journal article·2026-02-04Open access

HIFU and the Oxidative Echo: A Pilot Investigation of Free Radical Stress in Facial and Neck Procedures

Foteini Biskanaki, Dimitrios Chaniotis, Ioanna A. Anastasiou, Nikolaos Tentolouris, Vasilis Papadopoulos, George Skouras, Angeliki M. Mavreli, Fragiskos Chanioitis, Evaggelia Protopapa, Athanasia Varvaresou, Andreas C. Lazaris

Applied Sciences· Volume 16· Issue 3

Abstract

Background: High-Intensity Focused Ultrasound (HIFU) is widely used for non-invasive facial and neck rejuvenation, promoting collagen remodeling through controlled thermal and mechanical effects. While its clinical outcomes are well established, the immediate biochemical response—particularly oxidative stress—has not been directly quantified in humans. Objective: This pilot study aimed to evaluate acute changes in oxidative stress levels following a single HIFU session in healthy adult volunteers. Methods: Nineteen healthy volunteers were enrolled; fourteen received HIFU treatment and five served as contemporaneous controls. Venous blood samples were collected at baseline and immediately after treatment (or 40 min later for controls). Oxidative stress levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Pre–post differences were assessed using paired t-tests, and between-group comparisons were performed using Δ-scores and mixed-effects modeling. Results: Oxidative index values remained unchanged in controls (18.55 ± 0.57 μmol/L pre vs. 18.55 ± 0.57 μmol/L post; Δ = 0.00 ± 0.00; p = 1.00). In contrast, HIFU treatment induced a significant acute increase (19.99 ± 1.54 μmol/L pre vs. 22.39 ± 2.29 μmol/L post; Δ = 2.63 ± 2.22 μmol/L; p = 0.0007). Between-group Δ differences were significant, and mixed-effects modeling revealed a significant time × group interaction, indicating an HIFU-specific oxidative response. No adverse effects were observed, and all treated participants demonstrated immediate aesthetic improvement. Conclusions: A single HIFU session elicits an acute increase in oxidative stress, likely reflecting controlled thermal stimulation and early tissue remodeling. Longitudinal studies are warranted to assess the persistence of these biochemical changes and their contribution to long-term clinical outcomes.
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Research context

OpenAlex topics: Ultrasound and Hyperthermia Applications · Nasal Surgery and Airway Studies · Dermatologic Treatments and Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

First Department of Pathology, School of Medicine, The National and Kapodistrian University of Athens, GR-11527 Athens, Greece

Department of Biomedical Sciences, School of Health and Care Sciences, University of West Attica, GR-12243 Athens, Greece

Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, GR-11527 Athens, Greece

Department of Pharmacology, National and Kapodistrian University of Athens, GR-11527 Athens, Greece

Department of Pathology, Navy Hospital of Athens, Dinokratous 70, GR-11521 Athens, Greece

Department of Plastic Surgery, SkourasMed Clinics, Tsakalof 8, GR-10673 Athens, Greece

Laboratory of Chemistry-Biochemistry-Cosmetic Science, Department of Biomedical Sciences, School of Health and Care Sciences, University of West Attica, 28 Ag. Spyridonos Str., Panepistimioupolis Egaleo Park, GR-12243 Athens, Greece

References (20)

Show source-provided references
1. Biological effects of high-intensity focused ultrasound (HIFU): Mechanisms and clinical applications in medicine and aesthetic therapy
2. High-Intensity Focused Ultrasound: A Review of Mechanisms and Clinical Applications10.1007/s10439-021-02833-9 ↗
3. Safety and efficacy of high-intensity focused ultrasound in aesthetic medicine: A review
4. Clinical safety and efficacy of microfocused ultrasound in facial rejuvenation10.1111/jocd.13449 ↗
5. Histological and clinical evaluation of high-intensity focused ultrasound treatment for skin rejuvenation
6. Oh, S., Rhee, D.Y., Batsukh, S., Son, K.H., and Byun, K. (2023). High-Intensity Focused Ultrasound increases collagen and elastin fiber synthesis by modulating Caveolin-1 in aging skin. Cells, 12.10.3390/cells12182275 ↗
7. Ultrasound-assisted tissue engineering10.1038/s44222-024-00166-5 ↗
8. Low-intensity focused ultrasound regulates oxidative stress responses in biological tissues
9. Biskanaki, F., Tertipi, N., Sfyri, E., Kefala, V., and Rallis, E. (2025). Complications and Risks of High-Intensity Focused Ultrasound (HIFU) in Esthetic Procedures: A Review. Appl. Sci., 15.10.3390/app15094958 ↗
10. Advances in biomedical engineering technologies: Applications in human physiology, disease mechanisms, and therapeutic innovation
11. Potential contribution of ELISA and LFI assays to assessment of oxidative stress based on the 8-oxodG biomarker10.1016/j.ab.2021.114215 ↗
12. Wonisch, W., Tatzber, F., Lindschinger, M., Falk, A., Resch, U., Mörkl, S., Zarkovic, N., and Cvirn, G. (2024). Clinical relevance of antibodies against oxidized LDL within three decades by ELISA technology. Antioxidants, 13.10.20944/preprints202411.1296.v1 ↗
13. Yang, J., Luo, J., Tian, X., Zhao, Y., Li, Y., and Wu, X. (2024). Progress in understanding oxidative stress, aging, and aging-related diseases. Antioxidants, 13.10.3390/antiox13040394 ↗
14. Performance benchmarking of microplate immunoassays for quantifying cysteine oxidation10.1016/j.freeradbiomed.2023.05.006 ↗
15. The protective role of antioxidants against ROS/RNS-mediated damage
16. Natural and sun-induced aging of human skin
17. Best practice guidance for linear mixed-effects models in experimental research10.1016/j.jml.2020.104092 ↗
18. Considerations in determining sample size for pilot studies
19. Billingham, S.A., Whitehead, A.L., and Julious, S.A. (2023). An audit of sample sizes for pilot and feasibility trials. BMC Med. Res. Methodol., 23.
20. The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency