V ORIGINAL ARTICLES SPECIAL TOPIC A Preliminary Study of a ...€ŠA preliminary... · appearance of cellulite was reportedly demonstrated. A study by Van der Lugt and colleagues

November 2015 1272 Volume 14 • Issue 11

Copyright © 2015 ORIGINAL ARTICLES Journal of Drugs in Dermatology

SPECIAL TOPIC

A Preliminary Study of a Transdermal Radiofrequency Device for Body Slimming

Douglas J. Key MDKey Laser Institute for Cosmetic Regenerative Medicine, Portland, Oregon

Background: The use and potential of radiofrequency energy for tissue contracture and body contouring has been established in the literature. Maximum reduction of laxity can be achieved by simultaneously tightening surface tissue and reducing unwanted fat below by the transdermal application of heat to reach and maintain tissue temperature targets within a well-defined range, inducing collagen remodeling in skin as well as apoptosis of fat cells and creating an overall slimming effect. A novel device utilizes transcutaneous mo-nopolar RF for body slimming in this manner, employing a thermistor feedback control mechanism to safely manage energy delivery and tissue temperature.Methods: Subjects (n=14) presenting with abdominal laxity were treated up to four times using the transcutaneous monopolar RF device at one or two zones in the abdominal region (at operator’s discretion). Non-expert blinded graders rated correction on an arbitrary scale (0=no laxity, 4=maximum laxity) after choosing the order of the before-and-after photo sets. A patient satisfaction survey was also administered.Results and Discussion: The two graders correctly ordered 10 of 14 photo sets in agreement. Average rated improvement was 0.75 and 0.80 for graders 1 and 2, respectively. Patient survey results revealed average perceived tightening of 2.14 points on a 0 to 4 scale (0=lowest tightening result, 4=highest tightening), and 8 of 14 subjects would recommend treatment to others.Conclusion: Transdermal monopolar RF is a safe and effective modality for non-invasive body slimming.

J Drugs Dermatol. 2015;14(11):1272-1278.

ABSTRACT

INTRODUCTION

The transcutaneous application of RF energy is a well-established treatment for tissue contracture.1-7 As the electric current permeates a tissue layer, impedance

creates heat. This localized thermogenesis is calculable using the Specific Absorption Rate (SAR) equation (Figure 1) assess-ing local electrical conductivity and magnitude of local electric current density generated around the electrode; the electric field strengths generated is capable of heating tissue in close proximity to the electrode, creating a specific pattern of local-ized thermogenesis that can be controlled to keep the radius of effect close to the electrode, as shown in Figure 2, promoting predictable and specific heating of target tissue. Thermogenic stimulation of collagen remodeling is the desired outcome,8-9 optimized within a well-defined temperature range, suggesting the need for monitoring and feedback mechanisms that maxi-mize the ability to achieve and maintain therapeutically expedi-ent temperatures within that range while minimizing potential for unwanted tissue injury.

Tissue temperature is regulated by controlling power (the volt-age delivered to the electrode) adjusted to compensate for tissue impedance. Integrated thermocouples can provide automatic feedback-controlled power modulation to achieve and maintain therapeutically relevant tissue temperatures subcutaneously.

Additionally, a thermal infrared camera offers real-time monitor-ing of surface skin temperature. The end result is a device for selective subcutaneous thermogenesis for a variety of potential aesthetic dermatological applications, using real-time feedback mechanisms to safely optimize therapeutic energy delivery.10

In 2008 a trial by del Pino et al.11 evaluated the effect of con-trolled volumetric RF heating for cellulite of the buttocks and thighs in 26 healthy women (age range, 18 to 50 years) with visible bilateral cellulite. Patients received two sessions of uni-polar RF therapy with cooling to maximize patient comfort, at an interval of 15 days. Clinical improvement was evaluated via pre- and post-treatment measurement of the distance be-tween the stratum corneum to the Camper’s fascia and from the stratum corneum to the muscle, with additional evaluation of the structure and change shown in the thickening and re-alignment of the septae. Contraction and improvement in the appearance of cellulite was reportedly demonstrated. A study by Van der Lugt and colleagues in 200912 investigated the use of transcutaneous RF for treating cellulite with a frequency of 0.6 MHz to 2.4 MHz administered in twelve weekly sessions, 12 minutes on each buttock, with a thermal endpoint of 42°C as measured on the skin. Improvement in cellulite was report-ed, with high patient satisfaction.

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Journal of Drugs in DermatologyNovember 2015 • Volume 14 • Issue 11

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the body’s natural processes. The two concurrent effects pro-vide a visible slimming effect.

The device itself administers 250 Watts of power at a frequen-cy of 470 kHz. Lower frequency allows RF energy to penetrate deeply in comparison to other available RF devices. ThermiS-mooth 250 is capable of delivering monopolar RF and bipolar RF treatment, depending on the handpiece used; depth of pen-etration is 3 mm using the bipolar handpiece, or adjustable between 6 mm and 30 mm using the monopolar handpiece. Seven capacitive monopolar electrodes are available in sizes ranging from 20 mm to 100 mm, chosen as appropriate for the treatment site. With appropriate treatment settings and choice among one bipolar and seven monopolar treatment heads, ThermiSmooth 250 transcutaneous RF therapy may be safely applied at most anatomical locations from the forehead to the ankles.

The purpose of this preliminary study is to evaluate the Ther-miSmooth 250 for the treatment of unwanted adiposity, cellulite, and the overlying lax skin—termed ‘body slimming’—using monopolar RF.

PATIENTS AND METHODSThe study was IRB approved and performed in accordance with the International Conference on Harmonization Good Practice Guidelines (ICH E6) and any applicable local regulatory re-quirements and laws. Informed consent was obtained from all subjects.

Fourteen subjects (all women, mean age, 55.3) presenting with abdominal laxity were enrolled in the study. Exclusion criteria were presence of cardiovascular disease or implanted device such as a pacemaker; prior cardiac surgery; presence of diabetes mellitus requiring insulin or oral hypoglyce-mic medication; active cancer; any medication or condition known to affect weight or cause bloating; active infection, wound, or other external trauma to treatment site(s); diagno-sis of serious mental illness (dementia, schizophrenia, etc.) or psychiatric hospitalization within the two years previous to study commencement; participation in a clinical study or other research within the 30 days prior to study commence-ment; body mass index (BMI) greater than 35; or use of a containment medication (corticosteroids, anabolic steroids, immunosuppressive medication).

An important goal of transcutaneous RF therapy is avoid-ing unwanted damage to the epidermis,13 preserving barrier function. While several RF technologies have emerged for the treatment of a variety of aesthetic dermatological condi-tions including wrinkles, laxity and cellulite, patient comfort is a common concern with many devices because sufficient heat flow is transmitted to stimulate the nociceptive recep-tors of the papillary dermis. Epidermal cooling is often used to mitigate this effect. The non-invasive nature of treatment is a notable advantage, significantly reducing risk, down-time, and need for aftercare. A 2010 study of non-invasive transdermal RF heating on subcutaneous fat provided in vitro and in vivo evidence that transdermal RF can induce apoptosis (natural programmed cell death) of adipocytes without causing thermal trauma to overlying skin.14 In vitro testing of adipocytes assessed cell viability after application of heat, demonstrating significant reductions in cell viabil-ity when target tissue temperature was elevated to 45°C for three minutes or 50°C for one minute, inducing cell death rates of 60% and 80%, respectively, within 9 hours. A trans-dermal RF device was used on two groups of abdominoplasty patients during and days before surgery. Temperature of adi-pose tissue at depth was shown to be elevated to 50°C with concurrent skin temperatures less than 30°C. Histological study showed no damage to skin, but vascular alterations were noted beginning at day 4 post-procedure with signifi-cant death of adipocytes at death noted beginning at day 9. It was concluded that precisely controlled use of transdermal RF was selective for causing thermal damage to subcutane-ous fat without injuring the skin.

The ThermiSmooth 250 device (Thermi, Irving, TX) provides consistent thermal regulation and output control, maximizing therapeutic delivery of RF energy to the target tissue without overtreating and focal pain, eliminating the need for epidermal cooling. Theoretically this allows physicians to treat deposits of unwanted fat and simultaneously tighten the surface skin above to create a more complete result. The heating of the skin promotes immediate collagen contraction and stimulation of neocollagenesis with improved elasticity, as well as long term stimulation of neocollagenesis producing a tightening effect.8-9 Beneath the skin, the effect on fatty tissue is theoretically substantial.5 Apoptosis of adipocytes occurs and, over time, re-leased fat is metabolized and cellular debris is eliminated via

FIGURE 1. Specific absorption rate equation.

"While scales for facial laxity and tightening have emerged, the nature of the face provides numerous landmarks and easily discernable zones for the sake of comparison."



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constant, deliberate, sweeping circular motion with in a section of the treatment site for 2 to 3 minutes until the target tissue temperature of 42°C to 45°C (depending on patient tolerance) was reached based on feedback indications from the system’s graphical user interface; temperature was maintained for an ad-ditional 5 to 7 minutes. Total treatment time was approximately 10 minutes but progressed to 15 minutes per treatment area. The process was repeated to the opposite/contralateral side im-mediately afterward to ensure uniformity across the anatomical area. After treatment the subject was cleaned up and sent home.

Baseline evaluations included digital photography. Initial treat-ment occurred on the same day as baseline evaluation or

At each treatment visit the subject was situated in treatment chair in a position best suited to allow treatment of the selected area. A return pad was placed underneath the subject to com-plete the circuit, and the treatment site was thoroughly washed with a non-alcohol based, commercially available cleanser. Once prepared, a coupling gel was applied to the treatment area. The treatment site was sectioned into zones of surface area 4 to 6 times the diameter of the treatment probe.

The treatment probe was then applied directly to the dermis to ensure that electrodes were in direct contact with the skin, and remained flushed with the skin throughout treatment. Upon application of energy the user moved the probe in a

TABLE 1.

Transdermal RF for Body Slimming Treatment Results Data Table

Examiner 1 Scoring Examiner 2 Scoring Settings and Other Variables

Pt.Correct Order? A B Variance

Correct Order? A B Variance

Zones Treated

Default Temp (°C)

Tx Time (Min) FU

NW Y 3.5 2.5 1.0 Y 3.0 2.0 1.0 2 44 10 6

SN Y 2.0 1.5 0.5 Y 1.5 1.0 0.5 2 44-45 10 2

PW Y 2.5 1.0 1.5 Y 2.0 1.0 1.0 1 45 15 4

DM Y 2.5 2.0 0.5 Y 2.0 1.5 0.5 2 43 8 2

SG Y 2.0 1.0 1.0 Y 1.5 1.0 0.5 1 45 15 2

PM Y 2.0 1.5 0.5 Y 1.5 1.0 0.5 1 45 10 4

KW Y 3.0 2.5 0.5 Y 2.0 1.0 1.0 1 45 15 2

KC Y 3.5 2.0 1.5 Y 2.5 1.0 1.5 2 45 15 3

LB Y 3.5 3.0 0.5 Y 2.5 1.5 1.0 2 44 10 6

SO Y 1.5 1.5 0.0 Y 1.5 1.0 0.5 1 43 10 4

Mean Variance: 0.75 Mean Variance: 0.80

RB N 1.5 1.0 0.5 N 1.5 1.0 0.5 1 45 15 3

JG N 1.5 1.0 0.5 Y 1.5 1.0 0.5 1 44 10 3

AZ N 3.0 1.5 1.5 N 2.0 1.0 1.0 1 45 10 2

TC N 1.5 1.5 0.0 Y 1.5 1.0 0.5 1 45 15 2

A = Score before Treatment; B = Score at follow-up evaluation; FU = follow-up (mo.); mean variance values are listed for the patient subset of 10 for which both examiners successfully ordered before and after photographs.

FIGURE 2. Example of radius of effect of capacitive monopolar electrodes for body slimming using 60mm, 70 mm, 80 mm, and 100 mm treatment heads.



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within 7 to 10 days of baseline evaluation. The second and addi-tional (up to four) treatments occurred at intervals of 2 to 3 weeks. Based on the investigator’s individual assessment of laxity, pa-tients were treated in one zone (central abdomen, 9 subjects) or two (abdomen left and right of the umbilicus, 5 subjects).

Follow-up was to occur occurred at 90 days (±7 days) after the fi-nal treatment session, at which time additional photography and assessment of study endpoints occurred. Assessments included evaluations of before and after photography using a Skin Laxity Severity Scale by two blinded raters who were not physicians or treatment professionals, and did not know which pictures were before or after. Investigators determined efficacy based on the number of pictures each blinded rater were correctly able to identify as before and after, and by the average grade of im-provement blinded evaluators gave when correctly identifying photos. The scale was an arbitrary measure scoring from 0 to 4 in increments of 0.5 (where 0.0=no laxity and 4.0=maximum laxity).

Additionally, a Patient Satisfaction Survey questionnaire was administered to each patient at follow-up asking subjects to rate their result on a 0 to 4 scale where 0 is the lowest and 4 is the highest value, as well as if they would recommend

TABLE 2.

Patient Survey Data Table With Average Variance

Subj.Average Variance

Perceived TIghtening

Slimming Observed?

Recommend to a Friend?

NW 2 3 Y YSN 2 2 N YPW 1 4 N YDM 2 1 N NSG 1 3 N YPM 1 2 N YKW 1 4 N YKC 2 1 N NLB 2 1 N NSO 1 4 Y YRB 1 0 N NJG 1 1 N NAZ 1 0 N NTC 1 4 Y YAverage variance is based on a scale of 0 to 4 in increments of 0.5;Perceived Tightening was rated by patients on a 0 to 4 scale in which 0 was the least and 4 was the most tightening.

FIGURE 3. Photograph of the abdomen of a 61-year-old woman before (left) and 4 months after (right) a course of treatment with Transdermal RF. This represents what was graded as a one-point improvement on the Skin Laxity Severity Scale. Photos courtesy of Key Laser Institute.

FIGURE 4. Photograph of the abdomen of a 53-year-old woman before (left) and 8 months after (right) a course of treatment with Transdermal RF. This represents what was graded as a one-point improvement on the Skin Laxity Severity Scale. Photos courtesy of Key Laser Institute.



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RESULTSAll patients completed the study and no major adverse events were reported. Treatment time ranged between 8 and 15 min-utes, although all but one subject was treated for at least 10 minutes. Examiner 1 correctly identified the before and after photographs for 10 of 14 subjects (71.43%), and Examiner 2 reported correctly 12 of 14 (85.71%) times. Both examiners agreed on 10 subjects; that is, the second examiner correctly ordered the same ten sets of before and after photographs as the first examiner, plus two additional. Of those they agreed upon (10), Examiner 1 scored average improvement of 0.75 above baseline, and Examiner 2 scored subjects an average of 0.80 points above baseline. Basic overall scoring data and key treatment parameters are listed in Table 1.

Patient survey results included an average tightening of 2.14 points on a 0 to 4 scale (0 lowest, 4 highest). Of 14 subjects, 8 said they’d recommend treatment to a friend and 3 said they had noticeable slimming noted by looser clothing. Table 2 dis-plays survey results in tabular form with average variance.

Table 3 shows the data for the subset of patients (n=10, the ‘Successful Result’ subset) for which both independent grad-ers correctly ordered photographs; this data was parsed out because statistical analysis including patients in the remainder subset would invalidate results, as the graders incorrectly or-dered and rated the photo sets. Among the Successful Result subset, variance (A-B, or reduction in laxity versus baseline) was statistically significant (P<0.05).

Patient before and after photos show visible results (Figures 3, 4, and 5). Figure 5 is a four photograph series extending follow-up out to one year, further demonstrating a long-term notable result.

DISCUSSIONThe methodology of this study was designed to determine the clinical potential of transdermal RF for body slimming, or re-duction of laxity of the abdomen. Non-expert graders were utilized in a novel way to ferret out the ability of the device to deliver noticeable results of clinical significance, given that there is currently no consistent, reproducible method for measuring improvement in body shaping or tightening. While scales for facial laxity and tightening have emerged, the nature of the face provides numerous landmarks and eas-ily discernable zones for the sake of comparison. Variation among individuals and the dearth of landmarks make simi-lar comparisons much more problematic when considering the abdomen. One commonly used method is circumference measurement; despite being quite inconsistent even among trained experts, it still sees use in scientific literature simply because better methods do not yet exist. Figures 3 and 4 show examples of what was rated as a one point improvement.

treatment to a friend, and if they felt they had noticeable slim-ming (clothes fit more loosely, etc.).

FIGURE 5. A series of four photographs of the abdomen of a 47-year-old woman at baseline as well as 2 months, 5 months, and 10 months after a course of treatment with Transdermal RF, demonstrating continuous visible improvement over that period. Photos courtesy of Key Laser Institute.



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Further study using other measures to build upon these findings would be of great benefit. The use of larger patient populations would also strengthen the power of such a study.

CONCLUSIONData suggests that transdermal RF technology has strong po-tential for body slimming given these outcomes as well as the safety and tolerability of the modality. Additional study using larger patient populations and more standardized empirical outcome measures would be of great benefit.

DISCLOSURESDr. Key holds stock with ThermiRF and is a paid independent research consultant. The protocol for this study was approved by IRB. All informed consent and photo consent are on file with Key Laser Institute.

REFERENCES1. Huang SK, Graham AR, Bharati S, et al. Short- and long-term effects of trans-

catheter ablation of the coronary sinus by radiofrequency energy. Circula-tion. 198g;78(82):416-27.

2. Deneke T, Khargi K, Müller KM, et al. Histopathology of intraoperatively in-duced linear radiofrequency ablation lesions in patients with chronic atrial fibrillation. Eur Heart J. 2005;26(17):1797-803.

3. Hernández-Zendejas G, Guerrero-Santos J. Percutaneous selective radio-frequency neuroablation in plastic surgery. Aesthetic Plast Surg. 1994;18(1):41-8.

4. Lolis MS, Goldberg DJ. Radiofrequency in cosmetic dermatology: a review. Dermatol Surg. 2012;38(11):1765-76.

5. Paul M, Blugerman G, Kreindel M, Mulholland RS. Three-dimensional radio-frequency tissue tightening: a proposed mechanism and applications for body contouring. Aesthet Plast Surg. 2011;35(1):87-95.

6. Key DJ. Integration of thermal imaging with subsurface radiofrequency thermistor heating for the purpose of skin tightening and contour im-provement: a retrospective review of clinical efficacy. J Drugs Dermatol. 2014;13(12):51-5.

7. Gold MH. Tissue tightening: a hot topic utilizing deep dermal heating. J Drugs Dermatol. 2007;6(12):1238-42.

An emerging method, three-dimensional body scanning (My-Bodee), may solve this problem and a trial using this novel technology with transdermal RF for body slimming is currently underway.

While the methodology of interpreting these results may be novel and non-standard, obvious clinical outcomes were achieved in 10 of 14 subjects, as chosen by independent, non-expert graders as shown in Table A. Notably, both examiners successfully ordered the same photo sets, with one rater correctly identifying photo sets of 2 additional patients. This suggests that treatment produced visible results a non-expert can see. Follow-up times ranged from 2 to 6 months, due to difficulties in arranging patient visits. The mean follow-up time among both patient subsets was 2.5. Retrospective analysis revealed no statistical relationship between perceived re-sult and time of follow-up, and such analysis was not part of the original protocol, but results seem to improve over time. Continual improvement is visible in Figure P4, a four-picture progression of one patient’s results followed out to 10 months. This patient demonstrated visible laxity at baseline with demonstrable progression (2 months, 5 months, and 10 months).

Based on Patient Survey results, 8 of 14 overall (both subsets) said they would recommend treatment to a friend, while only three reported noticing a slimming effect by the way their cloth-ing fit around the middle. Incidentally, the most enthusiastic patient based on the survey results was patient TC, whose re-sults were too subtle for correct classification by one grader but who reported a tightening result of 4 with a ‘yes’ for both recommendation and slimming questions.

TABLE 3.

Scoring for Successful Result Patient Subset When Treated With Transdermal RF

Subj. Examiner 1 Scoring Examiner 2 Scoring FU (mo) Tightening Score

A B Variance A B Variance

NW 3.5 2.5 1.0 3.0 2.0 1.0 6.0 3.0

SN 2.0 1.5 0.5 1.5 1.0 0.5 2.0 2.0

PW 2.5 1.0 1.5 2.0 1.0 1.0 4.0 4.0

DM 2.5 2.0 0.5 2.0 1.5 0.5 2.0 1.0

SG 2.0 1.0 1.0 1.5 1.0 0.5 2.0 3.0

PM 2.0 1.5 0.5 1.5 1.0 0.5 4.0 2.0

KW 3.0 2.5 0.5 2.0 1.0 1.0 2.0 4.0

KC 3.5 2.0 1.5 2.5 1.0 1.5 3.0 1.0

LB 3.5 3.0 0.5 2.5 1.5 1.0 6.0 1.0

SO 1.5 1.5 0.0 1.5 1.0 0.5 4.0 4.0

p = 0.0039 (s) Median = .50 (0.54)* p = 0.0020 (s) Median = 0.75 (0.50)* Median = 3.5 (2.17)* Mean 2.50 ± 1.27 (SD)

A = Score before Treatment; B = Score at follow-up evaluation; FU = follow-up (mo.); SD = standard deviation.*Interquartile range, a measure if statistical dispersion, or the difference between the upper and lower quartiles.



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8. Zelickson BD, Kist D, Bernstein E, et al. Histological and ultrastructural evalu-ation of the effects of a radiofrequency-based nonablative dermal remodel-ing device: a pilot study. Arch Dermatol. 2004;140(2):204-9.

9. Meshkinpour A, Ghasri P, Pope K, et al. Treatment of hypertrophic scars and keloids with a radiofrequency device: a study of collagen effects. Lasers Surg Med. 2005;37(5):343-9.

10. Key DJ, Comprehensive thermoregulation for the purpose of skin tightening using a novel radiofrequency treatment device: a preliminary report. J Drugs Dermatol. 2014;13(2):185-9.

11. Emilia del Pino M, Rosado RH, et al. Effect of controlled volumetric tissue heating with radiofrequency on cellulite and the subcutaneous tissue of the buttocks and thighs. J Drugs Dermatol. 2006;5(8):714-22.

12. van der Lugt C, Romero C, Ancona D, et al. A multicenter study of cellulite treatment with a variable emission radio frequency system. Dermatol Ther. 2009;22(1):74-84.

13. Abraham MT, Mashkevich G. Monopolar radiofrequency skin tightening. Fa-cial Plast Surg Clin North Am. 2007;15(2):169-77, v.

14. Franco W, Kothare A, Ronan SJ, et al. Hyperthermic injury to adipocyte cells by selective heating of subcutaneous fat with a novel radiofrequency device: feasibility studies. Lasers Surg Med. 2010;42(5):361-70.

AUTHOR CORRESPONDENCE

Douglas J. Key MD E-mail:................…….............................. [email protected]



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V ORIGINAL ARTICLES SPECIAL TOPIC A Preliminary Study of a ...€ŠA preliminary... · appearance of cellulite was reportedly demonstrated. A study by Van der Lugt and colleagues