ИСТИНА

Therapeutic Ultrasound is currently emerging into many clinical applications. Major developments include the use of High Intensity Focused Ultrasound (Fig. 1, A) for treating tumors, neurological diseases, acoustic haemostasis and thrombolysis, targeted drug and gene delivery, nerve and brain stimulation. Other high pressure ultrasound-based therapies as lithotripsy and shock wave therapies utilize single shock pulses for stone comminution and tissue revascularisation. New low intensity treatments are used for healing of bone fractures and joints. Biological and therapeutic effects of ultrasound are determined in the first place by the in situ ultrasound field parameters. Understanding wave propagation effects in tissue, developing methods to predict in situ pressures from characterization measurements in water for medical devices, and physical mechanisms of ultrasound interaction with tissue that result in specific bioeffects are therefore critical initial steps in successful development of therapeutic ultrasound. Correspondingly, this lecture is divided into three parts. Basic ultrasound wave phenomena are considered first in water where calibration measurements are typically carried out. Acoustic quantities that are used as metrics of therapeutic fields are introduced. Wave propagation models, methods of calculating acoustic pressure distributions, and typical ultrasound fields generated by HIFU medical transducers are overviewed. Setting a boundary condition to the modelling using measurements for a specific transducer is discussed (Fig. 1, B). The effects of diffraction, focusing, and nonlinear propagation on the maximum values of ultrasound field parameters and their spatial distributions in water are shown. Physical effects of ultrasound propagation and interaction with soft biological tissue are overviewed next. Acoustic properties of different tissues are discussed: sound velocity, attenuation, absorption, scattering, and nonlinearity. Propagation of longitudinal waves is considered in detail; however some properties of shear waves are also presented. Major wave phenomena responsible for different biological effects in tissue are discussed introduced: acoustic energy attenuation and absorption, acoustic radiation force and streaming, nonlinear propagation, formation of shocks and enhanced tissue heating. Reflection and scattering from soft tissue layers and inhomogeneities are considered as well as the effects of strong obstacles like skull bones and ribs (Fig. 1, C). Ultrasound-induced bioeffects are presented in the third part of the lecture (Fig. 1, D). Thermal ablation of tissue, which is a major approach in current HIFU technologies, is overviewed. The concept of thermal dose is introduced. Mechanical fragmentation of tissue caused by interaction of microsecond-long shock pulses with cavitation clouds (histotripsy) or by millisecond-long shock wave pulses with boiling bubbles induced by shock wave heating (boiling histotripsy) is presented. Thermal and cavitation effects and typical ultrasound field parameters for approaches that involve the use of contrast agents, nanoparticles, and nanoemulsions, are given. Optimal choice of ultrasound frequency based on frequency dependence of attenuation and cavitation thresholds are discussed for particular therapeutic applications.