**2.2 HIFEM and synchronized radiofrequency**

With an increasing demand for both fat reduction and muscle enhancement, with patients having to go for multiple procedures to target each, the further innovation of the HIFEM technology was inevitable. Since HIFEM is selective to muscle tissue only, there has been a strong focus on developing a novel technology simultaneously combining HIFEM's muscle conditioning with radiofrequency (RF) heating intended for fat elimination. Emsculpt Neo device (BTL Industries Inc., Boston, MA), introduced in late 2020, is the first device that combines RF and HIFEM in a single applicator. The combination of HIFEM+RF allows administering two distinct procedures in a single treatment. At the same time, the synergy of two proven technologies ensures a high level of efficacy even in subjects with considerable fat depots and fat thickness over 3 cm. The device has been FDA-cleared for non-invasive lipolysis, strengthening, toning, and firming. The treatment areas so far include the abdomen, buttocks, outer thighs, inner thighs, front & back thighs, calves, biceps, and triceps. Similar to its predecessor, four 30-minute sessions scheduled once a week is recommended. Combined treatments are safe and comfortable. The only documented side effects are skin redness that resolves within 30–60 minutes post-treatment without any further consequences and muscle soreness the day after the therapy due to the HIFEM component.

## *2.2.1 Radiofrequency component combined with HIFEM*

RF is an electromagnetic wave in the frequency range of approximately 20 kHz to 300 GHz that can generate heat in the treated tissue by transforming its energy to the oscillation of molecules as propagating through. Utilizing specific frequencies of the RF spectrum allows for selective heating due to the difference in properties between the tissues in the targeted area. Most of the devices on the esthetic market utilize a solid metal electrode to emit RF energy. However, it would be impossible to simultaneously emit the HIFEM and RF alongside since there will be interference between them, resulting in the harmful overheating of the metallic electrode and increased risk of adverse events. Thus, the device employs a novel Synchrode RF electrode that eradicates this interference due to the unique interspaced design making it transparent to the propagating magnetic fields and allowing for synchronized emission of RF and HIFEM energy [13].

Fat tissue reduction is energy-dependent and may be achieved by reducing the lipids via lipolysis or permanently removing adipocytes. Therefore, the device's radiofrequency component (27.12 MHz) is designed to uniformly elevate the adipose tissue temperature to the levels of 42–45°C, inducing adipocytes deletion by the natural apoptotic pathways. Initially, the elevated temperature results in increased blood flow and acceleration of metabolic activity. In response, the lipids stored in fat cells are broken down into free fatty acids and glycerol. Also, the RF-induced fat loss is further enhanced during the intense localized muscle work provided by HIFEM, as described above. When the elevated temperature is sustained for a sufficient time period, the adipocytes exposed to temperatures up to 45°C lose viability. They are forced to enter the apoptotic process, i.e., natural and permanent cell deletion [26]. The apoptotic cells subsequently lose their membrane integrity and are ultimately digested by macrophages, responsible for clearing the degraded cells and the debris to maintain tissue homeostasis.

The combined use of HIFEM and RF not only enhances the effects on fat considerably but also introduces the synergy at the level of muscle tissue. It has been evidenced that controlled heating within safe limits for the muscle tissue (40–41°C) positively affects the muscle response during the workload. Additionally, muscle protein synthesis might be even more promoted when heat stress is combined with mechanical stress, as in the case of HIFEM application [27, 28]. The synergistic effect of simultaneous delivery of HIFEM and synchronized RF enhances muscle hypertrophy since it significantly increases the levels of myosatellite cells (musclederived stem cells), which activates the regeneration and strengthening of the existing muscle fibers through differentiation. Histology study in the animal model showed that the amount of activated satellite cells in muscle tissue after this dualenergy treatment is comparable with programs involving 12 to 16 weeks of intense exercise. Post-treatment, the increased number of large hypertrophic fibers and elevated levels of small-diameter muscle fibers were found, indicating that not only hypertrophy but muscle fiber hyperplasia may occur after the activation of satellite cells [29].

#### *2.2.2 Clinical evidence*

The synergistic effect of HIFEM+RF has already been studied and documented by several investigators [26, 30–32] by using proven diagnostic modalities such as MRI or USN. Like Emsculpt, device results improved with time and peaked at 3 months after the last treatment. However, the more profound effect on fat tissue due to the radiofrequency heating resulted in a bolstered average reduction of abdominal fat thickness by 29.6%, which showed to be highly consistent with a

#### *Non-invasive Alternatives for Liposuction DOI: http://dx.doi.org/10.5772/intechopen.101396*

maximum reduction of 30.8% measured by MRI [31]. Muscle tissue benefited from elevated temperatures as well, since it reached an increase of 25.2% at 3 months on average. Most probably, due to the more developed musculature, abdominal muscle separation was reduced up to 19.8% when compared to the pre-treatment condition. At the same time, the considerable fat reduction inevitably contributed to circumference reduction exceeding 6 cm. Although the improvement in all aspects mentioned above was most recognizable at 3 months post-treatment, most subjects maintained the results up to 6 months with a slight but insignificant decline in some individual cases.

Since the technology is still relatively novel, it undergoes extensive research, which may possibly reveal the evidence for the superior efficacy of the RF + HIFEM procedure in other areas than the abdomen. Given the results from abdominal studies, it is strongly assumed that simultaneous application of RF and HIFEM will lead to more pronounced results in body parts previously treated by HIFEM alone. Also, combining two technologies of different modus operandi may allow efficient treatment of additional body areas, especially those with a high amount of subcutaneous fat overlying the muscle tissue. For instance, interim data gathered by Palm et al. showed promising results of RF + HIFEM treatment when applied on the lateral thigh, causing significant fat reduction [33]. Future studies should build upon the existing evidence and reveal all the possible use of RF + HIFEM technology, from which patients may benefit.

### **2.3 Radiofrequency and targeted pressure energy**

Simultaneous use of targeted pressure energy (TPE) and RF for skin treatment was introduced in 2019 with the Emtone (BTL Industries Inc., Boston, MA) device, which is FDA-approved for reducing cellulite dimples appearance, and it is the first and only device that combines such technologies in a single applicator. The combination of monopolar RF with TPE allows physicians to treat major causes of loose skin and cellulite non-invasively and effectively. The synergistic emission of mechanical and thermal energy allows the procedure to focus on the root causes of the problem instead of focusing on merely treating the symptoms. The device treats major factors that cause cellulite, including loss of skin elasticity, loose connective tissue leading to dimpling and fat chambers protruding to the skin, metabolic waste accumulation, and lack of blood flow. RF and TPE treatment can be done in any part of the body affected by cellulite or skin laxity and has no downtime. Four treatments (often consisted of the bilateral application over both extremities) in a frequency of 1–2 sessions per week are recommended, while the duration of each treatment varies (10–25 minutes) depending on the area where it is administered. Application of monopolar RF + TPE is again safe and comfortable; harmless skin redness is visible up to 60 minutes after the therapy as a logical consequence of tissue heating.

The device uses monopolar RF (447 kHz) heating through a solid electrode that remains in direct contact with the patient's skin. The RF currents travel to the grounding pad, ensuring a safe flow of the energy through the treated area while controlling its delivery. TPE component consists of a tube with a floating projectile accelerated towards an applicator tip by the pneumatic system, transferring TPE energy of significant intensities (maximum of 4 bar) to the target tissue. A projectile is moved by the compressed air, hitting a transmitter that conveys energy from the impact to the patient's body. This process is repeated in quick succession (10 Hz). Both technologies are embedded in a single handpiece applicator, thus they are delivered simultaneously. During the therapy, the operator moves the applicator over the treated area to evenly distribute both energies. Handpiece also utilizes a

build-in thermometer, providing immediate feedback to the physician regarding skin surface temperature, indicating whether the temperature stays in the expected range of 40–45°C, thus minimizing the risk of under/over-treatment [14].

#### *2.3.1 RF and TPE for the reduction of cellulite and skin laxity*

Collagen and elastin are primary elements of the connective tissue and an integral part of the structure of the papillary and reticular dermis and hypodermis. Skin laxity is manifested by the gradual degradation of dermal connective tissue. At the same time, cellulite is mainly characterized by the rigid structure of fibrotic collagen fibrils and the thickening of hypodermal connective septae. The simultaneous emission of TPE and RF activates the metalloproteinases (MMPs), responsible for degrading the protein structure of the collagen [34]. The mechanical stress leads to the fibrils dissociation that reduces the structural density and increases the conformational freedom while also decreasing the thermal stability of existing fibers.

Moreover, this phenomenon also reduces the temperature needed for collagen denaturation. The thermal stimulation interrupts the intramolecular hydrogen bonds and also partially shrinks the collagen triple helix [35]. Consequently, the neocollagenesis and remodeling of the collagen are initiated as a direct consequence to the treatment [36], since the fibroblasts' micro-inflammatory stimulation due to accumulation of heat leads to the proliferation process that significantly increases the procollagen mRNA production. Mechanical energy speeds up the fibroblasts' proliferative activity, creating an ideal environment for elastin and collagen synthesis by decreasing the tissue's oxidative stress [37]. In summary, the thermal and mechanical energy's simultaneous effect leads to a better organization and increased density of collagen and elastin fibers in the dermis and interlobular septa in the hypodermis. This leads to an increase in skin elasticity and thickening of the dermis. The skin thus becomes more tight and resistant to bulging caused by the underlying fat cells [36].

Also, due to the mechanical and heat stimulation exposure, there is a change in the cell membrane properties. The higher amount of cell membrane permeability enables the fluids to move throughout the membrane rapidly, and one can observe the increase in cell metabolism. Besides, both of the energies enhance the blood circulation and may contribute to the new blood vessels formation [36]. The accelerated cell metabolism and blood flow activate the enzymes that break down the fat stored in adipocytes underlying the skin. This leads to a significant reduction in the sizes of fat chambers protruded into the dermis and enhancement of the skin's visual appearance. TPE also positively affects lymph transport and waste removal, supposedly another key aspect associated with cellulite [38].

#### *2.3.2 Clinical evidence*

Recently, Fritz et al. utilized various means for cellulite and skin quality evaluation, providing ample evidence to demonstrate the clinical efficacy of RF + TPE simultaneous application. In their first study [39], significant changes at the level of adipose and dermal tissues were noticed. Ultrasound images and digital photographs showed diminished cellulite dimples and improved esthetic appearance of treated areas at 3 months post-treatment. Additionally, the enhancement of skin topography was also verified by the improved homogeneity of surface temperature. The high patient satisfaction correlates with objective results since cellulite was reduced in 93% of cases. The second study [40] was focused on improving abdominal skin laxity, showing promising results again. The elasticity measurement performed in this study showed considerable improvement in 90.9% of subjects.

#### *Non-invasive Alternatives for Liposuction DOI: http://dx.doi.org/10.5772/intechopen.101396*

In comparison, an even higher number of subjects (95%) responded to the treatment in terms of reduction in waist circumference. The primary outcome – reduction in skin laxity – was achieved in 86% of treated subjects derived from photography evaluation.
