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Summary The ability to directly modify native and established biofilms has enormous potential in understanding microbial ecology and application of biofilm in 'real‐world' systems. However, efficient genetic transformation of established biofilms at any scale remains challenging. In this study, we applied an ultrasound‐mediated DNA delivery (UDD) technique to introduce plasmid to established non‐competent biofilms in situ. Two different plasmids containing genes coding for superfolder green fluorescent protein (sfGFP) and the flavin synthesis pathway were introduced into established bacterial biofilms in microfluidic flow (transformation efficiency of 3.9 ± 0.3 × 10‐7 cells in biofilm) and microbial fuel cells (MFCs), respectively, both employing UDD. Gene expression and functional effects of genetically modified bacterial biofilms were observed, where some cells in UDD‐treated Pseudomonas putida UWC1 biofilms expressed sfGFP in flow cells and UDD‐treated Shewanella oneidensis MR‐1 biofilms generated significantly (P, In this study, we applied an ultrasound‐mediated DNA delivery (UDD) technique to introduce plasmids containing genes coding for superfolder green fluorescent protein (sfGFP) and the flavin synthesis pathway into established bacterial biofilms in microfluidic flow and microbial fuel cells (MFCs) respectively. Gene expression and functional effects of genetically modified bacterial biofilms were observed, where some cells in UDD‐treated Pseudomonas putida UWC1 biofilms expressed sfGFP in flow cells and UDD‐treated Shewanella oneidensis MR‐1 biofilms generated significantly greater (61%) bioelectricity production in MFC than a wild‐type control group. The effects of UDD were amplified in subsequent growth under selection pressure due to antibiotic resistance and metabolism enhancement. This is the first study to report on a potentially scalable direct genetic engineering method for established non‐competent biofilms, which can be exploited in enhancing their capability towards environmental, industrial and medical applications.

Noise characterization of cavitation has use in biomedicine, sonochemistry, and waste degradation. Typically, spectral features of the cavitation noise signals obtained through Fourier analysis are specific to the experimental set-up and are analyzed to classify the signals in terms of presumed domains of bubble behaviors. The objective of this research was to develop the experimental capabilities and algorithm to monitor and classify cavitation a priori using machine learning (ML) in a precise, repeatable, and translatable fashion among various setups and applications. Initially, simultaneous high-speed videos and passive acoustics maps were acquired for a single oscillating bubble in a simple setup. Machine learning methods such as support vector machine and convolutional neural networks were used to classify the acoustic data and train a classification algorithm. The algorithm was then adapted for a novel sonochemical reactor that induces spontaneous cavitation nucleation and utilizes a passive cavitation detector to monitor cavitation noise. Further research will be done in correlating potassium iodide (KI) degradation with frequency spectra using ML classification in order to optimize the sonochemical efficiency.

The use of high-intensity focused ultrasound (HIFU) to induce irreversible changes in tissue due to heating is well established. We have shown that changes in tissue optical properties (scattering and absorption coefficients) could be used as a proxy to improve sensing and imaging of HIFU lesion formation, as an alternative to conventional methods such as thermometry. Optical coherence tomography (OCT) is a non-invasive optical imaging method which relies on low-coherence interferometry to determine the depth of individual scattering centres within the tissue. Previous studies have demonstrated that OCT signals are sensitive to morphological changes in heated tissue, likely due to denaturation of proteins concomitant with formation of crosslinked structures. The goal of this study was to assess the use of OCT for sensing and imaging HIFU lesions. We demonstrate the feasibility of imaging near-surface lesions in ex vivo chicken breast tissue exposed to HIFU. This technique has potential for detecting changes in optical properties corresponding to the progression of surface lesion formation which are antecedents of skin burn during HIFU exposures, thereby increasing safety and reducing treatment times.

Acoustic droplet vaporization (ADV) is an important process that enables the theragnostic application of acoustically-activated droplets, where the nucleation of inertial cavitation (IC) activity must be precisely controlled. This letter describes threshold pressure measurements for ADV and acoustic emissions consistent with IC activity of lipid-shelled non-superheated perfluoropentane nanodroplets over a range of physiologically-relevant concentrations at 1.1-MHz. Under the frequency investigated, results show that the thresholds were relatively independent of concentration for intermediate concentrations (10^5, 10^6 and 10^7 droplets/ml), thus indicating an optimal range of droplet concentrations for conducting threshold studies. For the highest concentration, the difference between the threshold for IC and the threshold for ADV was greatly reduced, suggesting that it might prove difficult to induce ADV without concomitant IC in applications that employ higher concentrations.

Ultrasound-mediated DNA delivery (UDD) is a technique that utilizes ultrasound to aid the transfer of genetic materials into bacterial cells of interest (either in their planktonic or biofilm modes), resulting in new functionalities being displayed by the target microorganisms in-situ. The physical mechanism of UDD is poorly understood, which hampers its widespread adoption and scaling. To investigate the role of cavitation in UDD, we utilized a static pressure vessel designed to suppress cavitation while leaving other acoustic effects unaltered. Pseudomonas putida UWC1, a soil bacterium that is not naturally competent, was suspended in water and exposed to 40 kHz burst-mode ultrasound (400 cycle burst, 10 Hz repetition frequency, 60 s total) at an ambient pressure of either 1 bar or 9.5 bars. Noise diagnostics yielded inertial cavitation levels and transformed cells were quantified using a doubly selective reporter plasmid DNA. Samples exposed at 9.5 bars overpressure exhibited a drastic reduction in both cavitation activity and the number of transformed cells compared to those exposed at 1 bar. (Cell viability was not affected by pressure change.) The fact that transformation rates are reduced significantly when cavitation is suppressed suggests that acoustic cavitation is the major contributing factor in UDD.

Sonochemistry involves several steps. First, an acoustic wave must be generated with sufficient energy to nucleate cavitation. This cavitation event must then be energetic enough to produce radicals through the sonolysis of the gas or vapor molecules in the bubble. Finally, these radical species must survive long enough to react with other chemical species to yield the desired product. The sonochemical efficiency (SE) is thus defined as the ratio of the product yield to the input acoustic power. Here, we put forward a novel approach to enhancing the SE by designing a multi-frequency (0.25 to 1MHz) sonochemical reactor that reflects a cylindrically spreading acoustic wave 180°. The reflected wave converges to cylindrically shaped high-intensity “hot zone” positioned along the axis of the reaction vessel. At modest power input, we detected noise with a passive cavitation detector in air-saturated water, suggesting the direct nucleation of cavitation. Using the Weissler reaction to determine the production of hydroxyl radicals, we determined the SE of our sonochemical reactor at various operation conditions. We also compared these values to conventional bath, horn, and plate sonochemical reactors. The comparison suggested that our reactor design had a better sonochemical efficiency for the Weissler reaction.

Measurements were undertaken to determine the unknown microbubble-size distribution of a dodecafluoropentane (DDFP) emulsion consisting of 1012 droplets/ml in surfactant-stabilized water. The acoustic backscatter of 2-microsecond-duration tonebursts of 30-MHz focused ultrasound was measured from the emulsion as it moved in a coaxial flow. Calibration for the system was accomplished using 3-μm-radius polystyrene spheres, using a linear scattering model and literature values for polystyrene. Applying viscous linear scattering theory to the backscatter data from individual DDFP bubbles allowed inversion of the radius–backscatter relation. A mean microbubble radius of 130 nm was inferred for the DDFP population.

The quantitative characterization of noise sources in the ocean is a task which has attracted growing attention in recent years. In the absence of breaking gravity waves, capillary waves may contribute to the generation of high-frequency ambient noise. Surface profiles of capillary water waves are peaked downward in the troughs and relatively flat at the crests. At a limiting amplitude given by H/λ= 0.73 (where H and λ are the wave height and wavelenght, respectively) the free surface in the trough may fold onto itself, encapsulating an air bubble. By blowing air over a water-filled, plexiglass tank, bubble-producing capillary waves can be generated in the laboratory. Underwater acoustic emissions from these bubbles were monitored and a visual record of their formation was established via a high-speed video tape. The initial findings of an experimental study of the generation, size distribtuion, and acoustic emissions of bubbles produced by capillary water waves is presented.

Summary The present study was undertaken to see if there was any variability in the power output of Piezon-Master 400 ultrasonic files when driven using different generators, tranducers and file holders. The displacement amplitude of the oscillating tip of the file in air was used as a measure of the power output. The results showed that there was considerable variability in the power output of Piezon-Master 400 ultrasonic files of similar size and length when driven using different generators, transducers and file holders. In consideration of this, it is recommended that a calibration device be incorporated in the ultrasonic unit so that the operator will have some knowledge of when the unit is working at its maximum efficiency.

We report on imaging of coral skeletal densities using pulse-echo ultrasound. Focused ultrasound transducers with frequencies ranging from 1 to 5 MHz were used to image coral skeletal samples. Each transducer was scanned over the surface of a coral and the reflected signal from the coral was recorded. Post-processing of the ultrasound signal was used to generate images of the acoustic impedance of the coral—a quantity that is related to the density of the coral. The ultrasound images were qualitatively consistent with X-ray images of the coral samples—X-ray absorption is also related to coral density. Both images showed a banding structure related to the annual growth cycle of the coral. The results indicate that ultrasound can be used for nondestructive imaging of coral skeletal structure. The ultimate goal would be an in situ system for quantitatively measuring skeletal densities of live corals underwater. The skeletal density of several massive reef coral species is strongly correlated with ocean temperature. A time series reconstructions of the skeletal density of long lived specimens would provide a history of surface ocean temperatures over time periods extending over several centuries, far beyond the available instrumental record.

Summary The pattern of oscillation of a Piezon-Master 400 ultrasonic file driven by a piezoelectric transducer was studied in air and on water. In addition, the displacement amplitudes of the files were measured. The findings were compared with those observed with the Cavi-Endo unit reported in another study (Ahmad 1969). It was observed that the file vibrated such that a standing wave was formed on the file and it exhibited points of maximum deflection (antinode) and points of minimum deflection (node) with the largest deflection occurring at the apical end. This pattern of oscillation was similar to that exhibited by the Cavi-Endo file which employed a magnetostrictive transducer. However, the displacement amplitudes were very much higher than those exhibited by the Cavi-Endo. It is considered that the 120° angle of the file holder inherent in the Piezon- Master 400 unit and the more effective power transmission with the piezoelectric transducer may have contributed to the large amplitudes.

Acousto-optic imaging in diffuse media is a dual wave-sensing technique in which an acoustic field interacts with multiply scattered laser light. The acoustic field causes a phase modulation in the optical field emanating from the interaction region, and this phase-modulated optical field carries with it information about the local optomechanical properties of the media. We report on the use of a pulsed ultrasound transducer to modulate the optical field and the use of a photorefractive-crystal-based interferometry system to detect ultrasound-modulated light. The use of short pulses of focused ultrasound allows for a one-dimensional acousto-optic image to be obtained along the transducer axis from a single, time-averaged acousto-optic signal. The axial and lateral resolutions of the system are controlled by the spatial pulse length and width of the ultrasound beam, respectively. In addition, scanning the ultrasound transducer in one dimension yields two-dimensional images of optical inhomogeneities buried in turbid media.

In this paper the results of two studies related to high-intensity focused ultrasound (HIFU) and cavitation are reported. The first study described used polyacrylamide phantoms to gain insight into the behavior of cavitation activity in the focal region of the HIFU transducer. Results indicate that cavitation is the source of a previously observed enhanced heating effect in HIFU. The second study discussed used agar-graphite phantoms to see if changing the duty cycle of the driving could effect some measure of control over the cavitation activity; the results indicate that it can. © 2005 Acoustical Society of America.

An acoustic backscattering technique for detecting transient cavitation produced by 10-microseconds-long pulses of 757-kHz ultrasound is described. The system employs 10-microseconds-long, 30-MHz center frequency tone bursts that scatter from cavitation microbubbles. Experiments were performed with suspensions of hydrophobic polystyrene spheres in ultraclean water. Transient cavitation threshold pressures measured with the active cavitation detector (ACD) were always less than or equal to those measured using a passive acoustic detection scheme. The measured cavitation thresholds decreased with increasing dissolved gas content and increasing suspended particle concentration. Results also show that ultrasonic irradiation of the polystyrene sphere suspensions by the ACD lowered the threshold pressure measured with the passive detector. A possible mechanism through which suspensions of hydrophobic particles might nucleate bubbles is presented.

High-intensity focused ultrasound (HIFU) is a promising modality that is used to noninvasively ablate soft tissue tumors. Nevertheless, real-time treatment monitoring with diagnostic ultrasound still poses a significant challenge since tissue necrosis, in the absence of cavitation or boiling, provides little acoustic contrast with normal tissue. In comparison, the optical properties of tissue are significantly altered accompanying lesion formation. A photorefractive crystal-based acousto-optic (AO) sensing system that uses a single HIFU transducer to simultaneously generate tissue necrosis and pump the AO interaction is used to monitor the real-time optical changes associated with thermal lesions induced in chicken breast ex vivo . It is found that the normalized change in AO response increases proportionally with the volume of necrosis. This study demonstrates AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposures, results in more predictable lesion formation. (E-mails: laipuxiang@gmail.com or ronroy@bu.edu )

The role of both inertial and stable cavitation was investigated during in vitro ultrasound-accelerated fibrinolysis by recombinant tissue plasminogen activator (rt-PA) in the presence and absence of Optison™. A unique treatment configuration applied ultrasound, rt-PA and Optison™ to the interior of a plasma clot. Lysis efficacy was measured as clot weight reduction. Cavitational mechanisms were investigated by monitoring subharmonic and broadband noise. In the absence of Optison™, 1.7 MHz pulsed ultrasound with 1.5 MPa peak-negative pressure applied for 30 min resulted in 45 ± 19% lysis enhancement relative to rt-PA alone. Cavitation was not detected, indicating a role of noncavitational effects of ultrasound. The addition of Optison™ increased lysis enhancement to 88 ± 25%. Inertial cavitation was present only at the start of the exposure, while low-amplitude subharmonic emissions persisted throughout. Additional protocols suggested a possible correlation between the increased lysis in the presence of Optison™ and the subharmonic emission, indicating a potentially important role of stable rather than inertial cavitation in microbubble-enhanced ultrasound-accelerated rt-PA-mediated thrombolysis.

Preliminary results are presented from a recent experiment carried out at the NUWC Seneca Lake test facility and designed to investigate the scattering properties of bubble clouds produced in fresh water in the absence of boundaries and under known propagation conditions. The test range consisted of both conventional and parametric sources, conventional receivers, and a transient bubbler that was submerged to 91 m. The cloud possessed an elongated teardrop shape (length≊1.4 m, diameter≊0.5 m) with a void fraction of 0.25% and a mean bubble radius of 1.5 mm, which corresponds to a single‐bubble resonance frequency of 6.6 kHz at depth. Backscatter target strengths were measured for frequencies ranging from 300 Hz to 14 kHz. These measurements revealed high target strengths (up to +1 dB) and distinctive peaks in the spectrum at 450 Hz, and 1.3, 3.0, 6.5, and 11 kHz. The low‐frequency results are consistent with calculations (based on the theory of collective bubble oscillations) of the resonance frequency and target strength of a comparably sized, spherical bubble cloud. Certain features of the high‐frequency backscatter data are consistent with single‐bubble resonance scattering. These preliminary results are consistent with the notion that, at low frequencies, the scattering characteristics of a bubble cloud are determined, not by the bubble sizes and number density, but rather by the free‐gas volume fraction and the length scales of the cloud proper.

The impact of a jet of water onto a still water surface results in the entrainment of large amounts of air and the eventual formation of a bubble plume. Densely populated bubble plumes are generated by dropping a fixed volume of water, held in a cylindrical container, onto a still‐water surface. The detached bubble plume, which is roughly spherical in shape, then undergoes volume pulsation and radiates relatively large‐amplitude, low‐frequency sound. The results of a laboratory study of the noise produced by this process were reported previously by Kolaini et al. [J. Acoust. Soc. Am. 94, 2809–2820 (1993)]. In this paper we report the results of a field study of noise produced by this process in both fresh water (Lake Washington, WA) and salt water (Puget Sound, WA). Studies of acoustic emissions from transient bubble plumes as a function of cylinder parameters are described, with specific attention devoted to a comparison of the results obtained in salt and fresh water. The measurements, which exhibit good agreement with laboratory study, indicate that there is a correlation between the acoustic intensity radiated from bubble plumes and the total potential energy of the water jet.

This study examines the effectiveness of the thermal dose model in accurately predicting thermally induced optical property changes of ex vivo chicken breast between 500–1100 nm. The absorption coefficient, μa, and the reduced scattering coefficient, $\mu _s^\prime$, of samples are measured as a function of thermal dose over the range 50 °C–70 °C. Additionally, the maximum observable changes in μa and $\mu _s^\prime$ are measured as a function of temperature in the range 50 °C–90 °C. Results show that the standard thermal dose model used in the majority of high-intensity focused ultrasound (HIFU) treatments is insufficient for modeling optical property changes, but that the isodose constant may be modified in order to better predict thermally induced changes. Additionally, results are presented that show a temperature dependence on changes in the two coefficients, with an apparent threshold effect occurring between 65 °C–70 °C.

In the ocean, natural and artificial processes generate clouds of bubbles that scatter and attenuate sound. Measurements have shown that at the individual bubble resonance frequency, sound propagation in this medium is highly attenuated and dispersive. The existing theory to explain this behavior is deemed adequate away from resonance. However, due to excessive attenuation near resonance, little experimental data exists for a comparison with model predictions. An impedance tube was developed specifically for exploring this regime. The effective medium phase speed and attenuation were inferred from measurements of the surface impedance of a layer of bubbly liquid composed of air bubbles and distilled water, for void fractions from 6.2 x 10(-5) to 5.4 x 10(-4) and bubble sizes centered around 0.62 mm in radius. Improved measurement speed, accuracy, and precision is possible with the new instrument, and both instantaneous and time-averaged measurements were obtained. The phase speed and attenuation at resonance was observed to be sensitive to the bubble population statistics and agreed with an existing model [J. Acoust. Soc. Am. 85, 732-746 (1989)], within the uncertainty of the bubble population parameters. Agreement between the model and the data reported here is better than for the data that was available when the model was originally published.

The speed of sound in a bubbly liquid is strongly dependent upon the volume fraction of the gas phase, the bubble size distribution, and the frequency of the acoustic excitation. At sufficiently low frequencies, the speed of sound depends primarily on the gas volume fraction. This effect can be audibly demonstrated using a one-dimensional acoustic waveguide, in which the flow rate of air bubbles injected into a water-filled tube is varied by the user. The normal modes of the waveguide are excited by the sound of the bubbles being injected into the tube. As the flow rate is varied, the speed of sound varies as well, and hence, the resonance frequencies shift. This can be clearly heard through the use of an amplified hydrophone and the user can create aesthetically pleasing and even musical sounds. In addition, the apparatus can be used to verify a simple mathematical model known as Wood’s equation that relates the speed of sound of a bubbly liquid to its void fraction.

A laboratory experiment was conducted to measure the speed of sound in an artificial water-saturated granular sediment composed of cleaned and sorted medium-grained sand and degassed distilled water. The experiment was conducted within a range of frequencies where dispersion is predicted by a number of existing models. Between 2 and 4 kHz, the sound speed was inferred from measurements of the resonance frequencies of a thin-walled cylindrical container filled with the material. An elastic waveguide model was used to account for the effect of the finite impedance of the walls, although this effect was found to be small. From 20 to 300 kHz, the sound speed was obtained directly from time-of-flight measurements within the sediment. Dispersion in close agreement with the Williams effective density fluid model [K. L. Williams, J. Acoust. Soc. Am. 110, 2276-2281 (2001)] was observed.

An experimental study was conducted of the nonlinear coupling between the surface and volume modes of an oscillating bubble. Through this coupling, the surface modes of a bubble can produce monopole sound radiation, which has a higher radiation efficiency than the surface modes. A hydrophone and a hypodermic needle, connected to an air supply, were submerged in water in a small (7.1×7.1×7.7 cm3) sealed cell that was also connected to a regulated vacuum system for control of the ambient pressure. The sound radiation produced by releasing a bubble from the needle was monitored by a hydrophone and displayed on a digital oscilloscope. Two high‐speed video cameras simultaneously recorded the radial motion of the bubble and the sound radiation trace as displayed on an analog oscilloscope. At low ambient pressures (i.e., a few cm Hg), it was observed that after the bubble creation sound died out, a sound of the same frequency but with a lower and relatively constant magnitude followed. Therefore, it is believed that these subsequent acoustical emissions are evidence of the coupling between the surface and the volume modes of the bubble. Observation of a constant phase angle between the surface oscillations of the bubble and the radiated sound suggests a causal relationship.

Acoustic phase velocity measurements of a bubbly liquid in a cylindrical tube have been made with a fiber optic laser interferometer (FOLI) and hydrophones. Past experimental configurations of sound propagation studies in tubes filled with air–water mixtures consisted of hydrophones or piezoelectric pill transducers (PZPTs). Since hydrophones are intrusive sensors they impose a lower limit on the tube diameter (the tube diameter should be large compared to the hydrophone). Embedded PZPTs are typically spaced periodically imposing a limit on the resolution of the measured profile of the standing wave due to the finite size of the transducers. The advantages of the FOLI are the nonintrusive nature of the detection scheme, enhanced resolution, flexibility, and continuous scanning capabilities over a wide range of frequencies limited by the frequency response of the receiving photodiode and the properties of the membrane. The FOLI consisted of a Helium–Neon laser, a fiber optic beam splitter, a miniature lens, a photodiode, and a very thin reflective membrane which resides against the interior tube wall. The membrane is suspended by a small torus‐shaped magnet located on the exterior of the tube wall allowing continuous maneuverability in the vertical position of the membrane. The magnet also serves as the mount for the lens assembly.

Optical pulse width measurements of sonoluminescence from cavitation-bubble fields have been obtained for two well-defined cavitation zones in an aqueous solution of Glycerin using a fast (650 ps rise-time) PMT and a fast (10 GS/S) digitizer. One zone corresponds to cavitation produced from an ultrasonic homogenizer. A lens was used to focus on a particular region of “streaming” sonoluminescence. A second, more localized cavitation zone was produced using a 2-in-diam PZT driving crystal in a rectangular fluid-filled container. Single-bubble sonoluminescence was used to characterize the response of the PMT to low-level light input. The measured rise-time and pulse width for sonoluminescence from cavitation fields is indicative of the response of the PMT and suggests that the pulse width of cavitation-field sonoluminescence is much less than 1.1 ns.

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86°C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of “volume cauterization”, offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.

Hypobaric activation is a new injection technique for use with the contrast agent EchoGen® and, in this study, the agent’s ability to produce parenchymal enhancement in vivo, with and without prior hypobaric activation, was investigated. Injections, ranging in dose from 0.05 to 0.5 mL/kg, were administrated through a peripheral vein to eight woodchucks with multiple hepatomas. At the 0.10 mL/kg dose level, seven of eight injections following hypobaric activation (88%) resulted in definite parenchymal enhancement. Conversely, dosages of 0.10 mL/kg without prior hypobaric activation produced no grey-scale changes. Only at the 0.4 and 0.5 mL/kg dosage level did the conventional administration technique obtain similar results (4 of 5 injections increased the echogenicity for a 0.4 mL/kg dose). These differences were statistically significant (p = 0.031). In vitro experiments were conducted to establish the physical mechanisms behind hypobaric activation. Relative measurements of contrast microbubble sizes were performed with a phase Doppler particle analyzer after hypobaric and after conventional (bolus) activation. Hypobaric activation produced approximately 20 times more microbubbles per unit volume than the conventional method. In conclusion, this investigation has demonstrated the benefits of prior hypobaric activation when performing in vivo contrast studies with EchoGen® and determined the physical mechanisms behind this new injection technique. Hypobaric activation of EchoGen® increases contrast enhancement and reduces dose size.

In 1985, Scrimger [Nature 318, 647 (1985)] reported measurements of noise levels significantly above the ambient level for snow falling on a quiet freshwater lake. He examined only the time-averaged sound levels and did not report measurements of individual snowflake impacts. Subsequently, the noise produced by individual and multiple snowflake impacts was examined for a number of different snowfalls. The radiated acoustic signals generated by the impact of individual snowflakes upon a body of water have a remarkable similarity to each other and differ principally in the frequency of the emitted sound wave. The acoustic signal of a snowflake impact thus generates a characteristic signature for snowfall that is clearly distinct from other forms of precipitation noise. Various aspects of this signature suggest that the radiated acoustic waveform from a snowflake impacting with water is due to the entrainment of a gas bubble into the liquid, and the subsequent oscillation of this bubble as it establishes its equilibrium state. Various scenarios are presented for bubble entrainment and approximations to the amplitude of the radiated signal and the acoustic waveform are obtained.

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.

Acoustic scattering from a bubbly cylinder has been studied experimentally to determine the utility of effective medium scattering theory for a well defined shape. A bubble filled latex tube was submerged horizontally in a large tank, and its backscatter strength was measured for frequencies ranging from 5–20 kHz. Results show that the effective medium theory continues to be valid at higher frequencies, provided the scatterer’s shape is known.

Heating from high intensity focused ultrasound (HIFU) can be used to control bleeding, both from individual blood vessels as well as from gross damage to the capillary bed. The presence of vascularity can limit one’s ability to elevate the temperature owing to convective heat transport. In an effort to better understand the heating process in tissues with vascular structure we have developed a numerical simulation that couples models for ultrasound propagation, acoustic streaming, ultrasound heating and blood cooling in a Newtonian viscous medium. The 3-D simulation allows for the study of complicated biological structures and insonation geometries. We have also undertaken a series of in vitro experiments employing non-uniform flow-through tissue phantoms and designed to provide verification of the model predictions. We show that blood flow of 2 cm/s (6.4 ml/min through a 2.6 mm ‘vessel’) can reduce peak temperature in a vessel wall by 25%. We also show that HIFU intensities of 6.5×105 W/m2 can induce acoustic streaming with peak velocities up to 5 cm/s and this can reduce heating near a vessel wall by more than 10%. These results demonstrate that convective cooling is important in HIFU and can be accounted for within simulation models.

A number of groups have reported measurements of the location in the parameter space of bubble size versus acoustic pressure amplitude of shape- and size-stable bubbles. For air/water systems, a general trend emerges: stable bubbles are found on one of two line paths in this space defined by their range of acoustic pressure. Bubbles on the higher-pressure path emit light. There have been few studies of the transition between these two paths. In this work we describe our observations of this transition regime. In this regime, a slow time scale oscillation (period 2–7 s) in the bubble size, position, and phase of flash timing can be observed. At lower dissolved gas concentrations, a hysteresis in the bubble size as a function of acoustic pressure is observed, complementing previous light intensity measurements reported in the literature.

Time-resolved measurements of the temperature field in an agar-based tissue-mimicking phantom insonated with a large aperture 1-MHz focused acoustic transducer are reported. The acoustic pressure amplitude and insonation duration were varied. Above a critical threshold acoustic pressure, a large increase in the temperature rise during insonation was observed. Evidence for the hypothesis that cavitation bubble activity in the focal zone is the cause of enhanced heating is presented and discussed. Mechanisms for bubble-assisted heating are presented and modeled, and quantitative estimates for the thermal power generated by viscous dissipation and bubble acoustic radiation are given. (E-mail: rgholt@bu.edu)

Scaled laboratory experiments are conducted to assess the efficacy of iterative, single-channel time reversal for enhancement of monostatic returns from resonant spheres in the free field and buried in a sediment phantom. Experiments are performed in a water tank using a broad-band piston transducer operating between 0.4 and 1.5 MHz and calibrated using free surface reflections. Solid and hollow metallic spheres, 6.35 mm in diameter, are buried in a consolidation of 128-mum-mean-diameter spherical glass beads. The procedure consists of exciting the target object with a broadband pulse, sampling the return using a finite time window, reversing the signal in time, and using this reversed signal as the source waveform for the next interrogation. Results indicate that the spectrum of the returns rapidly converges to the dominant mode in the backscattering response of the target. Signal-to-noise enhancement of the target echo is demonstrated for a target at several burial depths. Images generated by scanning the transducer over the location of multiple buried targets demonstrate the ability of the technique to distinguish between targets of differing type and to yield an enhancement of different modes within the response of a single target as a function of transducer position and processing bandwidth.

One of Bill Carey's many scientific interests throughout his career was the acoustics of bubbly liquids. Many underwater acousticians know of Carey's work associated with bubble clouds and more recently, gas-bearing sediments, but Bill got his start with the subject earlier in his career, studying flow in a boiling water reactor while employed at Argonne National Laboratory. Here, the acoustic velocity of bubbly liquid is of interest because of the possibility of supersonic flow, at comparatively low flow rates, in the high-void-fraction mixture within the reactor's piping system. In this talk, an overview of Bill's work with the acoustics of bubbly liquids will be presented, including scattering from bubble clouds, and sound propagation within bubbly liquid and gas-bearing sediments. Finally, Bill's campaign to rename a famous equation (Wood's Equation) in honor of its forgotten originator (Mallock) will be reviewed. [Work supported by ONR.]

High‐intensity focused ultrasound (HIFU) is a viable treatment option for small tumors. This study investigates the feasibility of employing a photoacoustic (PA) sensor to monitor the in situ temperature rise during HIFU exposures. The present method also provides means to simultaneously monitor inertial cavitation using the same sensor. Polyacrylamide phantoms with a cylindrical inclusion (3×20 mm) of graphite (0.01 g/ml) were heated using 30 s exposures from a 2 MHz HIFU transducer. The transducer focus was aligned to the tip of a wire thermocouple embedded in the inclusion. A 532 nm pulsed laser was used to illuminate the inclusion. A 15 MHz broadband transducer was employed as a passive receiver (PR) to detect the PA response, which was an ultrasonic pulse emanating from the inclusion due to thermoelastic expansion induced by optical absorption. The native temperature and PR signals were recorded before, during, and after HIFU exposure. Singular‐value decomposition (SVD) was performed on the matrix consisting of the PR signals to extract temperature data. SVD‐deduced, PA‐based temperatures correlated well with the thermocouple measurements (RMS error

Light-absorbing nanoparticles can be used to improve the signal-to-noise ratio of the thermoelastic emissions from tissue that are used in photoacoustic tomography (PAT) and microscopy (PAM). Nanoparticles can be functionalized to selectively target cancer cells and destroy them through the formation of vapour bubbles. It has been shown that heating of the nanoparticles with a laser whilst they are simultaneously under tension from a high intensity focused ultrasound (HIFU) field results in a significant reduction in the optical fluence and acoustic pressure thresholds required for bubble formation. The localised heating from HIFU exposures in tissue is believed to be increased through the presence of bubbles, or specifically inertial cavitation, in the focal region. Thus an ability to nucleate vapour bubbles from nanoparticles using laser light combined with a HIFU field presents a unique opportunity for imaging and therapeutic applications.

Local hyperthermia is widely studied as a treatment option for small tumors. This study investigates the feasibility of exploiting the photoacoustic (PA) effect to monitor the in situ temperature rise during high-intensity focused ultrasound (HIFU) exposures for therapeutic hyperthermia. Polyacrylamide phantoms with a cylindrical inclusion (3 × 20 mm) of graphite (0.01 g/ml) were heated using 30 s exposures from a 2 MHz HIFU transducer. The transducer focus was aligned to the tip of a wire thermocouple embedded in the inclusion. A 532 nm pulsed laser was used to illuminate the inclusion. A 15 MHz broadband transducer was employed as a passive receiver (PR) to detect the PA response, which was an ultrasonic pulse emanating from the inclusion due to thermoelastic expansion induced by optical absorption. The native temperature and PR signals were recorded before, during, and after HIFU exposure. Singular-value decomposition (SVD) was performed on the matrix consisting of the PR signals to extract temperature data. SVD-deduced, PA-based temperatures correlated well with the thermocouple measurements (RMS error

Ultrasound at frequencies greater than 1 MHz is known to accelerate clot dissolution by fibrinolytic agents. It is speculated that ultrasound accelerates enzymatic fibrinolysis primarily through non-thermal mechanisms by increasing transport of drug molecules into the clot. To elucidate the mechanisms of ultrasound-accelerated enzymatic fibrinolysis, the role of both stable and inertial cavitation were investigated during in vitro fibrinolysis by ultrasound in combination with recombinant tissue plasminogen activator (rt-PA) in the presence and absence of Optisontrade. A unique treatment configuration was used in which ultrasound, rt-PA, and contrast agent were all applied to the interior of a plasma clot. rt-PA was injected directly into the clot at a concentration of 5,000 IU/mL. Optisontrade was dispersed throughout the clot at a concentration of 2.6times106 bubbles/mL. The ultrasound exposure consisted of 1.7 MHz pulsed ultrasound with 1.5 MPa spatial-peak peak-negative pressure applied for 30 minutes by a transducer-tipped catheter. Lysis efficacy was measured as clot weight reduction. Cavitational mechanisms were investigated by passively monitoring acoustic emissions from the clot using a focused broadband hydrophone, and quantifying levels of subharmonic emission and broadband noise, indicators for stable and inertial cavitation, respectively. In the absence of Optisontrade, ultrasound plus rt-PA resulted in 45 plusmn 19% lysis enhancement relative to lysis from rt-PA alone. Cavitation signals were not detected in the corresponding radiated acoustic signal, indicating a role for non-cavitational mechanical effects of ultrasound. The addition of Optisontrade significantly increased lysis enhancement to 88 plusmn 25%. Broadband noise elevation was present only at the start of the exposure, while low-level subharmonic emissions persisted throughout. Additional experiments suggested that the lysis enhancement in the presence of Optisontradewas correlated to the subharmonic emission rather than the broadband noise, indicating a role for stable cavitation. Mechanisms related to stable cavitation, such as microstreaming near oscillating bubbles, may enhance fibrinolysis by promoting local mass transfer and thus increasing the rate of penetration of rt-PA throughout the clot matrix

A multimode imaging system, producing conventional ultrasound (US) and acousto-optic (AO) images, has been developed and used to detect optical absorbers buried in excised biological tissue. A commercially-available diagnostic ultrasound imaging transducer is used to both generate B-mode ultrasound images and as a pump for AO imaging. Due to the fact that the steered and focused beam used for US imaging and the US source for pumping the AO image are generated from the same ultrasound probe, the acoustical and optical images are intrinsically co-registered. AO imaging is performed using short ultrasound pulse trains at a frequency of 5 MHz. The phase-modulated light emitted from the interaction region is detected using a photorefractive-crystal based interferometry system. Experimental results have previously been presented for the two-dimensional imaging in tissue-mimicking phantoms. In this paper, we report further experimental developments demonstrating three-dimensional fusion of B-mode ultrasound imaging and pulsed acousto-optic imaging in excised biological tissue (~2 cm thick). By mechanically scanning the ultrasound transducer array in a direction perpendicular to its imaging plane, both the acoustical and optical properties of an embedded target are obtained in three dimensions. The results suggest that AO imaging could be used to supplement conventional B-mode ultrasound imaging with optical contrast, and the multimode imaging system may find application in the detection and diagnosis of cancer.

Acousto-photonic imaging (API) is a dual-wave sensing technique in which a diffusive photon wave in a turbid medium interacts with an imposed acoustic field that drives scatterers to coherent periodic motion. A phase-modulated photon field emanates from the interaction region and carries with it information about the local opto-mechanical properties of the insonated media. A technological barrier to API has been sensitivity - the flux of phase-modulated photons is very small and the incoherence of the resulting speckle pattern reduces the modulation of the scattered light leading to low sensitivity. We report preliminary results from a new detection scheme in which a photorefractive crystal is used to mix the diffusively scattered laser light with a reference beam. The crystal serves as a dynamic holographic medium where the signal beam interferes with the reference beam, creating a photorefractive grating from which beams diffract. In addition, the phase modulation is converted to an amplitude modulation so that the API signal can be detected. Measurements of the API signal are presented for gel phantoms with polystyrene beads used as scatterers, showing a qualitative agreement with a simple theoretical model developed.

Fast heat deposition during high‐intensity focused ultrasound (HIFU) therapy is often accompanied by acoustic cavitation. In vivo and in vitro experiments have shown that with cavitation the heating rate is greatly enhanced and HIFU efficacy can be favorably improved. However uncontrolled cavitation usually results in irregular lesions and other undesirable effects. This work studies the interaction between the ultrasound pressure, cavitation and temperature field in a medium containing cavitation bubbles, with size distribution estimated by stability criteria and number density estimated from empirical observations. Treating the bubbly mixture as an effective medium with effective sound speed and attenuation coefficient determined from bubble dynamics, iterative computations on acoustic propagation and subsequent cavitation and thermal effects can be performed. The thermal lesion development is then simulated in a tissue‐like medium exposed to 1‐MHz HIFU in CW with MPa pressure amplitudes, and compared with experiment.

One of the limitations of HIFU treatment for tissue necrosis is the difficulty in achieving a predictable lesion shape and size in a short amount of time. Simply increasing the HIFU intensity cannot solve this problem, as it leads to the formation of a so‐called “tadpole”—shaped lesion. Bubble shielding of the incident HIFU is one of the mechanisms implicated in the development of these deformed lesions; at super‐nucleation pressures inertial cavitation will commence and the scattering from bubbles in the path of the ultrasound propagation will reflect the HIFU energy back towards the transducer. In the past we have employed a single focused, passive broadband transducer (PCD) to detect inertial cavitation activity at the HIFU focus in agar‐graphite tissue phantoms. At sufficiently‐high pressures, the inertial cavitation signal decreases over time, giving rise to the notion that bubble shielding is at fault for the signal decrease. Here we present evidence that bubble shielding is not the only mechanism behind such a change in the signal. As the medium heats up, inertial bubble collapses are cushioned by vapor and a decrease in signal amplitude from cavitation is to be expected. In order to evaluate the relative effects of the temperature rise and bubble shielding on bubble activity, we positioned a second PCD to sense noise emissions from various locations in the pre‐focal region along the HIFU axis. A decline in the cavitation signal from the focus was accompanied by an increase in pre‐focal bubble activity. The timescale for these changes suggests that both temperature and bubble shielding effects play a role in the bubble activity at the focus, and may provide information on how best to monitor the cavitation signal and ultimately provide feedback information necessary to control the HIFU insonation parameters to avoid bubble shielding.

Real-time imaging of the heating of tissue and lesion formation is a major barrier to the clinical application of HIFU. Tissue necrosis results in a change in the optical properties of the tissue. We have employed the acousto-optical (A-O) interaction to image HIFU lesions formed in excised chicken breast. The tissue was illuminated with infrared light (1064 nm wavelength) resulting in a diffuse optical field throughout the tissue. Simultaneously, the tissue was insonified with a diagnostic ultrasound imager running in B-mode. The photons that passed through the region of tissue where the pulsed 5 MHz ultrasound beam was present were phase modulated by the sound field. These modulated photons were detected by means of an interferometric detector employing a photorefractive crystal (PRC). To first order the amplitude of the output from the PRC is related to the optical absorption of the tissue where the sound was present. By firing multiple acoustic beams along different pathways, the spatially dependent optical absorption coefficient (uncalibrated) within a tissue region of interest is determined and presented in the form of a 2-D image. Images thus generated were recorded in chicken breast before and after HIFU exposure (1.1 MHz, 6 s duration, 6 MPa peak pressure). The acoustic and optical beams were scanned across the tissue, and the waveforms combined to form a 2-D AO image. The imaged lesion size of 9 x 2 mm 2 agreed well with the measured lesions size 10 x 3 mm 2. © 2009 American Institute of Physics.

Several animal models have exhibited petechial hemorrhage in the lung within the current FDA output limit of diagnostic ultrasound systems. To elucidate the mechanism of damage, seven rat lungs were simultaneously exposed or sham exposed in vivo to 6‐MHz pulsed Doppler ultrasound and interrogated with a confocally aligned 30‐MHz active cavitation detector (ACD) [R. A. Roy, S. Madanshetty, and R. E. Apfel, J. Acoust. Soc. Am. 20, 2451–2455 (1990)]. The right lung lobes of four 200 g rats were insonified with an ATL HDI 3000 6.0‐MHz Doppler pulse for 1.5 min and three rats were sham exposed. At the termination of ultrasound or sham exposure, each animal was immediately euthanized with sodium pentobarbital (200 mg/kg IP) and lung tissues were removed intact, inflated with buffered formalin, and examined by a pathologist who was blind to the exposure conditions. Histologically, damage was observed in the lungs exposed to ultrasound as extravasation of erythrocytes into the alveolar spaces. The ACD signal received was analyzed for the presence of increased scattering and radiated noise from inertial cavitation. The variance of the sequentially obtained ACD received pulses correlated with the damage in the exposed lungs. We conclude that inertial cavitation mediated the damage from diagnostic ultrasound.