Introduction/proposed mechanism of action

Ultrasonic energy is used in medicine for a variety of applications, imaging, physical therapy, and tissue ablation. The focus of this chapter is to explore the use of high intensity focused ultrasound (HIFU) in noninvasive body contouring. HIFU is an ablative therapy, producing thermal damage to targeted tissue. Tissue thermodynamics, dosimetry, and mode of HIFU application are relevant for the successful use of HIFU to achieve tissue ablation for therapeutic or cosmetic outcomes.

Simply, sonic energy can be focused like light, according to the design of the transducer. Unfocused sonic energy can pass through skin and structures above and below the focal zone in fluence levels low enough to not produce substantive tissue heating. Yet within the focus zone, tissue can be rapidly heated to 55–65 °C, which will produce thermal necrosis. This rapid temperature rise affects all structures within the target zone, including tissue layers that involve subcutaneous adipose tissue (SAT) that is rich in collagen. Type I collagen will undergo denaturation and shrinkage at approximately 65 °C to 70 °C, a temperature far too high for tissue survival. Once denaturation occurs, a biologic response to wounding proceeds.

Biologic response to heating has been studied either by prolonged static exposure to heat or in terms of a temperature jump where tissue reaction (damage) rates relate to an Arrhenius equation. The transfer of heat into tissues has been quantified by the Pennes bioheat equation and finite element modeling. There has been meaningful experimental work done to understand the nature of thermal burns and the response of tissue to heating. Full thickness skin burns have been produced with skin temperatures in the 47 °C range in animals. Thermal damage to skin is thought to occur as low as 44 °C. Skin blood flow ceases at approximately 45 °C. If the thermal response of tissue necrosis is plotted, there is a break in the slope of the curve at 43 °C in terms of a dramatic decrease in exposure time required to produce skin necrosis. There is little margin for error in heating tissue at near-burn levels, when it is possible to transition to irreversible thermal damage very rapidly.

The lesions produced with HIFU in deeper layers are referred to as ‘trackless lesions’ because tissue ablation only occurs within the focal zone. High-amplitude millimeter wavelength ultrasound is focused within clinically relevant tissue volumes. Ultrasound propagates through the aqueous medium that comprises most of the human body. Depending on the tissue type, there can be attenuation of the energy. Within the focal zone, part of the mechanical energy carried by the incident wave is converted into heat by viscous absorption. This constitutes the primary mechanism for ultrasound-induced hyperthermia (thermal ultrasound). Frequencies near 1 MHz appear most effective for tissue heating. Lower frequencies of 500 kHz work best for deeper heating and higher frequencies in the 8 MHz range work optimally for more superficial heating. Another consideration is the need for deliberate avoidance of cavitation within the target zone, as the presence of microbubbles dramatically changes tissue impedance and causes energy reflection and dissipation.

Besides energy production and focusing, dosimetry and patterns of energy delivery are relevant to producing the uniform tissue heating required for a cosmetic or therapeutic effect. When using HIFU to ablate SAT, the improvement in body contour occurs due to volume loss of ablated fat, thermal modulation and remodeling of collagen, and passive skin tightening due to undersurface volume reduction over time.

In the case of the Liposonix® device (Solta Medical Inc., Hayward, CA), when focused into tissues, HIFU produces a lesion about the size of a grain of rice. The microprocessor-controlled transducer is moved through a grid pattern to produce an ‘X by Y’ zone of lesions. There are parallels between what is occurring with this device and fractional lasers, where a small proportion of the tissue within the treatment zone receives energy. This approach avoids excess bulk heating and ensuing thermal damage (e.g. skin burns, damage to collateral structures, or fat necrosis). By leaving intact tissue around lesions, blood supply is not compromised and macrophages can start removal of tissue debris and extracellular lipid within the treated SAT. Other forms of unfocused ultrasound produce a tissue effect in deeper layers by bulk heating. Adipocytes respond by releasing lipid, but are not destroyed.

Thus, the HIFU device provides a means to produce fractional ablation of SAT and thermally modulate collagen at a focal zone 13–26 mm below the epidermis. Following a HIFU treatment, a mild inflammatory response occurs, with macrophage infiltration. Cellular debris and extracellular lipid are removed and metabolized in the liver; collagen within the mid-lamellar matrix (MLM) that has been subjected to thermal heating remodels and tightens. Very soon after treatment, tissue haziness associated with extracellular lipid is noted on diagnostic ultrasound (DUS). The net clinical effect following the wound healing cascade is an internal ‘shrink wrap’ effect within the treatment zone. A 12–16-week period is required to achieve this final outcome.

The initial pre-clinical research performed with the Liposonix device determined that optimal tissue response required between 140 and 180 J/cm ² . Higher energy dosing did not produce a superior clinical outcome. During treatment, a 5 × 5 cm grid that approximates the size of the transducer is drawn around each treatment zone. Water is used as the coupling agent between the plastic window of the transducer assembly called the replaceable treatment cartridge (RTC). Transducer assemblies have finite lifespans and are replaced after approximately 6000 firings.

The approach for energy delivery consists of treating a zone and then moving on to the next treatment zone (‘grid repeat’). The process is repeated as often as appropriate, according to the fluence setting of the HIFU device. Alternatively, a second approach involves the repeated firing of the RTC within the same zone, as tolerated by the patient (‘site stacking’). This approach, while more time-efficient, may produce discomfort and a feeling of excess warmth within the deeper tissues, depending on fluence level. An advantage of site stacking is that treatment can be modified with lower fluences that maximize patient comfort.

Pre-clinical research with HIFU in pigs did not show collateral damage to blood vessels that were in the region of the treatment zone. That being said, cutaneous nerves within the treatment area may be irritated and inflamed with HIFU, given the large amount of lipid found within the myelin sheath. This phenomenon has been noted with ultrasonic-assisted lipoplasty devices. Dysesthesias can occur and are self-limiting. It would be theoretically possible to damage major nerve trunks if HIFU was applied to anatomic areas where these structures are located (inner arm, sub-gluteal banana roll, and posterior thigh).

Inflammatory fat necrosis from bulk tissue heating may occur with laser-assisted liposuction. Photomicrographs of laser-treated SAT show inflammatory fat necrosis and vascular occlusion but such necrosis has not been encountered in the Liposonix pre-clinical and pivotal studies. There is the possibility that inflammatory fat necrosis could develop if sufficient tissue heating were to occur, but this potential risk is minimized when HIFU is administered in a fractional approach.

HIFU for fat reduction is a novel therapy that will be further refined in the future. Future HIFU devices may combine both real-time imaging and shear wave elastography imaging to track and optimize treatment effectiveness. Additionally, a variable focus HIFU/RTC apparatus may permit more shallow treatment zones, including treatment of the dermis alone. HIFU may also be combined with other energy-emitting devices such as radiofrequency. Indeed, far downstream there is the possibility that HIFU may supplant ionizing radiation for the treatment of malignancies.

Patient selection

HIFU for fat reduction is a noninvasive body sculpting modality cleared by the FDA for circumferential waist reduction. This method is an alternative for selected patients who are unable to undergo, or would like to avoid, more invasive procedures, such as traditional liposuction. Pilot and confirmatory studies reveal that HIFU treatment of the flanks and abdomen consistently produces a greater than 2 cm reduction in abdominal circumference after a single treatment. In consultation with potential patients, clear expectations of post-treatment results should be extensively discussed and reviewed. It should also be made clear that HIFU is a body contouring procedure and is not indicated for weight reduction or treatment of obesity.

Ideal candidates for HIFU treatment are individuals with a localized collection of SAT of the abdomen or flanks that has proven resistant to conventional diet and exercise. Ideal patient characteristics include BMI<30, good skin tone and elasticity, at least 2.5 cm of SAT in the desired treatment area, a treatment zone free of scars, and realistic outcome expectations ( Box 8.1 ). In evaluation of potential patients, the pinch test or calipers can be used to evaluate SAT volume. To additionally verify and quantify the thickness of SAT, a DUS may be utilized.

Contraindications to HIFU treatment include hernia in the treatment area, pregnancy or possible pregnancy, and less than 1 cm of SAT in the treatment zone ( Box 8.2 ). Other relative contraindications for HIFU treatment include active systemic illnesses, therapeutic anticoagulation, history of thromboembolic disease, implanted metal or electronic devices, or severe hepatic disease. As such, a thorough medical history and physical examination should be performed prior to treatment.

Pain tolerance is another important patient factor to be considered before treatment initiation. Solish et al. report that the vast majority (90%) of patients undergoing HIFU treatment received pre-treatment analgesia with oral opiates. Procedure-associated pain was rated as minimal to mild for the majority of subjects receiving treatment with 47 J/cm ² , 52 J/cm ² , and 59 J/cm ² , and only two patients required additional intraoperative analgesia. There was a trend towards increased procedure associated discomfort in the higher fluence group, with patients in the 59 J/cm ² group experiencing the greatest discomfort. However, this difference did not reach statistical significance. Similar procedure-associated pain was reported by Jewell et al. Of the treated patients, 22% of patients received pre-, intra-, or post-procedure analgesic (acetaminophen, ibuprofen, or naproxen), and most patients reported mild to moderate procedural discomfort. In the 47 and 59 J/cm ² groups, 5.1% and 9.5% of subjects, respectively, reported severe procedural pain, thus echoing the observation made by Solish of increased pain with higher fluence treatments. There were no reports of severe post-procedural pain and all mild to moderate pain resolved within 7–10 days. Thus, providers may choose to have a candid conversation with prospective patients regarding their pain tolerance in order to ensure appropriate analgesia.

Typical treatment course

The concept of noninvasive body contouring procedures is particularly attractive to patients who seek to achieve a modest improvement in body contour without an invasive surgical procedure and the associated downtime. In order to evaluate patients for HIFU treatment, an understanding of body morphology and laminar anatomy is needed.

The human body has a variety of superficial tissue layers: skin; superficial fat; collagen-rich MLM; deep fat; and deep fascia (overlying muscles such as the rectus abdominis). Factors which influence the degree of fat deposition in each of the layers include genetics, gender, and BMI, as well as recent weight gain or loss. Various technologies target fat in specific layers. Cryolipolysis appears to work best on fat in the superficial to MLM compartments, provided that such regions can be sandwiched into the device handpiece. Because it is a cold-subtraction technology, cryolipolysis may be less likely to tighten collagen like the thermal HIFU technologies.

HIFU body contouring technologies work best with a relatively thicker layer of SAT because of their ability to focus energy into the MLM. Individuals with skin to deep fascia of ≈2.3 cm appear to achieve good results. Individuals with thinner SAT find HIFU treatments to be uncomfortable because the HIFU energy hits the deep fascia. Those with thicker layers and elevated BMI have too much superficial fat thickness, which prevents the HIFU from reaching the collagen-rich MLM where fat reduction and thermal modulation of collagen can occur. Other very thin individuals have tissue thickness primarily in the MLM, with inadequate overall tissue layer thickness for HIFU as it exists currently. These individuals are also poor candidates for liposuction due to the very fibrous nature of the MLM. In summary, two requisite conditions must exist for an optimal HIFU treatment candidate: BMI < 30 and skin to deep fascia measurements of approximately 2.3 cm. Most patients in this realm have a clearly demarcated start of the MLM at about 11 mm beneath the skin on DUS imaging.

Having a DUS machine available for the screening of patients seeking noninvasive body contouring can be helpful. DUS can accurately measure tissue to deep fascia depth. This determines suitability for HIFU treatment, conventional liposuction, or polite counseling regarding a weight loss program of diet, exercise, and lifestyle modification. Liposonix and other forms of noninvasive body contouring should not be viewed as an ‘all-comers’ type of body contouring.

Other important considerations for patient selection are adequate skin tone, absence of loose or hanging skin, and an adequate patient focus on fitness, weight, and lifestyle. Those who do not monitor their personal weight tend to have weight fluctuations that interfere with obtaining the best result with noninvasive body contouring procedures. Careful documentation of waist circumferences (e.g. precision measurement with a laser level device and spring-loaded measuring tape) may thus be an integral part of patient evaluation. Even in situations of diminished skin tone and elasticity in the post-menopausal female, change in waistline circumference can be produced with HIFU in patients who otherwise would not be considered for liposuction. Alternatively, excisional body contouring procedures, such as lipoabdominoplasty, remain the best option when there are loose tissues, diminished skin tone, and deep layer laxity.

The use of simple data templates for patient screening, treatment, and aftercare can help systematize and standardize the HIFU treatment process. In this fashion, the screening process is linked to the procedure and aftercare. Accurate determination of waist line circumferences is recorded at initiation, and the patient is weighed at every visit and their weight compared to their baseline measurements. Offering counseling on weight maintenance may also be helpful. When patients are held accountable for their weight and BMI, they may be more committed to their treatment.

Before any type of noninvasive treatment, informed consent document is obtained and requisite pre-treatment templates are completed that that record tissue thickness (DUS), the number of zones to be treated, the energy fluence, and the energy deposition mode (e.g. site stack or grid repeat). A simple point and shoot camera may be used to document the treatment zones. Standardized digital photography without underwear is typically utilized to depict pre-treatment and follow-up outcomes. If adverse events occur after treatment, photographic documentation is a necessity.

The patient’s waist at the point of greatest abdominal protuberance is measured with a spring-loaded tape at a fixed height off the floor (e.g. measured by laser level). The patient is weighed wearing only a simple tube top and disposable spa-style shorts. Accurate determination of baseline values is essential to ensure comparability to follow-up measurements at 12–16 weeks after treatment. During pre-treatment education patients may be told that it is not uncommon to have some post-treatment ecchymoses.

While the cryolipolysis device is relatively comfortable during treatment, the HIFU fat reduction procedure is somewhat more uncomfortable, given the deeper layer of treatment and the stimulation of superficial sensory nerves deep within the tissue. Discomfort varies with individual pain tolerance and the level of HIFU fluence. A lower fluence level of around 30 J/cm ² may be better tolerated. Conversely, higher fluence levels are more uncomfortable. Post-treatment dysesthesias and numbness has been reported for up to several weeks after cryolipolysis treatment. Cold appears able to produce structural changes within sensory nerves, although these resolve over time.

Maintaining patient comfort during HIFU should not be challenging, as most individuals with normal pain tolerance can tolerate a treatment without oral sedation. Distracting techniques such as utilizing a vibratory massager on the patient’s feet can be helpful. In some cases, oral narcotic pain medicines such as oxycodone or dihydromorphone, anxiolytics, or gabapentin-class medications may be needed for patient comfort. Other sedation approaches include the use of benzodiazopines, oral or parenteral NSAIDs, nitrous oxide, or intravenous agents. Narcotic analgesia exposes patients to the risk of nausea requiring treatment (e.g. with oral disintegrating ondansetron, 4 mg tablet). Directly infiltrated tumescent anesthesia may also be used. Patient comfort during the procedure is better established early in treatment, as it is more difficult to console a patient who is already experiencing procedure-related discomfort.

Patient and operator positioning during the procedure is also important. Use of a softly upholstered massage table with an electric height adjustment may be helpful, as may use of foam blocks and pillows for patient positioning. The treatment provider may similarly be most effective while sitting in an ergonomically designed and comfortable chair. While the Liposonix treatment head/RTC is lightweight and comfortable to hold, attention must be paid to correct ergonomics to avoid repetitive motion fatigue in the operator. Additional patient comfort aids include a warm room (e.g. 22 °C), a blanket or comforter, and slightly dimmed lights. Close attention should be paid to what the patient sees from their perspective on the treatment table – a cluttered room and dirty overhead air vents are potentially anxiety provoking elements. If a vibratory massager is used for patient distraction during the procedure this may require an assistant in addition to the treatment provider. Patient use of headphones and personal music players may impair communication with the treatment provider.

Water is used to couple the Liposonix treatment head to the skin so that the HIFU energy passes from the RTC to the patient. Excessive spraying of water onto the treatment area as a distraction during treatment may contribute to lesser outcomes because of excessive tissue cooling. Additionally, the water pooling may be messy, and the need for containment with towels may become an inconvenience. Ideally, water use should be sufficient to provide for coupling but drenching of the treatment area should be avoided. A dry wash cloth can be used to pick up modest quantities of excess water.

At the completion of treatment, the grid patterns are wiped off the patient and the patient is discharged from the clinic. Patients who have taken oral or parenteral sedation must have someone drive them home. Needless to say, such patients should not operate a vehicle or machinery until their medicated state resolves completely. At discharge, patients are reminded of the possibility of post-treatment ecchymoses that typically resolve after 14 days. They are also told that there may be firmness within the treatment zone for a few weeks.

Changes in body contour after a HIFU treatment start to occur as soon as 4 weeks post-treatment and are complete by 16 weeks. As mentioned earlier, follow-up visits with recording of circumferential standardized measurements and body weight are needed to document clinical outcome and body weight maintenance.

The future of HIFU body contouring looks promising. Future-generation devices may offer custom contouring, based on each individual’s laminar anatomy. The current generation device is an excellent starting point for noninvasive body contouring. Physicians can modify fluence levels and other treatment parameters to enable a range of patients to comfortably undergo treatment.