High‐frequency (20 MHz) high‐intensity focused ultrasound system for dermal intervention: A 12‐week local tolerance study in minipigs

Abstract

Background High‐intensity focused ultrasound (HIFU) operating at 20 MHz is new and applicable to skin. Details of use and instrumentation are not documented. Materials and Methods A GLP compliant 12‐week study of Göttingen minipigs (n = 3) was undertaken. Effects of HIFU treatment at different focal depths, energy levels and field size (single shot vs 5 × 5 multiple shots) were studied. Clinical scoring and histology of treated sites were made. Results High‐intensity focused ultrasound showed instant and initial effects with wheal and flare responses followed by delayed inflammatory reactions associated with outer skin necrosis, depending on energy dose. HIFU treatment was tunable in the range 0.3‐1.5 J, ablative at higher energy level. Transducers with deeper focal points gave more profound effects, while epidermal effects were comparable. Multiple doses of 5 × 5 shots produced stronger reactions than single dose indicating that nearby applied shots were synergistic. Recovery from single doses was faster than in multidose areas. Clinical scarring at the end point was not seen despite occasional fibrous change of dermis. Findings illustrated intended therapeutic use; no special safety issues of concern were raised. Conclusion The new 20 MHz HIFU was reproducible, tunable and produced targeted effects in the outer skin, for example instant wheal and flare followed by inflammation and possibly necrosis depending on energy setting. Reactions recovered during the study with only minor findings at study end. No special safety concerns were raised. The method can be controlled and modulated, and it is ready for clinical testing of dermatological disease indications including conditions presently treated with lasers.

High‐frequency (20 MHz) high‐intensity focused ultrasound: New ablative method for color‐independent tattoo removal in 1‐3 sessions. An open‐label exploratory study

“…Such horizontal synergy between ultrasound lesions applied nearby each other, that is, "shoulder by shoulder" mode, was compared to single dose, the latter clearly having lower effect. 23,27 Thus, the dose delivered to the skin, as determined by instrument setting, had an additional operator-dependent dimension, namely the number and closeness of applied treatment doses.…”

“…A clinical material of challenging cases of tattoo removal that mostly had been unsuccessfully treated with lasers F I G U R E 2 Schematic illustration of ablative effects of 20 MHz high-intensity focused ultrasound (HIFU) treatment dosed "shoulder by shoulder" according to preclinical study of pigs, extrapolated to treatment of tattoos. 27 The illustration shows the hypothetical mode of action and sequence of events of tattoo removal using 20 MHz HIFU. A, cross-sectional illustration of the skin with black tattoo pigment concentrated in the outer dermis, which is a typical location.…”

Removal of Common Warts by High-Intensity Focused Ultrasound: An Introductory Observation

“…The 20 MHz HIFU used for dermatological applications was studied in experimental laboratory models, animals, and humans. HIFU was concluded safe and relevant for different dermatological indications [ 6 , 11 ]. Actinic keratosis, basal cell carcinoma, and Kaposi Sarcoma were treated successfully [ 12 ].…”

High‐frequency (20 MHz) high‐intensity focused ultrasound: New Treatment of actinic keratosis, basal cell carcinoma, and Kaposi sarcoma. An open‐label exploratory study

“…It has recently been demonstrated in preclinical studies that HIFU operating at high frequency with a close focal distance can target selected small objects in media near the surface of the medium and reproducibly deliver a thermal insult. 10,11 The dose-effect curve in the range of interest has been demonstrated to be linearly dependent on energy, and thereby allow for the accurate dose-effect modulation needed in clinical applications. High-frequency HIFU therefore becomes relevant to dermatology, plastic surgery, and cosmetology.…”

“…The effect of 20 MHz HIFU, as mentioned above, was recently studied in pre-clinical laboratory studies, which included a study on Göttingen minipigs. 11 The study on pigs was designed to document local safety and efficacy, and issues of general safety. This study also produced key information on operation and dose settings needed before human use.…”