Emerging clinical applications of high-intensity focused ultrasound

ltrasound is an acoustic wave with frequencies greater than the hearing threshold of humans and can be used for both diagnostic and therapeutic purposes in medicine.Diagnostic ultrasound imaging uses ultrasonic pressure waves to image the human interior, whereas therapeutic ultrasound uses alternating compression and rarefaction of sound waves for therapeutic benefit, based on the simple principle of focusing energy waves on a targeted point to produce a thermal effect (Fig. 1).Diagnostic medical ultrasound is typically in the range of 3-20 MHz, while the majority of therapeutic ultrasound typically resides in the 0.54-2 MHz range (1).High-intensity focused ultrasound (HIFU) is a minimally invasive and non-ionizing technology and currently performs an important clinical role in many fields with abundant evidence on safety and efficacy.Therapeutic application of the HIFU modality, which can be used to treat many diseases by utilizing either thermal energy to induce denaturation of proteins or non-thermal energy to destroy tissue, is considered a rapidly emerging field (1).The HIFU beam passes through soft tissue, elevating the temperature at the target area (>55°C), thus generating cell death via local coagulative necrosis, which is the main principle for tumor cell damage.HIFU can hence be performed for chosen tissue elimination by generating well-defined volumes of coagulative necrosis deep inside the body without harming the surrounding tissues (Figs.2,3) (2).The biological effects of HIFU were investigated first in 1927 by Wood and Loomis (3).In the 1940s, the first therapeutic trial with focused ultrasound, performed by Lynn et al. ( 4) to treat tumors in bovine liver, suggested that a geometrically concave transducer could be exploited to elevate the local intensity by focusing the ultrasonic energy without harming the adjacent tissues, while surrounding areas are maintained at low intensity.In the 1950s, the Fry brothers (5) designed and tested the HIFU device for the treatment of neurologic disorders (e.g., Parkinson's disease).However, these early efforts at using HIFU ablation were hampered due to technologic limitations, such as lack of suitable image guidance, and were therefore discontinued in the clinical setting.Advances in ultrasound imaging and magnetic resonance imaging (MRI) modalities in the 1990s facilitated improved planning of HIFU treatment and monitoring of responses in real-time, and the recent development of high-power ultrasound transducers compatible with these imaging modalities has helped overcome the biggest obstacle in the field of therapeutic ultrasound.