High-Intensity Focused Ultrasound Treatment of Genitourinary Lesions

Principles of Focused Ultrasound Imaging

High-intensity focused ultrasound (HIFU) is a noninvasive thermoablative therapeutic technique that utilizes focused ultrasound beams to target and thermally heat tissue. First introduced in 1942, ultrasound-induced thermal coagulative necrosis has been studied for over 60 years. Although diagnostic ultrasound operates at frequencies ranging from 1 to 20 MHz, focused ultrasound treatments employ low frequencies of 0.8 to 3.5 MHz and continuous waves to deliver targeted, intense energy to a specific focal spot or target, while sparing surrounding tissues. The combined energy of the beams can cause a tissue temperature rise of a magnitude sufficient to induce coagulative necrosis and cell death. Additionally, the use of acoustic lenses such as phased arrays can magnify the intensity of the ultrasound waves to increase targeted ablation spatial resolution.

Ultrasound causes tissue damage through two primary mechanisms : conversion of mechanical energy into heat and cavitation. Focused ultrasound can rapidly elevate the temperature at the focal spot to 70 to 80°C, leading to cell death in less than a second after exposure. This results in thermal shock, necrosis, cavitation, and tissue coagulation. Similar to that of external beam radiotherapy, energy is delivered from multiple approaches and ablation occurs at the focal point. Unlike external beam radiotherapy, there is no ionizing radiation absorption by surrounding tissue. Energy applied to nontargeted tissue is dissipated as heat that is insufficient to cause therapeutic thermal ablation and rendered innate. The volume of ablation after a single focused ultrasound sonication depends on the transducer and is generally small and cigar-shaped. Therefore several adjacent focused ultrasound sonications are required to ablate a larger volume (Fig. e149. 1).

Cavitation is based on the principle that ultrasound waves subject the tissue molecules to alternating cycles of compression and rarefaction, during which gas can be drawn out of solution, creating bubbles. These bubbles oscillate and rapidly collapse, causing local energy release and resulting in damage to the cells and surrounding tissues.

Clinical applications of focused ultrasound have been hampered by the inability to accurately target the focus and control temperature during the procedure. Recent advances in magnetic resonance imaging (MRI) have overcome these limitations, thus MRI has been associated with HIFU for treatment planning and intra- and posttreatment evaluation. Magnetic resonance-guided focused ultrasound (MRgFUS) allows for precise target definition as well as temperature monitoring during the entire procedure. Also, MRI can generate quantitative temperature maps for monitoring safe and effective delivery of heat to the targeted tissue. Combining the use of anatomic, functional, and thermal guidance with MRI allows for safe, accurate targeting, real-time monitoring, and closed-loop control of energy deposition.

Focused ultrasound has been applied in the treatment of a variety of clinical conditions, including uterine fibroids, prostate cancer, bone metastases, kidney tumors, breast lesions, and, most recently, neurologic disorders such as essential tremor. Nonthermal effects of HIFU are also currently being evaluated for techniques such as drug delivery to gene therapy. In October 2004, the US Food and Drug Administration (FDA) approved MRgFUS for treatment of symptomatic uterine fibroids, representing the first commercially available method of treating patients with focused ultrasound in the United States (ExAblate 2000 device [InSightec, Haifa, Israel]). This chapter concentrates on focused ultrasound and the treatment of genitourinary lesions, specifically uterine leiomyomas and the early work on prostate cancer.

Uterine Leiomyomas

Uterine leiomyomas, also called fibroids , are hormone-dependent benign smooth muscle tumors arising from uterine muscle tissue. Fibroids are estimated to occur in 20% to 50% of women of reproductive age, representing the most common female pelvic tumor. The incidence of uterine fibroids is two to three times higher in African American women, who also present at a younger age and with more symptomatic cases. Significant symptoms related to fibroids occur in up to 25% of women and include menorrhagia, pressure-related symptoms such as pelvic fullness, urinary urgency and frequency, dyspareunia, and infertility.

Currently there are several treatment options available for symptomatic fibroids. Hysterectomy is the definitive treatment for uterine leiomyomas, with surgical removal of the uterus resulting in 100% relief of all fibroid-related symptoms. However, hysterectomy requires general anesthesia, potential several days in-hospital admission, and a 2- to 6-week outpatient recovery. In addition, there are several anatomic and psychological side effects of hysterectomy that many women wish to avoid. As a result, patients often pursue less invasive, uterine-sparing alternatives.

Myomectomy is a uterine-sparing procedure to palliate fibroid-related problems and treat fibroids interfering with fertility. It can be performed via laparotomy, laparoscopy, or hysteroscopy, but usually requires general anesthesia, and has a recovery time similar to hysterectomy. In addition, the number, size, and location of fibroids may limit its applicability.

Uterine fibroid embolization is an effective, minimally invasive alternative for treating a wide range of fibroid locations and sizes. However, the procedure leads to amenorrhea in 1% to 2% of women younger than 45 and 15% of women older than 45 and may be associated with postembolization syndrome (postprocedural pain and fatigue).

MRgFUS represents the only truly noninvasive procedure among the uterine-sparing therapeutic options. MRI has excellent anatomic resolution and high sensitivity for localizing tumors, and enables real-time temperature monitoring. There is no need for ionizing radiation, and preliminary results are encouraging in selected patients.

Prostate Cancer

Prostate cancer is the most common cancer in men in the United States, accounting for an estimated 19% of all newly diagnosed cancer in American men. The 10-year survival rate for all stages of prostate cancer is 98% in the United States. Given the favorable long-term outcomes and the morbidity associated with radical or systemic treatments, localized therapies for prostate cancer have become increasingly popular for appropriate patients. HIFU is one such localized therapy that has been used for the treatment of prostate cancer in several specific scenarios.

Indications

Contraindications