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Tom Matula

Director, CIMU Department & Senior Principal Physicist

Affiliate Assistant Professor, Electrical Engineering

Email

matula@apl.washington.edu

Phone

206-685-7654

Research Interests

Physical Acoustics, Cavitation, Sonoluminescence

Biosketch

Dr. Matula's research interest has been to understand cavitation and its effects in industrial and medical applications, and to transition technology to industry. His research areas include: - Ultrasound Contrast Agents - understanding their behavior in constrained vessels, and working towards using them to help improve targeting applications - Shock Wave Therapy - understanding and optimizing the application of shock waves for musculoskeletal and soft tissue injuries - Sonoluminescence - exploring the limits to energy concentration - Megasonic Cleaning - understanding and controlling cavitation cleaning in the semiconductor industry - Food Processing - understanding and controlling cavitation in food processing applications. Dr. Matula is a past-Chair of the Physical Acoustics Technical Committee of the Acoustical Society of America (ASA), a current Technical Program Committee member of the IEEE Ultrasonics Symposium, and a member of the International Society for Medical Shockwave Treatment (ISMST). He is now the Director of the Center for Industrial and Medical Ultrasound (CIMU) at APL-UW and Executive Director of the Center for Ultrasound-based Molecular Imaging and Therapy. In 2011 he served as General Chair, Acoustical Society of America Symposium in Seattle, Washington. Tom Matula spends time outside of work with family and friends, sailing Puget Sound, hiking, learning Italian, and playing music.

Education

B.S. Physics, California State University at Fresno, 1988

M.S. Physics, Washington State University, 1990

Ph.D. Physics, Washington State University, 1993

Publications

2000-present and while at APL-UW

Cardiovascular applications of therapeutic ultrasound

Nazer, B., E.P. Gerstenfeld, A. Hata, L.A. Crum, and T.J. Matula, "Cardiovascular applications of therapeutic ultrasound," J. Interv. Card. Electr., 39, 287-294, doi:10.1007/s10840-013-9845-z, 2014.

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1 Apr 2014

Ultrasound (US) has gained widespread use in diagnostic cardiovascular applications. At amplitudes and frequencies typical of diagnostic use, its biomechanical effects on tissue are largely negligible. However, these parameters can be altered to harness US's thermal and non-thermal effects for therapeutic indications. High-intensity focused ultrasound (HIFU) and extracorporeal shock wave therapy (ECWT) are two therapeutic US modalities which have been investigated for treating cardiac arrhythmias and ischemic heart disease, respectively. Here, we review the biomechanical effects of HIFU and ECWT, their potential therapeutic mechanisms, and pre-clinical and clinical studies demonstrating their efficacy and safety limitations. Furthermore, we discuss other potential clinical applications of therapeutic US and areas in which future research is needed.

Computational models of material interfaces for the study of extracorporeal shock wave therapy

Fagnan, K., R.J. Leveque, and T.J. Matula, "Computational models of material interfaces for the study of extracorporeal shock wave therapy," Comm. Appl. Math. Comp. Sci., 8, 159-194, doi: 10.2140/camcos.2013.8.159, 2013.

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22 Jan 2014

Extracorporeal shock wave therapy (ESWT) is a noninvasive treatment for a variety of musculoskeletal ailments. A shock wave is generated in water and then focused using an acoustic lens or reflector so the energy of the wave is concentrated in a small treatment region where mechanical stimulation in principle enhances healing. In this work we have computationally investigated shock wave propagation in ESWT by solving a Lagrangian form of the isentropic Euler equations in the fluid and linear elasticity in the bone using high-resolution finite volume methods. We solve a full three-dimensional system of equations and use adaptive mesh refinement to concentrate grid cells near the propagating shock. We can model complex bone geometries, the reflection and mode conversion at interfaces, and the propagation of the resulting shear stresses generated within the bone. We discuss the validity of our simplified model and present results validating this approach.

Micro/nanoparticles in ultrasound imaging and therapy

Matula, T.J., and H. Chen, "Micro/nanoparticles in ultrasound imaging and therapy," In Nanotechnology in Modern Medical Imaging and Interventions, X. Yang, ed., 143-164 (Nova Science Publishers, Hauppauge, NY, 2013.)

1 Dec 2013

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Mechanical characterization of ultrasonically synthesized microbubble shells by flow cytometry and AFM

Cavalieri, F., J.P. Best, C. Perez, J. Tu, F. Caruso, T.J. Matula, and M. Ashokkumar, "Mechanical characterization of ultrasonically synthesized microbubble shells by flow cytometry and AFM," ACS Appl. Mater. Interfaces, 5, 10,920-10,925, doi:10.1021/am403108y, 2013.

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14 Oct 2013

The mechanical properties of the shell of ultrasonically synthesized lysozyme microbubbles, LSMBs, were evaluated by acoustic interrogation and nanoindentation techniques. The Young's modulus of LSMBs was found to be 1.0 ± 0.3 MPa and 0.6 ± 0.1 MPa when analyzed by flow cytometry and AFM, respectively. The shell elasticity and Young's modulus were not affected by the size of the microbubbles (MBs). The hydrogel-like protein shell of LSMBs offers a softer, more elastic and viscous interface compared to lipid-shelled MBs. We show that the acoustic interrogation technique is a real-time, fast, and high-throughput method to characterize the mechanical characteristics of air-filled microbubbles coated by a variety of materials.

Mechanisms of microbubble–vessel interactions and induced stresses: A numerical study

Hosseinkhah, N., H. Chen, T.J. Matula, P.N. Burns, and K. Hynynen, "Mechanisms of microbubble–vessel interactions and induced stresses: A numerical study," J. Acoust. Soc. Am., 134, 1875-1885, doi:10.1121/1.4817843, 2013.

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1 Sep 2013

Oscillating microbubbles within microvessels could induce stresses that lead to bioeffects or vascular damage. Previous work has attributed vascular damage to the vessel expansion or bubble jet. However, ultra-high speed images of recent studies suggest that it could happen due to the vascular invagination. Numerical simulations of confined bubbles could provide insight into understanding the mechanism behind bubble–vessel interactions. In this study, a finite element model of a coupled bubble/fluid/vessel system was developed and validated with experimental data. Also, for a more realistic study viscoelastic properties of microvessels were assessed and incorporated into this comprehensive numerical model. The wall shear stress (WSS) and circumferential stress (CS), metrics of vascular damage, were calculated from these simulations. Resultant amplitudes of oscillation were within 15% of those measured in experiments (four cases). Among the experimental cases, it was numerically found that maximum WSS values were between 1.1–18.3 kPa during bubble expansion and 1.5–74 kPa during bubble collapse. CS was between 0.43–2.2 MPa during expansion and 0.44–6 MPa while invaginated. This finding confirmed that vascular damage could occur during vascular invaginations. Predicted thresholds in which these stresses are higher during vessel invagination were calculated from simulations.

Acoustic field characterization of the Duolith: Measurements and modeling of a clinical shock wave therapy device

Perez, C., H. Chen, and T.J. Matula, "Acoustic field characterization of the Duolith: Measurements and modeling of a clinical shock wave therapy device," J. Acoust. Soc. Am., 134, 1663-1674, doi:10.1121/1.4812885, 2013.

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1 Aug 2013

Extracorporeal shock wave therapy (ESWT) uses acoustic pulses to treat certain musculoskeletal disorders. In this paper the acoustic field of a clinical portable ESWT device (Duolith SD1) was characterized. Field mapping was performed in water for two different standoffs of the electromagnetic head (15 or 30 mm) using a fiber optic probe hydrophone. Peak positive pressures at the focus ranged from 2 to 45 MPa, while peak negative pressures ranged from –2 to –11 MPa. Pulse rise times ranged from 8 to 500 ns; shock formation did not occur for any machine settings. The maximum standard deviation in peak pressure at the focus was 1.2%, indicating that the Duolith SD1 generates stable pulses. The results compare qualitatively, but not quantitatively with manufacturer specifications. Simulations were carried out for the short standoff by matching a Khokhlov-Zabolotskaya-Kuznetzov equation to the measured field at a plane near the source, and then propagating the wave outward. The results of modeling agree well with experimental data. The model was used to analyze the spatial structure of the peak pressures. Predictions from the model suggest that a true shock wave could be obtained in water if the initial pressure output of the device were doubled.

Finite element modeling of acoustic wave propagation and energy deposition in bone during extracorporeal shock wave treatment

Wang, X., T.J. Matula, Y. Ma, Z. Liu, J. Tu, X. Guo, and D. Zhang, "Finite element modeling of acoustic wave propagation and energy deposition in bone during extracorporeal shock wave treatment," J. Appl. Phys., 113, 244901, doi:10.1063/1.4812232, 2013.

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1 Jun 2013

It is well known that extracorporeal shock wave treatment is capable of providing a non-surgical and relatively pain free alternative treatment modality for patients suffering from musculoskeletal disorders but do not respond well to conservative treatments. The major objective of current work is to investigate how the shock wave (SW) field would change if a bony structure exists in the path of the acoustic wave. Here, a model of finite element method (FEM) was developed based on linear elasticity and acoustic propagation equations to examine SW propagation and deflection near a mimic musculoskeletal bone. High-speed photography experiments were performed to record cavitation bubbles generated in SW field with the presence of mimic bone. By comparing experimental and simulated results, the effectiveness of FEM model could be verified and strain energy distributions in the bone were also predicted according to numerical simulations. The results show that (1) the SW field will be deflected with the presence of bony structure and varying deflection angles can be observed as the bone shifted up in the z-direction relative to SW geometric focus (F2 focus); (2) SW deflection angels predicted by the FEM model agree well with experimental results obtained from high-speed photographs; and (3) temporal evolutions of strain energy distribution in the bone can also be evaluated based on FEM model, with varied vertical distance between F2 focus and intended target point on the bone surface. The present studies indicate that, by combining MRI/CT scans and FEM modeling work, it is possible to better understand SW propagation characteristics and energy deposition in musculoskeletal structure during extracorporeal shock wave treatment, which is important for standardizing the treatment dosage, optimizing treatment protocols, and even providing patient-specific treatment guidance in clinic.

Modeling complicated rheological behaviors in encapsulating shells of lipid-coated microbubbles accounting for nonlinear changes of both shell viscosity and elasticity

Li, Q., T.J. Matula, J. Tu, X. Guo, and D. Zhang, "Modeling complicated rheological behaviors in encapsulating shells of lipid-coated microbubbles accounting for nonlinear changes of both shell viscosity and elasticity," Phys. Med. Biol., 58, 985-998, doi:10.1088/0031-9155/58/4/985, 2013.

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21 Feb 2013

It has been accepted that the dynamic responses of ultrasound contrast agent (UCA) microbubbles will be significantly affected by the encapsulating shell properties (e.g., shell elasticity and viscosity). In this work, a new model is proposed to describe the complicated rheological behaviors in an encapsulating shell of UCA microbubbles by applying the nonlinear 'Cross law' to the shell viscous term in the Marmottant model. The proposed new model was verified by fitting the dynamic responses of UCAs measured with either a high-speed optical imaging system or a light scattering system. The comparison results between the measured radius–time curves and the numerical simulations demonstrate that the 'compression-only' behavior of UCAs can be successfully simulated with the new model. Then, the shell elastic and viscous coefficients of SonoVue microbubbles were evaluated based on the new model simulations, and compared to the results obtained from some existing UCA models. The results confirm the capability of the current model for reducing the dependence of bubble shell parameters on the initial bubble radius, which indicates that the current model might be more comprehensive to describe the complex rheological nature (e.g., 'shear-thinning' and 'strain-softening') in encapsulating shells of UCA microbubbles by taking into account the nonlinear changes of both shell elasticity and shell viscosity.

Preliminary observations on the spatial correlation between short-burst microbubble oscillations and vascular bioeffects

Chen, H., A.A. Brayman, A.P. Evan, and T.J. Matula, "Preliminary observations on the spatial correlation between short-burst microbubble oscillations and vascular bioeffects," Ultrasound Med. Biol., 12, 2151-2162, doi:10.1016/j.ultrasmedbio.2012.08.014, 2012.

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1 Dec 2012

The objective of this preliminary study was to examine the spatial correlation between microbubble (MB)-induced vessel wall displacements and resultant microvascular bioeffects. MBs were injected into venules in ex vivo rat mesenteries and insonated by a single short ultrasound pulse with a center frequency of 1 MHz and peak negative pressures spanning the range of 1.5%u20135.6 MPa. MB and vessel dynamics were observed under ultra-high speed photomicrography. The tissue was examined by histology or transmission electron microscopy for vascular bioeffects. Image registration allowed for spatial correlation of MB-induced vessel wall motion to corresponding vascular bioeffects, if any. In cases in which damage was observed, the vessel wall had been pulled inward by more than 50% of the its initial radius. The observed damage was characterized by the separation of the endothelium from the vessel wall. Although the study is limited to a small number of observations, analytic statistical results suggest that vessel invagination comprises a principal mechanism for bioeffects in venules by microbubbles.

Characteristic microvessel relaxation timescales associated with ultrasound-activated microbubbles

Chen, H., A.A. Brayman, and T.J. Matula, "Characteristic microvessel relaxation timescales associated with ultrasound-activated microbubbles," Appl. Phys. Lett., 101, 163704, doi:10.1063/1.4761937, 2012.

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15 Oct 2012

Ultrasound-activated microbubbles were used as actuators to deform microvessels for quantifying microvessel relaxation timescales at megahertz frequencies. Venules containing ultrasound contrast microbubbles were insonified by short 1 MHz ultrasound pulses. Vessel wall forced-deformations were on the same microsecond timescale as microbubble oscillations. The subsequent relaxation of the vessel was recorded by high-speed photomicrography. The tissue was modeled as a simple Voigt solid. Relaxation time constants were measured to be on the order of ~10 µs. The correlation coefficients between the model and 38 data sets were never lower than 0.85, suggesting this model is sufficient for modeling tissue relaxation at these frequencies. The results place a bound on potential numerical values for viscosity and elasticity of venules.

Acoustic and optical characterization of ultrasound contrast agents via flow cytometry

Perez, C., A. Brayman, J. Tu, J. Swalwell, H. Chen, and T. Matula, "Acoustic and optical characterization of ultrasound contrast agents via flow cytometry," J. Acoust. Soc. Am., 132, 1906, 2012.

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1 Sep 2012

Characterizing ultrasound contrast agents (UCAs) involve measuring the size and population distribution. However, these instruments do not allow for characterization of shell properties, which are important for (1) stability to administration and circulation throughout the vasculature; (2) UCA response to ultrasound; and (3) conjugating ligands for molecular imaging. Thus it is critical to understand the physical and rheological properties of shells. We previously developed a light scattering technique to characterize the shell properties of UCAs [Guan and Matula, JASA, vol. 116(5), 2004; Tu, et al., IEEE Trans. Ultrason., Ferroelec., and Freq. Control, vol. 58(5), 2011]. The most recent manifestation involves a flow cytometer modified with a custom square quartz flow cell in place of the standard nozzle and fluid jet. Acoustic coupling to the carrier sheath fluid and UCA samples occurred through a PZT bonded to one side of the flow cell. The PZT-driven UCA oscillations were processed and fitted to the Marmottant UCA model. Shell properties for UCAs (including Definity, Optison, SonoVue, and even homemade bubbles) were determined. The focus of this talk will be on pressure calibration and additional measurements of unpublished data from Optison and homemade bubbles.

Observations of translation and jetting of ultrasound-activated microbubbles in mesenteric microvessels

Chen, H., A.A. Brayman, W. Kreider, M.R. Bailey, and T.J. Matula, "Observations of translation and jetting of ultrasound-activated microbubbles in mesenteric microvessels," Ultrasound Med. Biol., 37, 2139-2148, doi:10.1016/j.ultrasmedbio.2011.09.013, 2011.

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1 Dec 2011

High-speed photomicrography was used to study the translational dynamics of single microbubbles in microvessels of ex vivo rat mesenteries. The microbubbles were insonated by a single 2 microsecond ultrasound pulse with a center frequency of 1 MHz and peak negative pressures spanning the range of 0.8-4 MPa. The microvessel diameters ranged from 10-80 micrometers. The high-speed image sequences show evidence of ultrasound-activated microbubble translation away from the nearest vessel wall; no microbubble showed a net translation toward the nearest vessel wall. Microbubble maximum translation displacements exceeded 20 micrometers. Microjets with the direction of the jets identifiable were also observed; all microjets appear to have been directed away from the nearest vessel wall. These observations appear to be characteristic of a strong coupling between ultrasound-driven microbubbles and compliant microvessels. Although limited to mesenteric tissues, these observations provide an important step in understanding the physical interactions between microbubbles and microvessels.

Microbubble sizing and shell characterization using flow cytometry.

Tu, J., J.E. Swalwell, D. Giraud, W. Cui, W. Chen, and T.J. Matula, "Microbubble sizing and shell characterization using flow cytometry." IEEE Trans. Ultrason. Ferr. Freq. Control, 58, 955-963, doi:10.1109/TUFFC.2011.1896, 2011.

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1 May 2011

Experiments were performed to size, count, and obtain shell parameters for individual ultrasound contrast microbubbles using a modified flow cytometer. Light scattering was modeled using Mie theory, and applied to calibration beads to calibrate the system. The size distribution and population were measured directly from the flow cytometer. The shell parameters (shear modulus and shear viscosity) were quantified at different acoustic pressures (from 95 to 333 kPa) by fitting microbubble response data to a bubble dynamics model. The size distribution of the contrast agent microbubbles is consistent with manufacturer specifications. The shell shear viscosity increases with increasing equilibrium microbubble size, and decreases with increasing shear rate. The observed trends are independent of driving pressure amplitude. The shell elasticity does not vary with microbubble size. The results suggest that a modified flow cytometer can be an effective tool to characterize the physical properties of microbubbles, including size distribution, population, and shell parameters.

Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

Chen, H., A. Brayman, A. Evan, and T. Matula,"Mechanisms for microvascular damage induced by ultrasound-activated microbubbles," Proceedings, International Society for Therapeutic Ultrasound Symposium 1481, New York, New York, U.S.A., 11-13 April, 41-46, doi:http://dx.doi.org/10.1063/1.4757308 (AIP, 2011).

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11 Apr 2011

To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8%u20134 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

Characterization of the acoustic field of a clinical electromagnetic shockwave therapy device

Perez, C., H. Chen, and T.J. Matula, "Characterization of the acoustic field of a clinical electromagnetic shockwave therapy device," J. Acoust. Soc., 129, 2679, doi:10.1121/1.3588983, 2011.

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1 Apr 2011

Extracorporeal shockwave therapy devices are used in clinical settings for different medical applications such as orthopedics and urology. Having several clinical devices out in the field creates a challenge when comparing treatments and energy deposition mechanisms between different devices. In this work, the field of an electromagnetic shockwave device (Duolith SD1 T-Top, Storz) was characterized using a fiber optic hydrophone (FOPH2000, RP Acoustics). The acoustic field from two hand-held probes was measured: one probe was focused (with different length coupling cones) and the second one was a ballistic (radial therapy) probe. With the focused probe, measured pressures ranged from 45 MPa peak-positive to 12 MPa peak-negative. Axial and transverse beam profiles were acquired while analyzing the peak-positive and peak-negative pressures at each machine energy level and pulse repetition frequency. The focused source showed an extended -6 dB peak-positive focal region along the axis of propagation and shorter in the orthogonal planes to the propagation (30 x 3 x 3 mm3). Linear scans along the axis of propagation showed quadratic decay distal to the focus. Measured peak-negative pressures were higher pre-focal than post-focal. The results compared qualitatively, but not quantitatively with manufacturer specifications.

Comparison of single bubble collapse and cluster collapse in a high pressure vessel

Matula, T., B. MacConnaghy, L. Crum, and F. Gaitan, "Comparison of single bubble collapse and cluster collapse in a high pressure vessel," J. Acoust. Soc., 129, 2619, doi:10.1121/1.3588702, 2011.

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1 Apr 2011

Details of the collapse of single bubbles and bubble clusters leading to the emission of a shock wave under high overpressures will be presented. Ultrahigh speed photography captures the events at various stages of bubble (or cluster) growth and collapse. Shock waves are observed millimeters from the collapse center, suggesting very violent conditions at the source. For example, shock waves emitted by single-bubble sonoluminescence can reach 3 mm/microsecond about 5 micrometers from the bubble center. With a cluster, we observe shock waves at this speed over 500 micrometers from the center. The strength of the collapse is estimated by measuring the emitted shock wave velocity from images taken with the ultrahigh speed imaging system. Cluster collapses can be much stronger than from single bubbles. Cluster collapse appears to be initiated by the collapse of outer bubbles.

High speed imaging of shockwave-induced dynamics of cavitation bubbles and vessel wall

Chen, H., C. Perez, A.A. Brayman, and T.J. Matula, "High speed imaging of shockwave-induced dynamics of cavitation bubbles and vessel wall," J. Acoust. Soc. Am., 129, 2374, doi: 10.1121/1.3587689, 2011.

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1 Apr 2011

High speed optical imaging under a microscope (high speed photomicrography) was used to observe shockwave-induced bubble dynamics and bubble-induced vascular dynamics. Ultrasound contrast agent microbubbles, serving as cavitation nuclei, were injected into the vessels of ex vivo rat mesentery. The bubbles were then insonated by focused shock wave pulses with peak positive pressures of 42 MPa and peak negative pressures of 10 MPa, generated by an electromagnetic shockwave source (Storz Duolith). The recorded images were analyzed to obtain bubble radius-time curves, vessel wall displacement, as well as their corresponding velocities. In general, bubble dynamics induces vessel distention (outward displacement of vessel wall) and invagination (displacement of vessel wall into the lumen). Comparisons of shockwave-induced dynamics with HIFU-induced dynamics will also be presented.

The effects of hydrostatic pressure on conditions in and near a collapsing cavitation bubble

Church, C.C., D.F. Gaitan, Y.A. Pishchalnikov, and T.J. Matula, "The effects of hydrostatic pressure on conditions in and near a collapsing cavitation bubble," J. Acoust. Soc. Am., 129, 2620, doi: 10.1121/1.3588704, 2011.

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1 Apr 2011

It has long been understood that the conditions within a collapsing cavitation bubble become more extreme as hydrostatic pressure increases, but quantification of these conditions requires estimating the temperature, pressure, and density of the plasma in the bubble, a difficult task. To provide this information, we conducted numerical simulations using the plasma physics hydrocode HYADES, a 1-D, three-temperature, Lagrangean hydrodynamics, and energy transport code. The contents of a bubble at the center of a sphere of water at 1-3000 bars were specified at time = 0, and the bubble was driven by a spherically converging pressure wave of various frequencies (2.5-26 kHz) and amplitudes (10-3000 bars). Results were obtained for temperature, pressure, and density within and immediately outside the bubble. Calculations for bubble radius and the velocity and amplitude of the radiated shock wave compared well with experimental measurements at modest hydrostatic pressures (1-300 bars). At higher pressures, the maximum temperature within the bubble increases above 100 eV, the shock amplitude becomes greater than 1 Gbar, and its propagation speed is up to Mach 100. Also, the shock front heats the fluid, stimulating photon emissions in the liquid.

Transient cavitation in high-quality factor resonators at high static pressures

Gaitan, D.F., Y.A. Pishchalnikov, T.J. Matula, C.C. Church, J. Gutierrez, C. Scott, R.G. Holt, and L.A. Crum, "Transient cavitation in high-quality factor resonators at high static pressures," J. Acoust. Soc., 129, 2619, doi:10.1121/1.3588701, 2011.

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1 Apr 2011

Cavitation collapse can generate intense concentrations of energy, sufficient to erode even the hardest metals and to generate light emissions visible to the naked eye [sonoluminescence (SL)]. The phenomenon of 'single bubble sonoluminescence' (SBSL) in which a single stable cavitation bubble radiates light flashes each acoustic cycle typically occurs near 0.1 MPa static pressures. Impulse Devices, Inc. has developed a new tool for the study of SL and cavitation: a high quality factor, spherical resonator capable of achieving acoustic cavitation at ambient pressures in excess of 30 MPa. This system generates bursts of violent inertial cavitation events lasting only a few milliseconds (hundreds of acoustic cycles). Cavitation observed in this system is characterized by flashes of light with intensities up to 1000 times brighter than SBSL flashes as well as spherical shock waves with amplitudes exceeding 100 MPa (1000 bars) at 1 cm from the cavitation center. Computer simulations indicate shock wave amplitudes near the collapsing bubble around 1-10 TPa (10-100 mbars) and liquid temperatures on the order of 5000 K, possibly causing the liquid to become opaque. The implications of these extreme conditions on SL emission will be discussed.

Blood vessel deformations on microsecond time scales by ultrasonic cavitation

Chen, H., W. Kreider, A.A. Brayman, M.R. Bailey, and T.J. Matula, "Blood vessel deformations on microsecond time scales by ultrasonic cavitation," Phys. Rev. Lett., 106, 034301, doi:10.1103/PhysRevLett.106.034301, 2011.

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18 Jan 2011

Transient interactions among ultrasound, microbubbles, and microvessels were studied using high-speed photomicrography. We observed liquid jets, vessel distention (motion outward against the surrounding tissue), and vessel invagination (motion inward toward the lumen). Contrary to current paradigms, liquid jets were directed away from the nearest vessel wall and invagination exceeded distention. These observations provide insight into the mechanics of bubble-vessel interactions, which appear to depend qualitatively upon the mechanical properties of biological tissues.

Vascular damage by ultrasound-activated microbubble induced vessel invagination

Chen, H., A. Brayman, A. Evan, and T. Matula, "Vascular damage by ultrasound-activated microbubble induced vessel invagination," Proceedings, IEEE International Ultrasonics Symposium, San Diego, USA, 11-14 October, 678-681, doi:10.1109/ULTSYM.2010.5935994 (IEEE, 2010).

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11 Oct 2010

Vascular bioeffects produced by ultrasound contrast agent microbubbles are primarily manifested as damage to microvessels. The objective of this work is to directly observe the transient dynamics of bubble-vessel interactions and correlate the observed interactions with associated vascular damage. Microbubbles were perfused into microvessels in ex vivo rat mesenteries and then excited by a single 2 us long ultrasound pulse at 1 MHz. Meanwhile, 14 high-speed photomicrographic images were acquired using 50 ns shutter speeds. The targeted region was then examined by histology and transmission electron microscopy (TEM). Image registration was used to identify the specific vessels that the corresponding high-speed images were captured. The recorded high-speed images revealed that bubble-vessel interactions caused vessel wall distention (motion outward against the surrounding tissue) and invagination (motion inward toward the lumen). Invagination exceeding distention was observed in 60 out of 70 cases. Significant vessel invagination was correlated with vascular damage that was characterized by a separation of the endothelium from the surrounding tissue as revealed by both the histology and TEM analyses. The separation of the endothelium from the surrounding tissue is consistent with damage caused by tensile stresses at the vessel walls that lead to vessel invagination. This suggests that invagination may be an important mechanism by which microbubbles cause vascular damage.

The peculiar interactions of microbubbles and microvessels

Chen, H., A. Brayman, and T. Matula, "The peculiar interactions of microbubbles and microvessels," Proceedings, 20th International Congress on Acoustics, Sydney, Australia, 23-27 August, 1-5, (ICA, 2010).

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23 Aug 2010

The application of microbubbles for both diagnostic macro- and molecular imaging and therapeudic ultrasound requires an understanding of the coupled interactions involving microbubble dynamics with the surrounding compliant microvessel. In this study, ultra-high speed microphotography was used to directly observe transient behaviors of microbubbles in microvessels of ex vivo rat mesenteries. Definity® microbubbles were perfused through the vasculature, and then excited by a 2-µs long ultrasound pulse with a center frequency of 1 MHz with peak negative pressures between 0.8-7.2 MPa. These amplitudes span the diagnostic to therapeutic pressure levels. During insonation, ultrahigh speed images were captured with 50-ns exposure time and 150-ns or 300-ns interframe time. The recorded images show a wonderful assortment of microbubble dynamics, including oscillation, translation, jetting, coalescence and fragmentation. These microbubble behaviors were coupled with the dynamic responses of the vessel wall, which showed distention, invagination, and even rupture.

Blood vessel rupture by cavitation

Chen, H., A.A. Brayman, M.R. Bailey, and T.J. Matula, "Blood vessel rupture by cavitation," Urol. Res., 38, 321-326, doi:10.1007/s00240-010-0302-5, 2010.

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2 Aug 2010

Cavitation is thought to be one mechanism for vessel rupture during shock wave lithotripsy treatment. However, just how cavitation induces vessel rupture remains unknown. In this work, a high-speed photomicrography system was set up to directly observe the dynamics of bubbles inside blood vessels in ex vivo rat mesenteries. Vascular rupture correlating to observed bubble dynamics were examined by imaging bubble extravasation and dye leakage. The high-speed images show that bubble expansion can cause vessel distention, and bubble collapse can lead to vessel invagination. Liquid jets were also observed to form. Our results suggest that all three mechanisms, vessel distention, invagination and liquid jets, can contribute to vessel rupture.

Transient cavitation in high-quality-factor resonators at high static pressures

Gaitan, D.F., R.A. Tessien, R.A. Hiller, J. Gutierrez, C. Scott, H. Tardif, B. Callahan, T.J. Matula, L.A. Crum, R.G. Holt, C.C. Church, and J.L. Raymond, "Transient cavitation in high-quality-factor resonators at high static pressures," J. Acoust. Soc. Am., 127, 3456-3465, 2010.

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1 Jun 2010

It is well known that cavitation collapse can generate intense concentrations of mechanical energy, sufficient to erode even the hardest metals and to generate light emissions visible to the naked eye [sonoluminescence (SL)]. Considerable attention has been devoted to the phenomenon of "single bubble sonoluminescence" (SBSL) in which a single stable cavitation bubble radiates light flashes each and every acoustic cycle. Most of these studies involve acoustic resonators in which the ambient pressure is near 0.1 MPa (1 bar), and with acoustic driving pressures on the order of 0.1 MPa.

This study describes a high-quality factor, spherical resonator capable of achieving acoustic cavitation at ambient pressures in excess of 30 MPa (300 bars). This system generates bursts of violent inertial cavitation events lasting only a few milliseconds (hundreds of acoustic cycles), in contrast with the repetitive cavitation events (lasting several minutes) observed in SBSL; accordingly, these events are described as "inertial transient cavitation." Cavitation observed in this high pressure resonator is characterized by flashes of light with intensities up to 1000 times brighter than SBSL flashes, as well as spherical shock waves with amplitudes exceeding 30 MPa at the resonator wall. Both SL and shock amplitudes increase with static pressure.

Estimating the shell parameters of SonoVue microbubbles using light scattering

Tu, J., J. Guan, Y. Qiu, and T.J. Matula, "Estimating the shell parameters of SonoVue microbubbles using light scattering," J. Acoust. Soc. Am., 126, 2954-2962, doi:10.1121/1.3242346, 2009.

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1 Dec 2009

Experiments were performed to measure the dynamical response of individual SonoVue® microbubbles subjected to pulsed ultrasound. Three commonly used bubble dynamic models (i.e., Hof's, Sarkar's, and linearized Marmottant's models) were compared to determine the most appropriate model for fitting to the experimental data. The models were evaluated against published optical microscopy data. The comparison suggests that it is difficult to rank these models for lipid-shelled microbubbles undergoing small-amplitude oscillations, because under these conditions the shell parameters in these models are closely related. A linearized version of the Marmottant model was used to estimate the shell parameters (i.e., shear modulus and shear viscosity) of SonoVue® microbubbles from the experimental light scattering data, as a function of ambient microbubble radius. The SonoVue® microbubble shell elasticity and dilatational viscosity increase with ambient bubble radius, in agreement with previously published data. The results suggest that light scattering, used in conjunction with one of several popular bubble dynamics models, is effective at characterizing microbubble response and evaluating shell parameters.

Observations of bubble-vessel interaction in ultrasound fields

Chen, H., J. Kucewicz, W. Kreider, A. Brayman, M. Bailey, and T. Matula, "Observations of bubble-vessel interaction in ultrasound fields," Proceedings, IEEE International Ultrasonics Symposium, Rome, Italy, 20-23 September, 23-26, doi:10.1109/ULTSYM.2009.5441512 (IEEE, 2009).

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20 Sep 2009

Interactions between bubbles and nearby boundaries have been studied for some time; however, the direct interactions between bubbles and tissue boundaries, especially blood vessel walls, have not been studied to a large extent. In this work highspeed microscopy was used to study the dynamical interaction between microbubbles and microvessels of ex vivo rat mesentery subjected to a single pulse of ultrasound. Ultrasound contrast agent microbubbles were injected into the blood vessels of rat mesentery subsequent to having the blood flushed out. India ink was used to increase the contrast between microvessels and surrounding tissues. Tissue samples were aligned at the focus of both an ultrasound transducer with a center frequency of 1 MHz and an inverted microscope coupled to a high speed camera. Fourteen high-speed microphotographic images were acquired for each experiment using 50 ns shutter speeds. Observations of the coupled dynamics between bubbles and vessels ranging from 10 micrometer to 100 micrometer diameters under the exposure of ultrasound of peak negative pressure within the range of 1 MPa to 7.8 MPa suggest that the vessel wall dilates during bubble expansion, and invaginates during bubble contraction. A significant finding is that the ratio of invagination to distension is usually >1 and large circumferential strains can be imposed on the vessel wall during vessel invagination. In addition, the surrounding tissue response was also quantified. Based on these studies, we hypothesize that vessel invagination is the dominant mechanism for the initial induction of vascular damage via cavitation.

Potential mechanisms for vessel invagination caused by bubble oscillations

Kreider, W., H. Chen, M.R. Bailey, A.A. Brayman, and T.J. Matula, "Potential mechanisms for vessel invagination caused by bubble oscillations," In Proceedings, IEEE International Ultrasonics Symposium, Rome, Italy, 20-23 September, 353-356, doi:10.1109/ULTSYM.2009.5441744 (IEEE, 2009).

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20 Sep 2009

In medical ultrasound, acoustically excited bubbles are relevant to both imaging and therapeutic applications and have been implicated in causing vascular damage. A current paradigm for understanding interactions between bubbles and vessels considers the distention of small vessels and the impingement of bubble jets on vessel walls to be the most likely damage mechanisms. However, recent high-speed photographs suggest a type of interaction that is characterized by a prominent invagination of the vessel wall (i.e., an inward deflection toward the lumen) that appears to exceed any accompanying distention.

To elucidate mechanisms for such behavior, a confined flow geometry between an oscillating bubble and a nearby boundary is modeled and compared to fully spherical flow. From a Bernoulli-type equation for an incompressible and inviscid liquid, the pressure attributable to a bubble at a nearby boundary is found to become biased toward negative values as the flow becomes more confined and less spherical. Such negative values are consistent with invagination. Using radial bubble dynamics inferred from a high-speed photographic sequence of a bubble in a vessel, the aforementioned model was used to simulate the pressure radiated by the bubble at the vessel wall. At the 1 MHz acoustic frequency, the simulated negative pressure is 2.5 times the positive pressure; in turn, the observed vessel displacement inward was about 6 times the corresponding outward displacement.

Direct observation of microbubble interactions with ex vivo microvessels

Chen, H., A.A. Brayman, M.R. Bailey, and T.J. Matula, "Direct observation of microbubble interactions with ex vivo microvessels," J. Acoust. Soc. Am., 125, 2680, 2009.

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1 Apr 2009

The interaction between microbubbles with tissue is poorly understood. Experimental evidence, supported by numerical simulations, suggests that bubble dynamics is highly constrained within blood vessels. To investigate this further, a high-speed microimaging system was set up to study the effects of acoustically activated microbubbles on microvessels in ex vivo rat mesentery tissues. The microbubble-perfused tissues were placed under a microscope and insonified with MHz ultrasound. A variety of interactions was observed by a high-speed camera: arterioles, venules, and capillaries were all recorded to dilate and invaginate by activated microbubbles.

For small diameter microvessels, dilation and invagination were nearly symmetric, and bubble-induced rupture of the vessel was observed at high pressure. For larger microvessels, the portion of the vessel nearest the bubble coupled the strongest to the bubble dynamics, and the extent of dilation was smaller than invagination. Tissue jetting toward the bubble was recorded in many cases. The interaction of multiple bubbles inside microvessels was also observed. Bubble oscillation, vessel wall velocity, and tissue jet velocity were quantitatively measured. Invagination of vessel walls, especially tissue jetting, may be the major mechanism for tissue injury by a bubble.

Microbubble dynamics in microvessels: Observations of microvessel dilation, invagination and rupture

Chen, H., A. Brayman, and T. Matula, "Microbubble dynamics in microvessels: Observations of microvessel dilation, invagination and rupture," IEEE International Ultrasonics Symposium, Beijing, China, 2-5 November, 1163-1166, doi:10.1109/ULTSYM.2008.0280 (IEEE, 2008).

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2 Nov 2008

Understanding the interaction of acoustically activated microbubbles with small blood vessels is important for designing better imaging schemes, and for targeting and drug delivery applications. To understand the fundamental mechanisms of this interaction, high-speed microscopy was used to observe microbubble dynamics in microvessels of ex vivo rat mesenteries exposed to a single pulse of ultrasound with a center frequency of 1 MHz and peak negative pressure (PNP) of 1.2 MPa or 11 MPa. It was found that microbubble oscillation caused adjacent microvessel dilation, invagination and even rupture on a microsecond time scale. In small microvessels, microbubble contacted with the vessel wall during expansion under both low and high pressure levels, and microvessel dilation generated by microbubble expansion was larger than invagination induced by bubble collapse. Specifically, under 11 MPa PNP insonation, a small microvessel (17 mum) dilated to 2.7times, and then invaginated to 0.4times of its original diameter, followed by extravasation of re-expanding daughter microbubbles indicating that the microvessel had been ruptured. For large microvessels, microbubbles did not contact with the vessel wall during expansion, and generated much less dilation than invagination at both pressure levels. In one case, a large microbubble caused the wall of a 100 mum microvessel to form a jet-like structure during invagination.

Evaluation of a shock wave induced cavitation activity both in vitro and in vivo

Tu, J., T.J. Matula, M.R. Bailey, and L.A. Crum, "Evaluation of a shock wave induced cavitation activity both in vitro and in vivo," Phys. Med. Biol., 52, 5933-5944, 2007.

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1 Oct 2007

This study evaluated the cavitation activity induced by shock wave (SW) pulses, both in vitro and in vivo, based on the area measurements of echogenic regions observed in B-mode ultrasound images. Residual cavitation bubble clouds induced by SW pulses were detected as echogenic regions in B-mode images. The temporal evolution of residual bubble clouds, generated by SWs with varying lithotripter charging voltage and pulse repetition frequency (PRF), was analyzed by measuring the time-varying behaviors of the echogenic region areas recorded in B-mode images. The results showed that (1) the area of SW-induced echogenic regions enlarged with increased SW pulse number; (2) echogenic regions in the B-mode images dissipated gradually after ceasing the SWs, which indicated the dissolution of the cavitation bubbles; and (3) larger echogenic regions were generated with higher charging voltage or PRF.

Noncontact transportation in water using ultrasonic traveling waves

Nomura, S., Matula, T.J., J. Satonobu, and L.A. Crum, "Noncontact transportation in water using ultrasonic traveling waves," J. Acoust. Soc. Am., 121, 1332-1336, 2007.

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1 Mar 2007

A noncontact transport experiment in water using ultrasonic traveling waves was investigated. Acrylic, aluminum, and brass discs were used as test objects. Traveling waves were generated using two ultrasonic transducers attached at the ends of a vibrating plate. One side was used as the wave-source side and the other side was used as the wave-receiving side. Acrylic plates cemented to the sides of the vibrating plate formed a tank to hold water. Object transportation was accomplished by adding a small amount of water to the vibrating structure. The transport velocity of floating objects in water is faster than for floating transport in air because of buoyancy. The transport velocity of an object depends on water height. The minimum value of the velocity occurs when the disc thickness is equal to the water height. The transport velocity increases as the height of water increases. For very shallow depths, the largest velocity is obtained when cavitation-induced streaming occurs.

Shock-wave energy deflection due to the presence of bone

Matula, T., J. Tu, M.Bailey, K. Fagnan, and R. LeVeque, "Shock-wave energy deflection due to the presence of bone," J. Acoust. Soc. Am., 120, 3109, 2006.

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1 Nov 2006

The physical interaction of shock waves with musculoskeletal tissues is inherently different from other high-pressure acoustic therapies. Whereas high-intensity focused ultrasound and lithotripsy focus their energy in regions of soft tissue, musculoskeletal shock-wave therapy (SWT) involves focusing shock waves (SWs) near or at bones. The presence of bones will cause reflection, refraction, and diffraction of acoustic energy. In our analysis of cavitation generated during clinical SWT treatment, we noticed that the cavitation was occurring away from the SW focus. We confirmed this by performing an in vitro experiment on a bone embedded in gel. We also quantified the deflection angle as a function position near a bone in water: A talus was manufactured using rapid prototyping. It was placed near the focus of an electrohydraulic SW device. To visualize the pressure field, a high-speed camera imaged the cavitation field generated around the focus. As the bone was moved closer to the focus, the cavitation field (and thus, the pressure field) deflected away from the bone. The deflection angle was measured as a function of relative distance between the bone and focus. Numerical simulations were performed to model the deflection of energy away from the bone.

Intravascular inertial cavitation activity detection and quantification in vivo with Optison

Tu, J., J.H. Hwang, T.J. Matula, A.A. Brayman, and L.A. Crum, "Intravascular inertial cavitation activity detection and quantification in vivo with Optison," Ultrasound Med. Biol., 32, 1601-1609, 2006.

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1 Oct 2006

Inertial cavitation (IC) is an important mechanism by which ultrasound (US)-induced bioeffects can be produced. It has been reported that US-induced in vitro mechanical bioeffects with the presence of ultrasound contrast agents (UCAs) are highly correlated with quantified IC "dose" (ICD: cumulated root-mean-squared broadband noise amplitude in the frequency domain). The ICD has also been used to quantify IC activity in ex vivo perfused rabbit ear vessels. The in vivo experiments reported here using a rabbit ear vessel model were designed to: (1) detect and quantify IC activity in vivo within the constrained environment of rabbit auricular veins with the presence of Optison and (2) measure the temporal evolution of microbubble IC activity and the ICD generated during insonation treatment, as a function of acoustic parameters. Preselected regions-of-interest (ROI) in the rabbit ear vein were exposed to pulsed focused US (1.17 MHz, 1 Hz PRF). Experimental acoustic variables included peak rarefaction pressure amplitude ([PRPA]: 1.1, 3.0, 6.5 or 9.0 MPa) and pulse length (20, 100, 500 or 1000 cycles). ICD was quantified based on passive cavitation detection (PCD) measurements. The results show that: (1) after Optison injection, the time to onset of measurable microbubble IC activity was relatively consistent, approximately 20 s; (2) after reaching its peak value, the IC activity decayed exponentially and the half-life decay coefficient (t(1/2)) increased with increasing PRPA and pulse length; and (3) the normalized ICD generated by pulsed US exposure increased significantly with increasing PRPA and pulse length.

Acoustic cavitation and medical ultrasound

Kreider, W., L. Crum, M. Bailey, T. Matula, V. Khokhlova, and O. Sapozhnikov, "Acoustic cavitation and medical ultrasound," Proceedings, Sixth International Conference on Cavitation, 11-15 September, Wageningen, The Netherlands (MARIN, The Netherlands, 2006)(CD-ROM).

11 Sep 2006

New devices and old pitfalls in shock wave therapy

Bailey, M.R., T.J. Matula, O.A. Sapozhnikov, R.O. Cleveland, Yu A. Pishchalnikov, and J.A. McAteer, "New devices and old pitfalls in shock wave therapy," Proceedings, Fifth International Symposium on Therapeutic Ultrasound, edited by G.T. Clement, N.J. McDannold, and K. Hynynen, AIP Conference Proceedings, 829, 380-384, doi:10.1063/1.2205501, 2006.

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8 May 2006

Shock waves are now used to treat a variety of musculoskeletal indications and the worldwide demand for shock wave therapy (SWT) is growing rapidly. It is a concern that very little is known about the mechanisms of action of shock waves in SWT. The technology for SWT devices is little changed from that of shock wave lithotripters developed for the treatment of urinary stones. SWT devices are engineered on the same acoustics principles as lithotripters, but the targets of therapy for SWT and shock wave lithotripsy (SWL) are altogether different. For SWT to achieve its potential as a beneficial treatment modality it will be necessary to determine precisely how SWT shock waves interact with biological targets. In addition, for SWT to evolve, the future design of these devices should be approached with caution, and lithotripsy may serve as a useful model. Indeed, there is a great deal to be learned from the basic research that has guided the development of SWL.

Inertial cavitation dose produced in ex vivo rabbit ear arteries with Optison by 1-MHz pulsed ultrasound

Tu, J., T.J. Matula, A.A. Brayman, and L.A. Crum, "Inertial cavitation dose produced in ex vivo rabbit ear arteries with Optison by 1-MHz pulsed ultrasound," Ultrasound Med. Biol., 32, 281-288, 2006.

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1 Feb 2006

Previous in vitro studies have shown that ultrasound-induced mechanical bioeffects with contrast agents present are highly correlated with inertial cavitation (IC) "dose" (Chen et al. 2003a, 2003c). The ex vivo experiments conducted here addressed the following hypotheses: 1. IC activity can be generated by insonating perfused rabbit ear blood vessel, and 2. the IC "dose" developed during insonation treatment can be reliably measured and will vary with varying acoustic parameters and Optison concentration. Ex vivo rabbit auricular arteries were perfused with Optison suspensions and then exposed to 1.1-MHz pulsed focused ultrasound. Experimental variables included peak negative acoustic pressure (0.2 MPa to 5.2 MPa), pulse-repetition frequency (5, 50 or 500 Hz), pulse length (50, 100, 500 or 1000 cycles), and Optison volume concentration (0, 0.2, 0.5 or 1%). Cavitation activity was quantified as IC dose, based on passive cavitation detection measurements. The results show that: 1. The IC pressure threshold decreases with higher concentrations of Optison, and 2. IC dose increases significantly with increasing acoustic pressure, Optison concentration, pulse length or with decreasing pulse-repetition frequency.

Effect of surfacants on inertial caviation activity in a pulsed acoustic field

Lee, J., S. Kentish, T.J. Matula, and M. Ashokkumar, "Effect of surfacants on inertial caviation activity in a pulsed acoustic field," J. Phys. Chem. B, 109, 16860-16865, DOI: 10.1021/jp0533271, 2005

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8 Sep 2005

It has previously been reported that the addition of low concentrations of ionic surfactants enhances the steady-state sonoluminescence (SL) intensity relative to water (Ashokkumar; et al. J. Phys. Chem. B 1997, 101, 10845). In the current study, both sonoluminescence and passive cavitation detection (PCD) were used to examine the acoustic cavitation field generated at different acoustic pulse lengths in the presence of an anionic surfactant, sodium dodecyl sulfate (SDS). A decrease in the SL intensity was observed in the presence of low concentrations of SDS and short acoustic pulse lengths. Under these conditions, the inhibition of bubble coalescence by SDS leads to a population of smaller bubbles, which dissolve during the pulse "off time". As the concentration of surfactant was increased at this pulse length, an increase in the acoustic cavitation activity was observed. This increase is partly attributed to enhanced growth rate of the bubbles by rectified diffusion. Conversely, at long pulse lengths acoustic cavitation activity was enhanced at low SDS concentrations as a larger number of the smaller bubbles could survive the pulse "off time". The effect of reduced acoustic shielding and an increase in the "active" bubble population due to electrostatic repulsion between bubbles are also significant in this case. Finally, as the surfactant concentration was increased further, the effect of electrostatic induced impedance shielding or reclustering dominates, resulting in a decrease in the SL intensity.

A suppressor to prevent direct wave-induced cavitation in shock wave therapy devices

Matula, T.J., P.R. Hilmo, and M.R. Bailey, "A suppressor to prevent direct wave-induced cavitation in shock wave therapy devices," J. Acoust. Soc. Am., 118, 178, 2005.

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1 Jul 2005

Cavitation plays a varied but important role in lithotripsy. Cavitation facilitates stone comminution, but can also form an acoustic barrier that may shield stones from subsequent shock waves. In addition, cavitation damages tissue. Spark-gap lithotripters generate cavitation with both a direct and a focused wave. The direct wave propagates as a spherically diverging wave, arriving at the focus ahead of the focused shock wave. It can be modeled with the same waveform (but lower amplitude) as the focused wave. We show with both simulations and experiments that bubbles are forced to grow in response to the direct wave, and that these bubbles can still be large when the focused shock wave arrives. A baffle or "suppressor" that blocks the propagation of the direct wave is shown to significantly reduce the direct wave pressure amplitude, as well as direct wave-induced bubble growth. These results are applicable to spark-gap lithotripters and extracorporeal shock wave therapy devices, where cavitation from the direct wave may interfere with treatment. A simple direct-wave suppressor might therefore be used to improve the therapeutic efficacy of these devices.

Monitoring bubble growth in supersaturated blood and tissue ex vivo and the relevance to marine mammal bioeffects

Crum, L.A., M.R. Bailey, J.F. Guan, P.R. Hilmo, S.G. Kargl, T.J. Matula, and O.A. Sapozhnikov, "Monitoring bubble growth in supersaturated blood and tissue ex vivo and the relevance to marine mammal bioeffects," ARLO, 6, 214-220, 2005

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24 Jun 2005

There have been several recent reports that active sonar systems can lead to serious bioeffects in marine mammals, particularly beaked whales, resulting in strandings, and in some cases, to their deaths. We have devised a series of experiments to determine the potential role of low-frequency acoustic sources as a means to induce bubble nucleation and growth in supersaturated ex vivo bovine liver and kidney tissues, and blood. Bubble detection was achieved with a diagnostic ultrasound scanner. Under the conditions of this experiment, supersaturated tissues and blood led to extensive bubble production when exposed to short pulses of low frequency sound.

Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo

Hwang, J.H., A.A. Brayman, M.A. Reidy, T.J. Matula, M.B. Kimmey, and L.A. Crum, "Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo," Ultrasound Med. Biol., 31, 553-564, doi:10.1016/j.ultrasmedbio.2004.12.014, 2005

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11 Apr 2005

Previous in vivo studies have demonstrated that microvessel hemorrhages and alterations of endothelial permeability can be produced in tissues containing microbubble-based ultrasound contrast agents when those tissues are exposed to MHz-frequency pulsed ultrasound of sufficient pressure amplitudes. The general hypothesis guiding this research was that acoustic (viz., inertial) cavitation, rather than thermal insult, is the dominant mechanism by which such effects arise. We report the results of testing five specific hypotheses in an in vivo rabbit auricular blood vessel model: (1) acoustic cavitation nucleated by microbubble contrast agent can damage the endothelia of veins at relatively low spatial-peak temporal-average intensities, (2) such damage will be proportional to the peak negative pressure amplitude of the insonifying pulses, (3) damage will be confined largely to the intimal surface, with sparing of perivascular tissues, (4) greater damage will occur to the endothelial cells on the side of the vessel distal to the source transducer than on the proximal side and (5) ultrasound/contrast agent-induced endothelial damage can be inherently thrombogenic, or can aid sclerotherapeutic thrombogenesis through the application of otherwise subtherapeutic doses of thrombogenic drugs. Auricular vessels were exposed to 1-MHz focused ultrasound of variable peak pressure amplitude using low duty factor, fixed pulse parameters, with or without infusion of a shelled microbubble contrast agent. Extravasation of Evans blue dye and erythrocytes was assessed at the macroscopic level. Endothelial damage was assessed via scanning electron microscopy (SEM) image analysis. The hypotheses were supported by the data. We discuss potential therapeutic applications of vessel occlusion, e.g., occlusion of at-risk gastric varices.

Detecting cavitation in vivo from shock-wave therapy devices

Matula, T.J., J. Yu, and M.R. Bailey, "Detecting cavitation in vivo from shock-wave therapy devices," J. Acoust. Soc. Am., 117, 2371, 2005

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2 Apr 2005

Extracorporeal shock-wave therapy (ESWT) has been used as a treatment for plantar faciitis, lateral epicondylitis, shoulder tendonitis, non-unions, and other indications where conservative treatments have been unsuccessful. However, in many areas, the efficacy of SW treatment has not been well established, and the mechanism of action, particularly the role of cavitation, is not well understood. Research indicates cavitation plays an important role in other ultrasound therapies, such as lithotripsy and focused ultrasound surgery, and in some instances, cavitation has been used as a means to monitor or detect a biological effect. Although ESWT can generate cavitation easily in vitro, it is unknown whether or not cavitation is a significant factor in vivo. The purpose of this investigation is to use diagnostic ultrasound to detect and monitor cavitation generated by ESWT devices in vivo. Diagnostic images are collected at various times during and after treatment. The images are then post-processed with image-processing algorithms to enhance the contrast between bubbles and surrounding tissue. The ultimate goal of this research is to utilize cavitation as a means for optimizing shock wave parameters such as amplitude and pulse repetition frequency.

Occlusive thrombosis in the rabbit auricular vein in vivo targeted by induction of intralumenal cavitation using HIFU and ultrasound contrast agent

Brayman, A.A., J. Tu, T. Matula, L.A. Crum, J.H. Hwang, and M.B. Kimmey, "Occlusive thrombosis in the rabbit auricular vein in vivo targeted by induction of intralumenal cavitation using HIFU and ultrasound contrast agent," J. Acoust. Soc. Am., 117, 2558, 2005

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2 Apr 2005

Hypotheses tested: (1) inertial cavitation [IC] could be induced in the venous lumen in vivo by combined use of intravascular microbubble contrast agent and transcutaneous application of 1-MHz high intensity focused ultrasound [HIFU] of very low duty factor, and that IC activity could be detected and quantified in vivo as in earlier in vitro studies via passive cavitation detection methods; (2) robust IC activity would damage the venous endothelium in treated regions; (3) endothelial damage would be proportional to the IC dose developed in the region; (4) severe local endothelial damage alone may be sufficient to induce occlusive thrombosis, or may sensitize the region to low systemic doses of prothrombotic agents, and (5) biologically significant temperature rises and attendant thermal bioeffects in the vessel and perivascular tissues would not occur, even under the highest amplitude acoustic conditions applied. Each hypothesis was supported by the data. The principal result was that under treatment conditions involving very high peak negative acoustic pressures and contrast agent, treated areas thrombosed acutely but non-occlusively. When fibrinogen was administered locally after such treatment, occlusive thrombi formed acutely and only in the treated region, a response observed with none of the other treatments.

A noncontact transportation in water using ultrasonic traveling waves

Nomura, S., T.J. Matula, J. Satonobu, and L.A. Crum, "A noncontact transportation in water using ultrasonic traveling waves," J. Acoust. Soc. Am., 118, 1945, 2005.

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1 Apr 2005

A noncontact transport experiment in water using a traveling-wave-type linear motor was investigated. Acrylic disks were used as the floating objects. A vibrating plate was enclosed in acrylic plates, and a water tank was made that would allow the vibrating plate to be placed on the bottom. In order to propagate the traveling wave, two ultrasonic transducers were attached at both ends to the bottom of the vibrating plate. One side was used as the wave-sending side and the other side was used as the wave-receiving side. Comparing the transport experiments conducted in water with those conducted in air, the transport velocity becomes faster for floating transport in water than for floating transport in air. The occurrence of cavitation bubbles acts as a resistive force on the movement of the object being transported, and causes the transport velocity to be reduced. Transport velocity depends on the height of the water. If the height of the water surface is too shallow, the water surface freely deforms and the water surface forms bumpy standing waves, making it difficult for the object to be transported.

HIFU hemostasis of liver injuries enhanced by ultrasound contrast agents

Zderic, V., S. Vaezy, A.A. Brayman, T.J. Matula, G.E. O'Keefe, and L.A. Crum, "HIFU hemostasis of liver injuries enhanced by ultrasound contrast agents," Proceedings, American Institute of Physics Conference, number 754, 55-57 (2005).

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28 Mar 2005

Our objective was to investigate whether High-Intensity Focused Ultrasound (HIFU) hemostasis can be achieved faster in the presence of ultrasound contrast agents (UCA). Incisions (3 cm long and 0.5 cm deep) were made in surgically exposed rabbit liver. Optison at a concentration of 0.18 ml/kg was injected into the mesenteric vein, immediately before the incision was made. The HIFU applicator (frequency of 5.5 MHz, and intensity of 3,700 W/cm2) was scanned manually over the incision (at an approximate rate of 1 mm/s) until hemostasis was achieved. The times to complete hemostasis were measured and normalized with the initial blood loss. The hemostasis times were 59±23 s in the presence of Optison and 70±23 s without Optison. The presence of Optison produced a 37% reduction in the normalized hemostasis times (p<0.05). Optison also provided faster (by 34%) formation of the coagulum seal over the lesion. Gross observations showed that the lesion size did not change due to the presence of Optison. Histological analysis showed that lesions consisted of an area of coagulation necrosis in vicinity of the incision, occasionally surrounded by a congestion zone filled with blood. Our results suggest the potential utility of microbubble contrast agents for increasing efficiency of HIFU hemostasis of internal organ injuries.

Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro

Guan, J., and T.J. Matula, "Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro," J. Acoust. Soc. Am., 116, 2832-2842, 2004.

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1 Nov 2004

Light scattering was used to measure the radial pulsations of individual ultrasound contrast microbubbles subjected to pulsed ultrasound. Highly diluted Optison® or Sonazoid® microbubbles were injected into either a water bath or an aqueous solution containing small quantities of xanthan gum. Individual microbubbles were insonified by ultrasound pulses from either a commercial diagnostic ultrasound machine or a single element transducer. The instantaneous response curves of the microbubbles were measured. Linear and nonlinear microbubble oscillations were observed. Good agreement was obtained by fitting a bubble dynamics model to the data. The pulse-to-pulse evolution of individual microbubbles was investigated, the results of which suggest that the shell can be semipermeable, and possibly weaken with subsequent pulses. There is a high potential that light scattering can be used to optimize diagnostic ultrasound techniques, understand microbubble evolution, and obtain specific information about shell parameters.

Imaging the destruction of individual ultrasound contrast microbubbles with diagnostic ultrasound

Guan, J., T.J. Matula, and M. Averkiou, "Imaging the destruction of individual ultrasound contrast microbubbles with diagnostic ultrasound," ARLO, 5, 165-169, 2004.

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1 Oct 2004

Ultrasound imaging of ultrasound contrast agent fragmentation in a water bath was performed with the color Doppler mode of the HDI 5000 (Phillips Ultrasound). A highly diluted suspension of ultrasound contrast microbubbles (Optison®) was injected into the water bath such that individual microbubbles passed through the image plane every few seconds. Decorrelation of the signal, along with the appearance of multiple signals, suggests that single microbubble fragmentation was observed, with daughter bubbles being formed from the original microbubbles, depending on the applied acoustic pressure.

Direct measurements of individual contrastbubble dynamics using light-scattering

Matula, T.J., and J. Guan, "Direct measurements of individual contrastbubble dynamics using light-scattering," Proceedings of the 3rd International Symposium on Therapeutic Ultrasound, edited by J.Y. Chapelon and C. Lafon, 61-66 (Lyon, France, INSERM, 2004).

15 Sep 2004

Sonoluminescence bubble measurements using vision-based algorithms

Hall, N.R., J.R. Mackey, and T.J. Matula, "Sonoluminescence bubble measurements using vision-based algorithms," Proceedings, SPIE%u2014Two- and Three-Dimensional Vision Systems for Inspection, Control, and Metrology, vol. 5265, pp. 90-97, doi:10.1117/12.516150 (2004).

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26 Feb 2004

Vision-based measurement methods were used to measure bubble sizes in this sonoluminescence experiment. Bubble imaging was accomplished by placing the bubble between a bright light source and a microscope-CCDcamera system. A collimated light-emitting diode was operated in a pulsed mode with an adjustable time delay with respect to the piezo-electric transducer drive signal. The light-emitting diode produced a bubble shadowgraph consisting of a multiple exposure made by numerous light pulses imaged onto a charge-couple device camera. Each image was transferred from the camera to a computer-controlled machine vision system via a frame grabber. The frame grabber was equipped with on-board memory to accommodate sequential image buffering while images were transferred to the host processor and analyzed. This configuration allowed the host computer to perform diameter measurements, centroid position measurements and shape estimation in "real-time" as the next image was being acquired. Bubble size measurement accuracy with an uncertainty of 3 microns was achieved using standard lenses and machine vision algorithms. Bubble centroid position accuracy was also within the 3 micron tolerance of the vision system. This uncertainty estimation accounted for the optical spatial resolution, digitization errors and the edge detection algorithm accuracy. The vision algorithms include camera calibration, thresholding, edge detection, edge position determination, distance between two edges computations and centroid position computations.

A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents

Chen, W.-S., T.J. Matula, A.A. Brayman, and L.A. Crum, "A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents," J. Acoust. Soc. Am., 113, 643-651, 2003.

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1 Dec 2003

Contrast bubble destruction is important in several new diagnostic and therapeutic applications. The pressure threshold of destruction is determined by the shell material, while the propensity for of the bubbles to undergo inertial cavitation (IC) depends both on the gas and shell properties of the ultrasound contrast agent (UCA). The ultrasonic fragmentation thresholds of three specific UCAs (Optison, Sonazoid, and biSpheres), each with different shell and gas properties, were determined under various acoustic conditions. The acoustic emissions generated by the agents, or their derivatives, characteristic of IC after fragmentation, was also compared, using cumulated broadband-noise emissions (IC "dose"). Albumin-shelled Optison and surfactant-shelled Sonazoid had low fragmentation thresholds (mean = 0.13 and 0.15 MPa at 1.1 MHz, 0.48 and 0.58 MPa at 3.5 MHz, respectively), while polymer-shelled biSpheres had a significant higher threshold (mean = 0.19 and 0.23 MPa at 1.1 MHz, 0.73 and 0.96 MPa for thin- and thick-shell biSpheres at 3.5 MHz, respectively, p<0.01). At comparable initial concentrations, surfactant-shelled Sonazoid produced a much larger IC dose after shell destruction than did either biSpheres or Optison (p<0.01). Thick-shelled biSpheres had the highest fragmentation threshold and produced the lowest IC dose. More than two and five acoustic cycles, respectively, were necessary for the thin- and thick-shell biSpheres to reach a steady-state fragmentation threshold.

Time scales for quenching single-bubble sonoluminescence in the presence of alcohols

Guan, J.F., and T.J. Matula, "Time scales for quenching single-bubble sonoluminescence in the presence of alcohols," J. Phys. Chem. B, 107, 8917-8921, doi:10.1021/jp026494z, 2003.

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30 Jul 2003

The rate at which single-bubble sonoluminescence is quenched in the presence of alcohol is examined. Single-bubble sonoluminescence bubbles are generated in a partially degassed argon–water/alcohol mixture. Quenching rates are measured by recording the instantaneous bubble response and corresponding light emission during a sudden increase in driving pressure. The light emission intensity initially grows as the bubble settles into a steady-state. The intensity then decreases as endothermic processes begin to dominate. Quenching rates increase with the carbon chain length (C1–C4). Complete quenching in the presence of methanol requires over 8000 acoustic cycles, while quenching with butanol occurs in about 50 acoustic cycles (driving frequency = 22.5 kHz). These observations are consistent with the view that quenching requires the repetitive injection of alcohol molecules leading to the accumulation of (hydrocarbon) gaseous products within the bubbles.

Bubble levitation and translation under single-bubble sonoluminescence conditions

Matula, T.J., "Bubble levitation and translation under single-bubble sonoluminescence conditions," J. Acoust. Soc. Am., 114, 775-781, 2003.

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1 Jul 2003

Bubble levitation in an acoustic standing wave is re-examined for conditions relevant to single-bubble sonoluminescence. Unlike a previous examination [Matula et al., J. Acoust. Soc. Am. 102, 1522-1527 (1997)], the stable parameter space [Pa,R0] is accounted for in this realization. Forces such as the added mass force and drag are included, and the results are compared with a simple force balance that equates the Bjerknes force to the buoyancy force. Under normal sonoluminescence conditions, the comparison is quite favorable. A more complete accounting of the forces shows that a stably levitated bubble does undergo periodic translational motion. The asymmetries associated with translational motion are hypothesized to generate instabilities in the spherical shape of the bubble. A reduction in gravity results in reduced translational motion. It is hypothesized that such conditions may lead to increased light output from sonoluminescing bubbles.

The effects of microgravity on nanoparticle size distributions generated by the ultrasonic reduction of an aqueous gold-chloride solution

Reed, J.A., A. Cook, D.J. Halaas, P. Parazoli, A. Robinson, T.J. Matula, and F. Grieser, "The effects of microgravity on nanoparticle size distributions generated by the ultrasonic reduction of an aqueous gold-chloride solution," Ultrason. Sonochem., 10, 285-289, doi:10.1016/S1350-4177(03)00093-2, 2003.

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1 Jul 2003

A solution of gold chloride was reduced using ultrasound irradiation to prepare metallic gold nanoparticles under conditions of microgravity and normal gravity at sea level. Particle size distributions were measured using TEM analysis. A mean particle diameter of 10 nm was obtained in microgravity while a mean diameter of 80 nm was obtained in the laboratory. Absorbance measurements on the reacted solution found an enhanced reduction rate in the reduction of gold chloride in microgravity compared to that in the laboratory.

Mechanisms of lesion formation in HIFU therapy

Chen W.-S., C. Lafon, T.J. Matula, S. Vaezy, A. Brayman, and L.A. Crum, "Mechanisms of lesion formation in HIFU therapy," in Therapeutic Ultrasound, Proceedings of the 2nd International symposium, M.A. Andrew, L.A. Crum, and S. Vaezy, eds., 400-409 (American Institute of Physics Press, 2003).

1 Jun 2003

Inertial cavitation dose and hemolysis produced in vitro with or without Optison®

Chen, W.-S., A.A. Brayman, T.J. Matula, and L.A. Crum, "Inertial cavitation dose and hemolysis produced in vitro with or without Optison®," Ultrasound Med. Biol., 29), 725-737, doi:10.1016/S0301-5629(03)00013-9, 2003.

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9 May 2003

Gas-based contrast agents (CAs) increase ultrasound (US)-induced bioeffects, presumably via an inertial cavitation (IC) mechanism. The relationship between IC dose (ICD) (cumulated root mean squared [RMS] broadband noise amplitude; frequency domain) and 1.1-MHz US-induced hemolysis in whole human blood was explored with Optison®; the hypothesis was that hemolysis would correlate with ICD. Four experimental series were conducted, with variable: 1. peak negative acoustic pressure (P–), 2. Optison® concentration, 3. pulse duration and 4. total exposure duration and Optison® concentration. P– thresholds for hemolysis and ICD were ~0.5 MPa. ICD and hemolysis were detected at Optison® concentrations ≥ 0.01 V%, and with pulse durations as low as four or two cycles, respectively. Hemolysis and ICD evolved as functions of time and Optison® concentration; final hemolysis and ICD values depended on initial Optison® concentration, but initial rates of change did not. Within series, hemolysis was significantly correlated with ICD; across series, the correlation was significant at p < 0.001.

The pulse length-dependence of inertial cavitation dose and hemolysis

Chen, W.-S., A.A. Brayman, T.J. Matula, L.A. Crum, and M.W. Miller, "The pulse length-dependence of inertial cavitation dose and hemolysis," Ultrasound Med. Biol., 29, 739-748, doi:10.1016/S0301-5629(03)00029-2, 2003.

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9 May 2003

Gas-based ultrasound (US) contrast agents increase erythrocyte sonolysis, presumably via enhancing inertial cavitation (IC) activity. The amount of IC activity (IC "dose") and hemolysis generated by exposure to 1.15 MHz US were examined with different US pulse lengths, but with the same delivered acoustic energy, for Optison® and Albunex®. The hypotheses were that 1. at longer pulse lengths, IC would generate more bubbles that could nucleate additional IC activity; 2. if the interval between pulse pairs were short enough for the next pulse to hit derivative bubbles before their dissolution, more IC could be induced; and 3. hemolysis would be proportional to IC activity. Two types of studies were performed. In the first, bubble generation after each burst of IC activity was quantified using an active cavitation detector (ACD), for different pulse lengths (5, 10, 20, 30, 50, 100 or 200 cycles), but the same pressure level (3 MPa) and total "on" time (173.16 ms). Low concentrations of either Optison® or Albunex® were added into the tank with high-intensity and interrogating transducers orthogonal to each other. For pulse lengths > 100 cycles, and pulse repetition intervals < 5 ms, a "cascade" effect (explosive bubble generation) was observed. In the second, IC was measured by passive detection methods. IC dose and hemolysis were determined in whole blood samples at a pressure level (3 MPa) and interpulse interval (5 ms) that induced the "cascade" effect. Each blood sample was mixed with the same number of contrast microbubbles (Optison® ~ 0.3 v/v % and Albunex® ~ 0.5 v/v %), but exposed to different pulse lengths (5, 10, 20, 30, 50, 100 or 200 cycles). With Optison®, up to 60% hemolysis was produced with long pulses (100 and 200 cycles), compared with < 10% with short pulses (5 and 10 cycles). Albunex® generated considerably less IC activity and hemolysis. The r2 value was 0.99 for the correlation between hemolysis and IC dose. High pulse-repetition frequency (PRF) (500 Hz) generated more hemolysis than the low PRF (200 Hz) at 3 MPa. All experimental results could be explained by the dissolution times of IC-generated bubbles.

Mechanisms of lesion formation in high intensity focused ultrasound therapy

Chen, W.-S., C. Lafon, T.J. Matula, S. Vaezy, and L.A. Crum, "Mechanisms of lesion formation in high intensity focused ultrasound therapy," ARLO, 4, 41-46, 2003.

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30 Jan 2003

The lesions generated by high intensity ultrasound were studied in transparent tissue phantoms premixed with and without ultrasound contrast agents (UCA) at 1.1- and 3.5-MHz acoustic waves. Generation of small bubbles was observed at the very beginning of exposure, whereas cigar-shaped thermal lesions began to form at the focus after a delay. After further heating, boiling occurred and changed the lesion to tadpole-shape, with advancement toward the transducer. Broadband noise was detected in phantoms with UCA initially. UCA also lowered the pressure threshold and enlarged the lesion. Although thermal and cavitation effects are believed to be both important in lesion formation, tadpole-shaped transformation results from boiling activity.

Broadband noise emissions produced by pulsed 1-MHz ultrasound exposures in the presence or absence of Optison, and their relationship to the hemolytic bioeffect

Brayman, A.A., W.S. Chen, T.J. Matula, and L.A. Crum, "Broadband noise emissions produced by pulsed 1-MHz ultrasound exposures in the presence or absence of Optison, and their relationship to the hemolytic bioeffect," J. Acoust. Soc. Am., 111, 2462, 2002.

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1 Oct 2002

Gas-based contrast agents are known to increase ultrasound-induced bioeffects, presumably via an inertial cavitation (IC) mechanism. The relationship between IC "dose" (ICD) (cumulated rms broadband noise amplitude in the frequency domain) and 1.1-MHz ultrasound-induced hemolysis in whole human blood was explored with additions of Optison or degassed saline; the hypothesis was that hemolysis would correlate with ICD. Four experimental series were conducted, with variable: (1) peak negative acoustic pressure [P–]; (2) Optison concentration; (3) pulse duration; and (4) total exposure duration and variable Optison concentration. The P– thresholds for hemolysis and ICD above noise levels were ~0.5 MPa. Enhancement of ICD and hemolysis was detected even at the lowest Optison concentration tested (0.1%) at P–=3 MPa. At 2 MPa P–(0.3% Optison), significant hemolysis and ICD were detected with pulse durations as brief as 2 and 4 cycles, respectively. At 3 MPa P–, hemolysis and ICD evolved as functions of time and Optison concentration; ultimate levels of hemolysis and ICD depended strongly on initial Optison concentration, but initial rates of change did not. Within experimental series, hemolysis was significantly correlated with ICD; across series, the correlation was significant at p less than 0.001.

In vitro sonoluminescence and sonochemistry studies with an electrohydraulic shock wave lithotripter

Matula, T.J., P.R. Hilmo, M.R. Bailey, and L.A. Crum, "In vitro sonoluminescence and sonochemistry studies with an electrohydraulic shock wave lithotripter," Ultrasound Med. Biol., 28, 1199-1207, 2002.

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1 Sep 2002

Sonoluminescence and sonochemistry from a cavitation field generated by an electrohydraulic shock-wave lithotripter were investigated as functions of spark discharge voltage (13 to 21 kV) and pulse-repetition frequency (PRF) (0.5 to 2.0 Hz). Sonochemical activity, measured with an iodide dosimeter, increased with both voltage and PRF. Sonoluminescence was measured in an acoustically matched light-tight box. The envelope of the light intensity was measured in a temporally gated region extending from the initial arrival of the shock wave (resulting in bubble compression) to the final inertial collapse of the bubble cloud, which follows hundreds of micros after passage of the shock wave. The initial compression resulted in greater sonoluminescence emissions, suggesting that the initial bubble compression due to the leading positive pressure spike from the lithotripter generated higher temperatures than the inertial collapse of the bubble. These unexpected results are consistent with some recent calculations in which the vapor pressure of the liquid limits compressional heating.

Correlation between acoustic cavitation noise, bubble population, and sonochemistry

Segebarth, N., O. Eulaerts, J. Reisse, L.A. Crum, and T.J. Matula, "Correlation between acoustic cavitation noise, bubble population, and sonochemistry," J. Phys. Chem. B, 106, 9181-9190, doi:10.1021/jp0146566, 2002.

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13 Aug 2002

Quantitative studies of the correlation between sonochemical activity and acoustical noise spectra have been performed. The width of the second harmonic (fwhm2) of the acoustical signal in the frequency domain shows a sensitive dependence to the presence of small amounts (mM range) of an anionic surfactant in water. This sensitive dependence is also observed for other characteristics of the cavitation noise spectrum and in the sonochemical production of peroxides and correlates well with the sonoluminescence intensity observed by other researchers. Analysis of the experimental data shows that SDS probably modifies the coalescence phenomena.

The disappearance of ultrasound contract bubbles. Observations of bubble dissolution and cavitation nucleation

Chen, W.S., T.J. Matula, and L.A. Crum, "The disappearance of ultrasound contract bubbles. Observations of bubble dissolution and cavitation nucleation," Ultrasound Med. Biol., 28, 793-803, 2002.

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1 Jun 2002

The destruction process of biSphere and Optison ultrasound (US) contrast microbubbles were studied at 1.1 MHz. High-amplitude tone bursts caused shell disruption and/or fragmentation of the microbubbles, leading to dissolution of the freed gas. The bubble destruction and subsequent dissolution process was imaged with a high pulse-repetition frequency (PRF) 10-cycle, 5-MHz bistatic transducer configuration. Three types of dissolution profiles were measured: In one case, biSphere microbubbles showed evidence of dissolution through resonance, during which a temporary increase in the scattering amplitude was observed. In another case, both biSphere and Optison microbubbles showed evidence of fragmentation, during which the scattering amplitude decreased rapidly. Finally, in some cases, we observed the impulsive growth and subsequent rapid decay of signals that appear to be due to cavitation nucleation. Simulations of bubble dissolution curves show good agreement with experiments.

Effect of surfactants, polymers, and alcohol on single bubble dynamics and sonoluminescence

Ashokkumar, M., J. Guan, R. Tronson, T.J. Matula, J.W. Nuske, and F. Grieser, "Effect of surfactants, polymers, and alcohol on single bubble dynamics and sonoluminescence," Phys. Rev. E., 65, 046310, doi:10.1103/PhysRevE.65.046310, 2002.

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11 Apr 2002

The radial dynamics of an acoustically driven single bubble, levitated in water, along with the sonoluminescence (SL) signal, were recorded in the absence and in the presence of micromolar quantities of different surfactants and polymers. It was observed that these nonvolatile solutes, in the low concentration range used, did not significantly affect the radial dynamics nor the SL intensity of a single bubble in water. In contrast, the addition of micromolar quantities of a volatile solute, pentanol, quenched ~90% of the SL without affecting the radial dynamics of the bubble.

Radial response of individual bubbles subjected to shock wave lithotripsy pulses in vitro

Matula, T.J., P.R. Hilmo, B.D. Storey, and A.J. Szeri, "Radial response of individual bubbles subjected to shock wave lithotripsy pulses in vitro," Phys. Fluids, 14, 913-921, doi:10.1063/1.1433970, 2002.

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1 Mar 2002

Direct measurements of individual bubble oscillations in lithotripsy fields have been performed using light-scattering techniques. Studies were performed with bubble clouds in gassy water as well as single levitated bubbles in degassed water. There is direct evidence that the bubble survives the inertial collapse, rebounding several times before breaking up. Bubble dynamics calculations agree well with the observations, provided that vapor trapping (a reduction in condensation during bubble collapse) is included. Furthermore, the afterbounces are dominated by vapor diffusion, not gas diffusion. Vapor trapping is important in limiting the collapse strength of bubbles, and in sonochemical activity.

A light-scattering technique for investigating the destruction of ultrasound contrast agents

Chen, W.S., T.J. Matula, and L.A. Crum, "A light-scattering technique for investigating the destruction of ultrasound contrast agents," IEEE Ultrason. Symp. Proc., 2, 1683-1686, 2001.

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7 Oct 2001

A technique that utilizes light-scattering from a low-powered laser to probe ultrasound contrast agents is described. A He-Ne laser illuminates the focal zone of a high-intensity focused ultrasound (HIFU) source operating at 1.1 MHz. A focusing lens is used to collect the scattered light from bubbles in the focal region, focusing the scattered light onto a photodetector. During application of the HIFU source, the bubbles oscillate, and the resulting fluctuation in the light-scattering signal is detected by the photodetector. Measurements of the light fluctuation can be correlated with bubble activity, especially inertial cavitation. A description of the technique, and preliminary results of measurements with ultrasound contrast agents are shown.

Correlation between sonoluminescence, sonochemistry, and noise spectra

Segebarth, N., O. Eulaerts, J. Reisse, L.A. Crum, and T.J. Matula, "Correlation between sonoluminescence, sonochemistry, and noise spectra," Chem. Phys. Chem., 2, 536-538, 2001.

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17 Sep 2001

The acoustic signal from the sonochemical production of H2O2 in water, as measured by the intensity and the width of the second harmonic, show a sensitive and correlated dependence to the presence of small amounts (millimolar range) of an anionic surfactant (SDS) in water. The graphic shows the link from the ultrasonic reaction to the measurable quantities. New possibilities to reliably control such processes is therefore opened.

Near-infrared emissions in single-bubble and multibubble sonoluminescence

Matula, T.J., J. Guan, L.A. Crum, A.L. Robinson, L.W. Burgess, "Near-infrared emissions in single-bubble and multibubble sonoluminescence," Phys. Rev. E. Stat. Phys. Plasmas Fluids Interdiscip. Topic, 64, 0263101-0263103, 2001.

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24 Jul 2001

Comparisons of light emissions from multibubble and single-bubble sonoluminescence in the near-infrared band extending from 800 to 1050 nm have been investigated. In argon-water mixtures, single-bubble and multibubble spectra are similar in appearance. In sodium chloride-water mixtures, the multibubble spectrum shows evidence of the 3d-3p sodium emission line, whereas the single-bubble spectrum shows no such emission. For single bubbles, the near-infrared emissions change linearly with driving pressure. No evidence of near-infrared emissions are observed below the visible luminescence threshold.

Effect of solutes on single-bubble sonoluminescence in water

Ashokkumar, M., L.A. Crum, C.A. Frensley, F. Grieser, T.J. Matula, W.B. McNamara, and K.S. Suslick, "Effect of solutes on single-bubble sonoluminescence in water," J. Phys. Chem., 104, 8462-8465, 2000.

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14 Sep 2000

Low concentrations of short chain aliphatic alcohols and organic acids and bases suppress single-bubble sonoluminescence (SBSL) in water. The degree of SL quenching increases with the length of the aliphatic end of the alcohol, and is related to the concentration of the alcohol at the bubble/water interface. The light is preferentially quenched in the shorter wavelength region of the spectrum. Radius–time measurements of the bubble are not dramatically affected by the low levels of alcohol used. Butyric acid and propylamine behave in the same manner, but only in their neutral forms, indicating that the SBSL suppression is due to processes occurring within the bubble.

The effects of buoyancy on sonoluminescing bubbles

Matula, T.J., V.J. Bezzerides, P.R. Hilmo, L.N. Couret, T.W. Olson, L.A. Crum, J.E. Swalwell, D.W. Kuhns, and R.A. Roy, "The effects of buoyancy on sonoluminescing bubbles," ARLO, 1, 13-18, 2000.

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1 Aug 2000

Sonoluminescence from a single bubble was studied under microgravity and hypergravity environments to determine how buoyancy affects the light emission. The long-term objective of these experiments is to determine if buoyancy-related instabilities play a role in limiting the parameter space of single-bubble sonoluminescence. Understanding the parameter space limitations may ultimately lead to novel approaches for enhancing the extreme conditions within the bubble. Our results reveal several buoyancy-related effects, which should be further investigated in an extended microgravity environment.

Correlations between UCA-destruction-induced bioeffects and inertial cavitation

Chen, W.-S., P.P. Chang, T.J. Matula, and L.A Crum, "Correlations between UCA-destruction-induced bioeffects and inertial cavitation," J. Acoust. Soc. Am., 107, 2814, doi:10.1121/1.429071, 2000.

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1 May 2000

Certain therapeutic applications of ultrasound may be enhanced by the use of ultrasound contrast agents, whose controlled destruction may produce a desired bioeffect. It is therefore important to understand the mechanisms of microbubble destruction, and to quantify the relationship between bioeffects and the acoustical signature of these agents. In previous studies, we found two distinct thresholds for the ultrasonic destruction of shelled microbubbles: a fragmentation threshold (P1) at which the microbubble shell is disrupted, creating smaller bubbles, and an inertial cavitation [IC] threshold (P2) for sustained, vigorous IC activity. The inertial cavitation dose (ICD) was used to monitor continuous changes in IC activity. The samples, containing mixtures of Optison with either a buffer solution or whole blood, were insonified with a 1.1-MHz focused transducer (up to 4.4 MPa peak-to-0peak). Below P2, the ICD increased slowly with increasing pressure amplitude; hemolysis accumulated more rapidly. Above P2, the ICD decreased. Increased hemolysis was observed between P1 and P2, and was associated with short bursts of IC activity. At fixed PRF, or fixed total "on" time (by adjustment of pulse length and PRF), a pulse length threshold existed for the ICD and hemolysis measurements.

Simultaneous detection of acoustic and light emissions from cavitation bubbles in shock wave lithotripsy

Matula, T.J., M.R. Bailey, P.R. Hilmo, D.L. Sokolov, and L.A. Crum, "Simultaneous detection of acoustic and light emissions from cavitation bubbles in shock wave lithotripsy," J. Acoust. Soc. Am., 107, 2838, doi:10.1121/1.429165, 2000.

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1 May 2000

A typical pulse in electrohydraulic shock wave lithotripsy (SWL) consists of an intense positive pressure pulse, followed by a longer negative-pressure tail. Computer models of the bubble dynamics associated with such a pulse suggest that the positive pressure pulse compresses the bubble (R{0}=3–10 μm) to a submicron size. The negative-pressure tail then causes the bubble to undergo a dramatic expansion, followed by an inertially dominated (presumably spherical) collapse hundreds of microseconds later. Acoustic and light emissions are generated at both collapses. We have examined the simultaneous acoustic and optical emission from a cavitation field generated by SWL in order to determine whether the sonoluminescence is principally due to the initial compression of the bubble, or the final inertial collapse. Using two confocal 1-MHz, piezoceramic hydrophones and a PMT mounted on a light-tight water-filled container, we have observed acoustic and light emission corresponding to both the compression and inertial collapse of the bubble field. Our initial results suggest that the light emission occurs most frequently during the initial bubble compression. These results may have implications for understanding the sphericity of the bubble dynamics produced in SWL.

Single-bubble sonoluminescence in microgravity

Matula, T.J., "Single-bubble sonoluminescence in microgravity," Ultrasonics, 38, 559-565, 2000.

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27 Mar 2000

Single-bubble sonoluminescence refers to the emission of light from an acoustically trapped bubble undergoing highly nonlinear, presumably radial oscillations. The intensity of the emitted light depends strongly on the forcing pressure, and is limited by the development of instabilities that ultimately results in the extinction of the bubble. In this article, we discuss a possible contributing factor for the generation of instabilities; specifically, we examine the effect of the gravitational force on a sonoluminescence bubble.

The radial motion of a sonoluminescence bubble driven with multiple harmonics

Hargreaves, K., and T.J. Matula, "The radial motion of a sonoluminescence bubble driven with multiple harmonics," J. Acoust. Soc. Am., 107, 1774-1776, 2000.

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1 Mar 2000

Harmonic excitation has been reported to enhance the light emission of a single sonoluminescing bubble by as much as 300% [J. Holzfuss, M. Rüggeberg, and R. Mettin, Phys. Rev. Lett. 81, 1961-1964 (1998)]. In this paper it is shown that the effect of harmonic excitation on the radial motion of the bubble is consistent with bubble dynamics predictions. Also, it has been suggested that the energetic collapse of a sonoluminescence bubble can be enhanced with the addition of an acoustic "spike" drive [W. C. Moss et al., Phys. Lett. A 211, 69-74 (1996)]. Preliminary attempts to spike the bubble with an acoustic pulse (positive and negative) resulted in a temporary increase in light intensity of ≈ 200%; however, a strong acoustic radiation force pushes the bubble away from the antinodal region, suggesting that "spiking" the bubble each and every acoustic cycle may not be feasible.

Inventions

Acoustic Preconditioning for Protection from Injury

Record of Invention Number: 46759

Dan Leotta, Tom Matula, Wayne Monsky, Yak-Nam Wang

Disclosure

8 Dec 2013

Endocardial High-Intensity Focused Ultrasound (HIFU) Arrhythmia Ablation Catheter

Record of Invention Number: 46683

Tom Matula, Brian MacConaghy, Adam Maxwell

Disclosure

2 Oct 2013

Ultrasound Focusing Microplate

Record of Invention Number: 46578

Tom Matula, Brian MacConaghy

Disclosure

13 Jul 2013

More Inventions

Tagged Microbubble Cell Analyzer and Sorter

Record of Invention Number: 46461

Tom Matula

Disclosure

29 Mar 2013

Apparatus and Method for Disrupting Oil Pipeline Plugs

Record of Invention Number: 46417

Larry Crum, Barbrina Dunmire, Wayne Kreider, Tom Matula, Oleg Sapozhnikov

Disclosure

26 Feb 2013

Acoustic Ablation of Abscesses and Infected Fluid Collections

Record of Invention Number: 46378

Keith Chan, Tom Matula

Disclosure

24 Jan 2013

Flow Magnetosonoporation (fMSP) for Magnetic Stem Cell Labeling

Record of Invention Number: 46310

Tom Matula, Norman Beauchamp, Bensheng Qiu

Disclosure

8 Nov 2012

Dynamic Characterization of Particles with Flow Cytometry

Patent Number: 8,264,683

Tom Matula, Jarred Swalwell

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Patent

11 Sep 2012

Flow cytometry concepts are modified to enable dynamic characterizations of particles to be obtained using optical scattering data. Particles in flow will be introduced into a sample volume. Light scattered by a particle in the sample volume is collected and analyzed. What differentiates the concepts disclosed herein from conventional flow cytometry is the use of an acoustic source that is disposed to direct acoustic energy into the sample volume. As the particle passes through the sample volume, it responds to the acoustic energy, causing changes in the light scattered by the particle. Those changes, which are not measured during conventional flow cytometry, can be analyzed to determine additional physical properties of the particle.

Contrast Enhancement by Simultaneous Ultrasound/Laser Pulse Probing of Gold Nanosphere Encapsulated Emulsion Beads

Record of Invention Number: 46212

Matthew O'Donnell, Kjersta Larson-Smith, Tom Matula, Ivan Pelivanov, Danilo Pozzo, Chen-wei Wei, Jinjun Xia

Disclosure

25 Aug 2012

Method of Selective Foaming for Porous Polymeric Material

Patent Number: 8,247,464

Wei Li, Hai Wang, Vipin Kumar, Tom Matula

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Patent

21 Aug 2012

A selective high intensity ultrasonic foaming technique is described to fabricate porous polymers for biomedical applications. Process variables, including ultrasound power, scanning speed, and gas concentration have an affect on pore size. Pore size can be controlled with the scanning speed of the ultrasound insonation and interconnected porous structures could be obtained using a partially saturated polymers. A gas concentration range of 3-5% by weight creates interconnected open-celled porous structures. The selective high intensity ultrasonic foaming method can be used on biocompatible polymers so as not to introduce any organic solvents. The method has use in cell related biomedical applications such as studying cell growth behaviors by providing a porous environment with varying topological features.

Intracranial Method to Treat Bleeding Vessel

Record of Invention Number: 46063

Basavaraj Ghodke, Laligam Sekhar, Tom Matula

Disclosure

1 May 2012

Acoustic Radiation Cell Sorter (ARCS)

Record of Invention Number: 45897

Tom Matula

Disclosure

20 Dec 2011

Theranostic Ultrasound Contrast Agent Device

Record of Invention Number: 45896

Tom Matula, Amy Shen

Disclosure

20 Dec 2011

Pixelated Ultrasound (PIXUL) Microplate Processor

Tom Matula, Karol Bomsztyk, Oleg Denisenko

Disclosure

10 Jan 2011

Ultrasonic Particle Discriminator for Flow Cytometer

Record of Invention Number: 45473

Tom Matula, Justin Reed

Disclosure

28 Dec 2010

Ultrasound Imaging Integrated with an Aspiration Catheter to Improve the Surgical Management of Spontaneous Intracranial Hemorrhage

Record of Invention Number: 45393

Tom Matula, Neil Owen, Bob Wilcox, Daniel Cooke, Basavaraj Ghodke

Disclosure

5 Oct 2010

Prevention of decompression illness by bubble growing and monitoring with a wearable, individualized device giving real-time recommendations

Record of Invention Number: 45470

Tom Matula, Francesco Curra, Alex Gu, Peter Tobias

Disclosure

1 Oct 2010

Focused Shock-Wave Devices with Direct Wave Cavitation Suppressor

Patent Number: US 7,267,654 B2

Tom Matula, Paul Hilmo, Mike Bailey

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Patent

11 Sep 2007

A reflector reflects energy emitting from an energy source and focuses and directs it to a target. An aperture stop or suppressor disk is positioned between the energy source and target. The outer periphery of the aperture stop or suppressor disk is an irregular curve. This shape of the periphery prevents diffraction enhancement to the direct wave. In another embodiment, the suppressor disk is replaced by a a suppressor member that is directly mounted on a frame portion of the energy source. This energy source includes a spark-gap, or the like, and an open frame that surrounds the spark-gap or the like. This frame includes a pair of laterally spaced apart frame members on the side of the frame that faces the target. The suppressor member is connected to these frame members. It may have longitudinal grooves in its side edges into which the frame members snap-fit.

Direct Wave Cavitation Suppressor for Focused Shock-Wave Devices

Patent Number: US 7,033,328 B2

Tom Matula, Paul Hilmo, Mike Bailey

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Patent

25 Apr 2006

A reflector reflects energy emitting from an energy source and focuses and directs it to a target. An aperture stop or suppressor disk is positioned between the energy source and target. The outer periphery of the aperture stop or suppressor disk is an irregular curve. This shape of the periphery prevents diffraction enhancement to the direct wave.

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