Lasers in Surgery and Medicine 46:263–269 (2014)
Efficacy of High-Intensity Focused Ultrasonography for Noninvasive Body Sculpting in Chinese Patients Samantha Y.N. Shek, MBBS,1 Chi K. Yeung, MD, FRCP,1 Johnny C.Y. Chan, MBBS,1 and Henry H. L. Chan, MD, PhD, FRCP1,2 1 Division of Dermatology, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China 2 Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Background and Objectives: High-intensity focused ultrasound (HIFU) is a noninvasive technology for body contouring. HIFU is focused within the subcutaneous adipose tissue, causing coagulative necrosis and cell death. The objective of this study is to evaluate the effectiveness of a HIFU device for sculpting of the abdomen. Materials and Methods: The system has a set focal depth of 1.3 cm. Twelve subjects with adipose thickness no less than 2.5 cm who met the screening criteria were recruited. Each subject received one treatment to the abdomen. The total fluence used per site was 150–165 J/cm2 with a mean of 161 J/cm2. The waist circumference at iliac crest and the point of maximum circumference were recorded at baseline, 4, 8, and 12 weeks post-treatment, as well as their weight and BMI. Subjects’ rating on comfort level and satisfaction were collected via questionnaires at every follow-up. Standardized photographs were also taken with the Canfield System1 at each visit. Results: Seven out of 12 subjects were satisfied with the outcome and 9 out of 12 would recommend this treatment to their friends and family. There was statistically significant improvement in the waist circumference measured at both the iliac crest (P-value 0.013, 0.002, 0.005) and maximum waistline (P-value 0.003, 0.034, 0.023) at 4, 8, 12 weeks post-treatment. Spearman’s rho for correlation of energy level versus improvement showed that at 12 weeks post-treatment follow-up, the improvement significantly correlated with the total fluence per treatment (P-value 0.041). The higher the total fluence delivered, the larger the decrease in waist circumference. Conclusions: High-intensity focused ultrasound effectively decreases waist circumference in Chinese. The higher the total fluence delivered, the larger the decrease in waist circumference was observed. Lasers Surg. Med. 46:263–269, 2014. ß 2014 Wiley Periodicals, Inc. Key words: high-intensity focused ultrasound; noninvasive; body sculpting; Chinese BACKGROUND AND OBJECTIVES Non-invasive approaches to body contouring have gained much popularity in recent years. Such techniques include cryolipolysis, radiofrequency ablation, low-intensity ultrasound, low-level laser therapy, and high-intensity focused ß 2014 Wiley Periodicals, Inc.
ultrasound (HIFU). HIFU was initially developed to treat medical conditions such as kidney stones and uterine fibroids often times avoiding the need for more aggressive surgical measures [1,2]. HIFU creates areas of localized damage in the fat sparing superficial and surrounding tissue [3]. At high frequencies such as 2 MHz, ultrasound energy is highly convergent, confining tissue injury to a small focal point [4]. The energy delivered at that point induces molecular vibrations that increase temperature at the focal point, causing coagulative necrosis of adipocytes. Macrophages are then recruited to the area and engulf cellular debris and extracellular lipids [5]. In a patient safety study, no abnormalities in lipids, inflammatory markers or renal and hepatic function were identified after treatment with HIFU [6,7]. From our experience, body contouring procedures may have different efficacies in our population [8,9]. The objective of our present study is to evaluate the efficacy of HIFU for non-invasive body sculpting in Chinese subjects. METHODS Patients were recruited via the use of a subject database from our center. Interested candidates were screened over the telephone and potentially acceptable volunteers were invited in for an initial assessment. Men and women between18 and 65 years of age with body mass index (BMI) 30 mg/kg2 and subcutaneous adipose tissue 2.5 cm in the treatment region were eligible to participate. This is determined by use of a diagnostic ultrasound at screening. Exclusion criteria included pregnant or lactating females, adipose tissue of less than 1.0 cm beyond the treatment
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and have disclosed the following: Henry H. L. Chan receives honorarium and travel allowance. He holds stock options in Solta MedicalTM. Disclosure: The transducers used in this study were provided for free by Solta MedicalTM. Presented at the 33rd Annual Meeting of the American Society for Laser Medicine and Surgery, Boston, Massachusetts, April 5, 2013. Correspondence to: Samantha Shek, 11/F, Silver Fortune Plaza, 1 Wellington Street, Central, Hong Kong, China. E-mail: [email protected] Accepted 26 January 2014 Published online 3 March 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22232
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focal depth setting of the system in the area to be treated, hernia at the treatment area, any body contouring treatment within a year, coagulative disorders or medications affecting coagulation, diabetes, cardiovascular disease, and previous abdominal surgery in the treatment area. A total of 12 Chinese subjects were enrolled in the study. Ages ranged between 27 and 56 years with 9 (75%) females and 3 (25%) males. Risk factors such as pain, swelling, bruising, redness, dysesthesia, and infection were explained. Patients were also informed of the possibility that there may be no response to treatment. All patients received a physical exam and signed a written informed consent prior to commencement of the study. Patients were instructed to maintain their normal diet and exercise routine. Patients received a single treatment at baseline and results were reviewed after 4, 8, and 12 weeks. Prior to the procedure, the section of the anterior abdomen to be treated was determined by the physician. A minimum of 150 J/cm2 was delivered per treatment and the highest tolerable energy was used per pass. When the pain was reported as intolerable by the subject, the energy was decreased in increments of 5 J/cm2 each time. Each pass was applied at a focal depth of 1.3 cm below the skin in a 2.8 cm 2.8 cm grid. Oral acetaminophen was administered before the procedure. During treatment, the level of pain was recorded using a 0–10 visual analogue scale (VAS). At each visit, weight, BMI, and waist circumference at two sites (at the iliac crest and point of maximum waist circumference) were assessed by trained technicians. The experienced technicians were trained by physicians at our center and have taken part in multiple body contouring studies. The sites of measurements were determined by the primary investigator after physical examination and measurements. Circumferential measurements were taken with a special tape designed to have consistent tension when placed at the site to be measured. We attempted to analyze the patients’ postures, position and breathing in a standardized manner. The sites measured were marked on the patients’ abdomen and recorded on a clear plastic sheet with reference to anatomical landmarks also marked on the sheet. Subsequent re-measurements were based on these sites. The level of discomfort and satisfaction with the procedure was also recorded. All adverse effects were recorded. RESULTS All twelve subjects completed the single treatment, of which three quarters were female (9 out of 12) with a mean age of 39.5 years (range 27–56) and a mean BMI of 25.2 kg/ m2 (range 21.9–28.3 kg/cm2; Table 1). The total fluence delivered ranged from 150 to 165 J/cm2 (mean 161 J/cm2). Fluence per pass ranged from 30–55 J/cm2. All 12 patients were present at the 12-week follow-up visit. The mean number of 2.8 cm 2.8 cm sites treated on the abdomen was 12.2 (range 9–18). The mean treated area was 95.6 cm2 (range 70.6–141.1 cm2) and mean treatment time was 46.3 minutes (range 22–90 minutes). Although a decrease in body weight during the study was noted
TABLE 1. Patient Demographics No. of patients Sex Age BMI (kg/m2)
12 Female: 9 (75.0%) Male: 3 (25.0%) Mean (SD): 39.5 (10.140) Range: 27–56 Mean (SD): 25.230 (2.0310) Range: 21.9–28.3
(Table 2), it did not correlate with the endpoint results of this study. As per the Spearman’s Rho test, there was no statistically significant correlation of BMI change and the change in iliac or point of maximum waist circumference at follow-up (Table 3). A significant improvement in waist circumference at the iliac crest was observed at 4 weeks (P ¼ 0.013), 8 weeks (P ¼ 0.002), and 12 weeks (P ¼ 0.005; Table 4). The average circumferential decrease was 2.1 cm at 12 weeks (range 0.3–4.45 cm; Table 5). A similar observation was found at the maximum waist circumference with P ¼ 0.003 at 4 weeks, P ¼ 0.034 at 8 weeks, and P ¼ 0.023 at 12 weeks (Table 6). The average decrease in circumference was 1.0 cm (range 1.7–2.9 cm) (Table 7; Figs. 1a, b and 2a, b). The average pain score associated with the procedure was 5.7 (range 1.4–9.1) at a scale of 0–10. Two thirds of the patients thought the treatment was uncomfortable but stated that the level of discomfort quickly subsided over time (Table 8). Seven out of 12 subjects (58.3%) were satisfied with the overall result of the treatment (Table 9) and 9 out of the 12 subjects (75%) would recommend this treatment to family and friends (Table 10). The most common adverse effects were pain and bruising which resolved. No unexpected or serious side effects were noted. As a secondary measure we analyzed was the relationship between the total energy delivered and level of improvement. A Spearman’s Rho test was carried out and revealed that higher total fluence delivered was associated with greater improvement in waist circumference (Table 11). DISCUSSION In this single center prospective study, a single HIFU treatment with total fluence of 150–165 J/cm2 reduced waist circumference by 2.1 cm at 12 weeks post-treatment. The range of fluence per pass was 30–55 J/cm2. This wide range can be attributed to the need to adjust for the variable degree of pain experienced during treatment. We found that 55 J/cm2 was not tolerated by most patients and for those who tolerated it initially, they then complained of excess pain during subsequent passes. This is likely due to the rapid increase in temperature resulting from multiple passes. Using lower fluences and a greater number of passes, decreased the discomfort associated with the procedure. This is consistent with a trial by Robonson et al. that assessed pain scores when energy of 30 or 60 J/cm2
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TABLE 2. Patients’ Weight (kg) at Baseline and 4, 8, and 12 Weeks Follow-Up Percentiles
Baseline Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Std. Deviation
Minimum
Maximum
25th
50th (Median)
75th
12 12 12 12
68.633 68.292 67.708 67.242
11.7911 12.0171 11.6657 11.6271
53.0 53.6 52.9 53.3
89.5 91.0 90.0 89.1
60.900 59.575 59.750 58.500
66.250 65.150 64.650 64.200
80.350 79.300 78.650 76.700
TABLE 3. Spearman’s Rho Test for the Correlation of BMI Change Versus the Change in Iliac/Point of Maximum Waist Circumference Correlations At lilac waist circumference
At point of maximum waist circumference
0.164 0.277 46
0.298a 0.044 46
0.164 0.277 46
1.000
0.505b 0.000 46
0.298a 0.044 46
0.505b 0.000 46
BMI Spearman’s Rho BMI Correlation coefficient Sig. (two-tailed) N At lilac waist circumference Correlation coefficient Sig. (two-tailed) N At point of maximum waist circumference Correlation coefficient Sig. (two-tailed) N
1.000 46
46
1.000 46
a
Correlation is significant at the 0.05 level (two-tailed). Correlation is significant at the 0.01 level (two-tailed).
b
TABLE 4. Waist Circumference (cm) at Iliac Crest at Baseline, 4, 8, and 12 Weeks Follow-Up
Baseline Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Median
Std. deviation
Minimum
Maximum
P-value
12 12 12 12
90.00 88.66 88.12 87.85
91.75 89.93 89.75 88.90
8.38 8.24 7.81 7.59
76.75 75.15 76.15 76.20
104.10 102.15 101.00 99.90
0.013 0.002 0.005
was delivered per treatment cycle. Pain scores were reported as 3.2 and 6.1, respectively while the total fluence delivered was identical. Interestingly, the same study reported that there was no statistical significant difference in circumferential reduction between the 30 and 60 J/cm2 subgroups [10]. Since efficacy is not dependent on fluence
per pass but rather the total fluence delivered, our current approach to the use of HIFU for body sculpting is to use lower fluence per cycle with an increased number of passes. Fatemi et al. reported a 4.4 cm decrease in waist circumference at 12 weeks post-treatment in a retrospective case series of 282 patients who received a single HIFU
TABLE 5. Mean Change in Waist Circumference at Level of Iliac Crest (cm)
Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Std. deviation
Range
12 12 12
1.3375 1.8725 2.1458
1.32736 1.69748 1.72659
3.80 to 0.30 6.00 to 0.10 4.45 to 0.30
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TABLE 6. Point of Maximum Waist Circumference (cm) at Baseline, 4, 8, and 12 Weeks Follow-Up
Baseline Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Median
Std. deviation
Minimum
Maximum
P-value
12 12 12 12
92.93 92.00 91.23 91.97
95.25 93.23 91.53 92.60
6.52 6.34 6.22 6.45
81.90 81.35 81.20 81.35
101.50 101.25 101.70 101.05
0.003 0.034 0.023
TABLE 7. Mean Change in Point of Maximum Waist Circumference (cm)
Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Std. deviation
Range
12 12 12
0.9375 0.8750 0.9667
0.84373 1.16121 1.33661
2.60 to 0.00 2.60 to 1.10 2.90 to 1.70
Fig. 1. a: A 38/M at baseline and 12 weeks post-treatment. A total energy of 40 J/cm2 over eighteen 2.8 cm 2.8 cm grids were delivered over four passes. b: A 38/M at baseline (A) and 12 weeks posttreatment (B). A total energy of 40 J/cm2 over eighteen 2.8 cm 2.8 cm grids were delivered in four passes.
EFFICACY OF HIGH-INTENSITY FOCUSED
267
Fig. 2. a: A 36/F at baseline (A) and 12 weeks post-treatment (B). A total energy of 55 J/cm2 over
eleven 2.8 cm 2.8 cm grids were delivered in three passes. b: A 36/F at baseline (A) and 12 weeks post-treatment (B). A total energy of 55 J/cm2 over eleven 2.8 cm 2.8 cm grids were delivered in three passes.
treatment [11]. In another study by Fatemi et al. a single HIFU treatment with mean total fluence of 134.8 J/cm2 resulted in a 4.6 cm decrease in waist circumference 3 months after treatment [12]. Although the mean total fluence delivered in our study was similar to that used in
aforementioned report, the outcome was significantly less impressive. A possible explanation for the discrepancy in these results may be due to the difference in treatment area. On average, Chinese patients have a smaller frame than Caucasians which means that the treated area is
TABLE 8. Comfort Level During Treatment, 4 and 12 Weeks Follow-Up Visit
Very comfortable Comfortable Neutral Uncomfortable Very uncomfortable Total
During treatment
Four weeks follow-up
Twelve weeks follow-up
1; 8.3% 2; 16.7% 1; 8.3% 6; 50.0% 2; 16.7% 12; 100.0%
3; 25.0% 6; 50.0% 3; 25.0% 0; 0.0% 0; 0.0% 12; 100.0%
7; 58.3% 5; 41.7% 0; 0.0% 0; 0.0% 0; 0.0% 12; 100.0%
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TABLE 9. Level of Satisfaction at 4 and 12 Weeks Follow-Up Visit
Very satisfied Satisfied Neutral Very dissatisfied Total
Four weeks follow-up
Twelve weeks follow-up
3; 25.0% 4; 33.3% 5; 41.7% 0; 0.0% 12; 100.0%
4; 33.3% 3; 25.0% 4; 33.3% 1; 8.3% 12; 100.0%
necessarily smaller. The average number of treatment grids per patient was 12.2. This information was not reported in the study by Fatemi et al. Jewell et al. [7] published a trial of 180 patients who were randomized to one of two treatment groups with HIFU or a sham-
treatment control group. The mean of the 2.8 cm 2.8 cm grids in the two treatment groups were 35.1 and 31.6, an area nearly three times as large as that used in our study. Most Asian patients would be unable to accommodate over 30 grids on their abdomens. Jewell et al. reported a statistically significant reduction in waist circumference in both groups compared to the sham control group, however quantitative measurement was not shown. No long term results have been published as it is infeasible to obtain such long term results given patient reluctance to return and potential weight change due to lifestyle changes over that time. Compared with liposuction, there is minimal downtime associated with HIFU for body shaping. Additionally, due to the non-invasive nature of the procedure, HIFU has a significantly lower risk of infection and no need for tumescent or general anesthesia. This further minimizes the potential for post-operative complications. Adverse effects have largely been shown to be transient and are
TABLE 10. Willingness to Recommend the Treatment to Friends and Family Visit
Yes, absolutely Probably would No opinion Probably not Absolutely not Total
Immediately after tx
Four weeks follow-up
Twelve weeks follow-up
2; 16.7% 8; 66.7% 0; 0.0% 1; 8.3% 1; 8.3% 12; 100.0%
3; 25.0% 6; 50.0% 1; 8.3% 1; 8.3% 1; 8.3% 12; 100.0%
5; 41.7% 4; 33.3% 0; 0.0% 2; 16.7% 1; 8.3% 12; 100.0%
TABLE 11. Spearman’s Rho Correlation for the Total Fluence Per Treatment Versus Change in Waist Circumference at Level of Iliac Crest Total fluence per treatment Difference in lilac crest waist circumference at 4 weeks follow-up Correlation coefficient 0.069 Sig. (two-tailed) 0.832 Difference in lilac crest waist circumference at 8 weeks follow-up Correlation coefficient 0.084 Sig. (two-tailed) 0.795 Difference in lilac crest waist circumference at 12 weeks follow-up Correlation coefficient 0.374 Sig. (two-tailed) 0.231 Difference in point of max waist circumference at 4 weeks follow-up Correlation coefficient 0.389 Sig. (two-tailed) 0.211 Difference in point of max waist circumference at 8 weeks follow-up Correlation coefficient 0.444 Sig. (two-tailed) 0.149 Difference in point of max waist circumference at 12 weeks follow-up Correlation coefficient 0.595a Sig. (two-tailed) 0.041 a
Correlation is significant at the 0.05 level (two-tailed).
Energy level 0.049 0.880 0.057 0.861 0.418 0.176 0.441 0.151 0.257 0.420 0.513 0.088
EFFICACY OF HIGH-INTENSITY FOCUSED
usually well handled by managing patient expectations. The most commonly encountered side effects were redness, bruising, and pain, all of which resolved spontaneously. Recently, real-time temperature monitoring in fat and aqueous tissue during magnetic resonance-guided HIFU for tumor ablation by a hybrid proton resonance frequency/T1 technique has been investigated [13,14]. The adjunctive use of real-time temperature monitoring in adipose tissue during body contouring procedures could potentially increase treatment efficacy and further minimize adverse effects. REFERENCES 1. Yoshizawa S, Ikeda T, Ito A, Ota R, Takagi S, Matsumoto Y. High intensity focused ultrasound lithotripsy with cavitating microbubbles. Med Biol Eng Comput 2009;47:851–860. 2. Fruehauf JH, Back W, Eiermann A, Lang MC, Pessel M, Marlinghaus E, Melchert F, Volz-Ko¨ster S, Volz J. Highintensity focused ultrasound for the targeted destruction of uterine tissues: Experiences from a pilot study using a mobile HIFU Unit. Arch Gynecol Obstet 2008;277:143–150. 3. Jewell ML, Desilets C, Smoller BR. Evaluation of a novel highintensity focused ultrasound device: Preclinical studies in a porcine model. Aesthet Surg J 2011;31:429–434. 4. Haar GT, Coussios C. High intensity focused ultrasound: physical principles and devices. Int J Hyperthermia 2007; 23(2):89–104. 5. Smoller BR, Garcia-Murray E, Rivas OA. The histopathological changes from the use of high intensity focused ultrasound (HIFU) in adipose tissue. Presented at: American Academy of Dermatology 64th Annual Meeting; March 3–7, 2006; San Francisco, CA. 6. Jewell ML, Baxter RA, Cox SE, Donofrio LM, Dover JS, Glogau RG, Kane MA, Weiss RA, Martin P, Schlessinger J. Randomized sham-controlled trial to evaluate the safety and
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effectiveness of a high-intensity focused ultrasound device for noninvasive body sculpting. Plast Reconstr Surg 2011;128(1): 253–262. Jewell ML, Weiss RA, Baxter RA, Cox SE, Dover JS, Donofrio LM, Glogau RG, Kane MC, Martin P, Lawrence ID, Schlessinger J. Safety and tolerability of high-intensity focused ultrasonography for noninvasive body sculpting: 24-week data from a randomized, sham-controlled study. Aesthet Surg J 2012;32(7):868–876. Shek S, Yu C, Yeung CK, Kono T, Chan HH. The use of focused ultrasound for non-invasive body contouring in Asians. Lasers Surg Med 2009;41(10):751–759. Shek SY, Chan NP, Chan HH. Non-invasive cryolipolysis for body contouring in Chinese—A first commercial experience. Lasers Surg Med 2012;44(2):125–130. Robonson DM, Kaminer MS, Baumann L, Burns AJ, Geronemus RG, Jewell M, Lupin M, Narurkar VA, Struck SK, Elford E, Dover JS. Tissue using multiple treatment techniques. Presented at: American Society for Evaluation of high-intensity focused ultrasound for the reduction of subcutaneous adipose laser in medicine and surgery annual meeting: April 4–6, 2013, Boston, MA. Fatemi A. High-intensity focused ultrasound effectively reduces adipose tissue. Semin Cutan Med Surg 2009;28: 257–262. Fatemi A, Kane MA. High-intensity focused ultrasound effectively reduces waist circumference by ablating adipose tissue from the abdomen and flanks: A retrospective case series. Aesthetic Plast Surg 2010;34:577–582. Todd N, Diakite M, Payne A, Parker DL. Hybrid proton resonance frequency/T1 technique for simultaneous temperature monitoring in adipose and aqueous tissues. Magn Reson Med 2013;69(1):62–70. Diakite M, Odeen H, Todd N, Payne A, Parker DL. Toward real-time temperature monitoring in fat and aqueous tissue during magnetic resonance-guided high-intensity focused ultrasound using a three-dimensional proton resonance frequency T1 method. Magn Reson Med 2013.
Efficacy of High-Intensity Focused Ultrasonography for Noninvasive Body Sculpting in Chinese Patients Samantha Y.N. Shek, MBBS,1 Chi K. Yeung, MD, FRCP,1 Johnny C.Y. Chan, MBBS,1 and Henry H. L. Chan, MD, PhD, FRCP1,2 1 Division of Dermatology, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China 2 Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Background and Objectives: High-intensity focused ultrasound (HIFU) is a noninvasive technology for body contouring. HIFU is focused within the subcutaneous adipose tissue, causing coagulative necrosis and cell death. The objective of this study is to evaluate the effectiveness of a HIFU device for sculpting of the abdomen. Materials and Methods: The system has a set focal depth of 1.3 cm. Twelve subjects with adipose thickness no less than 2.5 cm who met the screening criteria were recruited. Each subject received one treatment to the abdomen. The total fluence used per site was 150–165 J/cm2 with a mean of 161 J/cm2. The waist circumference at iliac crest and the point of maximum circumference were recorded at baseline, 4, 8, and 12 weeks post-treatment, as well as their weight and BMI. Subjects’ rating on comfort level and satisfaction were collected via questionnaires at every follow-up. Standardized photographs were also taken with the Canfield System1 at each visit. Results: Seven out of 12 subjects were satisfied with the outcome and 9 out of 12 would recommend this treatment to their friends and family. There was statistically significant improvement in the waist circumference measured at both the iliac crest (P-value 0.013, 0.002, 0.005) and maximum waistline (P-value 0.003, 0.034, 0.023) at 4, 8, 12 weeks post-treatment. Spearman’s rho for correlation of energy level versus improvement showed that at 12 weeks post-treatment follow-up, the improvement significantly correlated with the total fluence per treatment (P-value 0.041). The higher the total fluence delivered, the larger the decrease in waist circumference. Conclusions: High-intensity focused ultrasound effectively decreases waist circumference in Chinese. The higher the total fluence delivered, the larger the decrease in waist circumference was observed. Lasers Surg. Med. 46:263–269, 2014. ß 2014 Wiley Periodicals, Inc. Key words: high-intensity focused ultrasound; noninvasive; body sculpting; Chinese BACKGROUND AND OBJECTIVES Non-invasive approaches to body contouring have gained much popularity in recent years. Such techniques include cryolipolysis, radiofrequency ablation, low-intensity ultrasound, low-level laser therapy, and high-intensity focused ß 2014 Wiley Periodicals, Inc.
ultrasound (HIFU). HIFU was initially developed to treat medical conditions such as kidney stones and uterine fibroids often times avoiding the need for more aggressive surgical measures [1,2]. HIFU creates areas of localized damage in the fat sparing superficial and surrounding tissue [3]. At high frequencies such as 2 MHz, ultrasound energy is highly convergent, confining tissue injury to a small focal point [4]. The energy delivered at that point induces molecular vibrations that increase temperature at the focal point, causing coagulative necrosis of adipocytes. Macrophages are then recruited to the area and engulf cellular debris and extracellular lipids [5]. In a patient safety study, no abnormalities in lipids, inflammatory markers or renal and hepatic function were identified after treatment with HIFU [6,7]. From our experience, body contouring procedures may have different efficacies in our population [8,9]. The objective of our present study is to evaluate the efficacy of HIFU for non-invasive body sculpting in Chinese subjects. METHODS Patients were recruited via the use of a subject database from our center. Interested candidates were screened over the telephone and potentially acceptable volunteers were invited in for an initial assessment. Men and women between18 and 65 years of age with body mass index (BMI) 30 mg/kg2 and subcutaneous adipose tissue 2.5 cm in the treatment region were eligible to participate. This is determined by use of a diagnostic ultrasound at screening. Exclusion criteria included pregnant or lactating females, adipose tissue of less than 1.0 cm beyond the treatment
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and have disclosed the following: Henry H. L. Chan receives honorarium and travel allowance. He holds stock options in Solta MedicalTM. Disclosure: The transducers used in this study were provided for free by Solta MedicalTM. Presented at the 33rd Annual Meeting of the American Society for Laser Medicine and Surgery, Boston, Massachusetts, April 5, 2013. Correspondence to: Samantha Shek, 11/F, Silver Fortune Plaza, 1 Wellington Street, Central, Hong Kong, China. E-mail: [email protected] Accepted 26 January 2014 Published online 3 March 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22232
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SHEK ET AL.
focal depth setting of the system in the area to be treated, hernia at the treatment area, any body contouring treatment within a year, coagulative disorders or medications affecting coagulation, diabetes, cardiovascular disease, and previous abdominal surgery in the treatment area. A total of 12 Chinese subjects were enrolled in the study. Ages ranged between 27 and 56 years with 9 (75%) females and 3 (25%) males. Risk factors such as pain, swelling, bruising, redness, dysesthesia, and infection were explained. Patients were also informed of the possibility that there may be no response to treatment. All patients received a physical exam and signed a written informed consent prior to commencement of the study. Patients were instructed to maintain their normal diet and exercise routine. Patients received a single treatment at baseline and results were reviewed after 4, 8, and 12 weeks. Prior to the procedure, the section of the anterior abdomen to be treated was determined by the physician. A minimum of 150 J/cm2 was delivered per treatment and the highest tolerable energy was used per pass. When the pain was reported as intolerable by the subject, the energy was decreased in increments of 5 J/cm2 each time. Each pass was applied at a focal depth of 1.3 cm below the skin in a 2.8 cm 2.8 cm grid. Oral acetaminophen was administered before the procedure. During treatment, the level of pain was recorded using a 0–10 visual analogue scale (VAS). At each visit, weight, BMI, and waist circumference at two sites (at the iliac crest and point of maximum waist circumference) were assessed by trained technicians. The experienced technicians were trained by physicians at our center and have taken part in multiple body contouring studies. The sites of measurements were determined by the primary investigator after physical examination and measurements. Circumferential measurements were taken with a special tape designed to have consistent tension when placed at the site to be measured. We attempted to analyze the patients’ postures, position and breathing in a standardized manner. The sites measured were marked on the patients’ abdomen and recorded on a clear plastic sheet with reference to anatomical landmarks also marked on the sheet. Subsequent re-measurements were based on these sites. The level of discomfort and satisfaction with the procedure was also recorded. All adverse effects were recorded. RESULTS All twelve subjects completed the single treatment, of which three quarters were female (9 out of 12) with a mean age of 39.5 years (range 27–56) and a mean BMI of 25.2 kg/ m2 (range 21.9–28.3 kg/cm2; Table 1). The total fluence delivered ranged from 150 to 165 J/cm2 (mean 161 J/cm2). Fluence per pass ranged from 30–55 J/cm2. All 12 patients were present at the 12-week follow-up visit. The mean number of 2.8 cm 2.8 cm sites treated on the abdomen was 12.2 (range 9–18). The mean treated area was 95.6 cm2 (range 70.6–141.1 cm2) and mean treatment time was 46.3 minutes (range 22–90 minutes). Although a decrease in body weight during the study was noted
TABLE 1. Patient Demographics No. of patients Sex Age BMI (kg/m2)
12 Female: 9 (75.0%) Male: 3 (25.0%) Mean (SD): 39.5 (10.140) Range: 27–56 Mean (SD): 25.230 (2.0310) Range: 21.9–28.3
(Table 2), it did not correlate with the endpoint results of this study. As per the Spearman’s Rho test, there was no statistically significant correlation of BMI change and the change in iliac or point of maximum waist circumference at follow-up (Table 3). A significant improvement in waist circumference at the iliac crest was observed at 4 weeks (P ¼ 0.013), 8 weeks (P ¼ 0.002), and 12 weeks (P ¼ 0.005; Table 4). The average circumferential decrease was 2.1 cm at 12 weeks (range 0.3–4.45 cm; Table 5). A similar observation was found at the maximum waist circumference with P ¼ 0.003 at 4 weeks, P ¼ 0.034 at 8 weeks, and P ¼ 0.023 at 12 weeks (Table 6). The average decrease in circumference was 1.0 cm (range 1.7–2.9 cm) (Table 7; Figs. 1a, b and 2a, b). The average pain score associated with the procedure was 5.7 (range 1.4–9.1) at a scale of 0–10. Two thirds of the patients thought the treatment was uncomfortable but stated that the level of discomfort quickly subsided over time (Table 8). Seven out of 12 subjects (58.3%) were satisfied with the overall result of the treatment (Table 9) and 9 out of the 12 subjects (75%) would recommend this treatment to family and friends (Table 10). The most common adverse effects were pain and bruising which resolved. No unexpected or serious side effects were noted. As a secondary measure we analyzed was the relationship between the total energy delivered and level of improvement. A Spearman’s Rho test was carried out and revealed that higher total fluence delivered was associated with greater improvement in waist circumference (Table 11). DISCUSSION In this single center prospective study, a single HIFU treatment with total fluence of 150–165 J/cm2 reduced waist circumference by 2.1 cm at 12 weeks post-treatment. The range of fluence per pass was 30–55 J/cm2. This wide range can be attributed to the need to adjust for the variable degree of pain experienced during treatment. We found that 55 J/cm2 was not tolerated by most patients and for those who tolerated it initially, they then complained of excess pain during subsequent passes. This is likely due to the rapid increase in temperature resulting from multiple passes. Using lower fluences and a greater number of passes, decreased the discomfort associated with the procedure. This is consistent with a trial by Robonson et al. that assessed pain scores when energy of 30 or 60 J/cm2
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TABLE 2. Patients’ Weight (kg) at Baseline and 4, 8, and 12 Weeks Follow-Up Percentiles
Baseline Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Std. Deviation
Minimum
Maximum
25th
50th (Median)
75th
12 12 12 12
68.633 68.292 67.708 67.242
11.7911 12.0171 11.6657 11.6271
53.0 53.6 52.9 53.3
89.5 91.0 90.0 89.1
60.900 59.575 59.750 58.500
66.250 65.150 64.650 64.200
80.350 79.300 78.650 76.700
TABLE 3. Spearman’s Rho Test for the Correlation of BMI Change Versus the Change in Iliac/Point of Maximum Waist Circumference Correlations At lilac waist circumference
At point of maximum waist circumference
0.164 0.277 46
0.298a 0.044 46
0.164 0.277 46
1.000
0.505b 0.000 46
0.298a 0.044 46
0.505b 0.000 46
BMI Spearman’s Rho BMI Correlation coefficient Sig. (two-tailed) N At lilac waist circumference Correlation coefficient Sig. (two-tailed) N At point of maximum waist circumference Correlation coefficient Sig. (two-tailed) N
1.000 46
46
1.000 46
a
Correlation is significant at the 0.05 level (two-tailed). Correlation is significant at the 0.01 level (two-tailed).
b
TABLE 4. Waist Circumference (cm) at Iliac Crest at Baseline, 4, 8, and 12 Weeks Follow-Up
Baseline Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Median
Std. deviation
Minimum
Maximum
P-value
12 12 12 12
90.00 88.66 88.12 87.85
91.75 89.93 89.75 88.90
8.38 8.24 7.81 7.59
76.75 75.15 76.15 76.20
104.10 102.15 101.00 99.90
0.013 0.002 0.005
was delivered per treatment cycle. Pain scores were reported as 3.2 and 6.1, respectively while the total fluence delivered was identical. Interestingly, the same study reported that there was no statistical significant difference in circumferential reduction between the 30 and 60 J/cm2 subgroups [10]. Since efficacy is not dependent on fluence
per pass but rather the total fluence delivered, our current approach to the use of HIFU for body sculpting is to use lower fluence per cycle with an increased number of passes. Fatemi et al. reported a 4.4 cm decrease in waist circumference at 12 weeks post-treatment in a retrospective case series of 282 patients who received a single HIFU
TABLE 5. Mean Change in Waist Circumference at Level of Iliac Crest (cm)
Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Std. deviation
Range
12 12 12
1.3375 1.8725 2.1458
1.32736 1.69748 1.72659
3.80 to 0.30 6.00 to 0.10 4.45 to 0.30
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TABLE 6. Point of Maximum Waist Circumference (cm) at Baseline, 4, 8, and 12 Weeks Follow-Up
Baseline Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Median
Std. deviation
Minimum
Maximum
P-value
12 12 12 12
92.93 92.00 91.23 91.97
95.25 93.23 91.53 92.60
6.52 6.34 6.22 6.45
81.90 81.35 81.20 81.35
101.50 101.25 101.70 101.05
0.003 0.034 0.023
TABLE 7. Mean Change in Point of Maximum Waist Circumference (cm)
Four weeks follow-up Eight weeks follow-up Twelve weeks follow-up
N
Mean
Std. deviation
Range
12 12 12
0.9375 0.8750 0.9667
0.84373 1.16121 1.33661
2.60 to 0.00 2.60 to 1.10 2.90 to 1.70
Fig. 1. a: A 38/M at baseline and 12 weeks post-treatment. A total energy of 40 J/cm2 over eighteen 2.8 cm 2.8 cm grids were delivered over four passes. b: A 38/M at baseline (A) and 12 weeks posttreatment (B). A total energy of 40 J/cm2 over eighteen 2.8 cm 2.8 cm grids were delivered in four passes.
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Fig. 2. a: A 36/F at baseline (A) and 12 weeks post-treatment (B). A total energy of 55 J/cm2 over
eleven 2.8 cm 2.8 cm grids were delivered in three passes. b: A 36/F at baseline (A) and 12 weeks post-treatment (B). A total energy of 55 J/cm2 over eleven 2.8 cm 2.8 cm grids were delivered in three passes.
treatment [11]. In another study by Fatemi et al. a single HIFU treatment with mean total fluence of 134.8 J/cm2 resulted in a 4.6 cm decrease in waist circumference 3 months after treatment [12]. Although the mean total fluence delivered in our study was similar to that used in
aforementioned report, the outcome was significantly less impressive. A possible explanation for the discrepancy in these results may be due to the difference in treatment area. On average, Chinese patients have a smaller frame than Caucasians which means that the treated area is
TABLE 8. Comfort Level During Treatment, 4 and 12 Weeks Follow-Up Visit
Very comfortable Comfortable Neutral Uncomfortable Very uncomfortable Total
During treatment
Four weeks follow-up
Twelve weeks follow-up
1; 8.3% 2; 16.7% 1; 8.3% 6; 50.0% 2; 16.7% 12; 100.0%
3; 25.0% 6; 50.0% 3; 25.0% 0; 0.0% 0; 0.0% 12; 100.0%
7; 58.3% 5; 41.7% 0; 0.0% 0; 0.0% 0; 0.0% 12; 100.0%
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TABLE 9. Level of Satisfaction at 4 and 12 Weeks Follow-Up Visit
Very satisfied Satisfied Neutral Very dissatisfied Total
Four weeks follow-up
Twelve weeks follow-up
3; 25.0% 4; 33.3% 5; 41.7% 0; 0.0% 12; 100.0%
4; 33.3% 3; 25.0% 4; 33.3% 1; 8.3% 12; 100.0%
necessarily smaller. The average number of treatment grids per patient was 12.2. This information was not reported in the study by Fatemi et al. Jewell et al. [7] published a trial of 180 patients who were randomized to one of two treatment groups with HIFU or a sham-
treatment control group. The mean of the 2.8 cm 2.8 cm grids in the two treatment groups were 35.1 and 31.6, an area nearly three times as large as that used in our study. Most Asian patients would be unable to accommodate over 30 grids on their abdomens. Jewell et al. reported a statistically significant reduction in waist circumference in both groups compared to the sham control group, however quantitative measurement was not shown. No long term results have been published as it is infeasible to obtain such long term results given patient reluctance to return and potential weight change due to lifestyle changes over that time. Compared with liposuction, there is minimal downtime associated with HIFU for body shaping. Additionally, due to the non-invasive nature of the procedure, HIFU has a significantly lower risk of infection and no need for tumescent or general anesthesia. This further minimizes the potential for post-operative complications. Adverse effects have largely been shown to be transient and are
TABLE 10. Willingness to Recommend the Treatment to Friends and Family Visit
Yes, absolutely Probably would No opinion Probably not Absolutely not Total
Immediately after tx
Four weeks follow-up
Twelve weeks follow-up
2; 16.7% 8; 66.7% 0; 0.0% 1; 8.3% 1; 8.3% 12; 100.0%
3; 25.0% 6; 50.0% 1; 8.3% 1; 8.3% 1; 8.3% 12; 100.0%
5; 41.7% 4; 33.3% 0; 0.0% 2; 16.7% 1; 8.3% 12; 100.0%
TABLE 11. Spearman’s Rho Correlation for the Total Fluence Per Treatment Versus Change in Waist Circumference at Level of Iliac Crest Total fluence per treatment Difference in lilac crest waist circumference at 4 weeks follow-up Correlation coefficient 0.069 Sig. (two-tailed) 0.832 Difference in lilac crest waist circumference at 8 weeks follow-up Correlation coefficient 0.084 Sig. (two-tailed) 0.795 Difference in lilac crest waist circumference at 12 weeks follow-up Correlation coefficient 0.374 Sig. (two-tailed) 0.231 Difference in point of max waist circumference at 4 weeks follow-up Correlation coefficient 0.389 Sig. (two-tailed) 0.211 Difference in point of max waist circumference at 8 weeks follow-up Correlation coefficient 0.444 Sig. (two-tailed) 0.149 Difference in point of max waist circumference at 12 weeks follow-up Correlation coefficient 0.595a Sig. (two-tailed) 0.041 a
Correlation is significant at the 0.05 level (two-tailed).
Energy level 0.049 0.880 0.057 0.861 0.418 0.176 0.441 0.151 0.257 0.420 0.513 0.088
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usually well handled by managing patient expectations. The most commonly encountered side effects were redness, bruising, and pain, all of which resolved spontaneously. Recently, real-time temperature monitoring in fat and aqueous tissue during magnetic resonance-guided HIFU for tumor ablation by a hybrid proton resonance frequency/T1 technique has been investigated [13,14]. The adjunctive use of real-time temperature monitoring in adipose tissue during body contouring procedures could potentially increase treatment efficacy and further minimize adverse effects. REFERENCES 1. Yoshizawa S, Ikeda T, Ito A, Ota R, Takagi S, Matsumoto Y. High intensity focused ultrasound lithotripsy with cavitating microbubbles. Med Biol Eng Comput 2009;47:851–860. 2. Fruehauf JH, Back W, Eiermann A, Lang MC, Pessel M, Marlinghaus E, Melchert F, Volz-Ko¨ster S, Volz J. Highintensity focused ultrasound for the targeted destruction of uterine tissues: Experiences from a pilot study using a mobile HIFU Unit. Arch Gynecol Obstet 2008;277:143–150. 3. Jewell ML, Desilets C, Smoller BR. Evaluation of a novel highintensity focused ultrasound device: Preclinical studies in a porcine model. Aesthet Surg J 2011;31:429–434. 4. Haar GT, Coussios C. High intensity focused ultrasound: physical principles and devices. Int J Hyperthermia 2007; 23(2):89–104. 5. Smoller BR, Garcia-Murray E, Rivas OA. The histopathological changes from the use of high intensity focused ultrasound (HIFU) in adipose tissue. Presented at: American Academy of Dermatology 64th Annual Meeting; March 3–7, 2006; San Francisco, CA. 6. Jewell ML, Baxter RA, Cox SE, Donofrio LM, Dover JS, Glogau RG, Kane MA, Weiss RA, Martin P, Schlessinger J. Randomized sham-controlled trial to evaluate the safety and
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