4.1 Introduction

Focused ultrasound technologies offer methods for noninvasive fat reduction and body contouring that are generally safe, targeted, require minimal to no recovery time, and can be performed in office. These technologies act to ablate areas of subcutaneous adipose tissue (SAT) and provide a more permanent improvement compared to devices that provide temporary improvement by heating and tightening. Focused ultrasound technologies can be classified as high-intensity focused ultrasound (HIFU) or low-frequency non-thermal focused ultrasound.

HIFU involves the delivery of high-frequency acoustic energy (2 MHz, >1,000 W/cm ² ) to focal areas of SAT, resulting in a rapid increase of local adipose tissue temperatures to greater than 55°C, and subsequent coagulative necrosis in the targeted area. Additionally, negative acoustic pressure contributes to adipocyte destruction by disrupting cell membranes and inducing cavitation bubbles. ^{1 , 2} Microscopic examination of abdominoplasty specimens collected within hours of HIFU revealed a focal area of hemorrhage, disrupted adipocytes, interstitial edema, and coagulation of cells and intercellular collagen. These lesions showed a consistent size, expected depth, and no involvement of surrounding skin or fascia on gross exam. ³ Destruction of SAT stimulates a wound healing response with eventual removal of lipids and cell debris by macrophages from the treatment area and induction of fibroblasts. Significant damage to adipocytes with focal areas of fat necrosis and an inflammatory infiltrate are apparent on histologic analysis 4 weeks after HIFU treatment. ² By 8 weeks, there is minimal inflammation, no fat necrosis, and lipid-filled vacuoles and foamy macrophages are observed. Thermal lesions are smaller, but remain apparent in the SAT on gross exam. Denaturation of collagen from the thermal effects of HIFU results in contraction and thickening of collagen fibers, which can be seen histologically and may produce skin tightening. ^{3 , 4} This effect does not occur with non-thermal focused ultrasound. Damage is limited to targeted areas of fat with no effects on surrounding tissues or overlying skin. Over 8–12 weeks the treatment zone is resorbed with about 95% resorbed by 18 weeks. ⁴

Multiple studies have shown HIFU to be safe with most adverse effects being transient. Commonly reported adverse effects include mild to severe procedural and postprocedural pain and dysesthesia, mild to severe ecchymoses (▶Fig. 4.1), mild to moderate erythema, and edema, which are reported to last from days to up to 12 weeks. ^{3 , 4 , 5} Transient hard lumps, induration, and headache have also been reported. No significant changes in liver function, renal function, lipid levels, chemistry panels, coagulation studies, or blood cell counts have been reported to occur following HIFU when measured up to 24 weeks post-treatment. ⁵ There have been no reports of skin dimpling, burns, scars, or increased skin laxity.

There have been several studies evaluating the efficacy of HIFU for noninvasive body contouring. Fatemi reported an average waist circumference reduction of 4.7 cm 3 months after treating the abdomen and flanks of 282 subjects with 1 session and 2 passes of HIFU using 2 different focal depths of 1.1 to 1.6 cm and a mean energy of 137 J/cm ² . Lower energy levels achieved satisfactory results, but it was suggested that the minimum energy per pass should be 47 J/cm ² . ⁴ Fatemi and Kane conducted another uncontrolled, retrospective study in which 85 subjects underwent treatment of the abdomen and flanks with 1 session and 2 passes of HIFU at a depth of 1.1 to 1.6 cm and total energy dose of 104–148 J/cm ² (average 134.8 J/cm ² ). Treatment resulted in an average waist circumference reduction of 4.6 cm at 3 months after treatment compared to baseline. They similarly treated the abdomen of 40 subjects with a single session of HIFU, which produced a mean reduction in waist circumference of 2.9 cm at 3 months. Post hoc analysis indicated that there was no significant difference in waist circumference reduction when a total energy >133 J/cm ² was used compared to a total energy ≤126 J/cm ² . ⁶ Jewell et al conducted a multicenter, randomized, sham-controlled, single-blind trial evaluating the effectiveness and safety of HIFU for waist circumference reduction. Subjects were randomized to receive total energy doses of 141 J/cm ² (3 passes at 47 J/cm ² ), 177 J/cm ² (3 passes at 59 J/cm ² ), or sham (3 passes at 0 J/cm ² ) at a depth of 1.3 cm. Per protocol, both treatment groups showed a significantly greater average waist reduction compared to sham (-2.10 cm at 47 J/cm ² and -2.52 cm at 59 J/cm ² versus -1.21 cm for sham) at 12 weeks following treatment. Less pain was reported in the 47 J/cm ² compared to the 59 J/cm ² group. ⁷ Solish et al performed a postmarketing, single-blind prospective study of 45 subjects evaluating HIFU for abdominal adipose tissue without treatment of the flanks. Subjects were randomized to receive 3 passes at 47 J/cm ² (total energy of 141 J/cm ² ), 52 J/cm ² (total energy of 156 J/cm ² ), or 59 J/cm ² (total energy of 177 J/cm ² ) with each pass at a different depth (1.6, 1.3, and 1.1 cm). Waist circumference was significantly reduced at 12 weeks in all 3 groups with a mean reduction of 2.51 cm. There was no significant difference in waist reduction between the 3 groups, though a significant reduction from baseline was achieved more rapidly in the 59 J/cm ² group. Additionally, the lowest energy group experienced the least discomfort. ⁸

The effectiveness and tolerability of multiple HIFU treatment protocols for the abdomen and flanks, including different fluences (150 or 180 J/cm ² total energy, 30 or 60 J/cm ² per pass) and a grid repeat (passes) technique versus a site repeat (pulse stacked) technique, were examined by Robinson et al in an unblinded, randomized study with 188 subjects. Treatment resulted in a mean waist circumference reduction of 2.3 cm ± 2.9 cm at 12 weeks with no significant difference seen between the different treatment protocols. Patients in the 30 J/cm ² groups reported significantly lower pain scores, again illustrating the advantage of using lower fluences. ⁹ Shek et al also noted lower fluences with more passes being associated with less discomfort in an uncontrolled single-center prospective study of 12 subjects treated with a single treatment of HIFU delivered at 30–55 J/cm ² per pass (total energy 50–165 J/cm ² ) based on the amount of pain experienced by the subject. Waist circumference was reduced by an average of 2.1 cm at 12 weeks after treatment with higher total energy, rather than the energy delivered per pass, being associated with greater improvement in waist circumference. ¹⁰

The efficacy of HIFU compared to cryolipolysis for adipose tissue on the flanks was examined by Friedman et al Eight female patients were randomized to have adipose tissue on their flanks treated either by HIFU with energy doses of 140 to 160 J/cm ² or cryolipolysis. There was no change in widest part waist circumference at 4 months, but both groups showed moderate improvement when scored by blinded investigators. There was no significant difference in improvement between the two groups. There was, however, a trend towards greater improvement with HIFU, suggesting that HIFU is at least as effective as cryolipolysis in treating flank adipose tissue. ¹¹ There are no other studies directly comparing HIFU to other methods of body contouring.

In contrast to HIFU, low frequency, non-thermal focused ultrasound (200 kHz, 17.5 W/cm ² ) leads to destruction of adipose tissue via mechanical disruption and cavitation without thermal effects at a depth of 1.5 cm. Using a porcine model, Brown et al demonstrated focal, well-defined cavitation of SAT with a length and diameter of 10 mm and 6 mm, respectively, and histologic evidence of adipocyte disruption with sparing of connective tissue, vessels, nerves, and overlying skin following treatment with non-thermal focused ultrasound. ¹² The denaturation of collagen with subsequent contraction and thickening of collagen fibers seen in HIFU does not occur with non-thermal focused ultrasound due to the lack of thermal effects. Following disruption, adipocyte contents, primarily consisting of triglycerides, are released into the interstitial fluid, cleared by the lymphatic system, transported to the vascular system, and metabolized by the liver.

The safety of non-thermal focused ultrasound has been evaluated in multiple studies with side effects being transient and milder than side effects with HIFU. Reported side effects include transient mild procedural pain and dysesthesia, mild erythema, mild purpura, and blistering localized to treatment sites. No significant changes in laboratory tests including complete blood counts, chemistry panels, liver functions tests, or lipid panels have been observed ^{13 , 14} with the exception of increased triglycerides that remained within normal limits in one study. ¹³ Liver ultrasound has shown no steatosis. No nodules, skin textural irregularities, hypo- or hyperpigmentation have been reported in the treated areas. ^{13 , 14}

Studies examining the efficacy of non-thermal focused ultrasound for body contouring have demonstrated favorable results. Moreno-Moraga et al performed a prospective study with 30 healthy adults examining the use of non-thermal focused ultrasound on the abdomen (n = 10), inner (n = 2) and outer thighs (n = 10), flanks (n = 3), inner knees (n = 2), pseudogynecomastia (n = 3). Three treatments were performed at 1-month intervals. Circumference and fat thickness were measured via ultrasound 1 month after the last treatment. All areas treated showed a reduction in circumference with a mean circumference reduction of 3.95 ± 1.99 cm. The greatest reductions were observed in the outer thighs at 4.60 cm followed by the abdomen at 4.15 cm, though the differences between areas were not statistically significant. The mean fat reduction measured by ultrasound was 2.28 cm. ¹³ A multicenter, controlled study by Teitelbaum et al evaluated a single treatment of non-thermal focused ultrasound for abdomen, flanks, and thighs in 164 patients (137 treated, 27 controls). The mean circumference reduction was 1.9 cm at 12 weeks with no significant difference between treatment areas or between men and women. Fat thickness, measured by ultrasound, was reduced from baseline by 2.6 mm on day 14 and by 2.9 mm on day 28. The overall response rate was 82%. ¹⁴ Ascher investigated the efficacy and safety of shorter intervals for the abdominal region, performing 3 treatments 2 weeks apart on 25 female subjects. The mean reduction in waist circumference reduction at 112 days was 3.58 cm measured 2 cm below midline and 3.12 cm measured midline, suggesting the effectiveness of shorter intervals between treatments. ¹⁵ Hotta reported clinical outcomes for 70 patients treated with 1–3 treatments of non-thermal focused ultrasound on the thighs, flanks, and abdomen with an average circumference reduction of 2.5 cm per area. ¹⁶ Niwa et al performed a retrospective study of 120 subjects undergoing 1–3 sessions of treatment with non-thermal focused ultrasound. Treatment areas included the abdomen (n = 72), hips (n = 46), thighs (n = 30), dorsum (n = 1) and infragluteal region (n = 4). Mean reduction in circumference following 3 sessions for abdomen, hips, and thighs was 4.95 cm, 4.88 cm, and 3 cm, respectively. Infragluteal and dorsum regions only received a single treatment with mean circumference reduction of 2.35 cm and 2.6 cm, respectively. ¹⁷ Results of a multicenter, randomized, controlled study evaluating non-thermal focused ultrasound for noninvasive fat reduction have not been published to date. Details regarding the combined use of non-thermal focused ultrasound and other procedures are described later in this chapter.