250 Adv Ther (2012) 29(3):249-266.makes an additional contribution to the RF Heat generation by RF energy operates byenergy penetration. The heating effect of RF transfer of energy from the electric field towas also found to increase blood circulation the charged particles in the target tissue. Thisand to induce collagen remodeling. The results transfer can be achieved by three mechanismsfrom the cellulite and body shaping treatments of interaction between the electromagneticshowed an overall average improvement of field and the charges: (i) orientation of electric55% in the appearance of cellulite, with an dipoles that already exist in the atoms andaverage circumferential reduction of 3.31 cm molecules in the tissue; (ii) polarization of atomsin the buttocks, 2.94 cm in the thighs, and and molecules to produce dipole moments; and2.14 cm in the abdomen. The results from the (iii) displacement of conduction electrons andskin tightening procedure showed moderate ions in the tissue . In the first and secondimprovement of skin appearance in 50% mechanisms, the heat is generated by theand significant improvement in 31%. At the energy use involved in the movement of thefollow-up visits the results were found to be particles in response to an electric field. In thesustained without any significant side effects. third mechanism, heat is generated by collisionsConclusion: Of all tissue heating techniques, between the transmission charges and immobileRF-based technologies appear to be the most particles. Heat is generated in tissue by both theestablished and clinically proven. The design incident electric and the magnetic field. Sinceand specifications of the described vacuum- the magnetic field does not transfer any netassisted bipolar RF device fall within the range energy it does not produce any heat .of the specifications currently prescribed for Therefore, the mechanism of tissue heatingesthetic, nonablative RF systems. by electrical current is based on generating joules of heat. Generated heat is described byKeywords: Body contouring; Cellulite; Joule’s law:Radiofrequency; Radiofrequency energy; Skin j2tightening; Vacuum H= , σINTRODUCTION where j is the density of electrical currentPhysics of RF Energy and σ is electrical conductivity . The opposite of conductivity is called resistanceRadiofrequency (RF) energy is a type of or impedance (R). The parts of the body withelectromagnetic wave which is exponentially high blood content have the highest electricalattenuated during transition into the target tissue. conductivity. Bone, for example, has veryAt high frequencies of electromagnetic wave, low electrical conductivity, and consequentlypower is transferred rapidly close to the surface, the electrical current flows around it withoutattenuating the wave as it is dispersed. At lower penetration. Dry skin also has very low electricalfrequencies, in the spectrum of RF for example, conductivity and must therefore be hydrated tobecause the wavelength is greater and therefore enhance the passage of the current .the heating cannot be localized to limited areas, In general, the electrical conductivitythe energy penetration is deeper. For this reason, influences the depth to which RF energythe term “bulk” tissue heating is used . penetrates. The RF energy penetration
Adv Ther (2012) 29(3):249-266. 251depth equation consists of π constant, the positively charged grounded electrode. Theelectromagnetic wave frequency (the test active electrode has a relatively small contactfrequency), the magnetic permeability of the point with the skin, while the ground electrode,tissue, and the tissue’s electrical conductivity, as which is larger in size, is applied to the bodyfollows: at a distance from the active electrode. The electrical energy is concentrated near the tip of 1 δ≈ the active electrode and decreases rapidly with √πfµσ distance. The calculation of assessed penetration depth of RF energy is that it is half the size of where δ is the standard depth of penetration the active electrode: for example, a 10-mm(mm), π is 3.14, f is the test frequency (Hz), unipolar electrode can penetrate to a depth ofμ is magnetic permeability (H/mm), and approximately 5 mm.σ is electrical conductivity (% International The ability of the monopolar configurationAnnealed Copper Standard, IACS). to create a high power density on the surface of From this equation it can be determined the electrode makes it popular in electrosurgery.that the depth of penetration of RF energy in In this type of procedure a small-sized electrodemillimeters is inversely proportional to the is usually used. However, the unpredictablesquare root of the frequency. Therefore, lower behavior of a unipolar system, as the currentfrequencies have higher penetration rates and passes through the body to the groundingvice versa. The ability to control heating depth is electrode, is a disadvantage in cosmeticparticularly desirable in a system that is designed procedures .to treat both body and facial areas. Bipolar SystemTypes of RF Configuration A bipolar configuration also carries energy via two negative (cathode) and positive (anode)Electrical conductivity depends on several electrodes but with a fixed distance, while bothparameters, including tissue type, the frequency electrodes are in contact to the skin. This wayof the electrical current, and tissue temperature. the RF’s electrical current propagation is limitedThe distribution of electrical current, on the other by the area between electrodes. The calculationhand, depends on the geometry of the electrodes. of assessed penetration depth of RF energy in a In medicine there are two typical RF bipolar system is half the distance between theconfigurations that are used: the monopolar and electrodes. For example, in a bipolar system withthe bipolar. The main difference between them a 4-mm distance between two electrodes, theis the way in which the current is controlled theoretical depth is approximately 2 mm.and directed to the body. However, at the same In contrast to the monopolar configuration,energy fluence there is no difference in the tissue the main advantage of a bipolar configurationeffect . is that the RF current inside the tissue has a controlled distribution that is limited byMonopolar System the volume between the two electrodes.A monopolar configuration carries energy Consequently, the bipolar system is lessvia two electrodes: one negatively charged appropriate for electrosurgery, but it s morecylindrical active electrode and a second suitable for homeostasis and controlled vessel
252 Adv Ther (2012) 29(3):249-266.contraction . Moreover, since bipolar energy is Initial reports of a nonablative RF systemmore localized, less energy is required to achieve describe bipolar RF energy used for collagenthe same heating effect as with the monopolar shrinkage in shoulder instability. This systemconfiguration . (CAPSure; Arthrocare Corp., Austin, TX, USA)  was used to thermally tighten theMultipolar System shoulder capsule and glenohumeral ligaments.In the esthetic market there are also “new” types Shortly following these reports, a nonablativeof RF energy, including multiple monopolar, commercial RF device was reported. Thistripolar, octapolar, etc., configurations. monopolar RF system, indicated for facial skinBasically, there are only monopolar or bipolar tightening, requires a cryogen spray to cool theRF electrodes. The multiple monopolar is active electrode in order to preserve the skinbased on two monopolar electrodes (negative) surface from thermal damage. In July 2000and one ground electrode (positive). The this system received its first US Food and Drugtripolar configuration, is a combination of Administration (FDA) clearance for indicationsone monopolar and one bipolar electrode or a which have since been extended to includecombination of one negative and two positive “noninvasive treatment of wrinkles and rhytids”electrodes (which creates two pairs of a bipolar as well as “temporary improvement in thesystem). The octapolar is a system that comprises appearance of cellulite” .four pairs of bipolar electrodes. Following the introduction of this system, several other monopolar and bipolar nonablative,History of RF Energy Applications esthetic RF systems have been cleared by the FDA. While some of these systems are RF-only systems,Electrical current has been used in medicine for others combine RF with various other treatmentmore than a century . RF energy has been modalities such as infrared light, vacuum, andused in medical treatment for over 75 years , mechanical massage. The FDA-cleared indicationsgenerally for minimally invasive surgical for these combination systems range fromprocedures using RF for ablation and coagulation, temporary improvement of blood circulation toincluding in the treatment of sleep apnea . temporary reduction of thigh circumference .The high efficiency of RF current for tissueheating has also made it useful for electrosurgery Indications and Contraindications for RFand an attractive source of energy for various Energy-Based Treatmentdermatologic applications . However, thetechnology is not solely limited to these fields. A RF current produces a pure thermal effect onIn fact, most devices used on a daily basis operate biological tissue. An assembly of technologieson a RF basis, such as radio, TV broadcasting, falls under the heading of noninvasive bodywireless internet and phones, point-to-point shaping. RF energy, which is safe for all skinlinks, microwaves, satellite communication, and types, is fairly new, but a number of firms haveso on. Although the energy utilized is the same successful RF devices on the market .(RF energy), the difference in applications comes The degree of heat-induced tissue shrinkagefrom the different frequencies employed. For is dependent on several factors, which includemedical and esthetic applications a RF frequency the maximum temperature reached, the heatof up to about 10 MHz is normally used. exposure time, tissue hydration, and tissue age.
Adv Ther (2012) 29(3):249-266. 253Skin Tightening blood flow in the adipose tissue , whichRF as a source of heat has been used for collagen in turn increases the metabolism of the tissue,denaturation which leads to shrinking of homogenizing subdermal fat and increasing skinredundant or lax connective tissue. Collagen elasticity. This results in an improvement in skinmolecules are produced by fibroblasts cells in texture. Moreover, Franco et al. in their in-vivothe dermis. The collagen protein is a compound experiments showed that 10 minutes of thermalof three polypeptide chains that wrap around exposure at 43°C resulted in a delayed adipocyteone another in a final triple helix structure. The cellular death response . Galitzky et al., onprocess of thermal shrinkage of collagen starts the other hand, showed in-vivo enhancementwith denaturation of the triple helix, in which of fat cell lipolysis by increased delivery ofthe heat-labile intramolecular cross-links are catecholamine hormones, which is improvedbroken and the collagen undergoes a transition by enhancement of blood flow .from a highly organized crystalline structure to arandom, gel-like state (denaturation). The collagen Contraindicationsshrinkage occurs through the cumulative effect Contraindications to the use of RF includeof the “unwinding” of the triple helix, due to pregnancy, any implanted electronic device, hipthe destruction of the heat-labile intermolecular replacement, hip or femur surgery, or any othercross-links, and the residual tension of the metallic device that could be disrupted by RFheat-stable intermolecular cross-links . In energy, and any active dermatologic or collagen–addition, heated fibroblasts are associated with vascular disorder. Active or recent malignancies,new collagen synthesis and therefore tissue any history of disease which may be stimulatedremodeling. Therefore, the RF effects are based by heat, current use of isotretinoin, andon mild heating of the collagen and elastin blood coagulopathy are all contraindicationsfibers, which can lead to collagen shrinkage and for electromagnetic source treatments. Also,dermal thickening, thus improving the firmness treatment over tattoo or permanent makeup andand elasticity of the skin. There are many studies synthetic fillers (e.g., silicone) is not advised.corroborating the need to reach a temperature As with any other RF-based device,range of 39–42°C (clinically effective temperature) appropriate selection of patients and managingin the skin for RF esthetic-related effects. Hiragami realistic expectations are key to ensuringet al. demonstrated that treating skin for 10 min satisfaction with results.at 43°C enhanced 3D-like proliferation of normal The main purpose of this article is to describehuman dermal fibroblasts, which consequently in detail the extensive use of existing medicalled to greater expression of new collagen . devices based on RF energy, the development of these devices over the years, differences inCellulite Reduction RF configurations, and present recent and novelRF systems have been reported as producing developments and trends in this technology.electrothermally mediated rejuvenation- As an example of the novel trends the presentrelated cutaneous and subcutaneous effects. It authors have chosen to describe their personalis feasible to use RF energy for selective heating experience with CORE (Channeling Optimizedof relatively large volumes of subcutaneous RF Energy) technology, and to show the scientificadipose tissue . The heating effect leads to aspects of different stages of clinical study of theincreased microcirculation, thus increasing technology.
254 Adv Ther (2012) 29(3):249-266.METHODS allows independent heating depth control by applying three separate RF frequencies,Literature Review Search Strategy and Data at 0.8 MHz, 1.7 MHz, and 2.45 MHz, andSources an additional mode that combines all three frequencies in a single pulse (Fig. 1). These fourThe authors conducted a systematic search of different frequency modes can be independentlypublications listed in Medline and PubMed. chosen with any energy and probe setting. ThisOnly articles published in well-known way it is possible to control the heating depthscientific journals in the dermatologic and as required by each patient’s symptoms and foresthetic fields were searched for. Key and each treatment application.free-text words included “radiofrequency”AND “skin tightening,” “radiofrequency” Device ApplicatorsAND “cellulite,” “radiofrequency” AND Three different treatment applicators are“contraindications,” “radiofrequency” available with the system.AND “indications,” “radiofrequency” AND B-Contour applicator: emits vacuum-assisted“efficacy,” “radiofrequency” AND “safety,” pulsed RF power of 50 W with a treatment“radiofrequency” AND “side effect,” footprint of 35×30 mm. Designed for treatment“radiofrequency” AND “vacuum,” and of large skin areas.“radiofrequency” AND “adverse event.” All F-Contour applicator: emits vacuum-assistedarticles revealed were reviewed by title for pulsed RF power of 8.5 W with a treatmentrelevance and potential duplication. The abstract footprint of 15×10 mm. Designed for treatmentof each of the relevant articles was examined. of small or sensitive body areas.Overall, 50 full-text articles were examined. Out ST applicator: emits pulsed RF power density ofof these publications the authors chose 26 that 130 J/cm3 with a treatment footprint of 8×8 mm.addressed safety and efficacy issues, technical This applicator operates without vacuumsystem specifications, and clinical techniques. assistance and is cooled to 6°C. It is indicated forThe search focused on clinical research studies, skin tightening on facial and body areas.the FDA 510(k) database for clearances, and anytechnical information on company web sites In-Vivo Measurement of Penetration Depthsand the clinicaltrials.org website. of Different RF Frequencies An in-vivo study was conducted on the skin ofRF Device two approximately 6-month-old male domestic pigs, weighing 146.5 kg and 157 kg, that wereA bipolar RF device (Reaction™; Viora Inc., Jersey under full anesthesia by inhalation of isofluraneCity, NJ, USA) combined with a mechanical (2–3%). A thermal video camera (TiR3FT; Flukemassage technique was designed to produce Corporation, Everett, WA, USA) was used tohigh-frequency electrical current in the skin determine the tissue heating depth effectsfor noninvasive skin tightening, reduction of at the different RF frequencies (0.8, 1.7, andcellulite, and elimination of fine wrinkles on 2.45 MHz). This thermal video camera enables avarious body areas such as the face, neck, arms, temperature measurement in the range of –20°Cabdomen, buttocks, and thighs. The system to 100°C with a sensitivity of 0.07°C and anintegrates unique CORE technology, which accuracy of ±2°C.
Adv Ther (2012) 29(3):249-266. 255 2.45 MHz 1.7 MHz 0.8 MHzFig. 1 Conceptual schematic representation of CORE™ technology, showing the independent heating effect createdin between two electrodes using three separate radiofrequency (RF) frequencies (0.8, 1.7, and 2.45 MHz). The lowestfrequency, 0.8 MHz, penetrates the deepest, while the highest frequency, 2.45 MHz, has the most superficial penetration To investigate the effect of a chosen frequency thermal effect faded (approximately 2 minuteson tissue heating depth, tests were performed after the last pulse). For comparison purposes,with three different RF applicators. In the test the heating depth was arbitrarily defined as thewith the B-Contour and F-Contour applicators, depth at which skin tissue temperature reachedthe RF and vacuum intensities were set to the 4°C above tissue baseline temperature, whichhighest level (level 4) and six sequential pulses was typically approximately 28°C.were applied. In the examination with theST applicator (which does not include the Cellulite and Body Shaping Treatmentsvacuum mechanism), the energy level of Twenty-seven healthy women aged 24–63 years50 J/cm3 was applied with a single pulse. with a body mass index (BMI) lower than To investigate the effect of vacuum on tissue 29 participated in this study. The inclusionheating depth, tests were performed with the criteria consisted of the presence of moderateB-Contour and F-Contour applicators at each bilateral cellulite, equal to or higher than 2frequency separately, with the RF intensity (on a 0–4 point cellulite scale), in the abdomen,fixed at level 4 and varying only the vacuum thighs, and buttocks. Participants were notintensity (levels 1–4), applying six sequential allowed to diet or induce any weight fluctuationspulses. greater than 2 kg throughout the entire study Thermal video imaging recording started period. All subjects underwent eight treatmentwith the first pulse and stopped only when the sessions at 1-week intervals.
256 Adv Ther (2012) 29(3):249-266. The treatment was performed with the visit, on the basis of clinical photographicB-Contour applicator on large skin areas and assessment, circumference measurements, andwith the F-Contour applicator on small or an assessment of participants’ satisfaction.sensitive areas. Each treatment session lasted Three independent evaluators were asked toabout 20 minutes in accordance with protocol complete a survey to rate the cellulite grade ofguidelines. The protocol is designed in three the photographs. Circumference was measuredphases: (i) preheating, (ii) adipose tissue by the independent evaluators accordingheating, and (iii) fibroblast stimulation. The to a standardized measurement method.purpose of the preheating phase is to obtain a Additionally, the investigators were asked toclinically effective temperature of 39–42°C, with record and immediately report any adverse orcontinuous monitoring of the skin temperature unexpected effects. Participants’ satisfactionwith an infrared thermometer. This phase targets scores were obtained at each of the threeall skin layers simultaneously and therefore is monthly follow-up visits.conducted in mode IV (a combination of all threefrequencies) with the highest RF and vacuum Skin Tightening Treatmentsintensity, according to each patient’s toleranceand test procedure. Once the clinically effective Sixteen healthy women ranging in age fromtemperature is obtained, the adipose tissue 37–66 years, with moderate to severe wrinklesheating phase starts, in which mode I (0.8 MHz) or/and lax, sagging skin, were treated using theis employed for 10 minutes for deep tissue RF system. All of the patients underwent threeheating to address the subcutaneous layer. The treatment sessions at 3-week intervals. Thelast phase is focused on the dermal fibroblasts patients who underwent facial treatment werein order to encourage fibroblast activity and treated on both sides of the treatment area, whileproduce a skin tightening effect. The fibroblast those who underwent body treatment, such asstimulation phase is performed in mode II the abdomen and buttocks, were treated only(1.7 MHz) for 2 minutes and mode III (2.45 MHz) on the right side of the body. Each treatmentfor 2 minutes, for a total of 4 minutes. session duration lasted an average of 25 minutes. Three of the participants dropped out of the Treatment was conducted according to thestudy for personal reasons unrelated to the study. protocol for the specific treatment area. For lower Photographs were taken in three phases: (i) at face and perioral regions, modes I and II (0.8 andbaseline, prior to the first treatment; (ii) during 1.7 MHz, respectively) were used. For foreheadthe treatment course, after the fourth treatment and cheek bone areas, the most superficialsession; and (iii) at the end of the treatment frequency was used (mode III, 2.45 MHz) andcourse, one week after the eighth treatment, and for body areas, mode IV was used. The RF energyalso at each of the three monthly (after 1, 2, was chosen according to individual toleranceand 3 months) follow-up visits and 6 months and test procedure.after the last treatment session. Circumference To monitor and evaluate final results, picturesmeasurements of thighs, buttocks, and abdomen of the patients were taken in a standardizedwere taken by independent evaluators and not method at the following points: at baseline,by the treating practitioner, to avoid bias. prior to each treatment, and at 1- and 3-month Analysis was performed at baseline, prior follow-up visits. Photographs from the secondto the fourth treatment, and at each follow-up follow-up visit were analyzed by three objective
Adv Ther (2012) 29(3):249-266. 257analysts who scored the improvements compared Abraham et al. reported on a study whichto the baseline evaluation. In addition, the focused on skin tightening of the upper eyebrow.appointed analysts compared photographs from In a follow-up visit 12 weeks after the treatmentthe first and second follow-up visits to monitor there was a statistically significant increaseany significant withdrawals in results. Patients’ in mean measured vertical brow height for allsatisfaction scores were obtained after the third patients, with minimal and self-limited sidetreatment session and at each follow-up visit. effects . Full verbal and written informed consent Fritz et al. were the first to report on a studywas obtained from the patients in respect of the comparing multiple RF treatments to a singlerelevant studies and publication. RF treatment, for mild-to-moderate laxity of the middle and lower face. These authors concludedRESULTS that two RF treatments produced significantly better improvement than a single treatment,Literature Review of RF-Based Systems although overall improvements were modest in both groups .The first RF device aimed at skin tightening In 2006, del Pino et al. reported on the effect(SoltaMedical, Inc. [formerly Thermage], of unipolar RF (AccentTM device; Alma Lasers Ltd.,Hayward, CA, USA) was initially studied on Caesarea, Israel) on cellulite and subcutaneousthe lower face and neck using a standard tissue of the buttocks and thighs. A volumeguinea pig model . The results showed contraction of approximately 20% was achievedthat dermal heating was achieved both at the in 68% of their patients. Adverse effects includedshallow level of the papillary dermis and deep small blisters and ecchymosis, which resolvedin the subcutaneous fat layer. According to spontaneously without complications .the authors, the heating of the dermal layer One year later, in 2007, Friedman and Gileadlead to collagen denaturation and subsequent used the combination of a unipolar handpiecethickening and shortening of collagen fibrils. for deep tissue heating and a bipolar handpieceThe increased fibroblast activity and new for superficial tissue heating. Photographiccollagen formation were observed over a period analysis showed moderate to significantof several months. Moreover, in the treatment improvement in 69% of the patients .areas where significant skin contraction was For many years a mechanical massageobserved, histological changes were noted technique with circulatory and dermotrophicassociated with new collagen formation in the properties was known to have an impact ondermis. FDA clearance of this device was based changes in morphometric measurements inon an institutional review board (IRB)-approved, cellulite areas, due to an improvement inmulticenter, blind clinical trial performed in lymphatic drainage leading to temporary86 patients with periorbital wrinkles or skin reduction in edema . Monteux and Lafontanlaxity who underwent a single treatment . also used microdialysis technique to show thatFifty percent of patients reported being satisfied mechanical massage has a directly enhancingor very satisfied with the results. Most patients effect on blood microcirculation, leading to anexperienced mild to moderate pain. Common increase in lipolytic responsiveness .immediate side effects included erythema (36%) This is why the “new generation” of RF-basedand edema (13.9%). systems also combines vacuum manipulations
258 Adv Ther (2012) 29(3):249-266.with RF energy. The first vacuum-assisted esthetic applications, and to devices that combinedevice has been described by Gold et al. . other technologies such as vacuum, ultrasoundThis vacuum-assisted, RF bipolar device draws infrared light, and more. In the next section anthe skin between two parallel electrodes before additional step in this evolution is discussed,applying the RF current. According to the describing the unique CORE technology whichauthors, a significant improvement in skin enables control over the heat penetration.appearance and texture was detected duringthe treatment course, and during the period of An In-Vivo Measurement of Penetration6 month follow-up it continued to increase. Depths of Different RF Frequencies Montesi et al. reported clinical and histologicalresults using the vacuum-assisted bipolar RF For all the enquiries tested, observed heatingdevice for the treatment of wrinkles, skin laxity, depth was greatest with the lowest RF frequencyacne scars, and striae distensae. Three-millimeter applied (0.8 MHz) and shallowest with thepunch biopsies of untreated skin showed atrophic highest frequency applied (2.45 MHz) (Fig. 2 andand intensely elastotic dermal collagen, whereas Table 1).treated skin showed a decrease in collagen In-vivo experiments also showed an increaseatrophy and increase in interstitial edema, which in the presence of red blood cells and plasmaindicates better dermal trophism . fluid, which provides strong evidence for Finally, several publications have addressed increased blood circulation (Fig. 3).the issue of safety with nonablative, RF skin In-vivo experiments on domestic pigstightening. For example, Weiss et al. published showed the ability of the system to create aa retrospective analysis of efficacy and safety “remodeling” effect on connective tissue (datain over 600 RF facial tightening treatments not shown). Eight hours after the conclusionperformed between May 2002 and June 2006. of the treatment, indications of discontinuousThe treatment algorithm evolved over this connective tissue as a result of microtraumaperiod from high-fluence single treatment to created by RF manipulation were notable in themultiple passes, multiple treatments, and lower subcutaneous tissue sample. Forty-eight hoursfluence, which is associated with better clinical after treatment, as a result of a healing process,outcomes and greater patient acceptance . formation of new connective tissue was clearlyNarins et al. reported on rare cases in which visible in the treated sample.overtreatment of tissue can lead to contour Beyond the benefits of the vacuumirregularities lasting for more than 6 months. manipulations illustrated above, the in-vivoWhile these can be corrected by subcision and experiments showed that the combinationautologous fat transfer, they can be prevented with vacuum technology also has a significantby eliciting patient feedback. Patient feedback influence on the RF penetration depth. Increasingregarding heat sensation is a reliable guide to the the intensity level of the vacuum function aloneselection of RF treatment energy settings that contributes to an increased penetration depth.significantly reduce the risk of overheating tissue For example, using vacuum level 4 in mode Iand subsequent adverse events . (0.8 MHz), increases penetration depth by The evolution of RF-based devices extends 7.3 mm and 2.7 mm with the B-Contour andfrom monopolar systems for skin tightening F-Contour applicators respectively, compared toto bipolar (and multipolar) devices for many vacuum intensity level 1 (Table 1).
Adv Ther (2012) 29(3):249-266. 259 Mode 1 Mode 2 Mode 3 0.8 MHz 1.7 MHz 2.45 MHzFig. 2 Thermal images of skin cross-section: the ST applicator set at a RF intensity of 50 J/cm3 and applied with a singlepulse at three RF frequencies: 0.8, 1.7, and 2.45 MHz. The background temperature during the test was 20.0°C, the averagetemperature was 29.2°C, and the highest temperature measured was 42°CTable 1 Heating depths measured with B-Contour and provides a broad range of penetration depths.F-Contour applicators at the highest and lowest vacuum For instance, with the B-Contour applicatorintensities and RF treatment modes this range extends from 6.2 mm with the Vacuum Frequency Depth highest-frequency mode (2.45 MHz – mode level (MHz) measured III) and lowest vacuum level (level 1) up to (mm) 18.6 mm with the lowest-frequency modeB-Contour 4 (highest) 0.8 18.6 A (0.8 MHz – mode I) and the highest vacuumapplicator 4 (highest) 2.45 11.8 B intensity (level 4) (Table 1). This way, the 12.4 1 (lowest) 0.8 11.3 C treatment platform affords practitioners the 1 (lowest) 2.45 6.2 D flexibility to offer a wide range of the industry’sF-Contour 4 (highest) 0.8 10.7 A most desired treatments.applicator 4 (highest) 2.45 6.4 B 6.5 1 (lowest) 0.8 8 C 1 (lowest) 2.45 4.2 D Untreated The clinical experience gathered using COREtechnology enables precise adapting of tissue 48 hours post RFheating effects for different applications andpatients. For example, thickness of the dermallayer in patients may vary from less than 2 mmto almost 5 mm at different anatomical sitesand skin properties, while some conditions,like cellulite, require deeper heating of the Fig. 3 Histological assessment of blood vessels in thesubcutaneous layers and others conditions, like adipose tissue of domestic pigs: sectioned with Paraffin- embedded tissue blot method (30 µm) and stained withrhytids, require shallower heating of the dermis. hematoxylin and eosin, 48 hours after RF treatment. The combination of the three RF frequencies Red and blue arrows indicate red blood cells and plasma,together with four different vacuum levels respectively
260 Adv Ther (2012) 29(3):249-266.Cellulite and Body Shaping Treatments show that 91.6% (22/24) of the participants demonstrated a cellulite grade of 1–2 and onlyAn overall average improvement of 55% 8.4% (2/24) a cellulite grade of 2–2.33. The meanin the appearance of cellulite was recorded circumference taken at baseline compared to thefor all participants. In 79% (19/24) of the mean circumference taken at the first (1-month)participants, the cellulite improvement scores follow-up visit showed an average reduction ofranged from moderate improvement to 3.31 cm in the buttocks, 2.94 cm in thighs, andsignificant improvement. The most significant 2.14 cm in the abdomen. Only at the 6-monthimprovement (> 75%) was recorded in subjects follow-up visit was a slight withdrawal observed,who initially demonstrated a cellulite grade which suggests that maintenance treatmentof 2–3 (see example in Fig. 4). According should be carried out every 3–4 months.to participants’ assessment of results, allparticipants indicated satisfactory results from Skin Tightening Treatmentsthe treatment course. There was no record ofany dissatisfaction by any of the participants. It In total, 50% of the patients demonstratedis noteworthy to mention that no withdrawals moderate improvement and 31% of thewere seen either during the study period or at patients significant improvement. A moderatethe 3 follow-up visits (after 1, 2, and 3 months), improvement (51–75%) was recorded in threeindicating consistency of CORE clinical results. of the patients and a significant improvementIn addition, both investigators and participants (> 75%) in two patients who underwentreported visible and significant improvement in treatments for skin laxity in the abdomenskin laxity and texture in the treatment area. (see example in Fig. 5). In treatment of the Evaluations performed at the first follow-up jowls, a moderate improvement (51–75%)visit clearly show an overall reduction in was recorded in two of the patients and acellulite appearance, with a mean cellulite grade significant improvement (> 75%) in oneof 1.38. Final results at the end of the study patient. In treatment of the cheeks, a moderate Before AfterFig. 4 A 49-year-old woman with grade 2 cellulite and dimpled skin on thighs before (left) and after eight treatment sessions(right). Results showed a reduction in cellulite volume
Adv Ther (2012) 29(3):249-266. 261improvement (51–75%) was recorded in three levels. This combination provides the operatorof the patients and a significant improvement accurate control when performing the full range(> 75%) in two (see example in Fig. 6). When of available RF esthetic applications on differentevaluations were taken at the 1- and 3-month body and facial areas. This combination alsofollow-up visits and compared to the baseline, plays an important role for patients’ variousthe results were sustained and no significant sensitivities and symptoms.withdrawal was recorded. Moreover, evaluations Since tissue conductivity correlatesindicate that results were sustained over the significantly with tissue temperature , thefollow-up duration time and no significant distribution of electrical current can be controlledwithdrawal was recorded in any of the patients. by preheating of the target tissue. Thus, if the These evaluations indicate that results were temperature of the target tissue is higher thanpersistent over the duration of the treatment that of the surrounding tissue, the RF currentcourse, and no significant withdrawal was will selectively focus in the target tissue . Therecorded in any of the patients. Furthermore, advantage of combining all three RF frequenciespatients’ satisfaction scores were consistent with in CORE technology enables the operator to heatthese results, with 82% of the patients scoring all the skin layers simultaneously. Preheating of“satisfied” or higher. the skin allows the target tissue temperature to be attained quickly, significantly decreasing theDISCUSSION duration of treatment. Once all layers of the skin reach the temperature of clinical efficacy (in theThe in-vivo experiments indicated that the range of 39–42°C), the operator can easily focusheating depth achieved using the different on the target tissue. For example, by changingRF frequencies confirms the theory that RF the operational mode to a low RF frequencypenetration depth in tissue is an inverse function (0.8 MHz), the operator can specifically focus theof frequency. These experiments showed that treatment on adipose tissue, without any lossthe unique variable frequency capability in of energy and treatment time. In addition, theCORE technology affects different tissue depths ability to use a different frequency in celluliteat different RF modes and vacuum intensity treatment can provide not only reduction of Treated side Treated side Before AfterFig. 5 A 40-year-old woman with lax, sagging skin on the tummy before (left) and after three treatment sessions (right).Results showed a noticeable improvement in lax, sagging skin on the tummy
262 Adv Ther (2012) 29(3):249-266. volumetric treatments. Given the fact that most patients who have lost weight also have stretch marks, Viora developed a special combination protocol with the ST applicator in order to achieve focused heating over the individual stria (Fig. 9). The improvement in elasticity of connective tissue was examined in vivo by the stress– relaxation mechanism of fibroblasts which Before After induces an ectocytotic process that plays a crucial role in extracellular matrix remodelingFig. 6 A 60-year-old woman with lax, sagging skin around that begins after the contraction phase ofthe cheeks before (left) and after six treatment sessions(right). Results showed a dramatic reduction in the wound repair . The increase in expressionappearance of wrinkles around the cheek of collagen types I and III due to mechanical stretch was also shown by Kim et al. . Their research showed that the mechanical stressthis condition but also improvement in skin affects the healing and remodeling process bylaxity and texture in the treated area, as was direct influence on gene expression of collagennoted by investigators and participants in the types I and III and transforming growth factorreported case study. The investigators postulated (TGF)-β1, which play a role in the regulation ofthis desired effect to be related to the different mechanical strain-induced gene expression.frequencies, specifically to modes II and III Therefore, in contrast to other systems in(1.7 and 2.45 MHz, respectively, which target which skin tightening procedures are conductedthe dermal layer). by heat delivery to the dermal layer, the addition Due to the versatility of the CORE technology of vacuum suction affords added value to the(ability to change RF energy intensity, vacuum clinical outcomes.intensity, and, most importantly, RF frequency) Since liposuction and laser-lipolysisit was possible to not only adjust treatment procedures cannot treat cellulite and saggingparameters to specific patients’ needs, but alsoto develop specific protocols, such as a treatmentprotocol for the neck and jowl line. This protocolis specific for patients both exhibiting local fatand in need of skin tightening, which combinesthe use of the F-Contour and ST applicators(Fig. 7). Another special protocol (ReFit protocol)was developed for patients with sagging loose Before Afterskin after rapid weight loss due to dieting,exercise, or childbirth (Fig. 8). This protocol is Fig. 7 A 34-year-old woman with lax skin and local fat ina skin tightening application using the BC or the jowl area treated by a combination protocol with FCFC applicator (not the ST applicator), which and ST applicators: before (left) and after three treatmentsis typically used for cellulite reduction and (right)
Adv Ther (2012) 29(3):249-266. 263 Before AfterFig. 8 A 27-year-old man with lax, loose skin treated by ReFit protocol, before (left) and after eight treatments (right)skin, other technologies such as endermologie, therapy requires a more significant investmentu l t r a s o u n d , l a s e r, a n d R F e n e r g y a r e in products or equipment, which is typicallyincreasingly being used after liposuction and only made by practices specializing in cellulitelaser-lipolysis treatments to smooth and firm treatment. Because for most practitionersthe skin, and remove any residual “lumpiness” cellulite reduction is only one of a largeor swelling. The “firming” procedure may be number of esthetic procedures they offer, thestarted 2 weeks after surgery and generally use of combination therapy tends to be limited.involves a series of 8–12 treatments, depending The exception is combination therapieson the technology used. Some practitioners involving liposuction, which is oftenalso use endermologie prior to liposuction, to performed by highly skilled surgeons alongenhance blood circulation and provide a more with a variety of other complex surgicalefficacious result. However, such combination procedures. These physicians often do not Before AfterFig. 9 A 27-year-old man with stretch marks, before (left) and after eight treatments (right)
264 Adv Ther (2012) 29(3):249-266.offer noninvasive procedures, and therefore Similar to skin rejuvenation technologies,may refer liposuction patients to estheticians many physicians use complex body shapingor others who can provide the finishing skin technologies in order to achieve more rapidsmoothing treatments. and effective clinical results, especially for The ReFit protocol is very useful for patients with more severe cellulite. For example,combination with liposuction, laser mesotherapy may also be used in combinationlipolysis (Fig. 10), cavitation ultrasound with other technologies such as RF, ultrasound,(Fig. 11), etc. and endermologie. Before AfterFig. 10 A 30-year-old woman before (left) and after two treatments (right) of combined laser lipolysis and ReFit protocol Before AfterFig. 11 A 45-year-old woman, before and 28 days after treatment of combined cavitation ultrasound and ReFit protocol.Circumference reduction of 6.8 cm and weight change of 0.2 kg
Adv Ther (2012) 29(3):249-266. 265CONCLUSION 2. Stuchly MA, Stuchly SS. Electrical properties of biological substances. In: Gandhi OP, ed. Biological Effects and Medical Applications ofVolumetric dermal tissue heating for noninvasive Electromagnetic Energy. Chapter 5. Upper Saddleand nonablative esthetic skin tightening River: Prentice Hall; 1990:76–112.is being increasingly studied and clinically 3. Gabriel S, Lau RW, Gabriel C. The dielectricapplied. Documented, published results properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues. Physindicate a high safety margin with moderate Med Biol. 1996;41:2271–93.efficacy which is dependent on correct patient 4. Sadick NS, Makino Y. Selective electro-thermolysisselection and realistic patient expectations. Of in aesthetic medicine: a review. Lasers Surg Med.all tissue heating techniques, RF appears to be 2004;34:91–7.more established and clinically proven. It has 5. Sung RJ, Lauer MR. Fundamental approaches tothe added advantage that by adjusting probe the management of cardiac arrhythmias. New York, NY: Springer; 2000:153.designs, various dermal tissue depths, from thereticular dermis to the hypodermis, may be 6. Shiffman MA, Mirrafati SJ, Lam SM, Cueteaux CG. Simplified facial rejuvenation. New York, NY:affected. Springer; 2007;157. The design and specifications of the 7. Carruthers A. Radiofrequency resurfacing:vacuum-assisted bipolar RF device described are technique and clinical review. Facial Plast Surgwithin the range of currently cleared esthetic, Clin N Am. 2001;9:311–19.nonablative RF systems. 8. Lopez MJ, Hayashi K, Fanton GS, Thabit G III, Markel MD. The effect of radiofrequency energy on the ultra-structure of joint capsular collagen.ACKNOWLEDGMENTS Arthroscopy. 1998;14:495–501. 9. U.S. Food and Drug Administration. Access data.Dr. Belenky is the guarantor for this article, Available at: http://www.accessdata.fda.gov/cdrh_and takes responsibility for the integrity of the docs/pdf2/K021402.pdf Last accessed: January 27, 2012.work as a whole. Dr. Belenky and Dr. Margulisare respectively manager and director of Viora’s 10. U.S. Food and Drug Administration. Access data. Available at: http://www.accessdata.fda.gov/cdrh_clinical department. Dr. Elman, Dr. Bar-Yosef, docs/pdf9/K090221.pdf. Last accessed: January 27,and Dr. Paundo do not have any financial 2012.interest in Viora, Inc. 11. Arnoczky SP, Aksan A. Thermal modification of We would like to thank Keren Or Medical connective tissues: basic science considerations and clinical implications. J Am Acad Orthop Surg.Aesthetic Center, Dr. Marina Vashkevich, 2000;8:305–13.Dr. Sandra Tagliollato and Dr. Hector Leal for 12. Hiragami F, Motoda H, Takezawa T, et al. Heatproviding their clinical materials, including shock-induced three-dimensional-like proliferationphotographs and clinical feedback. of normal human fibroblasts mediated by pressed silk. Int J Mol Sci. 2009;10:4963–76.REFERENCES 13. Hjelmdahl P, Linde B. Adrenergic control of blood flow and lipolysis in human adipose tissue. In: Refsum H, Mjos OD, eds. Alpha-Adrenoceptor1. Franco W, Kothare A, Ronan SJ, Grekin Blockers in Cardiovascular Disease. Edinburgh: RC, McCalmont TH. Hyperthermic injury Churchill Livingstone; 1985:151–64. to adipocyte cells by selective heating of 14. Galitzky J, Lafontan M, Nordenstrom J, Arner subcutaneous fat with a novel radiofrequency P. Role of vascular alpha-2 adrenoceptors in device: feasibility studies. Lasers Surg Med. regulating lipid mobilization from human adipose 2010;42;361–70. tissue. J Clin Invest. 1993;91:1997–2003.
266 Adv Ther (2012) 29(3):249-266.15. Hsu TS, Kaminer MS. The use of nonablative 23. Gold MH, Goldman MP, Rao J, Carcamo AS, Ehrlich radiofrequency technology to tighten the M. Treatment of wrinkles and elastosis using lower face and neck. Semin Cutan Med Surg. vacuum-assisted bipolar radiofrequency heating of 2003;22:115–23. the dermis. Dermatol Surg. 2007;33:300–9.16. Fitzpatrick R, Geronemus R, Goldberg D, Kaminer 24. Montesi G, Calvieri S, Balzani A, Gold MH. Bipolar M, Kilmer S, Ruiz-Esparza J. Multicenter study of radiofrequency in the treatment of dermatologic noninvasive radiofrequency for periorbital tissue imperfections:clinicopathological and tightening. Lasers Surg Med. 2003;33:232–42. immunohistochemical aspects. J Drugs Dermatol. 2007;6:890–6.17. Abraham MT, Chiang SK, Keller GS, Rawnsley JD, Blackwell KE, Elashoff DA. Clinical evaluation of 25. Weiss RA, Weiss MA, Munavalli G, Beasley KL. non-ablative radiofrequency facial rejuvenation. J Monopolar radiofrequency facial tightening: a Cosmet Laser Ther. 2004;6:136–44. retrospective analysis of efficacy and safety in over 600 treatments. J Drugs Dermatol.18. Fritz M, Counters JT, Zelickson BD. Radiofrequency 2006;5:707–12. treatment for middle and lower face laxity. Arch Facial Plast Surg. 2004;6:370–73. 26. Narins RS, Tope WD, Pope K, Ross EV. Overtreatment effects associated with a19. Del Pino E, Rosado RH, Azuela A, et al. Effect radiofrequency tissue-tightening device: rare, of controlled volumetric tissue heating with preventable, and correctable with subcision radiofrequency on cellulite and the subcutaneous and autologous fat transfer. Dermatol Surg. tissue of the buttocks and thighs. J Drugs Dermatol. 2006;32:115–24. 2006;5:714–22. 27. Duck FA. Physical properties of tissue. New York,20. Friedman DJ, Gilead LT. The use of hybrid NY: Academic Press; 1990:173. radiofrequency device for the treatment of rhytides and lax skin. Dermatol Surg. 2007;33:543–51. 28. Lee TL, Lin YC, Mochitate K, Grinnell F. Stress- relaxation of fibroblasts in collagen matrices21. Ikomi F, Schmid-Schonbein GW. Lymph transport triggers ectocytosis of plasma membrane vesicles in the skin. Clin Dermatol. 1995;13:419–27. containing actin, annexins II and VI, and b1 integrin receptors. J Cell Sci. 1993;105:167–77.22. Monteux C, Lafontan M. Use of the microdialysis technique to assess lipolytic responsiveness 29. Kim SG, Akaike T, Sasagaw T, Atomi Y, Kurosawa of femoral adipose tissue after 12 sessions of H. Gene expression of type I and type III collagen mechanical massage technique. J Eur Acad by mechanical stretch in anterior cruciate ligament Dermatol Venereol. 2008;22;1465–70. cells. Cell Struct Funct. 2002;27:139–44.99