Francesco P. Curra

Numerical simulations of heating patterns and tissue temperature response due to high-intensity focused ultrasound

The results of this paper show-for an existing high intensity, focused ultrasound (HIFU) transducer-the importance of nonlinear effects on the space/time properties of wave propagation and heat generation in perfused liver models when a blood vessel also might be present. These simulations are based on the nonlinear parabolic equation for sound propagation and the bio-heat equation for temperature generation. The use of high initial pressure in HIFU transducers in combination with the physical characteristics of biological tissue induces shock formation during the propagation of a therapeutic ultrasound wave. The induced shock directly affects the rate at which heat is absorbed by tissue at the focus without significant influence on the magnitude and spatial distribution of the energy being delivered. When shocks form close to the focus, nonlinear enhancement of heating is confined in a small region around the focus and generates a higher localized thermal impact on the tissue than that predicted by linear theory. The presence of a blood vessel changes the spatial distribution of both the heating rate and temperature.

Ultrasound Accelerates Functional Recovery after Peripheral Nerve Damage

OBJECTIVE Axonal injury in the peripheral nervous system is common, and often it is associated with severe long-term personal and societal costs. The objective of this study is to use an animal model to demonstrate that transcutaneous ultrasound can accelerate recovery from an axonotmetic injury. METHODS The sciatic nerve of adult male Lewis rats was crushed in the right midthigh to cause complete distal degeneration of axons yet maintain continuity of the nerve. Beginning 3 days after surgery, various transcutaneous ultrasound treatments or sham treatments were applied 3 days per week for 30 days to the crush site of rats that were randomly assigned to two groups. In the preliminary experiments, there were three animals in each ultrasound group and two control animals. In the final experiment, there were 22 animals in the ultrasound group and 20 animals in the control group. Recovery was assessed by use of a toe spread assay to quantify a return to normal foot function in the injured leg. Equipment included a hand-held transducer that emitted continuous-wave ultrasound. The most successful ultrasound protocol had a spatial peak, time-averaged intensity of 0.25 W/cm2 operated at 2.25 MHz for 1 minute per application. RESULTS Rats subjected to the most successful ultrasound protocol showed a statistically significant acceleration of foot function recovery starting 14 days after injury versus 18 days for the control group. Full recovery by the ultrasound group occurred before full recovery by the control group. CONCLUSION Transcutaneous ultrasound applied to an animal model of axonotmetic injury accelerated recovery. Future studies should focus on identification of the mechanism(s) by which ultrasound creates this effect, as a prelude to optimization of the protocol, demonstration of its safety, and its eventual application to humans.

Numerical simulations of tissue heating created by high‐intensity focused ultrasound

Modeling of high‐intensity focused ultrasound (HIFU) propagation and heating effects in tissue has usually been studied under the assumption of linear acoustics. Nevertheless, nonlinear propagation can lead to important differences in heat deposition depending on the degree of nonlinearity achieved in a HIFU field. To be presented are calculations of the spatial patterns of acoustic intensity (I) and heat generation [H=−(∂/∂z+1/r∂/∂r)I for strongly nonlinear acoustic waves and H=2αI for weakly nonlinear acoustic waves, where α is acoustic absorption] associated with focused weakly and strongly nonlinear acoustic wave propagation in biological tissue. The propagation is modeled using a KZK equation method with special attention to correct modeling of shock generation and biologically relevant attenuation, as well as using initializing data based on existing designs of transducers for acoustic hemostasis. The heat generation term forces the ‘‘bio‐heat’’ equation, which predicts the generation, movement, and...

Multilayer transducer for nonlinear imaging with application to targeting and monitoring of therapeutic ultrasound

Nonlinear acoustic wave propagation can improve the resolution of ultrasound imaging, and could be used to dynamically estimate the physical properties of tissue. However, transducers capable of launching a wave that becomes nonlinear through propagation can typically detect only the fundamental and second harmonic. Here we present the design and characterization of a multilayer transducer with a high power transmit layer to generate nonlinear waves and a broadband receive layer to detect nonlinear scatter. The transmit array was made from a narrow-band PZT, with nominal frequency of 2.0 MHz, that was diced into an array of 32 elements. Elements had 0.300 mm width and 6.3 mm elevation, and the pitch was 0.400 mm. The receive array, placed directly above the transmit array, was made from PVDF elements that were patterned by flex circuit pads that replicated the PZT element dimensions. The PZT and PVDF elements had identical apertures. Simulations were performed to guide the selection of the transducer materials and thicknesses. Characterization of electrical parameters and acoustic output were performed per standard methods, in which transmit and receive events were driven by a software-controlled ultrasound system. Nonlinear waveforms with peak positive pressure up to 2.14 MPa were measured by a calibrated hydrophone. Echo data, collected from ex vivo tissue and digitized at 45 MS/s, exhibited frequency content up to the 4th harmonic of the 2 MHz transmit frequency.

3D full wave ultrasonic field and temperature simulations in biological tissue containing a blood vessel

In order to simulate ultrasound propagation and subsequent thermal effects in biological media in which blood vessels and other structures may be present, a three‐dimensional model has been developed that eliminates the need for symmetry constraints. The model is based on the coupled solution of the full wave nonlinear equation of sound in a lossy medium and the bioheat equation obtained by a pseudospectral finite‐difference method in the time domain. It includes nonlinear sound propagation, an arbitrary frequency power law for attenuation, and is capable of treating material inhomogeneities. Unlike other models based on parabolic approximations, it is not restricted to near‐axis solutions and can account for reflections and backscattered fields. The program was used to simulate the application of high‐intensity focused ultrasound (HIFU) in liver with a blood vessel placed perpendicular to the axis of the transducer and near the focus. This approach follows recent work by the authors [Curra et al., IEEE Trans. Ultrason. Ferroelectr., Freq. Control (in press)]. Simulations are presented for different levels of driving pressure, sound nonlinearities, exposure times, and the relative position between the transducer focus and the blood vessel. [Work supported in part by DARPA and the CRDF Cooperative Grants Program.]

Ultrasound‐based targeting and monitoring of high intensity focused ultrasound fields.

A new method to address the challenging tasks of image‐guidance, targeting, and treatment monitoring during HIFU treatments is presented. The approach, enabled by the use of a novel multi‐layer PZT‐PVDF array with broad receive bandwidth in conjunction with a programmable ultrasound engine, uses the passive‐mode received echoes of the imaging array with a custom pixel‐based beamforming for HIFU focal tracking and targeting, allowing real‐time two‐dimensional (2D) B‐mode visualization of the HIFU beam. Temperature monitoring during treatment is based on acoustic nonlinear propagation theory and the physical relationship of sound speed and attenuation to frequency and temperature. The harmonics‐rich received echoes are processed differentially, encoded into an RGB additive color channel, beamformed, and overlayed in color over regular B‐mode images. Dynamic local temperature changes in the region of interest become visible as the 2D color image changes from frame to frame. Preliminary results on beam visual...

Multilayer Array Transducer for Nonlinear Ultrasound Imaging

The properties of nonlinear acoustic wave propagation are known to be able to improve the resolution of ultrasound imaging, and could be used to dynamically estimate the physical properties of tissue. However, transducers capable of launching a wave that becomes nonlinear through propagation do not typically have the necessary bandwidth to detect the higher harmonics. Here we present the design and characterization of a novel multilayer transducer for high intensity transmit and broadband receive. The transmit layer was made from a narrow‐band, high‐power piezoceramic (PZT), with nominal frequency of 2.0 MHz, that was diced into an array of 32 elements. Each element was 0.300 mm wide and 6.3 mm in elevation, and with a pitch of 0.400 mm the overall aperture width was 12.7 mm. A quarter‐wave matching layer was attached to the PZT substrate to improve transmit efficiency and bandwidth. The overlaid receive layer was made from polyvinylidene fluoride (PVDF) that had gold metalization on one side. A custom tw...

Visualization of a focused ultrasound beam to guide radiation force‐induced clearance of kidney stones.

The incidence of kidney stones within the US population is now 10%, and rising. Many patients present with small stones, primary or recurrent, do not indicate interventional stone removal. We previously described a new stone removal method employing selective application of acoustic radiation force, at diagnostic output levels, to reposition stones for passive clearance. In this method, an imaging array transducer transmits pulses for image guidance and focused pulses to reposition the stone. Here we propose a new flash imaging modality to visualize the focused pulse to confirm targeting on the stone. To visualize the focused beam, short pulses were phase‐delayed across the transducer aperture to transmit a focused wave, from which echo data were collected, beamformed, and overlaid on a B‐mode image. The beam profile is visible because echo amplitude is higher within the convergent, focal, and divergent regions. During experiment, a stone was placed within a tissue phantom simulating the kidney lower pole...

A modeling tool for therapeutic and imaging ultrasound applications.

The fields of therapeutic and imaging ultrasound have broad medical applications. However, the inherent complexity of biological media and the nonlinear nature of ultrasound propagation at therapeutic regimes make optimization and control of the therapy still a challenging task. An accurate modeling tool for solving multi‐dimensional ultrasound‐based problems in complex geometries that can greatly assist in the optimization and control of the treatment is presented. The model consists of 2‐D, 2.5‐D (cylindrical symmetry), and 3‐D coupled solutions for acoustic and elastic wave propagation in heterogeneous, lossy media complemented by the bioheat transfer equation for temperature estimation. It includes linear and nonlinear wave propagations, arbitrary frequency power law for attenuation, and can account for multiple reflections and backscattered fields. Work is underway for the inclusion of cavitation effects and the extension of the model to adaptive grid refinement and unstructured, deformable grids. Sa...

Acoustic virtual laboratory: A modeling tool for high‐intensity focused ultrasound applications

The field of high‐intensity focused ultrasound (HIFU) is emerging with strong potential and broad medical applications. Characterized by its ability to penetrate at depth inside the body without harming intervening tissue, therapeutic ultrasound has posed the basis for a new array of noninvasive therapies. However, the inherent complexity of biological media and the nonlinear nature of ultrasound propagation at HIFU regimes make optimization and control of the therapy still a challenging task. In this respect, an accurate modeling tool, the Acoustic Virtual Laboratory (AVL), will be presented for solving multidimensional HIFU problems in complex geometries that can greatly assists in predicting HIFU applications effects and, therefore, help in the optimization and control of the treatment. AVL consists of 2‐D, 2.5‐D (cylindrical symmetry), and 3‐D coupled solutions for acoustic and elastic wave propagation in heterogeneous, lossy, bubbly, and porous media with the bioheat equation for temperature estimati...