Publications by authors named "Pavel B Rosnitskiy"

9 Publications

  • Page 1 of 1

Ultrastructural Analysis of Volumetric Histotripsy Bio-effects in Large Human Hematomas.

Ultrasound Med Biol 2021 Sep 9;47(9):2608-2621. Epub 2021 Jun 9.

Laboratory for Industrial and Medical Ultrasound, Physics Faculty, M. V. Lomonosov Moscow State University, Moscow, Russian Federation; Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA.

Large-volume soft tissue hematomas are a serious clinical problem, which, if untreated, can have severe consequences. Current treatments are associated with significant pain and discomfort. It has been reported that in an in vitro bovine hematoma model, pulsed high-intensity focused ultrasound (HIFU) ablation, termed histotripsy, can be used to rapidly and non-invasively liquefy the hematoma through localized bubble activity, enabling fine-needle aspiration. The goals of this study were to evaluate the efficiency and speed of volumetric histotripsy liquefaction using a large in vitro human hematoma model. Large human hematoma phantoms (85 cc) were formed by recalcifying blood anticoagulated with citrate phosphate dextrose/saline-adenine-glucose-mannitol solution. Typical boiling histotripsy pulses (10 or 2 ms) or hybrid histotripsy pulses using higher-amplitude and shorter pulses (0.4 ms) were delivered at 1% duty cycle while continuously translating the HIFU focus location. Histotripsy exposures were performed under ultrasound guidance with a 1.5-MHz transducer (8-cm aperture, F# = 0.75). The volume of liquefied lesions was determined by ultrasound imaging and gross inspection. Untreated hematoma samples and samples of the liquefied lesions aspirated using a fine needle were analyzed cytologically and ultrastructurally with scanning electron microscopy. All exposures resulted in uniform liquid-filled voids with sharp edges; liquefaction speed was higher for exposures with shorter pulses and higher shock amplitudes at the focus (up to 0.32, 0.68 and 2.62 mL/min for 10-, 2- and 0.4-ms pulses, respectively). Cytological and ultrastructural observations revealed completely homogenized blood cells and fibrin fragments in the lysate. Most of the fibrin fragments were less than 20 μm in length, but a number of fragments were up to 150 μm. The lysate with residual debris of that size would potentially be amenable to fine-needle aspiration without risk for needle clogging in clinical implementation.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355095PMC
September 2021

"HIFU Beam:" A Simulator for Predicting Axially Symmetric Nonlinear Acoustic Fields Generated by Focused Transducers in a Layered Medium.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2837-2852. Epub 2021 Aug 27.

"HIFU beam" is a freely available software tool that comprises a MATLAB toolbox combined with a user-friendly interface and binary executable compiled from FORTRAN source code (HIFU beam. (2021). Available: http://limu.msu.ru/node/3555?language=en). It is designed for simulating high-intensity focused ultrasound (HIFU) fields generated by single-element transducers and annular arrays with propagation in flat-layered media that mimic biological tissues. Numerical models incorporated in the simulator include evolution-type equations, either the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation or one-way Westervelt equation, for radially symmetric ultrasound beams in homogeneous and layered media with thermoviscous or power-law acoustic absorption. The software uses shock-capturing methods that allow for simulating strongly nonlinear acoustic fields with high-amplitude shocks. In this article, a general description of the software is given along with three representative simulation cases of ultrasound transducers and focusing conditions typical for therapeutic applications. The examples illustrate major nonlinear wave effects in HIFU fields including shock formation. Two examples simulate propagation in water, involving a single-element source (1-MHz frequency, 100-mm diameter, 90-mm radius of curvature) and a 16-element annular array (3-MHz frequency, 48-mm diameter, and 35-mm radius of curvature). The third example mimics the scenario of a HIFU treatment in a "water-muscle-kidney" layered medium using a source typical for abdominal HIFU applications (1.2-MHz frequency, 120-mm diameter, and radius of curvature). Linear, quasi-linear, and shock-wave exposure protocols are considered. It is intended that "HIFU beam" can be useful in teaching nonlinear acoustics; designing and characterizing high-power transducers; and developing exposure protocols for a wide range of therapeutic applications such as shock-based HIFU, boiling histotripsy, drug delivery, immunotherapy, and others.
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http://dx.doi.org/10.1109/TUFFC.2021.3074611DOI Listing
September 2021

Inertial Cavitation Behaviors Induced by Nonlinear Focused Ultrasound Pulses.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2884-2895. Epub 2021 Aug 27.

Inertial cavitation induced by pulsed high-intensity focused ultrasound (pHIFU) has previously been shown to successfully permeabilize tumor tissue and enhance chemotherapeutic drug uptake. In addition to HIFU frequency, peak rarefactional pressure ( p ), and pulse duration, the threshold for cavitation-induced bioeffects has recently been correlated with asymmetric distortion caused by nonlinear propagation, diffraction and formation of shocks in the focal waveform, and therefore with the transducer F -number. To connect previously observed bioeffects with bubble dynamics and their attendant physical mechanisms, the dependence of inertial cavitation behavior on shock formation was investigated in transparent agarose gel phantoms using high-speed photography and passive cavitation detection (PCD). Agarose phantoms with concentrations ranging from 1.5% to 5% were exposed to 1-ms pulses using three transducers of the same aperture but different focal distances ( F -numbers of 0.77, 1.02, and 1.52). Pulses had central frequencies of 1, 1.5, or 1.9 MHz and a range of p at the focus varying within 1-18 MPa. Three distinct categories of bubble behavior were observed as the acoustic power increased: stationary near-spherical oscillation of individual bubbles, proliferation of multiple bubbles along the pHIFU beam axis, and fanned-out proliferation toward the transducer. Proliferating bubbles were only observed under strongly nonlinear or shock-forming conditions regardless of frequency, and only where the bubbles reached a certain threshold size range. In stiffer gels with higher agarose concentrations, the same pattern of cavitation behavior was observed, but the dimensions of proliferating clouds were smaller. These observations suggest mechanisms that may be involved in bubble proliferation: enhanced growth of bubbles under shock-forming conditions, subsequent shock scattering from the gel-bubble interface, causing an increase in the repetitive tension created by the acoustic wave, and the appearance of a new growing bubble in the proximal direction. Different behaviors corresponded to specific spectral characteristics in the PCD signals: broadband noise in all cases, narrow peaks of backscattered harmonics in the case of stationary bubbles, and broadened, shifted harmonic peaks in the case of proliferating bubbles. The shift in harmonic peaks can be interpreted as a Doppler shift from targets moving at speeds of up to 2 m/s, which correspond to the observed bubble proliferation speeds.
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http://dx.doi.org/10.1109/TUFFC.2021.3073347DOI Listing
September 2021

Bilayer aberration-inducing gel phantom for high intensity focused ultrasound applications.

J Acoust Soc Am 2020 12;148(6):3569

Department of Acoustics, Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia.

Aberrations induced by soft tissue inhomogeneities often complicate high-intensity focused ultrasound (HIFU) therapies. In this work, a bilayer phantom made from polyvinyl alcohol hydrogel and ballistic gel was built to mimic alternating layers of water-based and lipid tissues characteristic of an abdominal body wall and to reproducibly distort HIFU fields. The density, sound speed, and attenuation coefficient of each material were measured using a homogeneous gel layer. A surface with random topographical features was designed as an interface between gel layers using a 2D Fourier spectrum approach and replicating different spatial scales of tissue inhomogeneities. Distortion of the field of a 256-element 1.5 MHz HIFU array by the phantom was characterized through hydrophone measurements for linear and nonlinear beam focusing and compared to the corresponding distortion induced by an ex vivo porcine body wall of the same thickness. Both spatial shift and widening of the focal lobe were observed, as well as dramatic reduction in focal pressures caused by aberrations. The results suggest that the phantom produced levels of aberration that are similar to a real body wall and can serve as a research tool for studying HIFU effects as well as for developing algorithms for aberration correction.
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http://dx.doi.org/10.1121/10.0002877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097711PMC
December 2020

A Prototype Therapy System for Boiling Histotripsy in Abdominal Targets Based on a 256-Element Spiral Array.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 May 26;68(5):1496-1510. Epub 2021 Apr 26.

Boiling histotripsy (BH) uses millisecond-long ultrasound (US) pulses with high-amplitude shocks to mechanically fractionate tissue with potential for real-time lesion monitoring by US imaging. For BH treatments of abdominal organs, a high-power multielement phased array system capable of electronic focus steering and aberration correction for body wall inhomogeneities is needed. In this work, a preclinical BH system was built comprising a custom 256-element 1.5-MHz phased array (Imasonic, Besançon, France) with a central opening for mounting an imaging probe. The array was electronically matched to a Verasonics research US system with a 1.2-kW external power source. Driving electronics and software of the system were modified to provide a pulse average acoustic power of 2.2 kW sustained for 10 ms with a 1-2-Hz repetition rate for delivering BH exposures. System performance was characterized by hydrophone measurements in water combined with nonlinear wave simulations based on the Westervelt equation. Fully developed shocks of 100-MPa amplitude are formed at the focus at 275-W acoustic power. Electronic steering capabilities of the array were evaluated for shock-producing conditions to determine power compensation strategies that equalize BH exposures at multiple focal locations across the planned treatment volume. The system was used to produce continuous volumetric BH lesions in ex vivo bovine liver with 1-mm focus spacing, 10-ms pulselength, five pulses/focus, and 1% duty cycle.
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http://dx.doi.org/10.1109/TUFFC.2020.3036580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191454PMC
May 2021

Simulation of nonlinear trans-skull focusing and formation of shocks in brain using a fully populated ultrasound array with aberration correction.

J Acoust Soc Am 2019 09;146(3):1786

Department of Acoustics, Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia.

Multi-element high-intensity focused ultrasound phased arrays in the shape of hemispheres are currently used in clinics for thermal lesioning in deep brain structures. Certain side effects of overheating non-targeted tissues and skull bones have been revealed. Here, an approach is developed to mitigate these effects. A specific design of a fully populated 256-element 1-MHz array shaped as a spherical segment (F-number, F = 1) and filled by randomly distributed equal-area polygonal elements is proposed. Capability of the array to generate high-amplitude shock fronts at the focus is tested in simulations by combining three numerical algorithms for linear and nonlinear field modeling and aberration correction. The algorithms are based on the combination of the Rayleigh integral, a linear pseudo-spectral time domain Kelvin-Voigt model, and nonlinear Westervelt model to account for the effects of inhomogeneities, aberrations, reflections, absorption, nonlinearity, and shear waves in the skull. It is shown that the proposed array can generate nonlinear waveforms with shock amplitudes >60 MPa at the focus deep inside the brain without exceeding the existing technical limitation on the intensity of 40 W/cm at the array elements. Such shock amplitudes are sufficient for mechanical ablation of brain tissues using the boiling histotripsy approach and implementation of other shock-based therapies.
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http://dx.doi.org/10.1121/1.5126685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064313PMC
September 2019

Method for Designing Multielement Fully Populated Random Phased Arrays for Ultrasound Surgery Applications.

IEEE Trans Ultrason Ferroelectr Freq Control 2018 04;65(4):630-637

Maximizing the power of multielement phased arrays is a critical factor for high-intensity focused ultrasound (HIFU) applications such as histotripsy and transcostal sonications. This can be achieved by a tight packing of the array elements. Good electronic focusing capabilities are also required. Currently used quasi-random arrays with a relatively low filling factor of about 60% have this focusing ability. Here, a novel method of designing random HIFU arrays with the maximum possible filling factor (100% if no gaps between elements needed in practice are introduced) and polygonal elements of equal area and slightly different shapes based on the capacity-constrained tessellation is described. The method is validated by comparing designs of two arrays with the same geometric and physical parameters: an existing 256-element array with a compact 16-spirals layout of circular elements and the proposed array with the maximum possible filling factor. Introduction of a 0.5-mm gap between the elements of the new array resulted in a reduction of its filling factor to 86%, as compared with 61% for the spiral array. It is shown that for the same intensity at the elements, the proposed array provides two times higher total power while maintaining the same electronic focusing capabilities as compared to the spiral one. Furthermore, the surface of the capacity-constrained tessellation array, its boundary, and a central opening can have arbitrary shapes.
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http://dx.doi.org/10.1109/TUFFC.2018.2800160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903437PMC
April 2018

Design of HIFU Transducers for Generating Specified Nonlinear Ultrasound Fields.

IEEE Trans Ultrason Ferroelectr Freq Control 2017 02 20;64(2):374-390. Epub 2016 Oct 20.

Various clinical applications of high-intensity focused ultrasound have different requirements for the pressure levels and degree of nonlinear waveform distortion at the focus. The goal of this paper is to determine transducer design parameters that produce either a specified shock amplitude in the focal waveform or specified peak pressures while still maintaining quasi-linear conditions at the focus. Multiparametric nonlinear modeling based on the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation with an equivalent source boundary condition was employed. Peak pressures, shock amplitudes at the focus, and corresponding source outputs were determined for different transducer geometries and levels of nonlinear distortion. The results are presented in terms of the parameters of an equivalent single-element spherically shaped transducer. The accuracy of the method and its applicability to cases of strongly focused transducers were validated by comparing the KZK modeling data with measurements and nonlinear full diffraction simulations for a single-element source and arrays with 7 and 256 elements. The results provide look-up data for evaluating nonlinear distortions at the focus of existing therapeutic systems as well as for guiding the design of new transducers that generate specified nonlinear fields.
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http://dx.doi.org/10.1109/TUFFC.2016.2619913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300962PMC
February 2017

Design of HIFU transducers to generate specific nonlinear ultrasound fields.

Phys Procedia 2016 ;87:132-138

CIMU, Applied Physics Laboratory, University of Washington, Seattle, WA.

Various clinical applications of high intensity focused ultrasound (HIFU) have different requirements on the pressure level and degree of nonlinear waveform distortion at the focus. Applications that utilize nonlinear waves with developed shocks are of growing interest, for example, for mechanical disintegration as well as for accelerated thermal ablation of tissue. In this work, an inverse problem of determining transducer parameters to enable formation of shocks with desired amplitude at the focus is solved. The solution was obtained by performing multiple direct simulations of the parabolic Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation for various parameters of the source. It is shown that results obtained within the parabolic approximation can be used to describe the focal region of single element spherical sources as well as complex transducer arrays. It is also demonstrated that the focal pressure level at which fully developed shocks are formed mainly depends on the focusing angle of the source and only slightly depends on its aperture and operating frequency. Using the simulation results, a 256-element HIFU array operating at 1.5 MHz frequency was designed for a specific application of boiling-histotripsy that relies on the presence of 90-100 MPa shocks at the focus. The size of the array elements and focusing angle of the array were chosen to satisfy technical limitations on the intensity at the array elements and desired shock amplitudes in the focal waveform. Focus steering capabilities of the array were analysed using an open-source T-Array software developed at Moscow State University.
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http://dx.doi.org/10.1016/j.phpro.2016.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451200PMC
January 2016
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