Dynamic mode decomposition based Doppler monitoring of de novo cavitation induced by pulsed HIFU: an in vivo feasibility study.

Pulsed high-intensity focused ultrasound (pHIFU) has the capability to induce de novo cavitation bubbles, offering potential applications for enhancing drug delivery and modulating tissue microenvironments. However, imaging and monitoring these cavitation bubbles during the treatment presents a challenge due to their transient nature immediately following pHIFU pulses. A planewave bubble Doppler technique demonstrated its potential, yet this Doppler technique used conventional clutter filter that was originally designed for blood flow imaging.

Dynamic Mode Decomposition for Transient Cavitation Bubbles Imaging in Pulsed High-Intensity Focused Ultrasound Therapy.

Pulsed high-intensity focused ultrasound (pHIFU) can induce sparse de novo inertial cavitation without the introduction of exogenous contrast agents, promoting mild mechanical disruption in targeted tissue. Because the bubbles are small and rapidly dissolve after each HIFU pulse, mapping transient bubbles and obtaining real-time quantitative metrics correlated with tissue damage are challenging. Prior work introduced Bubble Doppler, an ultrafast power Doppler imaging method as a sensitive means to map cavitation bubbles.

Elastic Properties of Aging Human Hematoma Model In Vitro and Its Susceptibility to Histotripsy Liquefaction.

Objective: Tissue susceptibility to histotripsy disintegration has been reported to depend on its elastic properties. This work was aimed at investigation of histotripsy efficiency for liquefaction of human hematomas, depending on their stiffness and degree of retraction over time (0-10 d).

Methods: As an in vitro hematoma model, anticoagulated human blood samples (200 mL) were recalcified at different temperatures.

Dynamic Mode Decomposition for Transient Cavitation Bubbles Imaging in Pulsed High Intensity Focused Ultrasound Therapy.

Pulsed high-intensity focused ultrasound (pHIFU) can induce sparse inertial cavitation without the introduction of exogenous contrast agents, promoting mild mechanical disruption in targeted tissue. Because the bubbles are small and rapidly dissolve after each HIFU pulse, mapping transient bubbles and obtaining real-time quantitative metrics correlated to tissue damage are challenging. Prior work introduced Bubble Doppler, an ultrafast power Doppler imaging method as a sensitive means to map cavitation bubbles.

Treatment Planning and Aberration Correction Algorithm for HIFU Ablation of Renal Tumors.

High-intensity focused ultrasound (HIFU) applications for thermal or mechanical ablation of renal tumors often encounter challenges due to significant beam aberration and refraction caused by oblique beam incidence, inhomogeneous tissue layers, and presence of gas and bones within the beam. These losses can be significantly mitigated through sonication geometry planning, patient positioning, and aberration correction using multielement phased arrays. Here, a sonication planning algorithm is introduced, which uses the simulations to select the optimal transducer position and evaluate the effect of aberrations and acoustic field quality at the target region after aberration correction.

The histotripsy spectrum: differences and similarities in techniques and instrumentation.

Since its inception about two decades ago, histotripsy - a non-thermal mechanical tissue ablation technique - has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity.

Enhancement of Boiling Histotripsy by Steering the Focus Axially During the Pulse Delivery.

Boiling histotripsy (BH) is a pulsed high-intensity focused ultrasound (HIFU) method relying on the generation of high-amplitude shocks at the focus, localized enhanced shock-wave heating, and bubble activity driven by shocks to induce tissue liquefaction. BH uses sequences of 1-20 ms long pulses with shock fronts of over 60 MPa amplitude, initiates boiling at the focus of the HIFU transducer within each pulse, and the remainder shocks of the pulse then interact with the boiling vapor cavities. One effect of this interaction is the creation of a prefocal bubble cloud due to reflection of shocks from the initially generated mm-sized cavities: the shocks are inverted when reflected from a pressure-release cavity wall resulting in sufficient negative pressure to reach intrinsic cavitation threshold in front of the cavity.

Phase holograms for the three-dimensional patterning of unconstrained microparticles.

Acoustic radiation forces can remotely manipulate particles. Forces from a standing wave field align microscale particles along the nodal or anti-nodal locations of the field to form three-dimensional (3D) patterns. These patterns can be used to form 3D microstructures for tissue engineering applications.

Comparative Characterization of Nonlinear Ultrasound Fields Generated by Sonalleve V1 and V2 MR-HIFU Systems.

A Sonalleve magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) clinical system (Profound Medical, Mississauga, ON, Canada) has been shown to generate nonlinear ultrasound fields with shocks up to 100 MPa at the focus as required for HIFU applications such as boiling histotripsy of hepatic and renal tumors. The Sonalleve system has two versions V1 and V2 of the therapeutic array, with differences in focusing angle, focus depth, arrangement of elements, and the size of a central opening that is twice larger in the V2 system compared to the V1. The goal of this study was to compare the performance of the V1 and V2 transducers for generating high-amplitude shock-wave fields and to reveal the impact of different array geometries on shock amplitudes at the focus.

Initial Assessment of Boiling Histotripsy for Mechanical Ablation of Ex Vivo Human Prostate Tissue.

Boiling histotripsy (BH) is a focused ultrasound technology that uses millisecond-long pulses with shock fronts to induce mechanical tissue ablation. The pulsing scheme and mechanisms of BH differ from those of cavitation cloud histotripsy, which was previously developed for benign prostatic hyperplasia. The goal of the work described here was to evaluate the feasibility of using BH to ablate fresh ex vivo human prostate tissue as a proof of principle for developing BH for prostate applications.

Quantitative Assessment of Boiling Histotripsy Progression Based on Color Doppler Measurements.

Boiling histotripsy (BH) is a mechanical tissue liquefaction method that uses sequences of millisecond-long high intensity focused ultrasound (HIFU) pulses with shock fronts. The BH treatment generates bubbles that move within the sonicated volume due to acoustic radiation force. Since the velocity of the bubbles and tissue debris is expected to depend on the lesion size and liquefaction completeness, it could provide a quantitative metric of the treatment progression.

Mechanical damage thresholds for hematomas near gas-containing bodies in pulsed HIFU fields.

. Boiling histotripsy (BH) is a novel high intensity focused ultrasound (HIFU) application currently being developed for non-invasive mechanical fractionation of soft tissues and large hematomas. In the context of development of BH treatment planning approaches for ablating targets adjacent to gas-containing organs, this study aimed at investigation of the ultrasound pressure thresholds of atomization-induced damage to the tissue-air interface and correlation of the danger zone dimensions with spatial structure of nonlinear HIFU field parameters.

B/A Measurement of Clear Cell Renal Cell Carcinoma versus Healthy Kidney Tissue.

The acoustic parameter of non-linearity B/A has been found capable of discriminating some types of pathological tissue from healthy tissue. The literature on the utility of B/A for cancer diagnostics is very limited, with measurements on the human breast and liver. This work expands the current research on cancer diagnostics by B/A assessment of eight slices of human clear cell renal cell carcinoma (ccRCC) from two patients and four slices of healthy kidney tissue from two healthy kidney samples.

Improving Burst Wave Lithotripsy Effectiveness for Small Stones and Fragments by Increasing Frequency: Theoretical Modeling and Study.

In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure.

Maximizing mechanical stress in small urinary stones during burst wave lithotripsy.

Unlike shock wave lithotripsy, burst wave lithotripsy (BWL) uses tone bursts, consisting of many periods of a sinusoidal wave. In this work, an analytical theoretical approach to modeling mechanical stresses in a spherical stone was developed to assess the dependence of frequency and stone size on stress generated in the stone. The analytical model for spherical stones is compared against a finite-difference model used to calculate stress in nonspherical stones.

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

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.

A review on B/A measurement methods with a clinical perspective.

The nonlinear parameter of ultrasound B/A has shown to be a useful diagnostic parameter, reflecting medium content, structure, and temperature. Despite its recognized values, B/A is not yet used as a diagnostic tool in the clinic due to the limitations of current measurement and imaging techniques. This review presents an extensive and comprehensive overview of the techniques developed for B/A measurement of liquid and liquid-like media (e.

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

"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.

Inertial Cavitation Behaviors Induced by Nonlinear Focused Ultrasound Pulses.

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).

Holographic extraction of plane waves from an ultrasound beam for acoustic characterization of an absorbing layer of finite dimensions.

For the acoustic characterization of materials, a method is proposed for interpreting experiments with finite-sized transducers and test samples in terms of the idealized situation in which plane waves are transmitted through an infinite plane-parallel layer. The method uses acoustic holography, which experimentally provides complete knowledge of the wave field by recording pressure waveforms at points on a surface intersected by the acoustic beam. The measured hologram makes it possible to calculate the angular spectrum of the beam to decompose the field into a superposition of plane waves propagating in different directions.

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

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

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.

Biofabrication of a Functional Tubular Construct from Tissue Spheroids Using Magnetoacoustic Levitational Directed Assembly.

In traditional tissue engineering, synthetic or natural scaffolds are usually used as removable temporal support, which involves some biotechnology limitations. The concept of "scaffield" approach utilizing the physical fields instead of biomaterial scaffold has been proposed recently. In particular, a combination of intense magnetic and acoustic fields can enable rapid levitational bioassembly of complex-shaped 3D tissue constructs from tissue spheroids at low concentration of paramagnetic agent (gadolinium salt) in the medium.