From Incision to Precision: The Rise of Focused Ultrasound Surgery in Minimally Invasive Gynecology

Scientific and medical progress is rarely the result of steady and linear development. Instead, it is often driven by breakthroughs in key technologies, changes in the healthcare environment, and evolving societal needs – factors that collectively lead to exponential growth. However, such breakthroughs are not always appreciated at their inception. For example, laparoscopy laid the foundation for the development of robotic-assisted surgery; vaginal hysterectomy pioneered natural orifice transluminal endoscopic surgery; and the introduction of anesthesia was pivotal to the rise of modern surgical practice.[1-3] As Steve Jobs once said: “You can’t connect the dots looking forward; you can only connect them looking backwards.” Many innovations only reveal their true impact in hindsight. In recent years, we have witnessed a paradigm shift in surgery – from open procedures to minimally invasive and now to noninvasive approaches. The evolution has progressed from manual operations to robotic assistance,[4-6] and artificial intelligence (AI)-powered automation may soon redefine surgical precision and personalization. In this context, therapeutic ultrasound emerges as a forward-looking and noninvasive technique that may shape the future of gynecologic interventions. The biological changes caused by the interaction between ultrasound and tissue have long been known.[7] Ultrasound with higher energy, intensity, and frequency can induce mechanical, thermal, and cavitation effects through the propagation within living tissues, which can be used for various therapeutic applications. Therapeutic ultrasound can be conveniently classified into two categories: Applications using low intensity (0.125–3 W cm −2) and applications using high intensity (≥5 W cm −2). Low-intensity ultrasound mainly elicits normal physiological responses to injury, while high-intensity ultrasound is designed to selectively destroy tissue in a controlled manner, known as focused ultrasound surgery (FUS). Based on the mechanisms underlying the biological changes, FUS is further classified into FUS and histotripsy. The thermal effect is the most widely recognized mechanism in therapeutic ultrasound, and the technique primarily based on the thermal effect is called FUS, which has been proven safe and effective for treating various solid tumors. In fact, cavitation effect can also be triggered by FUS. The FUS modality has long been investigated and a comprehensive theoretical framework has been established. In an ideal acoustic environment, the size and shape of the focal zone are described by the “acoustic focal region (AFR).” Because biological tissues differ markedly from an idealized acoustic environment, our team proposed the concept of the “biological focal region (BFR)” in 1996.[8] BFR was defined as the single cigar-shaped or ellipsoidal coagulative necrosis area generated by one FUS exposure in tissue. BFR serves as the basic ablative unit in FUS tumor therapy, and its formation can be modeled as a function of AFR, acoustic intensity, exposure time, irradiation depth, the tissue structure, and its functional status.[8] The energy required to induce coagulative necrosis per cubic-millimeter of tissue is defined as the energy efficiency factor (EEF). The aggregate impact of tissue structure, functional dynamics, and their interaction with propagating ultrasound waves in an acoustic field is called the acoustic environment (AET). Using the BFR framework, the deposition and expression patterns of focused ultrasound energy in various tissues were explored.[9] Previous studies have demonstrated that the factors affecting EEF include acoustic power, irradiation time, irradiation depth, tissue structure, and tissue functional status. Notably, EEF exhibits a depth-dependent increase and a volume-dependent decrease when ablating equivalent volume. Therefore, the EEF required for ablating points, lines, slices, and volumes is decreasing, but it is nonlinear. Dynamic changes in AET during FUS are the another major determinant of EEF.[10] Histotripsy is predominant mediated by cavitation effect, is accompanied by a thermal effect, and ultimately induces mechanical tissue fractionation of the target tissue. Although histotripsy was recently approved by the US Food and Drug Administration for hepatic tumors, early data suggested a potential complementary effect when combined with existing immunologic therapies, its overall impact on oncologic therapy remains uncertain. Uterine fibroids are one of the most common benign gynecological tumors, often leading to symptoms such as menorrhagia, pelvic pain, bulk-related symptoms, and infertility. While surgical myomectomy remains the traditional treatment of choice-particularly for women with fertility desires has grown in minimally invasive and noninvasive alternatives that reduce surgical morbidity, preserve uterine integrity, and accelerate recovery. Among these, FUS has emerged as a promising modality. FUS utilizes the unique biophysical properties of ultrasound energy, transmitting it noninvasively through the abdominal wall and focusing it precisely on the fibroid target. Mechanical energy is converted into thermal energy, inducing localized coagulative necrosis at temperatures above 65°C without damaging overlying or surrounding tissues. Under real-time monitoring with either ultrasound or magnetic resonance imaging (MRI), the treatment offers excellent spatial control and safety. Over time, the necrotic fibroid tissue is gradually absorbed, leading to symptom relief and fibroid volume reduction [Figure 1].Figure 1: Pre- and postfocused ultrasound surgery (FUS) contrast-enhanced magnetic resonance imaging (MRI) obtained from a 40-year-old patient with uterine fibroids. (a) Pre-FUS contrast enhanced MRI showed the uterine fibroid with rich blood supply and the size of the fibroid was 5.5 cm × 5.3 cm × 5.3 cm. (b) 1-day post-FUS MRI showed the fibroid was completely ablated. (c) 3-month post-FUS showed the reduced size of the fibroid. The shrinkage rate of tumor volume was 56%Recent advances in image fusion technology – integrating pretreatment MRI with real-time ultrasound imaging – have addressed the limitations of single-modality guidance. Mounting clinical evidence supports the advantages of ultrasound-guided FUS over MRI-guided FUS, including shorter treatment times, larger ablation volumes, and lower long-term re-intervention rates. Moreover, ultrasound guidance permits real-time feedback and greater accessibility in clinical practice. From a technical standpoint, FUS is suitable for fibroids ≥1 cm in diameter that can be clearly visualized and targeted with fused imaging of MRI and ultrasound. The technique is particularly effective for fibroids with limited blood supply, achieving complete lesion ablation without harming the surrounding healthy tissue [Figure 2]. This feature is especially valuable for women who desire future fertility, as it maintains uterine architecture and may substantially shorten the time to conception compared with surgical myomectomy.Figure 2: Pre- and postfocused ultrasound surgery (FUS) magnetic resonance imaging (MRI) obtained from a 41-year-old patient with uterine fibroids. The power used was 400 watts, the total treatment time was 84 min, the total sonication time was 600 s (120 s for the small one, and 480 s for the bigger one), the total energy used was 184,200J. (a) Pre-FUS T2 weighted image showed two fibroids. The size of the large fibroid was 6.2 cm × 6.0 cm × 5.5 cm; the size of the small one was 2.6 cm × 2.5 cm × 2.1 cm. (b) Pre-FUS contrast-enhanced MRI showed rich blood supply of the large fibiroid and the small one with limited blood supply. (c) Post-FUS showed two fibroids were completely ablated. The NPV ratio achieved in both fibroids was 100%. There was no damage to the surrounding healthy tissueFUS provides selective, organ-sparing treatment, minimizing the risk of uterine rupture during subsequent pregnancy and delivery. Theoretical and preliminary clinical data suggest that the risk of uterine rupture may be lower than that associated with myomectomy, owing to minimal disruption of the myometrial wall. Furthermore, FUS significantly shortens the time to conception in fertility-preserving cases, an advantage increasingly recognized by reproductive gynecologists.[11-14] In summary, FUS is a maturing and highly promising technology for gynecological tumors offering distinct advantages in noninvasiveness, fertility preservation, and recurrence reduction. Continued advances in imaging guidance, equipment precision, and automated control systems – particularly the integration of ultrasound-based positioning with robotic probe manipulation are expected to further enhance diagnostic accuracy and therapeutic efficiency. Just as the fully automated intracytoplasmic sperm injection system (AI-Robotic ICSI System) has been successfully developed, FUS is poised to become a mainstream therapeutic strategy for uterine fibroids and other gynecological tumors. Author contributions Writing: Original Draft Preparation, Writing: Review and Editing, Supervision. Dr. Zhibiao Wang, Dr. Lian Zhang, Dr. H. Rosie Xing, Dr. Chyi-Long Lee. All authors have read and agreed to the final version of the manuscript. Data availability statement Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest Prof. Chyi-Long Lee , an Editor-in-Chief at Gynecology and Minimally Invasive Therapy, had no role in the peer review process of or decision to publish this article. All authors declared no conflicts of interest in writing this paper.