate the curved shape of an expanding wavefront that originates at the electrodes and to compress the skin when applied with moderate pressure. Cap member  136   a  can be coupled to cup-shaped member  132   a  with an O-ring or gasket (not shown, but similar to  140 ) and a retaining collar  144   a . In the embodiment shown, cup-shaped member  132   a  has a cylindrical shape with a circular cross-section (e.g., with a diameter of 2 inches or less). In some embodiments, cup-shaped member  132   a  can also include bayonet-style pins (not shown, but similar to  148 ,  152 ) configured to align with corresponding grooves in head  46   a  of probe  38   a  to lock the position of spark head  22   b  relative to the probe. 
     In the embodiment shown, conductors  160   d ,  160   e ,  160   f  extending through a rear portion (opposite outlet cap member  136   a ) of cup-shaped member  132   a , as shown. In this embodiment, central conductor  160   d  and peripheral conductors  160   e ,  160   f  can be molded into sidewall  120   a  such that grommets and the like are not necessary to seal the interface between the sidewall and the conductors. In the embodiment shown, a central conductor  160   d  serves as a ground to corresponding center electrodes  100   d - 1  and  100   d - 2 , which are also in electrical communication with each other. Peripheral conductors  160   e ,  160   f  are in communication with peripheral electrodes  100   e ,  100   f  to generate sparks across the spark gap between electrodes  100   d - 1  and  100   e , and between electrodes  100   d - 2  and  100   f . It should be understood that while two spark gaps are shown, any number of spark gaps may be used, and may be limited only by the spacing and size of the spark gaps. For example, other embodiments include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark gaps. 
     In the embodiment shown, central electrodes  100   d - 1  and  100   d - 2  are carried by, and may be unitary with, an elongated member  172  extending into chamber  124   a  toward cap member  136   a  from sidewall  120   a . In this embodiment, member  172  is mounted to a hinge  176  (which is fixed relative to sidewall  120   a ) to permit the distal end of the member (adjacent electrodes  100   d - 1 ,  100   d - 2  to pivot back and forth between electrodes  100   e  and  100   f , as indicated by arrows  180 . In the embodiment shown, the distal portion of member  172  is biased toward electrode  100   e  by spring arms  184 . In this embodiment, spring arms  184  are configured to position electrode  100   d - 1  at an initial spark gap distance from electrode  100   e . Upon application of an electrical potential (e.g., via a pulse-generation system, as described elsewhere in this disclosure) across electrodes  100   d - 1  and  100   e , a spark will arc between these two electrodes to release an electric pulse to vaporize liquid between these two electrodes. The expansion of vapor between these two electrodes drives member  172  and electrode  100   d - 2  downward toward electrode  100   f . During the period of time in which member  172  travels downward, the pulse-generation system can re-charge and apply an electric potential between electrodes  100   d - 2  and  100   f , such that when the distance between electrodes  100   d - 2  and  100   f  becomes small enough, a spark will arc between these two electrodes to release the electric pulse to vaporize liquid between these two electrodes. The expansion of vapor between electrodes  100   d - 2  and  100   f  then drives member  172  and electrode  100   d - 1  upward toward electrode  100   e . During the period of time in which member  172  travels upward, the pulse-generation system can re-charge and apply an electric potential between electrodes  100   d - 1  and  100   e , such that when the distance between electrodes  100   d - 1  and  100   e  becomes small enough, a spark will arc between these two electrodes to release the electric pulse and vaporize liquid between these two electrodes, causing the cycle to begin again. In this way, member  172  oscillates between electrodes  100   e  and  100   f  until the electric potential ceases to be applied to the electrodes. 
     The exposure to high-rate and high-energy electric pulses, especially in liquid, subjects the electrodes to rapid oxidation, erosion, and/or other deterioration that can vary the spark gap distance between electrodes if the electrodes are held in fixed positions (e.g., requiring electrodes to be replaced and/or adjusted). However, in the embodiment of  FIG. 2B , the pivoting of member  172  and electrodes  100   d - 1 ,  100   d - 2  between electrodes  100   e  and  100   f  effectively adjusts the spark gap for each spark. In particular, the distance between electrodes at which current arcs between the electrodes is a function of electrode material and electric potential. As such, once the nearest surfaces (even if eroded) of adjacent electrodes (e.g.,  100   d - 1  and  100   e ) reach a spark gap distance for a given embodiment, a spark is generated between the electrodes. As such, member  172  is configured to self-adjust the respective spark gaps between electrodes  100   d - 1  and  100   e , and between electrodes  100   d - 2  and  100   f.    
     Another example of an advantage of the present movable electrodes, as in  FIG. 4B , is that multiple coils are not required as long as the electrodes are positioned such that only one pair of electrodes is within arcing distance at any given time, and such a single coil or coil system is configured to recharge in less time than it takes for member  172  to pivot from one electrode to the next. For example, in the embodiment of  FIG. 4B , an electric potential may simultaneously be applied to electrodes  100   e  and  100   f  with electrodes  100   d - 1  and  100   d - 2  serving as a common ground, with the electric potential such that a spark will only arc between electrodes  100   d - 1  and  100   e  when member  172  is pivoted upward relative to horizontal (in the orientation shown), and will only arc between electrodes  100   d - 2  and  100   f  when member  172  is pivoted downward relative to horizontal. As such, as member  172  pivots upward and downward as described above, a single coil or coil system can be connected to both of peripheral electrodes  100   e ,  100   f  and alternately discharged through each of the peripheral electrodes. In such embodiments, the pulse rate can be adjusted by selecting the physical properties of member  172  and spring arms  184 . For example, the properties (e.g., mass, stiffness, cross-sectional shape and area, length, and/or the like) of member  172  and the properties (e.g., spring constant, shape, length, and/or the like) of spring arms  184  can be varied to adjust a resonant frequency of the system, and thereby the pulse rate of the spark head or module  22   b . Similarly, the viscosity of liquid  128   a  may be selected or adjusted (e.g., increased to reduce the speed of travel of arm  184 , or decreased to increase the speed of travel of arm  184 ). 
     Another example of an advantage of the present movable electrodes, as in  FIG. 4B , is that properties (e.g., shape, cross-sectional area, depth, and the like) of the electrodes can be configured to achieve a known effective or useful life for the spark head (e.g., one 30-minute treatment) such that spark head  22   b  is inoperative or of limited effectiveness after that designated useful life. Such a feature can be useful to ensure that the spark head is disposed of after a single treatment, such as, for example, to ensure that a new, sterile spark head is used for each patient or area treated to minimize potential cross-contamination between patients or areas treated. 
       FIG. 4C  depicts an enlarged cutaway side view of a third embodiment of a removable spark head or module  22   c . Spark head  22   c  is substantially similar to spark head  22   b , except as noted below, and similar reference numerals are therefore used to designate structures of spark head  22   c  that are similar to corresponding structures of spark head  22   b . The primary difference relative to spark head  22   b  is that spark head  22   c  includes a beam  172   a  that does not have a hinge, such that flexing of the beam itself provides the movement of electrodes  100   d - 1  and  100   d - 2  in the up and down directions indicated by arrows  180 , as described above for spark head  22   b . In this embodiment, the resonant frequency of spark head  22   c  is especially dependent on the physical properties (e.g., mass, stiffness, cross-sectional shape and area, length, and/or the like) of beam  172   a . As described for spring arms  184  of spark head  22   b , beam  172   a  is configured to be biased toward electrode  100   e , as shown, such that electrode  100   d - 1  is initially positioned at an initial spark gap distance from electrode  100   e . The function of spark head  22   c  is similar to the function of spark head  22   b , with the exception that beam  172   a  itself bends and provides some resistance to movement such that hinge  176  and spring arms  184  are unnecessary. 
     In the embodiment shown, spark head  22   b  also includes liquid connectors or ports  188 ,  192  via which liquid can be circulated through spark chamber  124   b . In the embodiment shown, a proximal end  196  of spark head  22   b  serves as a combined connection with two lumens for liquid (connectors or ports  188 ,  192 ) and two or more (e.g., three, as shown) electrical conductors (connectors  160   d ,  160   e ,  160   f ). In such embodiments, the combined connection of proximal end  196  can be coupled (directly or via a probe or handpiece) to a combined tether or cable having two liquid lumens (corresponding to connectors or ports  188 ,  192 ), and two or more electrical conductors (e.g., a first electrical conductor for connecting to connector  160   d  and a second electrical conductor for connecting to both peripheral connectors  160   e ,  160   f ). Such a combined tether or cable can couple the spark head (e.g., and a probe or handpiece to which the spark head is coupled) to a pulse-generation system having a liquid reservoir and pump such that the pump can circulate liquid between the reservoir and the spark chamber. In some embodiments, cap member  136   a  is omitted such that connectors or ports  188 ,  192  can permit liquid to be circulated through a larger chamber (e.g.,  18   a ) of a handpiece to which the spark head is coupled. Likewise, a probe or handpiece to which spark head  22   a  is configured to be coupled can include electrical and liquid connectors corresponding to the respective electrical connectors ( 160   d ,  160   e ,  160   f ) and ports ( 188 ,  192 ) of the spark head such that the electrical and liquid connectors of the spark head are simultaneously connected to the respective electrical and liquid connectors of the probe or handpiece as the spark module is coupled to the handpiece (e.g., via pressing the spark head and probe together and/or a twisting or rotating the spark head relative probe). 
     In the present embodiments, a pulse rate of a few Hz to many KHz (e.g., up to 5 MHz) may be employed. Because the fatiguing event produced by a plurality of pulses, or shockwaves, is generally cumulative at higher pulse rates, treatment time may be significantly reduced by using many moderately-powered shockwaves in rapid succession rather than a few higher powered shockwaves spaced by long durations of rest. As noted above, at least some of the present embodiments (e.g., those with multiple spark gaps) enable electro-hydraulic generation of shockwaves at higher rates. For example,  FIG. 5A  depicts a timing diagram  200  enlarged to show two sequences of voltage pulses  204 ,  208  applied to the electrodes of the present embodiments with a delay period  212  in between, and  FIG. 5B  depicts a timing diagram  216  showing a greater number of voltage pulses applied to the electrodes of the present embodiments. 
     In additional embodiments that are similar to any of spark head  22   a ,  22   b ,  22   c , a portion of the respective sidewall ( 120 ,  120   a ,  120   b ) may be omitted such that the respective spark chamber ( 124 ,  124   a ,  124   b ) is also omitted or left open such that liquid in a larger chamber (e.g.,  18  or  18   a ) of a corresponding handpiece can freely circulate between the electrodes. In such embodiments, the spark chamber (e.g., sidewall  120 ,  120   a ,  120   b  can include liquid connectors or liquid may circulate through liquid ports that are independent of spark chamber (e.g., as depicted in  FIG. 4 ). 
     A series of events (sparks) initiated by a plurality of bursts or groups  204  and  208  delivered with the present systems and apparatuses can comprise a higher pulse rate (PR) that can reduce treatment time relative to lower PRs which may need to be applied over many minutes. The embodiments can be used to deliver shockwaves at the desired pulse rate. 
       FIG. 6  depicts a schematic diagram of one embodiment  400  of a pulse-generation system for use in or with some embodiments of the present systems. In the embodiment shown, circuit  400  comprises a plurality of charge storage/discharge circuits each with a magnetic storage or induction type coil  404   a ,  404   b ,  404   c  (e.g., similar to those used in automotive ignition systems). As illustrated, each of coils  404   a ,  404   b ,  404   c , may be grounded via a resistor  408   a ,  408   b ,  408   c  to limit the current permitted to flow through each coil, similar to certain aspects of automotive ignition systems. Resistors  408   a ,  408   b ,  408   c  can each comprise dedicated resistors, or the length and properties of the coil itself may be selected to provide a desired level of resistance. The use of components of the type used automotive ignition systems may reduce costs and improve safety relative to custom components. In the embodiment shown, circuit  400  includes a spark head  22   b  that is similar to spark head  22   a  with the exceptions that spark head  22   b  includes three spark gaps  412   a ,  412   b ,  412   c  instead of two, and that each of the three spark gaps is defined by a separate pair of electrodes rather than a common electrode (e.g.,  100   a ) cooperating with multiple peripheral electrodes. It should be understood that the present circuits may be coupled to peripheral electrodes  100   b ,  100   c  of spark head  22   a  to generate sparks across the spark gaps defined with common electrode  22   a , as shown in  FIG. 4A . In the embodiment shown, each circuit is configured to function similarly. For example, coil  404   a  is configured to collect and store a current for a short duration such that, when the circuit is broken at switch  420   a , the magnetic field of the coil collapses and generates a so-called electromotive force, or EMF, that results in a rapid discharge of capacitor  424   a  across spark gap  412   a.    
     The RL or Resistor-Inductance time constant of coil  404   a —which may be affected by factors such as the size and inductive reactance of the coil, the resistance of the coil windings, and other factors—generally corresponds to the time it takes to overcome the resistance of the wires of the coil and the time to build up the magnetic field of the coil, followed by a discharge which is controlled again by the time it takes for the magnetic field to collapse and the energy to be released through and overcome the resistance of the circuit. This RL time constant generally determines the maximum charge-discharge cycle rate of the coil. If the charge-discharge cycle is too fast, the available current in the coil may be too low and the resulting spark impulse weak. The use of multiple coils can overcome this limitation by firing multiple coils in rapid succession for each pulse group (e.g.,  204 ,  208  as illustrated in  FIG. 5A ). For example, two coils can double the practical charge-discharge rate by doubling the (combined) current and resulting spark impulse, and three (as shown) can effectively triple the effective charge-discharge rate. When using multiple spark gaps, timing can be very important to proper generation of spark impulses and resulting liquid vaporization and shockwaves. As such, a controller (e.g., microcontroller, processer, FPGA, and/or the like) may be coupled to each of control points  428   a ,  428   b ,  428   c  to control the timing of the opening of switches  420   a ,  420   b ,  420   c  and resulting discharge of capacitors  424   a ,  424   b ,  424   c  and generation of shockwaves. 
       FIG. 7  depicts a block diagram of an embodiment  500  of a radio-frequency (RF) powered acoustic shockwave generation system. In the embodiment shown, system  500  comprises a nonlinear medium  504  (e.g., as in acoustic-delay chamber  58  or nonlinear member described above) that provides an acoustic path to from a transducer  512  to target tissue  508  to produce practical harmonic or acoustic energy (e.g., shockwaves). 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 a pulse generator  528  to produce timed RF pulses that drive amplifier  520  in a predetermined fashion. A typical driving waveform, for example, may comprise a sine wave burst (e.g., multiple sine waves in rapid succession). For example, in some embodiments, a typical burst may have a burst length of 10 milliseconds and comprise sine waves having a period duration of 0.1 (frequency of 100 MHz) to 100 microseconds (frequency of 10 Hz). 
       FIGS. 8A-8B and 9  depict two different spark chamber housings. The embodiments of  FIGS. 8A-8B  depict one embodiment of a spark chamber housing. Housing  600  is similar in some respects to the portion of housing  14   a  that defines head  46   a  of probe  38   a  ( FIG. 4 ). For example, housing  600  includes fittings  604 ,  608  to permit liquid to be circulated through spark chamber  612 . In the embodiment shown, housing  600  includes electrode supports  616  and  620  through which electrodes  624  can be inserted to define a spark gap  628  (e.g., of 0.127 mm or 0.005 inches in the experiments described below). However, housing  600  has an elliptical inner surface shaped to reflect the shockwaves that initially travel backwards from the spark gap into the wall. Doing so has the advantage of producing, for each shockwave generated at the spark gap, a first or primary shockwave that propagates from the spark gap to outlet  640 , followed by a secondary shockwave that propagates first to the elliptical inner wall and is then reflected back to outlet  640 . 
     In this embodiment, supports  616  and  620  are not aligned with (rotated approximately 30 degrees around chamber  612  relative to) fittings  604 ,  608 . In the embodiment shown, housing  600  has a hemispherical shape and electrodes  624  are positioned such that an angle  632  between a central axis  636  through the center of shockwave outlet  640  and a perimeter  644  of chamber  612  is about 57 degrees. Other embodiments can be configured to limit this angular sweep and thereby direct the sound waves and/or shockwaves through a smaller outlet. For example,  FIG. 9  depicts a cross-sectional view of a second embodiment of a spark chamber housing. Housing  600   a  is similar to housing  600 , with the exception that fittings  604   a ,  608   a  are rotated 90 degrees relative to support  620   a . Housing  600   a  also differs in that chamber  612   a  includes a hemispherical rear or proximal portion and a frusto-conical forward or distal portion. In this embodiment, electrodes  624   a  are positioned such that an angle  632   a  between a central axis  636   a  through the center of shockwave outlet  640   a  and a perimeter  644   a  of chamber  612   a  is about 19 degrees. 
       FIG. 10  depicts a schematic diagram of an electric circuit for a prototyped pulse-generation system used with the spark chamber housing of  FIGS. 8A-8B . 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 the relaxation discharge mode with embodiments of the present shockwave heads (e.g.,  46 ,  46   a , etc.). As shown, the circuit comprises a 110V alternating current (AC) power source, an on-off switch, a timer (“control block”), a step-up transformer that has a 3 kV or 3000V secondary voltage. The secondary AC voltage is rectified by a pair of high voltage rectifiers in full wave configuration. These rectifiers charge a pair of oppositely polarized 25 mF capacitors that are each protected by a pair of resistors (100 kΩ and 25 kΩ) in parallel, all of which together temporarily store the high-voltage energy. When the impedance of the shockwave chamber is low and the voltage charge is high, a discharge begins, aided by ionization switches, which are large spark gaps that conduct when the threshold voltage is achieved. A positive and a negative voltage flow to each of the electrodes so the potential between the electrodes can be up to about 6 kV or 6000 V. The resulting spark between the electrodes results in vaporization of a portion of the liquid into a rapidly-expanding gas bubble, which generates a shockwave. During the spark, the capacitors discharge and become ready for recharge by the transformer and rectifiers. In the experiments described below, the discharge was about 30 Hz, regulated only by the natural rate of charge and discharge—hence the term “relaxation oscillation.” In other embodiments, the discharge rate can be higher (e.g., as high as 100 Hz), such as for the multi-gap configuration of  FIG. 6 . 
     A further embodiment  38   b  of the present (e.g., handheld) probes for use with some method embodiments are depicted in  FIGS. 11-13C . Probe  38   b  is similar in some respects to probes  38  and  38   a , and the differences are therefore primarily described here. In this embodiment, probe  38   b  comprises: a housing  14   b  defining a chamber  18   b  and a shockwave outlet  20   b ; a liquid disposed in chamber  18   b ; a plurality of electrodes (e.g., in spark head or module  22   d ) configured to be disposed in the chamber to define one or more spark gaps; and is configured to be coupled to a pulse-generation system (e.g., system  26  of  FIG. 2 ) configured to apply voltage pulses to the electrodes at a rate of 10 Hz to 1000 Hz or at a rate of 10 Hz to 100 Hz. 
     In the embodiment shown, spark head  22   d  includes a housing  120   d  and a plurality of electrodes  100   g  that define a spark gap. In this embodiment, probe  38   b  is configured to permit liquid to be circulated through chamber  18   b  via liquid connectors or ports  112   b  and  116   b , one of which is coupled to spark head  22   d  and the other of which is coupled to housing  14   b , as shown. In this embodiment, housing  14   b  is configured to receive spark head  22   d , as shown, such that housing  14   b  and housing  120   d  cooperate to define chamber  18   b  (e.g., such that spark head  22   d  and housing  14   b  include a complementary parabolic surfaces that cooperate to define the chamber). In this embodiment, housing  14   b  and spark head  22   d  includes acoustically-reflective liners  700 ,  704  that cover their respective surfaces that cooperate to define chamber  18   b . In this embodiment, housing  120   d  of spark head  22   d  includes a channel  188   b  (e.g., along a central longitudinal axis of spark head  22   d ) extending between liquid connector  112   b  and chamber  18   b  and aligned with the spark gap between electrodes  100   g  such that circulating water will flow in close proximity and/or through the spark gap. In the embodiment shown, housing  14   b  includes a channel  192   b  extending between connection  116   b  and chamber  18   b . In this embodiment, housing  120   d  includes a groove  708  configured to receive a resilient gasket or O-ring  140   a  to seal the interface between spark head  22   d  and housing  14   b , and housing  14   b  includes a groove  712  configured to receive a resilient gasket or O-ring  140   b  to seal the interface between housing  14   b  and cap member  136   b  when cap member  136   b  is secured to housing  14   b  by ring  716  and retaining collar  144   b.    
     In the embodiment shown, electrodes  100   g  each includes a flat bar portion  724  and a perpendicular cylindrical portion  728  (e.g., comprising tungsten for durability) in electrical communication (e.g., unitary with) bar portion  724  such that cylindrical portion  728  can extend through a corresponding opening  732  in spark head  22   d  into chamber  18   b , as shown. In some embodiments, part of the sides of cylindrical portion  728  can be covered with an electrically insulative and/or resilient material (e.g., shrink wrap) such as, for example, to seal the interface between portion  728  and sidewall  120   b . In this embodiment, sidewall  120   b  also includes longitudinal grooves  733  configured to receive bar portions  724  of electrodes  100   g . In the embodiment shown, housing  14   b  also includes set screws  736  positioned to align with cylindrical portions  728  of electrodes  100   g  when spark head  22   d  is disposed in housing  14   b , such that set screws  736  can be tightened to press cylindrical portions  728  inward to adjust the spark gap between the cylindrical portions of electrodes  100   g . In some embodiments, spark head  22   d  is permanently adhered to housing  14   b ; however, in other embodiments, spark head  22   d  may be removable from housing  14   b  such as, for example, to permit replacement of electrodes  100   g  individually or as part of a new or replacement spark head  22   d.    
       FIG. 14  depicts a schematic diagram of another embodiment of an electric circuit for a pulse-generation system. The circuit of  FIG. 14  is substantially similar to the circuit of  FIG. 10  with the primary exception that the circuit of  FIG. 14  includes an arrangement of triggered spark gaps instead of ionization switches, and includes certain components with different properties than corresponding components in the circuit of  FIG. 10  (e.g., 200 kΩ resistors instead of 100 kΩ resistors). In the circuit of  FIG. 14 , block “1” corresponds to a primary controller (e.g., processor) and block “2” corresponds to a voltage timer controller (e.g., oscillator), both of which may be combined in a single unit in some embodiments. 
     EXPERIMENTAL RESULTS 
     Experiments were conducted on minipigs to observe effects of EH-generated shockwaves on adipose tissue. 
     Example 1: Adipose Tissue Inflammation 
     A study was undertaken to evaluate the induction of inflammation in subcutaneous fat using high-frequency shockwave. A Gottingen minipig (˜30 Kg) was anesthetized. The mid-ventral sites were prepared by removing the skin hair here using hair clippers and then razor. High-frequency shockwaves were then applied to the two treatment sites. Following the high frequency shockwave treatment, and 48 hours post treatment, biopsies were taken of treatment sites using 3 mm circular punch biopsy instruments. Tissue samples were placed in buffered formalin for microscopic examination. 
     The high frequency shockwave treatment protocols are shown in Table 1. The probe had a 30 mm diameter shockwave outlet window and was configured to generate electrohydraulic shockwaves. All five sites that were treated using different high frequency shockwave settings demonstrated inflammation in the subcutaneous fat. No evidence of cavitation or thermal damage was noted on any of the tissue in the slides. 
     
       
         
           
               
               
               
               
               
             
               
                   
                   
               
               
                   
                 Site 
                 Total J 
                 J/P 
                 Hz 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 4.6 
                 20,700 
                 9.2 
                 25 
               
               
                   
                 4.7 
                 41,400 
                 9.2 
                 25 
               
               
                   
                 4.8 
                 20,700 
                 6.9 
                 33 
               
               
                   
                 4.9 
                 41,400 
                 6.9 
                 33 
               
               
                   
                 4.10 
                 20,700 
                 4.6 
                 50 
               
               
                   
                   
               
            
           
         
       
     
     By way of example, histological evaluations of site 4.6 were conducted on the day of treatment and 2 days post treatment. As noted in Table 1, Site 4.6 was treated using a high frequency shockwave treatment for 90 seconds at 9.2 J/p at a rate of 25 Hz. The adipose tissue demonstrated marked inflammatory cell infiltration two days post treatment indicating that inflammation had been induced. Furthermore, there was no evidence of cavitation, thermal damage or other tissue damage at the treatment site. 
     Example 2: Adipose Tissue Volume Loss 
     A study was undertaken to evaluate subcutaneous volume loss following treatment with high frequency shockwaves. A Gottingen minipig (˜30 Kg) was prepared as described in Example 1. Two separate test sites (1.7, 1.8) were treated using high-frequency shockwaves (9.2j/p, 25 Hz, 240 seconds). The probe had a 30 mm diameter shockwave outlet window and was configured to generate electrohydraulic shockwaves. 
     Two weeks following the high frequency shockwave treatment, the amount of post-treatment volume change was assessed utilizing a Canfield Scientific Vectra three-dimensional camera and software. Volumetric pictures of the test sites (1.7, 1.8) were compared to adjacent control sites (Sites 1.9, 1.10). A loss of volume was indicated from the treated sites (1.7, 1.8). Furthermore, the skin for both test sites demonstrated discoloration of the overlying skin. This is consistent with the appearance skin overlying panniculitis. Thus, the discoloration likely indicates underlying inflammation. 
     Example 3: Lipid Crystallization 
     A study was performed to demonstrate that non-cavitating, non-thermal, high intensity shockwaves when applied to adipose tissue results in the crystallization of the adipocyte lipids. A Gottingen Minipig (˜30 Kg) was prepared as described in Example 1. Site 1.8 after treatment described in Example 2 was measured immediately following the high frequency shockwave treatment. A biopsy was taken of the subcutaneous fat at the treated site. For comparison, a biopsy was taken at a non-treated site. Samples of the biopsied tissues were stored in saline and then prepared for cross-polarized light microscopic examination to see if evidence of crystal nucleation had occurred. To aid in visualizing crystal nucleation, tissue samples were cooled to allow crystal growth at the crystal nucleation sites. 
     Both samples were heated to  45 C, and then cooled to OC for 45 minutes. The treated adipose sample had a luminosity of  34  compared to the control adipose sample&#39;s luminosity of  32 . The bigger the luminosity value the brighter the sample which is indicative of more polarized crystals. Based on this study, the adipose tissue from high frequency shockwave treated sites had evidence of significant crystallization when compared to untreated adipose tissue. 
     The above specification and examples provide a description of the process and use of exemplary embodiments. Although certain embodiments have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the scope of this invention. As such, the various illustrative embodiments of the present methods are not intended to be limited to the particular steps disclosed. Rather, they include all modifications and alternatives falling within the scope of the claims, and embodiments other than the one shown may include some or all of the features of the depicted embodiment. Further, where appropriate, aspects of any of the examples described above may be combined with aspects of any of the other examples described to form further examples having comparable 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 may relate to several embodiments. 
     The claims are not intended to include, and should not be interpreted to include, means-plus- or step-plus-function limitations, unless such a limitation is explicitly recited in a given claim using the phrase(s) “means for” or “step for,” respectively. 
     REFERENCES 
     
         
         [1] Manstein, D; Laubach, H; Watanabe, K; Farinelli, W et al. (2008). “Selective cryolysis: A novel method of non-invasive fat removal”. Lasers in Surgery and Medicine 40 (9): 595-604. 
         [2] Krueger N, Mai S V, Luebberding S, Sadick N S, Cryolipolysis for noninvasive body contouring: clinical efficacy and patient satisfaction. Clinical, Cosmetic and Investigational Dermatology, 2014:7 
         [3] Ferraro G A, De Francesco F, Cataldo C, Rossano F, Nicoletti G, D&#39;Andrea F, Synergistic effects of cryolipolysis and shock waves for noninvasive body contouring. Aesthetic Plast Surg. 2012 June; 36(3):666-7