High Intensity Focused Ultrasound (HIFU) is used to perform surgical procedures non-invasively by using high amplitude focused sound waves to induce irreversible tissue damage within a mm-size focal `hot spot.' HIFU is rapidly gaining widespread clinical use and is poised to reach even broader patient populations. However, there has been a rising concern within all parts of the HIFU community that no standards exist for measuring or reporting of HIFU fields. It has been also realized that the relation between HIFU output and the produced bioeffects is poorly understood. This lack of standards and relations of acoustics to bioeffects is a major impediment to broad clinical adoption of HIFU. The proposal addresses this current gap in development of such standards as well as understanding the bioeffect mechanisms. Nonlinear acoustics is the study of high amplitude sound. Nonlinear acoustic propagation leads to shocks, discontinuities in the acoustic wave, which encompass a very broad range of frequencies. Shock formation and strong focusing distinguish HIFU from other medical ultrasound approaches and combine to make accurate measurements difficult. Also, since ultrasound energy losses that create heating are frequency dependent, the relatively high absorption in tissue counteracts nonlinear propagation, which means that no simple way exists to extrapolate water measurements directly to tissue. Since the broadest frequency content is in the shocks, absorption at the shocks is the critical mechanism of tissue heating.
The specific aims of this proposed project are: (1) Use combined simulations and measurements to determine the high amplitude acoustic output of HIFU sources in water. (2) Determine the fields in tissue phantoms and tissue and define methods to derate water measurements to tissue. (3) Quantify the mechanism of enhanced tissue heating due to nonlinear acoustics and corresponding bioeffects in ex-vivo tissue and in vivo animal studies (4) Synthesize results of Aims 1-3 into practical recommendations for characterization of HIFU devices to improve regulatory oversight, understanding bioeffects, and efficacy and safety of clinically relevant HIFU therapeutic devices. Our method is a combined approach of numerical simulation and experimental measurement. Our model includes nonlinear acoustic propagation effects, diffraction, absorption, and tissue heterogeneities. Our acoustic measurements tools include small broad bandwidth hydrophones and a new step-shock source to calibrate the hydrophones. Our thermal measurement techniques involve the noninvasive observation of boiling with high speed photography and active and passive acoustic transducers. Tissue phantoms, excised and in vivo tissue will be used in experiments and modeling. This proposed work will benefit public health by providing tools and recommendations to help regulate and control HIFU exposures, which will improve efficacy and safety and facilitate a more rapid clinical acceptance of this promising therapy.
High Intensity Ultrasound (HIFU) is gaining wider acceptance in the clinic as a form of noninvasive or minimally invasive surgery. However, no agreed system for calibration of HIFU output currently exists today. This proposed work will benefit public health by providing tools and recommendations to help regulate and control HIFU exposures which will improve efficacy and safety and facilitate a more rapid clinical acceptance of this promising therapy. ? ? ?
| Khokhlova, Tatiana; Rosnitskiy, Pavel; Hunter, Christopher et al. (2018) Dependence of inertial cavitation induced by high intensity focused ultrasound on transducer F-number and nonlinear waveform distortion. J Acoust Soc Am 144:1160 |
| Ghanem, Mohamed A; Maxwell, Adam D; Kreider, Wayne et al. (2018) Field Characterization and Compensation of Vibrational Nonuniformity for a 256-Element Focused Ultrasound Phased Array. IEEE Trans Ultrason Ferroelectr Freq Control 65:1618-1630 |
| Rosnitskiy, Pavel B; Vysokanov, Boris A; Gavrilov, Leonid R et al. (2018) Method for Designing Multielement Fully Populated Random Phased Arrays for Ultrasound Surgery Applications. IEEE Trans Ultrason Ferroelectr Freq Control 65:630-637 |
| Brayman, Andrew A; MacConaghy, Brian E; Wang, Yak-Nam et al. (2018) Inactivation of Planktonic Escherichia coli by Focused 1-MHz Ultrasound Pulses with Shocks: Efficacy and Kinetics Upon Volume Scale-Up. Ultrasound Med Biol 44:1996-2008 |
| Rosnitskiy, Pavel B; Yuldashev, Petr V; Sapozhnikov, Oleg A et al. (2017) Design of HIFU Transducers for Generating Specified Nonlinear Ultrasound Fields. IEEE Trans Ultrason Ferroelectr Freq Control 64:374-390 |
| Chevillet, John R; Khokhlova, Tatiana D; Giraldez, Maria D et al. (2017) Release of Cell-free MicroRNA Tumor Biomarkers into the Blood Circulation with Pulsed Focused Ultrasound: A Noninvasive, Anatomically Localized, Molecular Liquid Biopsy. Radiology 283:158-167 |
| Maxwell, Adam D; Yuldashev, Petr V; Kreider, Wayne et al. (2017) A Prototype Therapy System for Transcutaneous Application of Boiling Histotripsy. IEEE Trans Ultrason Ferroelectr Freq Control 64:1542-1557 |
| Khokhlova, Tatiana D; Haider, Yasser A; Maxwell, Adam D et al. (2017) Dependence of Boiling Histotripsy Treatment Efficiency on HIFU Frequency and Focal Pressure Levels. Ultrasound Med Biol 43:1975-1985 |
| Khokhlova, Tatiana D; Monsky, Wayne L; Haider, Yasser A et al. (2016) Histotripsy Liquefaction of Large Hematomas. Ultrasound Med Biol 42:1491-8 |
| Hunter, Christopher; Sapozhnikov, Oleg A; Maxwell, Adam D et al. (2016) An ultrasonic caliper device for measuring acoustic nonlinearity. Phys Procedia 87:93-98 |
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