Aesth Plast Surg DOI 10.1007/s00266-014-0286-6
REVIEW
NON-SURGICAL AESTHETIC
Use of Transcutaneous Ultrasound for Lipolysis and Skin Tightening: A Review Lindsay R. Sklar • Abdel Kader El Tal Leonard Y. Kerwin
•
Received: 31 July 2013 / Accepted: 19 January 2014 Ó Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery 2014
Abstract Several ultrasonic devices have recently been investigated for their ability to decrease areas of focal adiposity and tighten small areas of the skin. Studies show that ultrasound technology offers a safe, reliable, and predictable means to sculpt the body of nonobese patients, but its efficacy remains uncertain. Although most studies claim statistically significant results, the clinical significance of ultrasound technology has yet to be determined. Most studies use waist circumference measurements to determine statistical significance and efficacy. The majority of the current studies also have a relatively a short follow-up period of 3 months. More studies are needed to assess the true efficacy of ultrasound technology using more reliable measurements such as diagnostic ultrasound and computed tomography (CT) imaging and to include a follow-up period longer than 6 months to obtain more valid results. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
L. R. Sklar L. Y. Kerwin Department of Dermatology, Wayne State University, 18100 Oakwood Blvd, Ste 300, Dearborn, MI 48124, USA A. K. El Tal (&) Department of Dermatology, American University of Beirut, 3 DagHammarskjold Plaza, 8th floor, New York, NY 10017-2303, USA e-mail: [email protected]
Keywords Ultrasound Lipolysis Fat destruction Fat dissolution Rejuvenation Tightening Skin
Introduction Ultrasound technology has recently been investigated for a variety of nontraditional applications such as cancer treatment, drug delivery, and cosmetic procedures to sculpt the body by lysing focal areas of adiposity and tightening small areas of skin [1–3]. Although surgical interventions such as liposuction, lipoplasty, face-lifts, and other surgical lifting procedures used for various parts of the body still are considered the gold standards for sculpting the body and lifting the skin, these invasive approaches come with inherent risks including hospitalization and morbidity [4–11]. Noninvasive techniques for battling the visible signs of aging are in high demand. Current methods used to ablate fat and tighten the skin include cryolipolysis, radiofrequency, injection lipolysis, laser ablation, and infrared light sources [4, 12–22]. These less invasive procedures often provide only modest and temporary results [4, 23]. This has prompted the investigation of ultrasound technology as a noninvasive potential alternative option for nonobese patients to lift, tighten, and reduce small areas of unwanted fat and wrinkles. The ability of ultrasound technology to disrupt adipocytes selectively and effectively and to induce a spatial rearrangement of the dermal collagen network and elastic fibers while sparing the epidermis makes ultrasound a unique and distinguished method. In this report, we review the existing literature on the applicability of low-intensity, low-frequency nonthermal (mechanical) focused ultrasound and high-intensity (thermal) focused ultrasound regarding their ability to reduce focal areas of adiposity and tighten the skin.
123
Aesth Plast Surg
Methods A PubMed literature search using the keywords ‘‘ultrasound,’’ ‘‘body contouring,’’ ‘‘intense ultrasound,’’ ‘‘noninvasive lipolysis,’’ ‘‘fat dissolution,’’ ‘‘fat resorption,’’ ‘‘skin tightening,’’ ‘‘high-intensity focused ultrasound,’’ and ‘‘low-intensity low-frequency nonthermal ultrasound’’ was performed. Original articles reporting studies that investigated the application of ultrasound energy to induce lipolysis and skin tightening were reviewed and included. A relevant discussion on the function of the ultrasound is included in this report followed by a critical analysis of the studies available in the literature. The Ultrasounds Ultrasonic waves need a material medium through which to propagate [24, 25]. Sufficient quantities of ultrasound energy absorbed in the tissue induce molecular vibrations that generate heat [26]. Both mechanical and thermal ultrasound energy can lyse adipocytes. Thermal energy also can modify and contract collagen [4]. Ultrasounds operate with frequencies from 20 kHz up to several gigahertz [4, 25]. The higher frequencies are associated with a decreased depth of penetration, whereas the lower frequencies are associated with cavitations [11, 25]. Nonthermal ultrasounds (e.g., low-intensity, low-frequency nonthermal ultrasound) operate at low intensity (17.5 W/cm2) and low frequency (200 kHz) to induce cavitations through mechanical stress while generating minimal heat [4]. Thermal ultrasounds (e.g., high-intensity focused ultrasound [HIFU] and intense ultrasound) use heat as the primary mechanism to ablate adipose tissue and modify collagen [4]. In contrast to HIFU, which operates at intensities exceeding 1,000 W and a frequency of 2 MHz, intense ultrasound tends to avoid cavitations by depositing short pulses within the millisecond domain at lower energies at each site (0.5–10 J/cm2) than does the HIFU (100 J/cm2). Thus, intense ultrasound is ideal for skin tightening, whereas HIFU and low-intensity, low-frequency nonthermal ultrasound is ideal for lipolysis [27]. Ultrasounds for Lipolysis Low-Intensity, Low-Frequency Nonthermal Ultrasound The Contour I device (UltraShape Ltd., Tel Aviv, Israel) was the first noninvasive ultrasound developed for body contouring (Table 1) [28]. The pulse waves of low frequency (200 ± 30 kHz) and low intensity (17.5 W/cm2) induce confined cavitations that create stress and mechanically induced disruption of adipocytes [2, 23, 29–31]. The energy density focuses at the depth of the subcutaneous fat,
123
penetrating 10–30 mm deep and inducing zones of coagulation larger than 100 mm3, whereas the energy delivered through the epidermis and dermis is low (Fig. 1) [23, 32]. Neighboring structures such as skin, blood vessels, and nerves are left unharmed because of the ultrasound’s ability to focus the beam at the depth of the subcutaneous fat in addition to the different susceptibilities these structures have to mechanical stress (compared with adipocytes) [23, 30, 31]. Several studies have analyzed the safety and efficacy of the Contour I device’s ability to reduce local fat deposits (Charts 1 and 2). Teitelbaum et al. [23] investigated the effects of a single 60- to 120-min treatment with the UltraShape device on the abdomen, thighs, or flanks. In their study, 164 subjects (with a fat thickness of at least 1.5 cm in the areas to be treated) were divided into a control group (n = 27) and an experimental group (n = 137). The experimental group received a single treatment that resulted in a mean circumference reduction of 1.9 cm (with an 82 % response rate), assessed by a standardized measuring technique. Diagnostic ultrasound measurements showed a pretreatment fat thickness of 24.7 mm with a 2.9-mm reduction, which was an 11.7 % decrease 28 days after treatment. The peak effects were seen within 2 weeks and sustained during the 12-week follow-up period. The response across each of the clinical sites was comparable, with no statistically significant difference between the two measurement techniques. It would be interesting to have a comparison of the preand posttreatment measurements for each specific body part treated, but the authors did not include these data. Although the authors mention that no statistical weight change occurred, they fail to mention a control for diet or physical activity, which may compromise the results of this study. Moreno-Moraga et al. [30] analyzed the effects of multiple treatments with the UltraShape device in reducing local fat deposits in the abdomen, inner and outer thighs, flanks, inner knees, and breasts (males only). In their study, 30 patients (who had C2 cm of fat in the areas to be treated) underwent a total of three treatments at 1-month intervals. Diagnostic ultrasound and circumference measurements were used to assess efficacy. The investigators noted significant improvement after a single treatment session (1.28 cm reduction in fat thickness by ultrasonographic measurement and 1.88 cm reduction in circumference) as well as incremental improvement with subsequent sessions. After three sessions, a mean cumulative reduction of 2.28 cm in fat thickness and 3.95 cm in circumference was noted. Neither circumference changes nor fat thickness differed significantly across the treated areas. The authors included data on the mean circumference and fat thickness measurements at baseline compared with
Year
2007
2007
2009
2010
Author
Teitelbaum et al. [23]
MorenoMoraga et al. [30]
Shek et al. [33]
Ascher [29]
25
30
164
Participants (n)
The abdomen was treated with three 30- to 90-min ultrasound treatments at 2-week intervals. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
The abdomen or flanks were treated with up to three 2to 3-h ultrasound treatment sessions separated by 1-month intervals. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
The abdomen, inner and outer thighs, flanks, inner knees, or breasts (males only) were treated with three treatments at 1-month intervals. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
The abdomen, thighs, or flanks were treated with a single 60- to 120-min ultrasound treatment. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
Areas and treatment
Diagnostic ultrasound and a standardized measuring apparatus showed a mean reduction of 1.9 cm in treatment area circumference and 2.9 mm reduction in fat thickness. The majority of the effects were seen within the first 2 weeks and sustained at 12 weeks posttreatment. No significant changes in weight or lab values were observed. Mild and transient adverse events were anticipated: mild tingling (n = 1), mild erythema (n = 3), purpuric lesions (n = 1), small blisters (n = 2) Diagnostic ultrasound and circumference measurements showed a mean reduction in fat thickness of 2.28 ± 0.80 cm and a circumference reduction of 3.95 ± 1.99 cm. No changes in lab values or adverse events were observed other than transient blisters (n = 1) due to inadequate contact oil. The majority of the patients (n = 28) reported no pain Objective measurements of the change in abdominal circumference, the change in caliper fat thickness, and the change in ultrasound-measured fat thickness showed no significant difference after treatment
Mean midline circumference measurements (2 cm below midline) showed a 2.47-cm reduction on day 14 after the first treatment, a 3.51-cm reduction on day 56, and a 3.58-cm reduction on day 112. Most patients (n = 14) reported a subjective positive change in body contour. No adverse events occurred. The majority of the subjects (n = 23) reported no pain
No anesthesia or analgesic was used
No anesthesia or analgesic was used
No anesthesia or analgesic was used
Outcome
Pretreatment with a topical anesthetic cream containing lidocaine 2.5 % and prilocaine 2.5 % was applied under occlusion for 90 min
Anesthesia
Table 1 Summary of studies using the low-intensity, low-frequency contour I Ultrashape device to induce lipolysis
Aesth Plast Surg
123
Aesth Plast Surg
Fig. 2 Ecchymosis is the second most common side effect seen with the high-intensity focused ultrasound (HIFU) device. Photo of a patient on day 4 after Liposonix treatment showing ecchymotic areas over the abdomen
Fig. 1 Ultrasounds used to ablate adipose tissue, such as the Liposonix and UltraShape devices, focus their pulses of high energy at the depth of the subcutaneous fat to disrupt discrete areas of adipocytes without damaging neighboring structures. The epidermis and dermis remained unharmed because the energy delivered through these structures is low
Chart 1 Measurement of waist circumference reduction (cm) using standardized measuring techniques in the different UltraShape studies with corresponding numbers of patients
Chart 2 Measurement of fat thickness reduction (cm) using ultrasound in the different UltraShape studies with corresponding numbers of patients
123
the data after the third treatment session for each of the treated areas. The circumference measurements were as follows: the abdomen measured 96.10 cm at baseline and was reduced 4.15 cm (4.3 %); the flanks measured 93.33 cm at baseline and were reduced 2.67 cm (2.9 %); the outer thighs measured 102.15 cm at baseline and were reduced 4.6 cm (4.5 %); the inner thighs measured 60.25 cm at baseline and were reduced 2 cm (3.3 %); the inner knees measured 44.50 cm at baseline and were reduced 2.75 cm (6.2 %); and the pseudogynecomastia measured 112.83 cm at baseline and was reduced 4.5 cm (4 %). The fat thickness measurements were as follows: the abdomen measured 4.35 cm at baseline and was reduced 2.16 cm; the outer thighs measured 5.44 cm at baseline and were reduced 3.02 cm; the flanks measured 3.36 cm at baseline and were reduced 1.63 cm; the breasts measured 3.38 cm at baseline and were reduced 1.88 cm; the knees measured 4.30 cm at baseline and were reduced 2.06 cm; and the inner thighs measured 3.23 cm at baseline and were reduced 0.96 cm. Ascher [29] demonstrated that a reduction in time between treatment intervals yields results comparable with those of prior studies [23, 30]. Ascher’s study included 25 Caucasian women with a body mass index (BMI) of 26 kg/m2 or lower and a mean baseline fat thickness of 3.24 cm. The patients underwent three 30- to 90-min treatments to the abdomen at 2-week intervals [29]. A standardized measuring technique showed reductions in mean abdominal circumference of 2.47 cm on day 14 (after the first treatment), 3.52 cm on day 28, 3.51 cm on day 56, and 3.58 cm (a peak) on day 112 (84 days after the last treatment). The statistically significant decrease in circumference recorded at all intervals increased over time. This study suggests that desired results may be achieved faster than previously thought. Although this study claimed the greatest numbers reported on waist circumference, it did not measure change in fat thickness by ultrasound and did not account for diet control.
Aesth Plast Surg
Shek et al. [33] investigated the efficacy of the UltraShape device in reducing unwanted fat deposits on the abdomen and flanks of 53 Asian patients. Patients who had more than 1.5 cm of fat thickness in the areas to be treated were included in the study. The subjects underwent up to three treatment sessions separated by 1-month intervals. After 3 months, the investigators noted no statistically significant change after treatment, as measured by abdominal circumference, ultrasound fat thickness, and caliper fat thickness. The authors concluded that the UltraShape device was not as effective for Asians as for Caucasians and attributed this finding to the smaller body figures of the Asian subjects. Studies show the UltraShape device to be safe and well tolerated. Treatment has not been associated with any significant changes in lab values including complete blood count, serum chemistry, fasting lipids, liver markers, and serum lipids [23, 30, 33]. Liver ultrasounds assessing for steatosis, urinalysis, and pulse oximetry monitoring showed no changes after treatment [23, 30]. All side effects were mild and transient; pain and bruising were the most common [23, 29, 30]. However, most patients reported no pain, and studies show the procedure to be equally well tolerated without analgesics [29, 30]. Teitelbaum et al. [23] reported seven cases of mild tingling, erythema, purpuric lesions, and small blisters, all of which were anticipated and resolved within the study period. Moreno-Moraga et al. [30] reported one case of blisters attributed to insufficient acoustic contact oil. The UltraShape studies [23, 29, 30] showed no statistically significant weight change in the treatment or control group. Also, no change in the circumference of the internal control (untreated) areas was observed. These two facts support the conclusion that the decrease in fat thickness and circumference may be a result of the ultrasound treatment and not the result of diet or exercise [23, 29, 30]. However, whereas diagnostic ultrasound measurements are reliable, circumference measurements are not. The greatest reported reduction of fat thickness by ultrasound measurement was approximately 2.3 cm [30]. For people with a thin habitus, this might constitute a significant difference, but it surely would not be significant for overweight individuals. Ascher [29] reported that 63 % of patients noted a subjective change in body contour. Although subjective measures are commonly used in cosmetic research, it is the objective measurable and reproducible effect on which clinicians can rely. In addition, these studies had a relatively short follow-up period (the longest being less than 3 months). Additional studies with longer follow up periods and more reliable measuring techniques are needed to determine the true effects and duration of the treatment effects.
The UltraShape manufacturer has just marketed a new version of its machine called UltraShape v3. The advantage of the newer machine over the older model is that it can go to double the power. Hence, it can perform the same treatment in half the time (personal communication with the company). More side effects are expected, but we must wait for more studies to be published.
High-Intensity Focused Ultrasound (HIFU) The Liposonix device (Liposonix system; Medicis Technologies Corporation, Bothell, WA, USA) is Food and Drug Administration (FDA) approved for noninvasive waist circumference reduction (Table 2) [22, 34]. It operates at high frequency (2 MHz) and high intensity ([1,000 W/cm2) to induce temperatures above 58° C localized to a focal point while much lower intensities (1–3 W/cm2) remain at the skin surface. These high temperatures result in coagulative necrosis of adipocytes and thickened, contracted collagen. These changes are localized to a focal targeted area, whereas neighboring structures are left unharmed (Fig. 1) [26, 35–38]. Similar to the low-intensity, low-frequency nonthermal ultrasound, the dead adipocytes attract macrophages that ingest and transport them away from the treatment area, which results in a reduction in local fat volume [21, 35, 39]. Several studies have analyzed the safety and efficacy of the Liposonix device’s ability to reduce local fat deposits (Chart 3). In 2009, Fatemi [35] investigated the ability of the Liposonix device to reduce fat deposits over the anterior abdomen and flanks. In that study, 282 subjects (with C3.3 cm of adipose tissue thickness in the areas to be treated) underwent a single HIFU treatment. A mean total energy of 137 J/cm2 was divided into two passes at different focal depths (1.1–1.8 cm). The total treatment time ranged between 45 and 60 min. At 3 months after treatment, a 4.7-cm reduction in waist circumference was noted, and 70 % of the patients were satisfied with the results. A year after Fatemi’s initial study, Fatemi and Kane [40] performed a retrospective chart review of 85 subjects who underwent a single Liposonix treatment to the anterior abdomen and flanks. All the subjects had a BMI lower than 30 kg/m2 and a fat thickness of 2.6 cm or more in the pre treated areas. They used a mean total energy level of 137 J/cm2, divided into two passes, at a focal depth of 1.1–1.6 cm (determined by the thickness of the adipose tissue being treated). The time required to complete the treatment ranged from 1 to 1.5 h. A mean reduction of 4.6 cm was observed 3 months after treatment. However, neither of the Fatemi studies used an internal control or a radiographic measurement of fat thickness. In addition, they failed to
123
Year
2009
2010
2011
2012
Author
Fatemi [35]
123
Fatemi & Kane [40]
Jewell et al. [41]
Solish et al. [42]
45
180
85
282
Participants (n)
The anterior abdomen underwent a single HIFU treatment of three passes of decreasing depth (1.6, 1.3, and 1.1 cm). Patients were randomly assigned to energy levels of 47, 52, or 59 J/ cm2 (a total energy dose of 141, 156, and 177 J/cm2, respectively)
The anterior abdomen and flanks were treated with a single HIFU treatment of three passes. The subjects were randomly divided 1:1:1: to receive a total dose of either 177, 141, or 0 J/ cm2 (the ‘‘sham’’ group)
The anterior abdomen and flanks were treated with a single HIFU treatment consisting of two passes with the device calibrated to deliver a total energy dose of 104–148 J/cm2 at a focal depth of 1.1–1.6 cm, determined by the amount of adipose in the treated area
The anterior abdomen and flanks were treated using a single HIFU treatment with a mean energy dose of 137 J/cm2 divided into two passes with two different focal depths (1.1–1.8 cm) depending on the thickness of the adipose in the treated tissue
Areas and treatment
At posttreatment week 12 in the ‘‘per-protocol population,’’ treatment with a total dose of 177 J/cm2 (three passes of 59 J/cm2) was associated with a 2.52cm decrease in waist circumference. Treatment with a total dose of 141 J/cm2 (three passes of 47 J/cm2) was associated with a 2.10-cm decrease in waist circumference. The most common adverse events were transient pain, bruising, and edema. Severe treatment pain was reported for three patients in the 47-J/cm2 treatment group and six patients in the 59-J/ cm2 treatment group. One patient in the 59-J/cm2 group reported severe bruising
Analgesic products (primarily acetaminophen, ibuprofen, and naproxen) were administered to 40 patients before, during, or after the procedure at the discretion of the treating investigator. Use of analgesics was greater before than during or after treatment for all treatment groups
At posttreatment week 12, a 2.51-cm reduction in waist circumference was reported for the average of all the treatment groups combined. Each of the three energy levels provided equal effectiveness. Significant results were observed at 1 month in the 59-J/cm2 treatment group and at week 8 in the other groups. The 47-J/cm2 energy level was associated with the least discomfort, and the 59-J/cm2 energy level was associated with the most discomfort. The discomfort was mild overall. The majority of patients reported mild and transient abdominal bruising and redness
After 3 months, a mean energy level of 134.8 J/cm2 resulted in a 4.6 ± 2.4-cm decrease in waist circumference. Adverse events were transient and included prolonged tenderness (n = 3), ecchymosis (n = 3), hard lumps (n = 2), and edema (n = 1). One patient reported significant pain, which prevented completion of treatment
The use of anesthesia or analgesia was not noted
90 % of the patients received analgesic premedication with one to two tablets of 5 mg oxycodone per 325 mg acetaminophen
The waist circumference decreased by an average of 4.7 cm after 3 months. Adverse events were temporary and not serious including prolonged tenderness (n = 10), edema (n = 6), hard lumps (n = 3), ecchymosis (n = 28), and pain during treatment (n = 5). The histology of 30 patients who subsequently underwent abdominoplasty showed well-defined zones of adipocyte necrosis located a safe and consistent distance from the epidermis and dermis and evidence of collagen remodeling
Outcome
The use of anesthesia or analgesia was not noted
Anesthesia
Table 2 Summary of studies using the high-intensity focused ultrasound (HIFU) LipoSonix device to induce lipolysis
Aesth Plast Surg
Energy levels of 47–59 J/cm2 were well tolerated and produced acceptable improvements in localized abdominal fat deposits, whereas higher energy levels induced more adverse events without significantly greater tissue destruction. No biochemical or metabolic abnormalities were reported. A total of 703 adverse events were reported, all of which were temporary and resolved spontaneously. The most commonly reported adverse events included pain, edema, ecchymosis, and dysesthesia. The histology of 30 subjects who underwent abdominoplasty 2 weeks after treatment showed lesions localized to the focal point of subcutaneous adipose tissue without injury to the surrounding tissue The first 120 patients received an unspecified intravenous analgesic before treatment, and the remaining 32 patients received an unspecified oral analgesic before treatment The anterior abdomen and flanks underwent a single (n = 138) or double (n = 14) HIFU treatment consisting of either single or multiple passes for a total energy dose of 47–331 J/cm2. Abdominoplasty was performed 14 weeks after the HIFU procedure, and a histopathologic analysis of the excised tissue was preformed 2011 Gadsden et al. [38]
152
Year Author
Table 2 continued
Participants (n)
Areas and treatment
Anesthesia
Outcome
Aesth Plast Surg
control for weight, diet, or exercise. Thus, the validity of these results is compromised. Jewell et al. [41] found less drastic results 3 months after treatment with the Liposonix device to the abdomen and flanks. The subjects with an abdominal fat thickness of 2.5 cm or more were randomized to receive a total of 47, 59, or 0 J/cm2 (the ‘‘sham’’ group) divided into three passes. The treatment time ranged from 42.7 min (59-J/cm2 treatment group) to 47.4 min (47-J/cm2 treatment group). A standardized measuring technique with a tape measure showed a waist circumference reduction of 2.52 cm in the 59-J/cm2 group and 2.21 cm in the 47-J/cm2 group among the subjects who did not violate the treatment protocol (i.e., the 168 patients who did not change their diet or exercise routine or use any substance for weight loss). The ability of the Liposonix device to sculpt the abdomen yielded results in the study of Solish et al. [42] comparable with those in the study of Jewell et al. [41]. In the Solish et al. [42] study, 45 subjects (with a BMI of 30 kg/m2 or lower and an adipose tissue thickness of 2.6 cm or more in the areas to be treated) underwent three ultrasound passes of decreasing depths (1.6, 1.3, and 1.1 cm) and randomized total energy levels (141, 156, or 177 J/cm2 divided into three passes). An average reduction in waist circumference of 2.51 cm was noted 3 months after treatment, and 69–85 % of the patients were satisfied with these results. The patients did not change their diet or exercise routines, and no significant weight change occurred throughout the study. No significant difference between the treatment groups was noted at any time point, indicating that a higher energy level may not be necessary to achieve better overall results. Gadsden et al. [38] assessed the histopathologic changes induced by the Liposonix device at energies of 47–331 J/cm2 to suggest that lower energy levels are optimal. In their study, 30 patients with a BMI of 30 kg/m2 or less and at least 2 cm of abdominal fat underwent abdominoplasty 2 weeks after ultrasound treatment. Energy levels of 47–59 J/cm2 were well tolerated and reduced areas of localized abdominal fat deposits to an amount statistically comparable with those at higher energy levels but resulted in more adverse events. When control was used for body weight, it did not fluctuate substantially in the Liposonix studies, which may suggest that the reduction in waist circumference was a result of the ultrasound treatment [41, 42]. When control is not used for external factors that influence body weight, the validity of the results is truly compromised. More studies controlling for these factors are needed. Unfortunately, none of the Liposonix studies have used any radiologic imaging to assess for the change in fat thickness. This puts the relevance of these results in question. More studies using imaging, such as diagnostic ultrasound and computed tomography (CT) technology, as a measure of fat thickness may offer more valid results.
123
Aesth Plast Surg
Chart 3 Measurement of waist circumference reduction (cm) using standardized measuring techniques in the different Liposonix studies with corresponding numbers of patients
The Liposonix device is safe and well tolerated. The vast majority of adverse events are mild and transient and most commonly include pain (even with the use of analgesics), tenderness, edema, hard lumps, and ecchymosis (Fig. 2) [35, 38, 40–42]. In isolated cases, the adverse events are more severe. In the study by Fatemi and Kane [40] the pain of one subject was severe enough to prevent completion of treatment. Adverse events, such as pain and dysesthesias, are more common and longer lasting with higher energy settings [38, 41, 42]. Jewell et al. [41] reported one rare case of severe bruising induced by 59 J/cm2 of energy. The Liposonix device yields no significant change in the lab values of lipid profiles, liver enzymes, renal function, coagulation, or creatinine phosphokinase [38, 41].
Ultrasounds for Skin Lifting and Tightening Intense ultrasounds work by using energy to vibrate tissue and cause friction between molecules, which secondarily generates heat to induce coagulation. The Ulthera device (Ulthera Inc., Mesa, AZ, USA), specifically developed to lift and tighten the skin, is FDA approved for the noninvasive lifting of lax tissue on the neck and submentum [5]. It acts by targeting the superficial musculoaponeurotic system (SMAS), in which its microthermal lesions create a zone of coagulation of about 1 mm, reaching the mid to deep reticular dermis up to the fibromuscular layer (Table 3; Fig. 3) [3, 12, 32, 39, 43]. The SMAS is a continuous fibromuscular layer of tissue that invests and interlinks the muscles of facial expression [44–46]. The waves penetrate 4–5 mm into the facial skin to deliver focal, intense, discrete, linear pulses 20–50 ms long [32]. The device focuses its energy to induce a 25-mm line of discrete lesions spaced 0.5–5.0 mm apart [43]. The thermal injury results in collagen contraction, tissue coagulation, and new collagen deposition [12, 27, 32, 43, 47].
123
White et al. [43] were the first to report the ability of the Ulthera device to induce focused, discrete, and reproducible zones of thermal collagen denaturation in the SMAS. The thermal injury zones (TIZs) reached as far as 7.8 mm and spared neighboring tissue in each of the six human cadaveric specimens. The researchers used two hand pieces, which operated at 7.5 and 4.4 MHz (at a fixed focal depth of 4.5 mm), as well as varying combinations of power and exposure time at energies ranging from 0.5 to 8.0 J/cm2. Higher energy settings and higher density exposures resulted in a greater degree of tissue shrinkage. Other investigators have confirmed these findings on cadaveric and porcine skin [48, 49]. Using porcine skin, White et al. [49] later found that increasing energies caused the TIZs to grow larger by growing toward the tissue surface. Gliklich et al. [47] evaluated the histologic effects of the Ulthera device on the face and neck of live humans. In their study, 15 subjects were pretreated using one of three hand pieces with different frequencies and focal depths (7.5 MHz, 3 mm; 7.5 MHz, 4.5 mm; and 4.4 MHz, 4.5 mm). In contrast to previous studies, increasing source power was not associated with an increase in the depth of the TIZ. Histologic evaluation 24 h after treatment confirmed the observations in their previous study [43]. No significant changes were noted 4–12 weeks after treatment, suggesting that the tissue had time to recover. Alam et al. [32] were the first to investigate the efficacy of the Ulthera ultrasonic device in assessing skin tightening for live patients whose skin was not resected. The entire face of 35 subjects underwent a single ultrasound treatment with probes of different frequencies and focal depths (7 MHz, 3 mm; 7 MHz, 4.5 mm, and 4 MHz, 4.5 mm) selected according to the thickness of the tissue at each of the anatomic landmarks. At posttreatment day 90, the mean average elevation in eyebrow height (measured objectively with photography) was 1.7–1.9 mm. Although these statistically significant results seem minimal, three masked clinicians assessed pre- and postoperative photos to judge clinically significant results in 86 % of the patients. Compared with the normal distance of 2.5 cm between the midpupillary line and the upper edge of the eyebrow hair, 1.9 mm constitutes a change of only 7 % at most [50]. Suh et al. [27] analyzed the efficacy of a single treatment with the Ulthera device in lifting the skin of the face of 22 Koreans with facial laxity. Specific probe selection (7.5 MHz, 3 mm or 4.4 MHz, 4.5 mm) was based on the thickness of the tissue at each of the anatomic landmarks. After 2 months, two blinded clinicians noted an improvement in the nasolabial folds and jaw lines of all the subjects, assessed by pre- and postoperative photos. More than 70 % of the subjects noted much improvement in their own nasolabial folds and jaw lines. Biopsies at this time showed increased dermal collagen fibers in the reticular dermis,
Year
2007
2010
2011
2011
Author
Gliklich et al. [47]
Alam et al. [32]
Chan et al. [12]
Suh et al. [27]
22 (Korean patients)
49 (Chinese patients)
36
15
Participants (n)
The forehead, temples, cheeks, infraorbital, and preauricular areas underwent a single pass of one to three ultrasound treatments. Depending on the amount of subcutaneous soft tissue of the anatomic location, patients were treated with one of the following transducers: 7 MHz, 3-mm focal depth; 7 MHz, 4.5-mm focal depth; or 4 MHz, 4.5-mm focal depth The forehead, temples, malar area, cheeks, and submentum were treated with a single pass of either probe depending on the amount of subcutaneous soft tissue of the anatomic location: 7.5 MHz, 3-mm focal depth or 4.4 MHz, 4.5-mm focal depth
The forehead, temples, cheeks, submentum, and sides of the neck underwent a single treatment with the following probes depending on the amount of subcutaneous soft tissue of the anatomic location: 4 MHz, 4.5-mm focal depth; 7 MHz, 4.5-mm focal depth, or 7 MHz, 3-mm focal depth
The entire face and neck underwent a single treatment with one of the following transducers depending on the amount of subcutaneous soft tissue within the anatomic location: 7.5 MHz, 3-mm focal depth; 7.5 MHz, 4.5-mm focal depth; or 4.4 MHz, 4.5-mm focal depth. The subjects were divided into two groups: immediate (those undergoing face-lift within 24 h after ultrasound treatment) and delayed (those undergoing face-lift within 4–12 weeks after ultrasound treatment)
Areas and treatment
Topical (unspecified) anesthetic cream was applied 60 min before the procedure
No oral analgesia or topical anesthetics were used
Topical 7 %/7 % lidocaine was applied 45 min before the procedure
Topical anesthetic cream containing 2.5 % lidocaine and 2.5 % prilocaine was applied 45 min before treatment
Anesthesia
Table 3 Summary of studies using the intense ultrasound Ulthera device to lift and tighten skin
Nasolabial folds and jaw lines significantly improved in all the patients, assessed by photographs. Subjectively, 77 % of the patients reported improvement in nasolabial folds, and 73 % reported improvement in the jaw line. The reported pain was no more than minimal. Mild and transient erythema and edema were noted by all the subjects. White wheals were observed on the cheek and submentum of two subjects with the use of the 4.5-mm probe. Four patients reported temporary numbness in the mandible. Histologic evaluation of the 11 biopsies of the skin showed an increased amount of dermal collagen with thickening of the dermis and straightening of the elastic fibers in the reticular dermis
Most subjects reported transient erythema and edema. Focal bruising accompanied 25 % of the treatment sessions. PIH was seen on the forehead 1 month after treatment in two subjects. Severe pain was associated with 54 % of the treatment sessions
Mean brow height elevation measured by photographs 90 days after treatment was 1.7 mm. All subjects experienced immediate erythema and edema, which resolved at 1 week. During treatment, the majority of patients reported pain no greater than 4/10, but five patients reported pain greater than 7/10. Two patients treated with the 3-mm probe experienced transient elevated white striations on the neck
TIZs, which were consistently wide and deep focal areas of denatured collagen localized to the dermis and subcutaneous tissue, were induced at an exposure threshold of 0.5 J/cm2 primarily in the immediate treatment group. This threshold was associated with transient erythema and slight to mild discomfort. Increasing the power did not increase the depth of the thermal injury zones. When the hand pieces were compared under similar source conditions, the superficial hand piece (7.5 MHZ, 3-mm focal depth) was more tolerable than the intermediate (7.5 MHZ, 4.5-mm focal depth) and deep (4.4 MHZ, 4.5-mm focal depth) hand pieces. An inflammatory wheal, which resolved within 48 h, was induced in two patients treated with the superficial hand piece at 1 J/cm2
Outcome
Aesth Plast Surg
123
123
Fig. 3 Ultrasounds used to tighten and lift the skin, such as the Ulthera device, target the superficial musculoaponeurotic system (SMAS) and induce microthermal lesions that reach the mid to deep reticular dermis up to the fibromuscular layer. The focal, intense, discrete linear pulses result in thermally induced collagen contraction while sparing the epidermis, dermis, and neighboring structures
TIZ thermal injury zone, PIH postinflammatory hyperpigmentation
Photographs showed significant improvement in all treated areas, with upper arms and knees showing more skin lifting and tightening than in the thighs. Dual probe passes showed slightly better results in all three sites. Discomfort levels were reported as mild to moderate. Side effects of erythema, warmth, and tenderness were mild and transient. Focal bruising was noted on the upper arms of two patients Oral diazepam (5–10 mg) and intramuscular injection of meperidine (50 mg) were administered 20 to 30 min before treatment 2012 Alster and Tanzi [51]
18
The upper arms, medial thighs, and extensor knees were randomly treated with either transducer: 4 MHz, 4.5-mm focal depth or 7 MHz, 3-mm focal depth. A single pass with the 4-MHz transducer was randomly assigned to one side of the body, whereas the contralateral side received an additional pass with the 7-MHz transducer
Outcome Participants (n) Year Author
Table 3 continued
Areas and treatment
Anesthesia
Aesth Plast Surg
with increased parallelism of elastic fibers, resulting in an increased dermal thickness (1.32 ± 0.18 mm before treatment vs 1.63 ± 0.31 mm after treatment). Alster and Tanzi [51] analyzed the efficacy of the Ulthera device for nonfacial areas of the body. They treated one side of the upper arms, medial thighs, and knees with a single pass of a 4-MHz, 4.5-mm-depth transducer, and the contralateral side with an additional pass of a 7-MHz, 3-mm transducer. Using standardized photographs, two masked clinicians noted significant improvement in all treated areas, which showed continued improvement 3–6 months after treatment. The upper arms and knees showed more lifting and tightening than the thighs. Although both sides exhibited significantly improved skin contours, the side exposed to two passes showed better clinical outcomes. The authors recommended repeating the treatment every 3–6 months to maintain the outcome given the significant improvement seen at 3 months compared with the slight continued improvement at 6 months. As noted from the aforementioned studies, most of the Ulthera studies relied on subjective measurement tools or a pathologic assessment on a short-term basis. The only study by Alam et al. [32] that assessed skin contracture objectively found at most a 7 % change. The Ulthera device appears to offer a safe procedure because adverse events are mild and transient. No severe
Aesth Plast Surg
adverse events have been reported other than severe pain reported by 54 % of the subjects in a study that used no anesthetics [12]. Mild erythema and edema are the most common of these events [27, 32, 47, 51]. Whereas some investigators have observed a complete resolution of erythema within 2 h [51], others have reported a 90–100 % resolution of the erythema and edema 1 week after treatment [12, 32]. Mild to moderate discomfort often is induced, even with the use of analgesics [27, 32, 47, 51]. Increased power and focal depth settings appear to be associated with more pain [47]. Less common adverse reactions have been reported. Inflammatory wheals have been reported in four subjects, which resolved within 48 h. Two of these subjects were treated with a 4.4-MHz, 4.5-mm probe [27], whereas the remaining two were treated with a more superficial 7.5-MHZ, 3-mm probe [47]. The investigators attributed this occurrence to inadequate uncoupling of heat energy to the skin during treatment [27]. Two subjects treated with the 7.5-MHz, 3-mm probe experienced the development of elevated white linear striations on the neck, which resolved within 1 week using topical steroids [32]. The 7-MHz, 4.5-mm probe was not associated with any further occurrences. It was reassuring that the deeper probe directed energy into the subcutis (beyond the papillary dermis which was more vulnerable to injury) [32]. Several cases of mandibular numbness, tenderness, and focal bruising have been reported, all of which resolved within 1–3 weeks [12, 27, 51]. Two cases of postinflammatory hyperpigmentation (PIH) on the forehead of Asian skin have been reported 1 month after treatment with a 7-MHz, 4.5-mm transducer (pulse energy, 1.05 J/cm2) [12]. Because ultrasound energy is not absorbed by melanin, the PIH likely was the result of underlying inflammation and not a direct effect of the ultrasound. After replacement with a more superficial 7-MHz, 3-mm transducer, no more cases of PIH were observed.
Conclusion Ultrasound devices may offer a noninvasive and safe procedure that can be performed in the clinical setting to decrease focal areas of adiposity and tighten skin. However, their efficacy remains uncertain. The results of the current studies have relied mostly on subjective assessment. Although the absolute values of the circumference and fat thickness reduction may be significant, the objective assessments indicate that the results are minimal at most. Further rigorous studies are definitely needed for effective evaluation of these devices, especially considering the large media coverage they have received and the high charges that patients are paying for treatment.
It must be noted that ultrasounds for lipolysis and lifting are not a replacement for liposuction, nor are they a replacement for excisional and lifting surgery. They are targeted to a specific clientele with a BMI lower than 30 kg/m2 who are seeking minimal touchups in body contour and minor skin lifts. Future studies must obtain more accurate measurements of fat reduction by using diagnostic ultrasound or CT imaging. Additionally, future studies must include longer follow-up periods as well as clinical and histologic assessments at fixed intervals after treatment. Most studies do not follow the patient longer than 3 months, but one study using the Ulthera device found continued improvement at the 6-month mark [51]. Another study of the UltraShape device also noted persistent results at 12 weeks. However, none of these studies reported results beyond 6 months although the machines have been available on the market longer than 3 years [23, 29]. A maximum follow-up period of 3 months is not sufficient because continued efficacy, and in some cases, peak results are noted at this time. It would be beneficial to know how long the effects of the ultrasound treatment last in order to develop recommendations for follow-up treatments and optimal results. Conflict of interest The authors declare that they have no conflicts of interest to disclose.
References 1. Hwang JH, Crum LA (2009) Current status of clinical highintensity focused ultrasound. Conf Proc IEEE Eng Med Biol Soc 2009:130–133 2. Kennedy JE, Ter Haar GR, Cranston D (2003) High-intensity focused ultrasound: surgery of the future? Br J Radiol 76:590–599 3. Capla JM, Rubin JP (2011) Discussion: randomized sham-controlled trial to evaluate the safety and effectiveness of a highintensity focused ultrasound device for noninvasive body sculpting. Plast Reconstr Surg 128:263–264 4. Jewell ML, Solish NJ, Desilets CS (2011) Noninvasive body sculpting technologies with an emphasis on high-intensity focused ultrasound. Aesthetic Plast Surg 35:901–912 5. LipoSonix. Retrieved at http://liposonix.com/. Accessed 18 Dec 2013 6. Hughes CE III (2001) Reduction of lipoplasty risks and mortality: an ASAPS survey. Aesthet Surg J 21:120–127 7. Lehnhardt M, Homann HH, Daigeler A, Hauser J, Palka P, Steinau HU (2008) Major and lethal complications of liposuction: a review of 72 cases in Germany between 1998 and 2002. Plast Reconstr Surg 121:396e–403e 8. Grazer FM, Grazer FM, de Jong RH (2000) Fatal outcomes from liposuction: census survey of cosmetic surgeons. Plast Reconstr Surg 105:436–446 discussion 47–48 9. Commons GW, Halperin B, Chang CC (2001) Large-volume liposuction: a review of 631 consecutive cases over 12 years. Plast Reconstr Surg 108:1753–1763 discussion 64–67 10. Jewell ML (2001) Prevention of deep vein thrombosis in aesthetic surgery patients. Aesthet Surg J 21:161–163
123
Aesth Plast Surg 11. Triana L, Triana C, Barbato C, Zambrano M (2009) Liposuction: 25 years of experience in 26,259 patients using different devices. Aesthet Surg J 29:509–512 12. Chan NP, Shek SY, Yu CS, Ho SG, Yeung CK, Chan HH (2011) Safety study of transcutaneous focused ultrasound for noninvasive skin tightening in Asians. Lasers Surg Med 43:366–375 13. Avram MM (2004) Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther 6:181–185 14. Sadick NS, Mulholland RS (2004) A prospective clinical study to evaluate the efficacy and safety of cellulite treatment using the combination of optical and RF energies for subcutaneous tissue heating. J Cosmet Laser Ther 6:187–190 15. van Vliet M, Ortiz A, Avram MM, Yamauchi PS (2005) An assessment of traditional and novel therapies for cellulite. J Cosmet Laser Ther 7:7–10 16. Coleman KM, Coleman WP III, Benchetrit A (2009) Noninvasive, external ultrasonic lipolysis. Semin Cutan Med Surg 28:263–267 17. Atiyeh BS, Dibo SA (2009) Nonsurgical nonablative treatment of aging skin: radiofrequency technologies between aggressive marketing and evidence-based efficacy. Aesthetic Plast Surg 33:283–294 18. Manuskiatti W, Wachirakaphan C, Lektrakul N, Varothai S (2009) Circumference reduction and cellulite treatment with a TriPollar radiofrequency device: a pilot study. J Eur Acad Dermatol Venereol 23:820–827 19. Caruso-Davis MK, Guillot TS, Podichetty VK, Mashtalir N, Dhurandhar NV, Dubuisson O et al (2011) Efficacy of low-level laser therapy for body contouring and spot fat reduction. Obes Surg 21:722–729 20. Jackson RF, Dedo DD, Roche GC, Turok DI, Maloney RJ (2009) Low-level laser therapy as a noninvasive approach for body contouring: a randomized, controlled study. Lasers Surg Med 41:799–809 21. Fodor PB SB, Stecco KA, Desilets CS (2006): Biochemical Changes in Adipocytes and Lipid Metabolism Secondary to the Use of High-Intensity Focused Ultrasound for Noninvasive Body Sculpting. Presented at the annual meeting of the American Society of Aesthetic Plastic Surgery, Orlando, FL 22. Weiss M (2012) Commentary: noninvasive skin tightening: ultrasound and other technologies: where are we in 2011? Dermatol Surg 38:28–30 23. Teitelbaum SA, BurTeitelbaum SA, Burns JL, Kubota J, Matsuda H, Otto MJ, Shirakabe Y et al (2007) Noninvasive body contouring by focused ultrasound: safety and efficacy of the Contour I device in a multicenter, controlled, clinical study. Plast Reconstr Surg 120:779–789 discussion 90 24. O’Brien WD Jr (2007) Ultrasound-biophysics mechanisms. Prog Biophys Mol Biol 93:212–255 25. Quistgaard JU, Desilets C, Martin P (2010) High-Intensity Focused Ultrasound. Retrieved xxxx at http://digital.miinews. com/publication/?i=34631&page=1: Medicis Technologies Corporation, Bothell, WA. Accessed 18 Dec 2013 26. Haar GT, Coussios C (2007) High-intensity focused ultrasound: physical principles and devices. Int J Hyperthermia 23:89–104 27. Suh DH, Shin MK, Lee SJ, Rho JH, Lee MH, Kim NI et al (2011) Intense focused ultrasound tightening in Asian skin: clinical and pathologic results. Dermatol Surg 37:1595–1602 28. UltraShapeÒ V3 Body Shaping via Fat Cell Destruction. Retrieved xxxxx at http://syneron-candela.com/int/product/ ultrashape: SyneronÒ Medical Ltd., 2012. Accessed 18 Dec 2013 29. Ascher B (2010) Safety and efficacy of UltraShape Contour I treatments to improve the appearance of body contours: multiple treatments in shorter intervals. Aesthet Surg J 30:217–224 30. Moreno-Moraga J, Valero-Altes T, Riquelme AM, Isarria-Marcosy MI, de la Torre JR (2007) Body contouring by noninvasive transdermal focused ultrasound. Lasers Surg Med 39:315–323
123
31. Brown SA, Greenbaum L, Shtukmaster S, Zadok Y, Ben-Ezra S, Kushkuley L (2009) Characterization of nonthermal focused ultrasound for noninvasive selective fat cell disruption (lysis): technical and preclinical assessment. Plast Reconstr Surg 124:92–101 32. Alam M, White LE, Martin N, Witherspoon J, Yoo S, West DP (2010) Ultrasound tightening of facial and neck skin: a raterblinded prospective cohort study. J Am Acad Dermatol 62:262–269 33. Shek S, Yu C, Yeung CK, Kono T, Chan H (2009) The use of focused ultrasound for noninvasive body contouring in Asians. Laser Surg Med 41:751–759 34. Medicis Announces FDA Clearance of LIPOSONIX(R) System. Investor Relations Press Releases. Retrieved xxxx at http://www. globenewswire.com/newsarchive/mrx/pages/news_releases.html? d=231745. Accessed 18 Dec 2013 35. Fatemi A (2009) High-intensity focused ultrasound effectively reduces adipose tissue. Semin Cutan Med Surg 28:257–262 36. Avelar J (1989) Regional distribution and behavior of the subcutaneous tissue concerning selection and indication for liposuction. Aesthetic Plast Surg 13:155–165 37. Ferraro GA, De Francesco F, Nicoletti G, Rossano F, D’Andrea F (2008) Histologic effects of external ultrasound-assisted lipectomy on adipose tissue. Aesthetic Plast Surg 32:111–115 38. Gadsden E, Aguilar MT, Smoller BR, Jewell ML (2011) Evaluation of a novel high-intensity focused ultrasound device for ablating subcutaneous adipose tissue for noninvasive body contouring: safety studies in human volunteers. Aesthet Surg J 31:401–410 39. Garcia-Murray E, Rivas O, Stecco K, Desilets C, Kunz L: The Use and Mechanism of Action of High-Intensity Focused Ultrasound for Adipose Tissue Removal and Noninvasive Body Sculpting. Presented at the annual meeting of the American Society of Plastic Surgeons, Chicago, IL, 2005 40. Fatemi A, Kane MA (2010) High-intensity focused ultrasound effectively reduces waist circumference by ablating adipose tissue from the abdomen and flanks: a retrospective case series. Aesthetic Plast Surg 34:577–582 41. Jewell ML, Baxter RA, Cox SE, Donofrio LM, Dover JS, Glogau RG et al (2011) Randomized sham-controlled trial to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for noninvasive body sculpting. Plast Reconstr Surg 128:253–262 42. Solish N, Lin X, Axford-Gatley RA, Strangman NM, Kane M (2012) A randomized, single-blind, postmarketing study of multiple energy levels of high-intensity focused ultrasound for noninvasive body sculpting. Dermatol Surg 38:58–67 43. White WM, Makin IR, Barthe PG, Slayton MH, Gliklich RE (2007) Selective creation of thermal injury zones in the superficial musculoaponeurotic system using intense ultrasound therapy: a new target for noninvasive facial rejuvenation. Arch Facial Plast Surg 9:22–29 44. Larrabee WFJ MK, Henderson JL: Surgical Anatomy of the Face: Superficial Musculoaponeurotic System. In: Merritt J (ed) Lippincott, Williams, and Wilkins, Philadelphia, PA, 2004 45. Mendelson BC (2001) Surgery of the superficial musculoaponeurotic system: Principles of release, vectors, and fixation. Plast Reconstr Surg 107:1545–1552 discussion 53–55, 56–57, 58–61 46. Har-Shai Y, Bodner SR, Egozy-Golan D, Lindenbaum ES, BenIzhak O, Mitz V et al (1996) Mechanical properties and microstructure of the superficial musculoaponeurotic system. Plast Reconstr Surg 98:59–70 discussion 1–3 47. Gliklich RE, White WM, Slayton MH, Barthe PG, Makin IR (2007) Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues. Arch Facial Plast Surg 9:88–95
Aesth Plast Surg 48. Laubach HJ, Makin IR, Barthe PG, Slayton MH, Manstein D (2008) Intense focused ultrasound: evaluation of a new treatment modality for precise microcoagulation within the skin. Dermatol Surg 34:727–734 49. White WM, Makin IR, Slayton MH, Barthe PG, Gliklich R (2008) Selective transcutaneous delivery of energy to porcine soft tissues using intense ultrasound (IUS). Lasers Surg Med 40:67–75
50. McKinney P, Mossie RD, Zukowski ML (1991) Criteria for the forehead lift. Aesthetic Plast Surg 15:141–147 51. Alster TS, Tanzi EL (2012) Noninvasive lifting of arm, thigh, and knee skin with transcutaneous intense focused ultrasound. Dermatol Surg 38:754–759
123
REVIEW
NON-SURGICAL AESTHETIC
Use of Transcutaneous Ultrasound for Lipolysis and Skin Tightening: A Review Lindsay R. Sklar • Abdel Kader El Tal Leonard Y. Kerwin
•
Received: 31 July 2013 / Accepted: 19 January 2014 Ó Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery 2014
Abstract Several ultrasonic devices have recently been investigated for their ability to decrease areas of focal adiposity and tighten small areas of the skin. Studies show that ultrasound technology offers a safe, reliable, and predictable means to sculpt the body of nonobese patients, but its efficacy remains uncertain. Although most studies claim statistically significant results, the clinical significance of ultrasound technology has yet to be determined. Most studies use waist circumference measurements to determine statistical significance and efficacy. The majority of the current studies also have a relatively a short follow-up period of 3 months. More studies are needed to assess the true efficacy of ultrasound technology using more reliable measurements such as diagnostic ultrasound and computed tomography (CT) imaging and to include a follow-up period longer than 6 months to obtain more valid results. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
L. R. Sklar L. Y. Kerwin Department of Dermatology, Wayne State University, 18100 Oakwood Blvd, Ste 300, Dearborn, MI 48124, USA A. K. El Tal (&) Department of Dermatology, American University of Beirut, 3 DagHammarskjold Plaza, 8th floor, New York, NY 10017-2303, USA e-mail: [email protected]
Keywords Ultrasound Lipolysis Fat destruction Fat dissolution Rejuvenation Tightening Skin
Introduction Ultrasound technology has recently been investigated for a variety of nontraditional applications such as cancer treatment, drug delivery, and cosmetic procedures to sculpt the body by lysing focal areas of adiposity and tightening small areas of skin [1–3]. Although surgical interventions such as liposuction, lipoplasty, face-lifts, and other surgical lifting procedures used for various parts of the body still are considered the gold standards for sculpting the body and lifting the skin, these invasive approaches come with inherent risks including hospitalization and morbidity [4–11]. Noninvasive techniques for battling the visible signs of aging are in high demand. Current methods used to ablate fat and tighten the skin include cryolipolysis, radiofrequency, injection lipolysis, laser ablation, and infrared light sources [4, 12–22]. These less invasive procedures often provide only modest and temporary results [4, 23]. This has prompted the investigation of ultrasound technology as a noninvasive potential alternative option for nonobese patients to lift, tighten, and reduce small areas of unwanted fat and wrinkles. The ability of ultrasound technology to disrupt adipocytes selectively and effectively and to induce a spatial rearrangement of the dermal collagen network and elastic fibers while sparing the epidermis makes ultrasound a unique and distinguished method. In this report, we review the existing literature on the applicability of low-intensity, low-frequency nonthermal (mechanical) focused ultrasound and high-intensity (thermal) focused ultrasound regarding their ability to reduce focal areas of adiposity and tighten the skin.
123
Aesth Plast Surg
Methods A PubMed literature search using the keywords ‘‘ultrasound,’’ ‘‘body contouring,’’ ‘‘intense ultrasound,’’ ‘‘noninvasive lipolysis,’’ ‘‘fat dissolution,’’ ‘‘fat resorption,’’ ‘‘skin tightening,’’ ‘‘high-intensity focused ultrasound,’’ and ‘‘low-intensity low-frequency nonthermal ultrasound’’ was performed. Original articles reporting studies that investigated the application of ultrasound energy to induce lipolysis and skin tightening were reviewed and included. A relevant discussion on the function of the ultrasound is included in this report followed by a critical analysis of the studies available in the literature. The Ultrasounds Ultrasonic waves need a material medium through which to propagate [24, 25]. Sufficient quantities of ultrasound energy absorbed in the tissue induce molecular vibrations that generate heat [26]. Both mechanical and thermal ultrasound energy can lyse adipocytes. Thermal energy also can modify and contract collagen [4]. Ultrasounds operate with frequencies from 20 kHz up to several gigahertz [4, 25]. The higher frequencies are associated with a decreased depth of penetration, whereas the lower frequencies are associated with cavitations [11, 25]. Nonthermal ultrasounds (e.g., low-intensity, low-frequency nonthermal ultrasound) operate at low intensity (17.5 W/cm2) and low frequency (200 kHz) to induce cavitations through mechanical stress while generating minimal heat [4]. Thermal ultrasounds (e.g., high-intensity focused ultrasound [HIFU] and intense ultrasound) use heat as the primary mechanism to ablate adipose tissue and modify collagen [4]. In contrast to HIFU, which operates at intensities exceeding 1,000 W and a frequency of 2 MHz, intense ultrasound tends to avoid cavitations by depositing short pulses within the millisecond domain at lower energies at each site (0.5–10 J/cm2) than does the HIFU (100 J/cm2). Thus, intense ultrasound is ideal for skin tightening, whereas HIFU and low-intensity, low-frequency nonthermal ultrasound is ideal for lipolysis [27]. Ultrasounds for Lipolysis Low-Intensity, Low-Frequency Nonthermal Ultrasound The Contour I device (UltraShape Ltd., Tel Aviv, Israel) was the first noninvasive ultrasound developed for body contouring (Table 1) [28]. The pulse waves of low frequency (200 ± 30 kHz) and low intensity (17.5 W/cm2) induce confined cavitations that create stress and mechanically induced disruption of adipocytes [2, 23, 29–31]. The energy density focuses at the depth of the subcutaneous fat,
123
penetrating 10–30 mm deep and inducing zones of coagulation larger than 100 mm3, whereas the energy delivered through the epidermis and dermis is low (Fig. 1) [23, 32]. Neighboring structures such as skin, blood vessels, and nerves are left unharmed because of the ultrasound’s ability to focus the beam at the depth of the subcutaneous fat in addition to the different susceptibilities these structures have to mechanical stress (compared with adipocytes) [23, 30, 31]. Several studies have analyzed the safety and efficacy of the Contour I device’s ability to reduce local fat deposits (Charts 1 and 2). Teitelbaum et al. [23] investigated the effects of a single 60- to 120-min treatment with the UltraShape device on the abdomen, thighs, or flanks. In their study, 164 subjects (with a fat thickness of at least 1.5 cm in the areas to be treated) were divided into a control group (n = 27) and an experimental group (n = 137). The experimental group received a single treatment that resulted in a mean circumference reduction of 1.9 cm (with an 82 % response rate), assessed by a standardized measuring technique. Diagnostic ultrasound measurements showed a pretreatment fat thickness of 24.7 mm with a 2.9-mm reduction, which was an 11.7 % decrease 28 days after treatment. The peak effects were seen within 2 weeks and sustained during the 12-week follow-up period. The response across each of the clinical sites was comparable, with no statistically significant difference between the two measurement techniques. It would be interesting to have a comparison of the preand posttreatment measurements for each specific body part treated, but the authors did not include these data. Although the authors mention that no statistical weight change occurred, they fail to mention a control for diet or physical activity, which may compromise the results of this study. Moreno-Moraga et al. [30] analyzed the effects of multiple treatments with the UltraShape device in reducing local fat deposits in the abdomen, inner and outer thighs, flanks, inner knees, and breasts (males only). In their study, 30 patients (who had C2 cm of fat in the areas to be treated) underwent a total of three treatments at 1-month intervals. Diagnostic ultrasound and circumference measurements were used to assess efficacy. The investigators noted significant improvement after a single treatment session (1.28 cm reduction in fat thickness by ultrasonographic measurement and 1.88 cm reduction in circumference) as well as incremental improvement with subsequent sessions. After three sessions, a mean cumulative reduction of 2.28 cm in fat thickness and 3.95 cm in circumference was noted. Neither circumference changes nor fat thickness differed significantly across the treated areas. The authors included data on the mean circumference and fat thickness measurements at baseline compared with
Year
2007
2007
2009
2010
Author
Teitelbaum et al. [23]
MorenoMoraga et al. [30]
Shek et al. [33]
Ascher [29]
25
30
164
Participants (n)
The abdomen was treated with three 30- to 90-min ultrasound treatments at 2-week intervals. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
The abdomen or flanks were treated with up to three 2to 3-h ultrasound treatment sessions separated by 1-month intervals. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
The abdomen, inner and outer thighs, flanks, inner knees, or breasts (males only) were treated with three treatments at 1-month intervals. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
The abdomen, thighs, or flanks were treated with a single 60- to 120-min ultrasound treatment. The device was set at the manufacturer’s preset and unchangeable settings (frequency, 200 ± 30 kHz; acoustic output intensity, 17.5 W/cm2)
Areas and treatment
Diagnostic ultrasound and a standardized measuring apparatus showed a mean reduction of 1.9 cm in treatment area circumference and 2.9 mm reduction in fat thickness. The majority of the effects were seen within the first 2 weeks and sustained at 12 weeks posttreatment. No significant changes in weight or lab values were observed. Mild and transient adverse events were anticipated: mild tingling (n = 1), mild erythema (n = 3), purpuric lesions (n = 1), small blisters (n = 2) Diagnostic ultrasound and circumference measurements showed a mean reduction in fat thickness of 2.28 ± 0.80 cm and a circumference reduction of 3.95 ± 1.99 cm. No changes in lab values or adverse events were observed other than transient blisters (n = 1) due to inadequate contact oil. The majority of the patients (n = 28) reported no pain Objective measurements of the change in abdominal circumference, the change in caliper fat thickness, and the change in ultrasound-measured fat thickness showed no significant difference after treatment
Mean midline circumference measurements (2 cm below midline) showed a 2.47-cm reduction on day 14 after the first treatment, a 3.51-cm reduction on day 56, and a 3.58-cm reduction on day 112. Most patients (n = 14) reported a subjective positive change in body contour. No adverse events occurred. The majority of the subjects (n = 23) reported no pain
No anesthesia or analgesic was used
No anesthesia or analgesic was used
No anesthesia or analgesic was used
Outcome
Pretreatment with a topical anesthetic cream containing lidocaine 2.5 % and prilocaine 2.5 % was applied under occlusion for 90 min
Anesthesia
Table 1 Summary of studies using the low-intensity, low-frequency contour I Ultrashape device to induce lipolysis
Aesth Plast Surg
123
Aesth Plast Surg
Fig. 2 Ecchymosis is the second most common side effect seen with the high-intensity focused ultrasound (HIFU) device. Photo of a patient on day 4 after Liposonix treatment showing ecchymotic areas over the abdomen
Fig. 1 Ultrasounds used to ablate adipose tissue, such as the Liposonix and UltraShape devices, focus their pulses of high energy at the depth of the subcutaneous fat to disrupt discrete areas of adipocytes without damaging neighboring structures. The epidermis and dermis remained unharmed because the energy delivered through these structures is low
Chart 1 Measurement of waist circumference reduction (cm) using standardized measuring techniques in the different UltraShape studies with corresponding numbers of patients
Chart 2 Measurement of fat thickness reduction (cm) using ultrasound in the different UltraShape studies with corresponding numbers of patients
123
the data after the third treatment session for each of the treated areas. The circumference measurements were as follows: the abdomen measured 96.10 cm at baseline and was reduced 4.15 cm (4.3 %); the flanks measured 93.33 cm at baseline and were reduced 2.67 cm (2.9 %); the outer thighs measured 102.15 cm at baseline and were reduced 4.6 cm (4.5 %); the inner thighs measured 60.25 cm at baseline and were reduced 2 cm (3.3 %); the inner knees measured 44.50 cm at baseline and were reduced 2.75 cm (6.2 %); and the pseudogynecomastia measured 112.83 cm at baseline and was reduced 4.5 cm (4 %). The fat thickness measurements were as follows: the abdomen measured 4.35 cm at baseline and was reduced 2.16 cm; the outer thighs measured 5.44 cm at baseline and were reduced 3.02 cm; the flanks measured 3.36 cm at baseline and were reduced 1.63 cm; the breasts measured 3.38 cm at baseline and were reduced 1.88 cm; the knees measured 4.30 cm at baseline and were reduced 2.06 cm; and the inner thighs measured 3.23 cm at baseline and were reduced 0.96 cm. Ascher [29] demonstrated that a reduction in time between treatment intervals yields results comparable with those of prior studies [23, 30]. Ascher’s study included 25 Caucasian women with a body mass index (BMI) of 26 kg/m2 or lower and a mean baseline fat thickness of 3.24 cm. The patients underwent three 30- to 90-min treatments to the abdomen at 2-week intervals [29]. A standardized measuring technique showed reductions in mean abdominal circumference of 2.47 cm on day 14 (after the first treatment), 3.52 cm on day 28, 3.51 cm on day 56, and 3.58 cm (a peak) on day 112 (84 days after the last treatment). The statistically significant decrease in circumference recorded at all intervals increased over time. This study suggests that desired results may be achieved faster than previously thought. Although this study claimed the greatest numbers reported on waist circumference, it did not measure change in fat thickness by ultrasound and did not account for diet control.
Aesth Plast Surg
Shek et al. [33] investigated the efficacy of the UltraShape device in reducing unwanted fat deposits on the abdomen and flanks of 53 Asian patients. Patients who had more than 1.5 cm of fat thickness in the areas to be treated were included in the study. The subjects underwent up to three treatment sessions separated by 1-month intervals. After 3 months, the investigators noted no statistically significant change after treatment, as measured by abdominal circumference, ultrasound fat thickness, and caliper fat thickness. The authors concluded that the UltraShape device was not as effective for Asians as for Caucasians and attributed this finding to the smaller body figures of the Asian subjects. Studies show the UltraShape device to be safe and well tolerated. Treatment has not been associated with any significant changes in lab values including complete blood count, serum chemistry, fasting lipids, liver markers, and serum lipids [23, 30, 33]. Liver ultrasounds assessing for steatosis, urinalysis, and pulse oximetry monitoring showed no changes after treatment [23, 30]. All side effects were mild and transient; pain and bruising were the most common [23, 29, 30]. However, most patients reported no pain, and studies show the procedure to be equally well tolerated without analgesics [29, 30]. Teitelbaum et al. [23] reported seven cases of mild tingling, erythema, purpuric lesions, and small blisters, all of which were anticipated and resolved within the study period. Moreno-Moraga et al. [30] reported one case of blisters attributed to insufficient acoustic contact oil. The UltraShape studies [23, 29, 30] showed no statistically significant weight change in the treatment or control group. Also, no change in the circumference of the internal control (untreated) areas was observed. These two facts support the conclusion that the decrease in fat thickness and circumference may be a result of the ultrasound treatment and not the result of diet or exercise [23, 29, 30]. However, whereas diagnostic ultrasound measurements are reliable, circumference measurements are not. The greatest reported reduction of fat thickness by ultrasound measurement was approximately 2.3 cm [30]. For people with a thin habitus, this might constitute a significant difference, but it surely would not be significant for overweight individuals. Ascher [29] reported that 63 % of patients noted a subjective change in body contour. Although subjective measures are commonly used in cosmetic research, it is the objective measurable and reproducible effect on which clinicians can rely. In addition, these studies had a relatively short follow-up period (the longest being less than 3 months). Additional studies with longer follow up periods and more reliable measuring techniques are needed to determine the true effects and duration of the treatment effects.
The UltraShape manufacturer has just marketed a new version of its machine called UltraShape v3. The advantage of the newer machine over the older model is that it can go to double the power. Hence, it can perform the same treatment in half the time (personal communication with the company). More side effects are expected, but we must wait for more studies to be published.
High-Intensity Focused Ultrasound (HIFU) The Liposonix device (Liposonix system; Medicis Technologies Corporation, Bothell, WA, USA) is Food and Drug Administration (FDA) approved for noninvasive waist circumference reduction (Table 2) [22, 34]. It operates at high frequency (2 MHz) and high intensity ([1,000 W/cm2) to induce temperatures above 58° C localized to a focal point while much lower intensities (1–3 W/cm2) remain at the skin surface. These high temperatures result in coagulative necrosis of adipocytes and thickened, contracted collagen. These changes are localized to a focal targeted area, whereas neighboring structures are left unharmed (Fig. 1) [26, 35–38]. Similar to the low-intensity, low-frequency nonthermal ultrasound, the dead adipocytes attract macrophages that ingest and transport them away from the treatment area, which results in a reduction in local fat volume [21, 35, 39]. Several studies have analyzed the safety and efficacy of the Liposonix device’s ability to reduce local fat deposits (Chart 3). In 2009, Fatemi [35] investigated the ability of the Liposonix device to reduce fat deposits over the anterior abdomen and flanks. In that study, 282 subjects (with C3.3 cm of adipose tissue thickness in the areas to be treated) underwent a single HIFU treatment. A mean total energy of 137 J/cm2 was divided into two passes at different focal depths (1.1–1.8 cm). The total treatment time ranged between 45 and 60 min. At 3 months after treatment, a 4.7-cm reduction in waist circumference was noted, and 70 % of the patients were satisfied with the results. A year after Fatemi’s initial study, Fatemi and Kane [40] performed a retrospective chart review of 85 subjects who underwent a single Liposonix treatment to the anterior abdomen and flanks. All the subjects had a BMI lower than 30 kg/m2 and a fat thickness of 2.6 cm or more in the pre treated areas. They used a mean total energy level of 137 J/cm2, divided into two passes, at a focal depth of 1.1–1.6 cm (determined by the thickness of the adipose tissue being treated). The time required to complete the treatment ranged from 1 to 1.5 h. A mean reduction of 4.6 cm was observed 3 months after treatment. However, neither of the Fatemi studies used an internal control or a radiographic measurement of fat thickness. In addition, they failed to
123
Year
2009
2010
2011
2012
Author
Fatemi [35]
123
Fatemi & Kane [40]
Jewell et al. [41]
Solish et al. [42]
45
180
85
282
Participants (n)
The anterior abdomen underwent a single HIFU treatment of three passes of decreasing depth (1.6, 1.3, and 1.1 cm). Patients were randomly assigned to energy levels of 47, 52, or 59 J/ cm2 (a total energy dose of 141, 156, and 177 J/cm2, respectively)
The anterior abdomen and flanks were treated with a single HIFU treatment of three passes. The subjects were randomly divided 1:1:1: to receive a total dose of either 177, 141, or 0 J/ cm2 (the ‘‘sham’’ group)
The anterior abdomen and flanks were treated with a single HIFU treatment consisting of two passes with the device calibrated to deliver a total energy dose of 104–148 J/cm2 at a focal depth of 1.1–1.6 cm, determined by the amount of adipose in the treated area
The anterior abdomen and flanks were treated using a single HIFU treatment with a mean energy dose of 137 J/cm2 divided into two passes with two different focal depths (1.1–1.8 cm) depending on the thickness of the adipose in the treated tissue
Areas and treatment
At posttreatment week 12 in the ‘‘per-protocol population,’’ treatment with a total dose of 177 J/cm2 (three passes of 59 J/cm2) was associated with a 2.52cm decrease in waist circumference. Treatment with a total dose of 141 J/cm2 (three passes of 47 J/cm2) was associated with a 2.10-cm decrease in waist circumference. The most common adverse events were transient pain, bruising, and edema. Severe treatment pain was reported for three patients in the 47-J/cm2 treatment group and six patients in the 59-J/ cm2 treatment group. One patient in the 59-J/cm2 group reported severe bruising
Analgesic products (primarily acetaminophen, ibuprofen, and naproxen) were administered to 40 patients before, during, or after the procedure at the discretion of the treating investigator. Use of analgesics was greater before than during or after treatment for all treatment groups
At posttreatment week 12, a 2.51-cm reduction in waist circumference was reported for the average of all the treatment groups combined. Each of the three energy levels provided equal effectiveness. Significant results were observed at 1 month in the 59-J/cm2 treatment group and at week 8 in the other groups. The 47-J/cm2 energy level was associated with the least discomfort, and the 59-J/cm2 energy level was associated with the most discomfort. The discomfort was mild overall. The majority of patients reported mild and transient abdominal bruising and redness
After 3 months, a mean energy level of 134.8 J/cm2 resulted in a 4.6 ± 2.4-cm decrease in waist circumference. Adverse events were transient and included prolonged tenderness (n = 3), ecchymosis (n = 3), hard lumps (n = 2), and edema (n = 1). One patient reported significant pain, which prevented completion of treatment
The use of anesthesia or analgesia was not noted
90 % of the patients received analgesic premedication with one to two tablets of 5 mg oxycodone per 325 mg acetaminophen
The waist circumference decreased by an average of 4.7 cm after 3 months. Adverse events were temporary and not serious including prolonged tenderness (n = 10), edema (n = 6), hard lumps (n = 3), ecchymosis (n = 28), and pain during treatment (n = 5). The histology of 30 patients who subsequently underwent abdominoplasty showed well-defined zones of adipocyte necrosis located a safe and consistent distance from the epidermis and dermis and evidence of collagen remodeling
Outcome
The use of anesthesia or analgesia was not noted
Anesthesia
Table 2 Summary of studies using the high-intensity focused ultrasound (HIFU) LipoSonix device to induce lipolysis
Aesth Plast Surg
Energy levels of 47–59 J/cm2 were well tolerated and produced acceptable improvements in localized abdominal fat deposits, whereas higher energy levels induced more adverse events without significantly greater tissue destruction. No biochemical or metabolic abnormalities were reported. A total of 703 adverse events were reported, all of which were temporary and resolved spontaneously. The most commonly reported adverse events included pain, edema, ecchymosis, and dysesthesia. The histology of 30 subjects who underwent abdominoplasty 2 weeks after treatment showed lesions localized to the focal point of subcutaneous adipose tissue without injury to the surrounding tissue The first 120 patients received an unspecified intravenous analgesic before treatment, and the remaining 32 patients received an unspecified oral analgesic before treatment The anterior abdomen and flanks underwent a single (n = 138) or double (n = 14) HIFU treatment consisting of either single or multiple passes for a total energy dose of 47–331 J/cm2. Abdominoplasty was performed 14 weeks after the HIFU procedure, and a histopathologic analysis of the excised tissue was preformed 2011 Gadsden et al. [38]
152
Year Author
Table 2 continued
Participants (n)
Areas and treatment
Anesthesia
Outcome
Aesth Plast Surg
control for weight, diet, or exercise. Thus, the validity of these results is compromised. Jewell et al. [41] found less drastic results 3 months after treatment with the Liposonix device to the abdomen and flanks. The subjects with an abdominal fat thickness of 2.5 cm or more were randomized to receive a total of 47, 59, or 0 J/cm2 (the ‘‘sham’’ group) divided into three passes. The treatment time ranged from 42.7 min (59-J/cm2 treatment group) to 47.4 min (47-J/cm2 treatment group). A standardized measuring technique with a tape measure showed a waist circumference reduction of 2.52 cm in the 59-J/cm2 group and 2.21 cm in the 47-J/cm2 group among the subjects who did not violate the treatment protocol (i.e., the 168 patients who did not change their diet or exercise routine or use any substance for weight loss). The ability of the Liposonix device to sculpt the abdomen yielded results in the study of Solish et al. [42] comparable with those in the study of Jewell et al. [41]. In the Solish et al. [42] study, 45 subjects (with a BMI of 30 kg/m2 or lower and an adipose tissue thickness of 2.6 cm or more in the areas to be treated) underwent three ultrasound passes of decreasing depths (1.6, 1.3, and 1.1 cm) and randomized total energy levels (141, 156, or 177 J/cm2 divided into three passes). An average reduction in waist circumference of 2.51 cm was noted 3 months after treatment, and 69–85 % of the patients were satisfied with these results. The patients did not change their diet or exercise routines, and no significant weight change occurred throughout the study. No significant difference between the treatment groups was noted at any time point, indicating that a higher energy level may not be necessary to achieve better overall results. Gadsden et al. [38] assessed the histopathologic changes induced by the Liposonix device at energies of 47–331 J/cm2 to suggest that lower energy levels are optimal. In their study, 30 patients with a BMI of 30 kg/m2 or less and at least 2 cm of abdominal fat underwent abdominoplasty 2 weeks after ultrasound treatment. Energy levels of 47–59 J/cm2 were well tolerated and reduced areas of localized abdominal fat deposits to an amount statistically comparable with those at higher energy levels but resulted in more adverse events. When control was used for body weight, it did not fluctuate substantially in the Liposonix studies, which may suggest that the reduction in waist circumference was a result of the ultrasound treatment [41, 42]. When control is not used for external factors that influence body weight, the validity of the results is truly compromised. More studies controlling for these factors are needed. Unfortunately, none of the Liposonix studies have used any radiologic imaging to assess for the change in fat thickness. This puts the relevance of these results in question. More studies using imaging, such as diagnostic ultrasound and computed tomography (CT) technology, as a measure of fat thickness may offer more valid results.
123
Aesth Plast Surg
Chart 3 Measurement of waist circumference reduction (cm) using standardized measuring techniques in the different Liposonix studies with corresponding numbers of patients
The Liposonix device is safe and well tolerated. The vast majority of adverse events are mild and transient and most commonly include pain (even with the use of analgesics), tenderness, edema, hard lumps, and ecchymosis (Fig. 2) [35, 38, 40–42]. In isolated cases, the adverse events are more severe. In the study by Fatemi and Kane [40] the pain of one subject was severe enough to prevent completion of treatment. Adverse events, such as pain and dysesthesias, are more common and longer lasting with higher energy settings [38, 41, 42]. Jewell et al. [41] reported one rare case of severe bruising induced by 59 J/cm2 of energy. The Liposonix device yields no significant change in the lab values of lipid profiles, liver enzymes, renal function, coagulation, or creatinine phosphokinase [38, 41].
Ultrasounds for Skin Lifting and Tightening Intense ultrasounds work by using energy to vibrate tissue and cause friction between molecules, which secondarily generates heat to induce coagulation. The Ulthera device (Ulthera Inc., Mesa, AZ, USA), specifically developed to lift and tighten the skin, is FDA approved for the noninvasive lifting of lax tissue on the neck and submentum [5]. It acts by targeting the superficial musculoaponeurotic system (SMAS), in which its microthermal lesions create a zone of coagulation of about 1 mm, reaching the mid to deep reticular dermis up to the fibromuscular layer (Table 3; Fig. 3) [3, 12, 32, 39, 43]. The SMAS is a continuous fibromuscular layer of tissue that invests and interlinks the muscles of facial expression [44–46]. The waves penetrate 4–5 mm into the facial skin to deliver focal, intense, discrete, linear pulses 20–50 ms long [32]. The device focuses its energy to induce a 25-mm line of discrete lesions spaced 0.5–5.0 mm apart [43]. The thermal injury results in collagen contraction, tissue coagulation, and new collagen deposition [12, 27, 32, 43, 47].
123
White et al. [43] were the first to report the ability of the Ulthera device to induce focused, discrete, and reproducible zones of thermal collagen denaturation in the SMAS. The thermal injury zones (TIZs) reached as far as 7.8 mm and spared neighboring tissue in each of the six human cadaveric specimens. The researchers used two hand pieces, which operated at 7.5 and 4.4 MHz (at a fixed focal depth of 4.5 mm), as well as varying combinations of power and exposure time at energies ranging from 0.5 to 8.0 J/cm2. Higher energy settings and higher density exposures resulted in a greater degree of tissue shrinkage. Other investigators have confirmed these findings on cadaveric and porcine skin [48, 49]. Using porcine skin, White et al. [49] later found that increasing energies caused the TIZs to grow larger by growing toward the tissue surface. Gliklich et al. [47] evaluated the histologic effects of the Ulthera device on the face and neck of live humans. In their study, 15 subjects were pretreated using one of three hand pieces with different frequencies and focal depths (7.5 MHz, 3 mm; 7.5 MHz, 4.5 mm; and 4.4 MHz, 4.5 mm). In contrast to previous studies, increasing source power was not associated with an increase in the depth of the TIZ. Histologic evaluation 24 h after treatment confirmed the observations in their previous study [43]. No significant changes were noted 4–12 weeks after treatment, suggesting that the tissue had time to recover. Alam et al. [32] were the first to investigate the efficacy of the Ulthera ultrasonic device in assessing skin tightening for live patients whose skin was not resected. The entire face of 35 subjects underwent a single ultrasound treatment with probes of different frequencies and focal depths (7 MHz, 3 mm; 7 MHz, 4.5 mm, and 4 MHz, 4.5 mm) selected according to the thickness of the tissue at each of the anatomic landmarks. At posttreatment day 90, the mean average elevation in eyebrow height (measured objectively with photography) was 1.7–1.9 mm. Although these statistically significant results seem minimal, three masked clinicians assessed pre- and postoperative photos to judge clinically significant results in 86 % of the patients. Compared with the normal distance of 2.5 cm between the midpupillary line and the upper edge of the eyebrow hair, 1.9 mm constitutes a change of only 7 % at most [50]. Suh et al. [27] analyzed the efficacy of a single treatment with the Ulthera device in lifting the skin of the face of 22 Koreans with facial laxity. Specific probe selection (7.5 MHz, 3 mm or 4.4 MHz, 4.5 mm) was based on the thickness of the tissue at each of the anatomic landmarks. After 2 months, two blinded clinicians noted an improvement in the nasolabial folds and jaw lines of all the subjects, assessed by pre- and postoperative photos. More than 70 % of the subjects noted much improvement in their own nasolabial folds and jaw lines. Biopsies at this time showed increased dermal collagen fibers in the reticular dermis,
Year
2007
2010
2011
2011
Author
Gliklich et al. [47]
Alam et al. [32]
Chan et al. [12]
Suh et al. [27]
22 (Korean patients)
49 (Chinese patients)
36
15
Participants (n)
The forehead, temples, cheeks, infraorbital, and preauricular areas underwent a single pass of one to three ultrasound treatments. Depending on the amount of subcutaneous soft tissue of the anatomic location, patients were treated with one of the following transducers: 7 MHz, 3-mm focal depth; 7 MHz, 4.5-mm focal depth; or 4 MHz, 4.5-mm focal depth The forehead, temples, malar area, cheeks, and submentum were treated with a single pass of either probe depending on the amount of subcutaneous soft tissue of the anatomic location: 7.5 MHz, 3-mm focal depth or 4.4 MHz, 4.5-mm focal depth
The forehead, temples, cheeks, submentum, and sides of the neck underwent a single treatment with the following probes depending on the amount of subcutaneous soft tissue of the anatomic location: 4 MHz, 4.5-mm focal depth; 7 MHz, 4.5-mm focal depth, or 7 MHz, 3-mm focal depth
The entire face and neck underwent a single treatment with one of the following transducers depending on the amount of subcutaneous soft tissue within the anatomic location: 7.5 MHz, 3-mm focal depth; 7.5 MHz, 4.5-mm focal depth; or 4.4 MHz, 4.5-mm focal depth. The subjects were divided into two groups: immediate (those undergoing face-lift within 24 h after ultrasound treatment) and delayed (those undergoing face-lift within 4–12 weeks after ultrasound treatment)
Areas and treatment
Topical (unspecified) anesthetic cream was applied 60 min before the procedure
No oral analgesia or topical anesthetics were used
Topical 7 %/7 % lidocaine was applied 45 min before the procedure
Topical anesthetic cream containing 2.5 % lidocaine and 2.5 % prilocaine was applied 45 min before treatment
Anesthesia
Table 3 Summary of studies using the intense ultrasound Ulthera device to lift and tighten skin
Nasolabial folds and jaw lines significantly improved in all the patients, assessed by photographs. Subjectively, 77 % of the patients reported improvement in nasolabial folds, and 73 % reported improvement in the jaw line. The reported pain was no more than minimal. Mild and transient erythema and edema were noted by all the subjects. White wheals were observed on the cheek and submentum of two subjects with the use of the 4.5-mm probe. Four patients reported temporary numbness in the mandible. Histologic evaluation of the 11 biopsies of the skin showed an increased amount of dermal collagen with thickening of the dermis and straightening of the elastic fibers in the reticular dermis
Most subjects reported transient erythema and edema. Focal bruising accompanied 25 % of the treatment sessions. PIH was seen on the forehead 1 month after treatment in two subjects. Severe pain was associated with 54 % of the treatment sessions
Mean brow height elevation measured by photographs 90 days after treatment was 1.7 mm. All subjects experienced immediate erythema and edema, which resolved at 1 week. During treatment, the majority of patients reported pain no greater than 4/10, but five patients reported pain greater than 7/10. Two patients treated with the 3-mm probe experienced transient elevated white striations on the neck
TIZs, which were consistently wide and deep focal areas of denatured collagen localized to the dermis and subcutaneous tissue, were induced at an exposure threshold of 0.5 J/cm2 primarily in the immediate treatment group. This threshold was associated with transient erythema and slight to mild discomfort. Increasing the power did not increase the depth of the thermal injury zones. When the hand pieces were compared under similar source conditions, the superficial hand piece (7.5 MHZ, 3-mm focal depth) was more tolerable than the intermediate (7.5 MHZ, 4.5-mm focal depth) and deep (4.4 MHZ, 4.5-mm focal depth) hand pieces. An inflammatory wheal, which resolved within 48 h, was induced in two patients treated with the superficial hand piece at 1 J/cm2
Outcome
Aesth Plast Surg
123
123
Fig. 3 Ultrasounds used to tighten and lift the skin, such as the Ulthera device, target the superficial musculoaponeurotic system (SMAS) and induce microthermal lesions that reach the mid to deep reticular dermis up to the fibromuscular layer. The focal, intense, discrete linear pulses result in thermally induced collagen contraction while sparing the epidermis, dermis, and neighboring structures
TIZ thermal injury zone, PIH postinflammatory hyperpigmentation
Photographs showed significant improvement in all treated areas, with upper arms and knees showing more skin lifting and tightening than in the thighs. Dual probe passes showed slightly better results in all three sites. Discomfort levels were reported as mild to moderate. Side effects of erythema, warmth, and tenderness were mild and transient. Focal bruising was noted on the upper arms of two patients Oral diazepam (5–10 mg) and intramuscular injection of meperidine (50 mg) were administered 20 to 30 min before treatment 2012 Alster and Tanzi [51]
18
The upper arms, medial thighs, and extensor knees were randomly treated with either transducer: 4 MHz, 4.5-mm focal depth or 7 MHz, 3-mm focal depth. A single pass with the 4-MHz transducer was randomly assigned to one side of the body, whereas the contralateral side received an additional pass with the 7-MHz transducer
Outcome Participants (n) Year Author
Table 3 continued
Areas and treatment
Anesthesia
Aesth Plast Surg
with increased parallelism of elastic fibers, resulting in an increased dermal thickness (1.32 ± 0.18 mm before treatment vs 1.63 ± 0.31 mm after treatment). Alster and Tanzi [51] analyzed the efficacy of the Ulthera device for nonfacial areas of the body. They treated one side of the upper arms, medial thighs, and knees with a single pass of a 4-MHz, 4.5-mm-depth transducer, and the contralateral side with an additional pass of a 7-MHz, 3-mm transducer. Using standardized photographs, two masked clinicians noted significant improvement in all treated areas, which showed continued improvement 3–6 months after treatment. The upper arms and knees showed more lifting and tightening than the thighs. Although both sides exhibited significantly improved skin contours, the side exposed to two passes showed better clinical outcomes. The authors recommended repeating the treatment every 3–6 months to maintain the outcome given the significant improvement seen at 3 months compared with the slight continued improvement at 6 months. As noted from the aforementioned studies, most of the Ulthera studies relied on subjective measurement tools or a pathologic assessment on a short-term basis. The only study by Alam et al. [32] that assessed skin contracture objectively found at most a 7 % change. The Ulthera device appears to offer a safe procedure because adverse events are mild and transient. No severe
Aesth Plast Surg
adverse events have been reported other than severe pain reported by 54 % of the subjects in a study that used no anesthetics [12]. Mild erythema and edema are the most common of these events [27, 32, 47, 51]. Whereas some investigators have observed a complete resolution of erythema within 2 h [51], others have reported a 90–100 % resolution of the erythema and edema 1 week after treatment [12, 32]. Mild to moderate discomfort often is induced, even with the use of analgesics [27, 32, 47, 51]. Increased power and focal depth settings appear to be associated with more pain [47]. Less common adverse reactions have been reported. Inflammatory wheals have been reported in four subjects, which resolved within 48 h. Two of these subjects were treated with a 4.4-MHz, 4.5-mm probe [27], whereas the remaining two were treated with a more superficial 7.5-MHZ, 3-mm probe [47]. The investigators attributed this occurrence to inadequate uncoupling of heat energy to the skin during treatment [27]. Two subjects treated with the 7.5-MHz, 3-mm probe experienced the development of elevated white linear striations on the neck, which resolved within 1 week using topical steroids [32]. The 7-MHz, 4.5-mm probe was not associated with any further occurrences. It was reassuring that the deeper probe directed energy into the subcutis (beyond the papillary dermis which was more vulnerable to injury) [32]. Several cases of mandibular numbness, tenderness, and focal bruising have been reported, all of which resolved within 1–3 weeks [12, 27, 51]. Two cases of postinflammatory hyperpigmentation (PIH) on the forehead of Asian skin have been reported 1 month after treatment with a 7-MHz, 4.5-mm transducer (pulse energy, 1.05 J/cm2) [12]. Because ultrasound energy is not absorbed by melanin, the PIH likely was the result of underlying inflammation and not a direct effect of the ultrasound. After replacement with a more superficial 7-MHz, 3-mm transducer, no more cases of PIH were observed.
Conclusion Ultrasound devices may offer a noninvasive and safe procedure that can be performed in the clinical setting to decrease focal areas of adiposity and tighten skin. However, their efficacy remains uncertain. The results of the current studies have relied mostly on subjective assessment. Although the absolute values of the circumference and fat thickness reduction may be significant, the objective assessments indicate that the results are minimal at most. Further rigorous studies are definitely needed for effective evaluation of these devices, especially considering the large media coverage they have received and the high charges that patients are paying for treatment.
It must be noted that ultrasounds for lipolysis and lifting are not a replacement for liposuction, nor are they a replacement for excisional and lifting surgery. They are targeted to a specific clientele with a BMI lower than 30 kg/m2 who are seeking minimal touchups in body contour and minor skin lifts. Future studies must obtain more accurate measurements of fat reduction by using diagnostic ultrasound or CT imaging. Additionally, future studies must include longer follow-up periods as well as clinical and histologic assessments at fixed intervals after treatment. Most studies do not follow the patient longer than 3 months, but one study using the Ulthera device found continued improvement at the 6-month mark [51]. Another study of the UltraShape device also noted persistent results at 12 weeks. However, none of these studies reported results beyond 6 months although the machines have been available on the market longer than 3 years [23, 29]. A maximum follow-up period of 3 months is not sufficient because continued efficacy, and in some cases, peak results are noted at this time. It would be beneficial to know how long the effects of the ultrasound treatment last in order to develop recommendations for follow-up treatments and optimal results. Conflict of interest The authors declare that they have no conflicts of interest to disclose.
References 1. Hwang JH, Crum LA (2009) Current status of clinical highintensity focused ultrasound. Conf Proc IEEE Eng Med Biol Soc 2009:130–133 2. Kennedy JE, Ter Haar GR, Cranston D (2003) High-intensity focused ultrasound: surgery of the future? Br J Radiol 76:590–599 3. Capla JM, Rubin JP (2011) Discussion: randomized sham-controlled trial to evaluate the safety and effectiveness of a highintensity focused ultrasound device for noninvasive body sculpting. Plast Reconstr Surg 128:263–264 4. Jewell ML, Solish NJ, Desilets CS (2011) Noninvasive body sculpting technologies with an emphasis on high-intensity focused ultrasound. Aesthetic Plast Surg 35:901–912 5. LipoSonix. Retrieved at http://liposonix.com/. Accessed 18 Dec 2013 6. Hughes CE III (2001) Reduction of lipoplasty risks and mortality: an ASAPS survey. Aesthet Surg J 21:120–127 7. Lehnhardt M, Homann HH, Daigeler A, Hauser J, Palka P, Steinau HU (2008) Major and lethal complications of liposuction: a review of 72 cases in Germany between 1998 and 2002. Plast Reconstr Surg 121:396e–403e 8. Grazer FM, Grazer FM, de Jong RH (2000) Fatal outcomes from liposuction: census survey of cosmetic surgeons. Plast Reconstr Surg 105:436–446 discussion 47–48 9. Commons GW, Halperin B, Chang CC (2001) Large-volume liposuction: a review of 631 consecutive cases over 12 years. Plast Reconstr Surg 108:1753–1763 discussion 64–67 10. Jewell ML (2001) Prevention of deep vein thrombosis in aesthetic surgery patients. Aesthet Surg J 21:161–163
123
Aesth Plast Surg 11. Triana L, Triana C, Barbato C, Zambrano M (2009) Liposuction: 25 years of experience in 26,259 patients using different devices. Aesthet Surg J 29:509–512 12. Chan NP, Shek SY, Yu CS, Ho SG, Yeung CK, Chan HH (2011) Safety study of transcutaneous focused ultrasound for noninvasive skin tightening in Asians. Lasers Surg Med 43:366–375 13. Avram MM (2004) Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther 6:181–185 14. Sadick NS, Mulholland RS (2004) A prospective clinical study to evaluate the efficacy and safety of cellulite treatment using the combination of optical and RF energies for subcutaneous tissue heating. J Cosmet Laser Ther 6:187–190 15. van Vliet M, Ortiz A, Avram MM, Yamauchi PS (2005) An assessment of traditional and novel therapies for cellulite. J Cosmet Laser Ther 7:7–10 16. Coleman KM, Coleman WP III, Benchetrit A (2009) Noninvasive, external ultrasonic lipolysis. Semin Cutan Med Surg 28:263–267 17. Atiyeh BS, Dibo SA (2009) Nonsurgical nonablative treatment of aging skin: radiofrequency technologies between aggressive marketing and evidence-based efficacy. Aesthetic Plast Surg 33:283–294 18. Manuskiatti W, Wachirakaphan C, Lektrakul N, Varothai S (2009) Circumference reduction and cellulite treatment with a TriPollar radiofrequency device: a pilot study. J Eur Acad Dermatol Venereol 23:820–827 19. Caruso-Davis MK, Guillot TS, Podichetty VK, Mashtalir N, Dhurandhar NV, Dubuisson O et al (2011) Efficacy of low-level laser therapy for body contouring and spot fat reduction. Obes Surg 21:722–729 20. Jackson RF, Dedo DD, Roche GC, Turok DI, Maloney RJ (2009) Low-level laser therapy as a noninvasive approach for body contouring: a randomized, controlled study. Lasers Surg Med 41:799–809 21. Fodor PB SB, Stecco KA, Desilets CS (2006): Biochemical Changes in Adipocytes and Lipid Metabolism Secondary to the Use of High-Intensity Focused Ultrasound for Noninvasive Body Sculpting. Presented at the annual meeting of the American Society of Aesthetic Plastic Surgery, Orlando, FL 22. Weiss M (2012) Commentary: noninvasive skin tightening: ultrasound and other technologies: where are we in 2011? Dermatol Surg 38:28–30 23. Teitelbaum SA, BurTeitelbaum SA, Burns JL, Kubota J, Matsuda H, Otto MJ, Shirakabe Y et al (2007) Noninvasive body contouring by focused ultrasound: safety and efficacy of the Contour I device in a multicenter, controlled, clinical study. Plast Reconstr Surg 120:779–789 discussion 90 24. O’Brien WD Jr (2007) Ultrasound-biophysics mechanisms. Prog Biophys Mol Biol 93:212–255 25. Quistgaard JU, Desilets C, Martin P (2010) High-Intensity Focused Ultrasound. Retrieved xxxx at http://digital.miinews. com/publication/?i=34631&page=1: Medicis Technologies Corporation, Bothell, WA. Accessed 18 Dec 2013 26. Haar GT, Coussios C (2007) High-intensity focused ultrasound: physical principles and devices. Int J Hyperthermia 23:89–104 27. Suh DH, Shin MK, Lee SJ, Rho JH, Lee MH, Kim NI et al (2011) Intense focused ultrasound tightening in Asian skin: clinical and pathologic results. Dermatol Surg 37:1595–1602 28. UltraShapeÒ V3 Body Shaping via Fat Cell Destruction. Retrieved xxxxx at http://syneron-candela.com/int/product/ ultrashape: SyneronÒ Medical Ltd., 2012. Accessed 18 Dec 2013 29. Ascher B (2010) Safety and efficacy of UltraShape Contour I treatments to improve the appearance of body contours: multiple treatments in shorter intervals. Aesthet Surg J 30:217–224 30. Moreno-Moraga J, Valero-Altes T, Riquelme AM, Isarria-Marcosy MI, de la Torre JR (2007) Body contouring by noninvasive transdermal focused ultrasound. Lasers Surg Med 39:315–323
123
31. Brown SA, Greenbaum L, Shtukmaster S, Zadok Y, Ben-Ezra S, Kushkuley L (2009) Characterization of nonthermal focused ultrasound for noninvasive selective fat cell disruption (lysis): technical and preclinical assessment. Plast Reconstr Surg 124:92–101 32. Alam M, White LE, Martin N, Witherspoon J, Yoo S, West DP (2010) Ultrasound tightening of facial and neck skin: a raterblinded prospective cohort study. J Am Acad Dermatol 62:262–269 33. Shek S, Yu C, Yeung CK, Kono T, Chan H (2009) The use of focused ultrasound for noninvasive body contouring in Asians. Laser Surg Med 41:751–759 34. Medicis Announces FDA Clearance of LIPOSONIX(R) System. Investor Relations Press Releases. Retrieved xxxx at http://www. globenewswire.com/newsarchive/mrx/pages/news_releases.html? d=231745. Accessed 18 Dec 2013 35. Fatemi A (2009) High-intensity focused ultrasound effectively reduces adipose tissue. Semin Cutan Med Surg 28:257–262 36. Avelar J (1989) Regional distribution and behavior of the subcutaneous tissue concerning selection and indication for liposuction. Aesthetic Plast Surg 13:155–165 37. Ferraro GA, De Francesco F, Nicoletti G, Rossano F, D’Andrea F (2008) Histologic effects of external ultrasound-assisted lipectomy on adipose tissue. Aesthetic Plast Surg 32:111–115 38. Gadsden E, Aguilar MT, Smoller BR, Jewell ML (2011) Evaluation of a novel high-intensity focused ultrasound device for ablating subcutaneous adipose tissue for noninvasive body contouring: safety studies in human volunteers. Aesthet Surg J 31:401–410 39. Garcia-Murray E, Rivas O, Stecco K, Desilets C, Kunz L: The Use and Mechanism of Action of High-Intensity Focused Ultrasound for Adipose Tissue Removal and Noninvasive Body Sculpting. Presented at the annual meeting of the American Society of Plastic Surgeons, Chicago, IL, 2005 40. Fatemi A, Kane MA (2010) High-intensity focused ultrasound effectively reduces waist circumference by ablating adipose tissue from the abdomen and flanks: a retrospective case series. Aesthetic Plast Surg 34:577–582 41. Jewell ML, Baxter RA, Cox SE, Donofrio LM, Dover JS, Glogau RG et al (2011) Randomized sham-controlled trial to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for noninvasive body sculpting. Plast Reconstr Surg 128:253–262 42. Solish N, Lin X, Axford-Gatley RA, Strangman NM, Kane M (2012) A randomized, single-blind, postmarketing study of multiple energy levels of high-intensity focused ultrasound for noninvasive body sculpting. Dermatol Surg 38:58–67 43. White WM, Makin IR, Barthe PG, Slayton MH, Gliklich RE (2007) Selective creation of thermal injury zones in the superficial musculoaponeurotic system using intense ultrasound therapy: a new target for noninvasive facial rejuvenation. Arch Facial Plast Surg 9:22–29 44. Larrabee WFJ MK, Henderson JL: Surgical Anatomy of the Face: Superficial Musculoaponeurotic System. In: Merritt J (ed) Lippincott, Williams, and Wilkins, Philadelphia, PA, 2004 45. Mendelson BC (2001) Surgery of the superficial musculoaponeurotic system: Principles of release, vectors, and fixation. Plast Reconstr Surg 107:1545–1552 discussion 53–55, 56–57, 58–61 46. Har-Shai Y, Bodner SR, Egozy-Golan D, Lindenbaum ES, BenIzhak O, Mitz V et al (1996) Mechanical properties and microstructure of the superficial musculoaponeurotic system. Plast Reconstr Surg 98:59–70 discussion 1–3 47. Gliklich RE, White WM, Slayton MH, Barthe PG, Makin IR (2007) Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues. Arch Facial Plast Surg 9:88–95
Aesth Plast Surg 48. Laubach HJ, Makin IR, Barthe PG, Slayton MH, Manstein D (2008) Intense focused ultrasound: evaluation of a new treatment modality for precise microcoagulation within the skin. Dermatol Surg 34:727–734 49. White WM, Makin IR, Slayton MH, Barthe PG, Gliklich R (2008) Selective transcutaneous delivery of energy to porcine soft tissues using intense ultrasound (IUS). Lasers Surg Med 40:67–75
50. McKinney P, Mossie RD, Zukowski ML (1991) Criteria for the forehead lift. Aesthetic Plast Surg 15:141–147 51. Alster TS, Tanzi EL (2012) Noninvasive lifting of arm, thigh, and knee skin with transcutaneous intense focused ultrasound. Dermatol Surg 38:754–759
123
