High Intensity Focused Ultrasound (20 MHz) and Cryotherapy as Therapeutic Options for Granuloma Annulare and Other Inflammatory Skin Conditions.

Dermatol Ther (Heidelb) 2024;1-22.  

Calik, J., Zawada, T., Sauer, N. et al.  




In dermatology, inflammatory skin conditions impose a substantial burden worldwide, with existing therapies showing limited efficacy and side effects. This report aims to compare a novel immunological activation induced by hyperthermic 20 MHz high intensity focused ultrasound (HIFU) with conventional cryotherapy. The bioeffects from the two methods are initially investigated by numerical models, and subsequently compared to clinical observations after treatment of a patient with the inflammatory disease granuloma annulare (GA). 


Clinical responses to moderate energy HIFU and cryotherapy were analysed using numerical models. HIFU-induced pressure and heat transfer were calculated, and a three-layer finite element model simulated temperature distribution and necrotic volume in the skin. Model output was compared to 22 lesions treated with HIFU and 10 with cryotherapy in a patient with GA. 


Cryotherapy produced a necrotic volume of 138.5 mm3 at − 92.7 °C. HIFU at 0.3–0.6 J/exposure and focal depths of 0.8 or 1.3 mm generated necrotic volumes up to only 15.99 mm3 at temperatures of 68.3–81.2 °C. HIFU achieved full or partial resolution in all treated areas, confirming its hyperthermic immunological activation effect, while cryotherapy also resolved lesions but led to scarring and dyspigmentation. 


Hyperthermic immunological activation of 20 MHz HIFU shows promise for treating inflammatory skin conditions as exemplified by GA. Numerical models demonstrate minimal skin necrosis compared to cryotherapy. Suggested optimal HIFU parameters are 1.3 mm focal depth, 0.4–0.5 J/exposure, 1 mm spacing, and 1 mm margin. Further studies on GA and other inflammatory diseases are recommended.

Analytical modeling of harmonically driven focused acoustic sources with experimental verification. 

Applied Acoustics, 2024;221,1-19:

T. Zawada, T. Bove. 



Recently, a high intensity focused ultrasound (HIFU) is drawing a lot of attention from medical and non-medical fields due to its potential for extreme high pressure levels as well as ultra high spatial resolution. At the heart of every HIFU system is a focused ultrasound transducer, and its electrical and acoustic properties play a key role. During the transducer design phase, it is important to quickly obtain the electrical and acoustic parameters corresponding to the transducer structure. Currently, researchers mainly use finite element methods for simulation, but by doing so they lose the deeper insight into the key aspects of the complex electro-acoustic interaction between the transducer, the electric matching network and the front and back acoustic load. A theoretical model based on the Krimholtz-Leedom-Matthaei (KLM) approach of a focused acoustic source is presented. The model includes the impact of the dielectric and mechanical losses and allows for evaluation of the performance of the transducer in terms of electro-acoustic efficiency. The theoretical performance and the impact of the included loss mechanisms on it is calculated up to 9th harmonic resonance frequency. The model is verified using test transducers operating at 4 MHz (fundamental), 12 MHz (3rd harmonic) and 20 MHz (5th harmonic) resonance frequencies. Both the predicted input impedance and predicted electro-acoustic efficiency exhibit very good agreement with the experimental data. An effective material and device parameter identification method based on multi-dimensional minimization algorithm is presented, as well. The results can be directly applied to optimization and development of high-frequency focused acoustic sources taking advantage of the high focusing gain and very high spatial resolution. 

High‐intensity focused ultrasound: safety and efficacy of a novel treatment modality for neurofibromatosis type 1 cutaneous neurofibroma.

JEADV Clin Pract. 2024;1–12: 

Peltonen S, Serup J, Tang M, Gillstedt M, Kantere D, Neittaanmäki N,et al.




High-intensity focused ultrasound (HIFU) is widely used in the treatment of deep tumours, but clinical trials on skin tumours are not yet available. Neurofibromatosis Type I (NF1) is among the most common single-gene inherited conditions worldwide and predisposes to benign and malignant neoplasms of the nervous system. Multiple cutaneous neurofibromas (cNFs) often cause social and functional limitations, itching and pain. 


The objective of this study was to investigate the safety, local tolerability and efficacy of a novel method utilizing HIFU for the treatment of cNFs. 


A 20 MHz HIFU-device with an integrated dermoscopic guidance and a handpiece with a focus depth of 2.3 mm below the skin surface was used. Doses of acoustic energy with 0.7 J/dose and pulse duration of 250 ms/dose were manually positioned with 1–2 mm distance between each applied dose. Number of applied doses depended on the size of the cNF. No anaesthetic was applied. 


Twenty patients with NF1 were recruited in two centres, and 147 cNFs were treated. There were no serious adverse events. Immediate and transient wheal-and-flare reactions occurred at treatment sites and occasionally there was minor epidermal damage which healed in 1–2 weeks. Dyspigmentation occurred in some tumours after 3–9 months but no scarring was observed at 9-month follow-up. During treatment, the patient-reported pain-score median was 3.5 (range 1–7) on a 0–10-point scale. Clinical rating of cNFs after 9 months showed 48.9% full or major tumour reduction. The median reduction in tumour thickness measured by ultrasound at 9 months was 0.53 mm (range: –100% to +19%). 


HIFU treatment is a new noninvasive, rapid and tolerable treatment modality that with high precision targets intradermal lesions. This study demonstrates acceptable safety, local tolerance and efficacy of HIFU for the treatment of cNFs that may further be developed also for other skin tumours. 

Healing Process after High-Intensity Focused Ultrasound Treatment of Benign Skin Lesions: Dermoscopic Analysis and Treatment Guidelines.

Journal of Clinical Medicine. 2024;13(4):931:  

Calik J, Zawada T, Bove T, Dzięgiel P, Pogorzelska-Antkowiak A, Mackiewicz J, Woźniak B, Sauer N. 




High-Intensity Focused Ultrasound (HIFU) has emerged as a precise and non-invasive modality for tissue ablation and healing. This study presents a detailed dermoscopic analysis of skin healing post-High-Intensity Focused Ultrasound (HIFU) treatment, focusing on common benign skin lesions, such as seborrheic keratosis, sebaceous hyperplasia, vascular lesions, and sebaceous nevi.  


Prior to HIFU treatment, a comprehensive assessment was conducted, integrating ultrasound scanning and clinical evaluations. The TOOsonix System ONE-M was employed for HIFU treatments, with parameters tailored to each lesion type.  


A common pattern observed across all lesions includes initial whitening post treatment, followed by scab formation and the development of a pink area with reparative vessels. This study, however, highlights distinct differences in fibrosis patterns and healing timelines across different lesion types. Each lesion type exhibited unique fibrosis patterns post treatment. Flatter variants of seborrheic keratosis healed within a month, displaying hypopigmentation and reparative vessels, alongside a distinct lattice fibrosis pattern in more verrucous forms, which took about two months to heal. Sebaceous hyperplasia, characterized by rapid healing within three weeks, demonstrated fibrosis with pink areas and perpendicular white lines, concluding with a slight depression. Vascular lesions varied in healing time based on depth, with superficial ones showing whitening and crust formation, while deeper lesions had vessel occlusion and size reduction accompanied by concentric fibrotic bands. Sebaceous nevi presented the longest healing duration of three months, characterized by amorphous white-gray structures, scab formation, and the emergence of pink areas with branching vessels, leading to clear skin with reduced white lines.  


In conclusion, this meticulous clinical evaluation highlights the unique healing characteristics and timelines for each skin lesion type treated with HIFU. These insights are invaluable for optimizing follow-up assessments, identifying potential complications, and refining treatment protocols. By providing detailed insights into the healing timelines and patterns for different types of lesions, patients can be better informed about their post-treatment journey. 

Head-to-Head Comparison of Acoustic Properties of Lead-Free and PZT-Based HIFU Transducers Operating at 12 MHz.  

IEEE Trans Ultrason Ferroelectr Freq Control. 2024 Jan;71(1):16-26:

Zawada T, Bove T, Lou-Moller R, Ringgaard E. 



A direct comparison of performance and acoustic properties of high-intensity focused ultrasonic transducers utilizing lead-free (sodium bismuth titanate—NBT) and lead-based (lead zirconate titanate—PZT) piezoceramics is discussed. All transducers operate at 12 MHz at third harmonic frequency, having an outer diameter of 20 mm, a central hole of 5 mm in diameter, and a radius of curvature of 15 mm. The electroacoustic efficiency determined by a radiation force balance is evaluated in a range of input power levels up to 15 W. Schlieren tomography as well as hydrophone measurements are used for evaluation of the acoustic field distribution. It is found that the average electroacoustic efficiency of NBT-based transducers is approximately 40%, while it is around 80% in the PZT-based devices. NBT devices show significantly higher inhomogeneity of the acoustic field under schlieren tomography compared to PZT devices. From pressure measurements in the prefocal plane, it was found that the inhomogeneity could be attributed to depoling of significant areas of the NBT piezo-component during the fabrication process. In conclusion, PZT-based devices performed significantly better than those using lead-free material. However, the NBT devices show promise for this application and their electroacoustic efficiency as well as the uniformity of the acoustic field could be improved by employing a low-temperature fabrication process or repoling after processing. 

Treatment of Cutaneous Neurofibromas in Patients with Neurofibromatosis Type 1.

Case Rep Dermatol 2023;15(1):194–201:  

Wozniak B, Bove T, Zawada T, Calik J. 



Neurofibromatosis type 1 is a genetic disorder impacting approximately 2.5 million people worldwide, often leading to development of numerous benign yet disfiguring cutaneous neurofibromas (cNF). Removal of cNF is limited to excision or laser ablation with common post-operation complications and scarring. The current case explores a new approach to removal or reduction of cNF by a minimally invasive and pain-reduced treatment modality. A 40-year-old female patient with numerous cNF across her body underwent a single treatment using a 20 MHz dermatologically focused ultrasound device on seven selected cNF on the upper back. Each cNF was treated in a single session of 20–60 s without anesthesia due to manageable pain. Only one minimal adverse reaction in the form of dyspigmentation in a single treated tumor was noted from treatment or during the healing of a thin scab that formed on each cNF a few days after treatment. At the 12-month follow-up, four out of seven treated cNF showed full remission, two showed partial or significant reduction in tumor volume, while two did not respond to treatment. The reason for the variability is not fully understood, but speculations include difference in tissue content, e.g., due to tumor age. The method is concluded to be a promising candidate for a new safe and minimally invasive treatment that can potentially be used for single-session removal/reduction of a large number of cNF. Further research should focus on refining treatment parameters and strategies to enhance response predictability. 

High-Frequency (20 MHz) Focused Ultrasound: A Novel Method for Noninvasive Tattoo Removal.

Curr Probl Dermatol. 2022;56:268-280: 

Bove T, Zawada T, Serup J, Jessen A, Poli M. 



Alternatives or complements to laser tattoo removal are needed. Laser removal requires 8-12 session and can easily take more than a year. Some colors cannot be removed, and scars may appear. Applied to allergic reactions in red tattoos, lasers can boost the allergy. 

A recently developed 20 MHz High Intensity Focused Ultrasound (HIFU) is introduced as a complementary method to lasers, but also as a stand-alone treatment for selected groups. 20 MHz HIFU allows for application of high-power ultrasound energy to very small focal targets in the dermis, and thereby precise confinement of thermal lesions in the outer layers of human skin, precisely where tattoo inks are deposited. 

HIFU treatment is “color blind” and can target any type of colored pigment in the dermis. It produces a controlled thermal lesion (up to 65 °C) with superficial necrosis followed by an eschar with embedded tattoo pigment. This eschar, containing the tattoo pigment, is discharged over some weeks, and finally replaced by healed skin. HIFU can efficiently remove tattoos of any color in only 1-3 sessions. It can be applied to tattoos when lasers fail to produce efficient removal. The type of side effects are the same as with lasers. The operator shall be trained and knowledgeable. 20MHz HIFU can furthermore be used in clinical and esthetic dermatology for various other applications, and a range of applications are open in clinical dermatology. 

Acoustic field of strongly focused HIFU transducer operating at 20 MHz – comparison of public domain numerical simulators with experimental observations.

2022 IEEE International Ultrasonics Symposium (IUS), Venice, Italy, 2022;1-4: 

T. Zawada and T. Bove, 



Recently, a new modality for dermatological intervention involving therapeutic ultrasound with integrated optical imaging has been demonstrated for treatments of actinic keratosis, basal cell carcinoma, vascular malformations etc. Such modality requires very confined focal zones which are typically generated by strongly focused transducers operating at relatively high frequency (e.g., 20 MHz). Several public domain solvers exist, but they are however typically used and validated for simulation of HIFU devices for treatment of deep pathologies, therefore operating with larger f-numbers and lower frequencies. The objective of this work is to evaluate selected solvers against experimental data, when used for a strongly focused transducer (f-number=0.75) operating at 20 MHz. Three simulators are evaluated: HIFUbeam-KZK, HIFUbeam-WAPE and HITU-Simulator. The experimental data consist of peak pressure measurements around the focal zone in axial and radial direction using a Fiber Optic Hydrophone as well as schlieren imaging. Both modules of the HIFUbeam package seem to underestimate value of the peak pressure around the focal zone, and simultaneously overestimating the size of the focal zone, especially along the axial direction. HITU-Simulator, on the other hand, shows good agreement with experimental data when it comes to both absolute pressure values as well as location of pre- and side-lobes. It is therefore a preferable simulator when it comes to simulation of acoustic fields from strongly focused high-frequency transducers. 

Treatment of Condylomata Acuminata Using a New Non-Vapor-Generating Focused Ultrasound Method following Imiquimod 5% Cream. 

Case Rep Dermatol 2022:275-282: 

Calik J, Zawada T, Bove T 



Condylomata acuminata is the most common sexually transmitted disease in the world. Physical treatments include excision, cryotherapy, electrocautery and ablative CO2, and Nd:YAG laser ablation, while topical treatments include imiquimod immunotherapy and antimitotic podophyllotoxin or sinecatechins. Efficacies of all methods are low, and recurrences are very common. A new combined method is presented as a single case in a 25-year-old male patient diagnosed with numerous condylomas on the penis, scrotum, and lower abdomen. The treatment consisted of a 7-week topical monotherapy using 5% imiquimod cream followed by local treatment with 20 MHz high-intensity focused ultrasound on remaining recalcitrant lesions. Results showed resolution of approximately 70% of the condylomas after imiquimod treatment, and full resolution of all recalcitrant condylomas treated subsequently with high-intensity focused ultrasound. The method is concluded to be safe and effective and, furthermore, presents a new physical method that does not generate airborne infectious human papillomavirus particles that pose a health risk for the medical team performing therapy. Further studies in larger populations are recommended to confirm the combined efficacy of the proposed method.