Cavitation Monitoring Research Articles

Dual-Array Passive Acoustic Mapping for Cavitation Imaging With Enhanced 2-D Resolution.

Passive acoustic mapping (PAM) techniques have been developed for the purposes of detecting, localizing, and quantifying cavitation activity during therapeutic ultrasound procedures. Implementation with conventional diagnostic ultrasound arrays has allowed planar mapping of bubble acoustic emissions to be overlaid with B-mode anatomical images, with a variety of beamforming approaches providing enhanced resolution at the cost of extended computation times. However, no passive signal processing techniques implemented to date have overcome the fundamental physical limitation of the conventional diagnostic array aperture that results in point spread functions with axial/lateral beamwidth ratios of nearly an order of magnitude. To mitigate this problem, the use of a pair of orthogonally oriented diagnostic arrays was recently proposed, with potential benefits arising from the substantially expanded range of observation angles. This article presents experiments and simulations intended to demonstrate the performance and limitations of the dual-array system concept. The key finding of this study is that source pair resolution of better than 1 mm is now possible in both dimensions of the imaging plane using a pair of 7.5-MHz center frequency conventional arrays at a distance of 7.6cm. With an eye toward accelerating computations for real-time applications, channel count reductions of up to a factor of eight induce negligible performance losses. Modest sensitivities to sound speed and relative array position uncertainties were identified, but if these can be kept on the order of 1% and 1 mm, respectively, then the proposed methods offer the potential for a step improvement in cavitation monitoring capability.

Measurement of fluid flow rate using nanocomposite silicone rubber sensor

This paper describes the use of an elastic nanocomposite sensor to measure the water flow rate in open and closed hydraulic circuits. A sensor was constructed of multiwalled carbon nanotubes (MWCNTs) dispersed in silicone rubber (SR) and subsequently tested to verify its ability to measure water flow rate. The results reveal that the correlation between the fluid flow rate and the pressure variation across the sensor entails that its electrical resistance can be correlated to the flow rate. The sensor constructed of 2 and 3 wt,% of MWCNTs in SR-based nanocomposite sensors exhibited a low percolation threshold. An electron microscope (HRSEM) was used to characterize the manufactured nanocomposite sensors and confirm the conductive networks. The variation in the electrical resistance of the sensor in terms of both water pressure and flow rate is described. The elastic sensor was calibrated to measure the water flow rate in the range of 0–35 l/min. The results show that an elastic sensor fabricated from MWCNTs dispersed in silicone rubber does exhibit sensitivity to the slight strain levels produced by dynamic water pressure and, as such, can be used to measure flow rate. In addition, the sensor's response to water flow in the presence of bubbles enables pump cavitation monitoring. This paper also investigates the reduction of sensor electrical conductivity in response to water immersion. The findings reveal that the elastic nanocomposite sensor could potentially be used as a liquid sensor to detect water leakage in hydraulic circuits.

Cavitation Status Recognition Method of Centrifugal Pump Based on Multi-Pointand Multi-Resolution Analysis

Cavitation monitoring is particularly important for pump efficiency and stability. It is easy to misjudge cavitation by using a given threshold of a single eigenvalue. In this work, based on the vibration signal, a method for multi-resolution cavitation status recognition of centrifugal pump is proposed to improve the accuracy and universality of cavitation status recognition., wavelet packet decomposition (WPD) is used to extract the statistical eigenvalues of multi-scale time-varying moment of cavitation signal after reducing the clutter, such as root mean square value, energy entropy value and so on. The characteristic matrix is constructed. Principal component analysis method (PCA) is employed to reduce the dimension of the characteristic matrix and remove the redundancy, which constructs the radial basis function (RBF) neural network as the input. The results show that the overall recognition rate of non-cavitation, inception cavitation and serious cavitation by using the vibration signal of one measuring point is more than 97.7%. The recognition rate of inception cavitation is more than 80%. Based on the vibration signal information fusion method of two measuring points, the recognition rate of centrifugal pump inception cavitation status reaches more than 99%, and the recognition rate of vibration signal information fusion method of three measuring points reaches 100% for all three cavitation statuses. Due to the influence of factors such as change of external excitation and abrupt change of working conditions, sensor data acquisition is often subjected to unpredictable disturbance. To study the ability of single-point cavitation status recognition method to resist unknown disturbances, by constantly adjusting the value of the interference coefficient of the interference term. It is found that the recognition rate of cavitation status using single measuring point decreases almost linearly with the increase of the interference coefficient. When five measuring points are used for information fusion cavitation status recognition, the cavitation status recognition rate still reaches over 90% even if the interference factor of one measuring point reaches 50%.

Mehanizmi i morfologije kavitacionog oštećenja čelika Nionikral 70

Broken test tubes for low-cycle fatigue testing of Nionicral 70 (NN-70) parent material (PM) steel and simulated heat-affected zones (SHAZ) were used to produce samples for cavitation resistance testing. Ultrasonic vibrational cavitation method (stationary sample method) was applied for testing in laboratory conditions. The test conditions and procedure, sample preparation and interpretation of results are defined by ASTM G32. The surfaces of the NN-70 PM and SHAZ steel samples were exposed to cavitation and damage monitoring over time. Measuring the weight loss of samples on the analytical balance after a certain time allowed us to determine the cavitation velocity as a measure of the material's resistance to the effect of cavitation. Scanning electron microscopy (SEM) was applied to monitor variations in surface morphology with changing test time. On the basis of the results of the cavitation resistance test, the morphologies of the surface damage for different exposure times of the cavitation of PM and SHAZ steel NN-70 samples were analyzed, as well as the mechanisms that led to the damage of the sample surfaces.

Feature Selection for Monitoring Erosive Cavitation on a Hydroturbine

This paper presents a method for comparing and evaluating cavitation detection features - the first step towards estimating remaining useful life (RUL) of hydroturbine runners that areimpacted by erosive cavitation. The method can be used to quickly compare features created from cavitation survey data collected on any type of hydroturbine, sensor type, sensor location, and cavitation sensitivity parameter (CSP). Although manual evaluation and knowledge of hydroturbine cavitation is still required for our feature selection method, the use of principal component analysis greatly reduces the number of plots that require evaluation. We present a case study based on a cavitation survey data collected on a Francis hydroturbine located at a hydroelectric plant and demonstrate the selection of the most advantageous sensor type, sensor location, and CSP to use on this hydroturbine for long-term monitoring of erosive cavitation. Our method provides hydroturbine operators and researchers with a clear and effective means to determine preferred sensors, sensor placements, and CSPs while also laying the groundwork for determining RUL in the future.

Transcranial cavitation localization by time difference of arrival algorithm using four sensors

Cavitation is widely existing in focused ultrasound (FUS)-mediated therapies in the brain, such as FUS in combination with microbubble-induced blood-brain barrier disruption, nonthermal ablation, as well as transcranial histotripsy therapy. Accurately knowing the 3-D location of cavitation in real time can improve the treatment targeting accuracy and avoid off-target tissue damage. However, the skull induces strong phase and amplitude aberration to the cavitation signals and presents a significant challenge to the transcranial cavitation localization. Existing techniques for 3-D cavitation localization use hemispherical multi-element arrays combined with passive beamforming and adaptive skull-specific correction algorithm. However, these techniques require expensive equipment and treatment planning. Their time-consuming computations limit applications in real-time cavitation monitoring, which is critically needed to ensure the safety and efficacy of the FUS treatment. The object of this study was to investigate the feasibility of using a four-sensor network to transcranially locate the cavitation source in 3-D by time difference of arrival algorithm. The positional error of transcranial cavitation localization with the human skull along x, y, and z axes were 1.7 ± 1.2 mm, 1.6 ± 1.7 mm, and 4.1 ± 1.5 mm, respectively. For comparison, the positional error of without the human skull were 1.2 ± 1.8 mm, 0.9 ± 1.6 mm, and 3.1 ± 2.3 mm, respectively.

A High-Throughput Image-Guided Stereotactic Neuronavigation and Focused Ultrasound System for Blood-Brain Barrier Opening in Rodents.

The blood-brain barrier (BBB) has been a major hurdle for the treatment of various brain diseases. Endothelial cells, connected by tight junctions, form a physiological barrier preventing large molecules (>500 Da) from entering the brain tissue. Microbubble-mediated focused ultrasound (FUS) can be used to induce a transient local BBB opening, allowing larger drugs to enter the brain parenchyma. In addition to large-scale clinical devices for clinical translation, preclinical research for therapy response assessment of drug candidates requires dedicated small animal ultrasound setups for targeted BBB opening. Preferably, these systems allow high-throughput workflows with both high-spatial precision as well as integrated cavitation monitoring, while still being cost effective in both initial investment and running costs. Here, we present a bioluminescence and X-ray guided stereotactic small animal FUS system that is based on commercially available components and fulfills the aforementioned requirements. A particular emphasis has been placed on a high degree of automation facilitating the challenges typically encountered in high-volume preclinical drug evaluation studies. Examples of these challenges are the need for standardization in order to ensure data reproducibility, reduce intra-group variability, reduce sample size and thus comply with ethical requirements and decrease unnecessary workload. The proposed BBB system has been validated in the scope of BBB opening facilitated drug delivery trials on patient-derived xenograft models of glioblastoma multiforme and diffuse midline glioma.

Evaluation of the Uncertainty of Passive Cavitation Measurements for Blood–Brain Barrier Disruption Monitoring

Exposure to ultrasound combined with intravenous injection of microbubbles is a technique that can be used to temporarily disrupt the blood–brain barrier. Transcranial monitoring of cavitation can be done with one or more passive cavitation detectors (PCDs). However, the positioning of the PCDs relative to the cavitation site and the attenuation of these signals by the skull are two sources of error in the quantification of cavitation activity. The aim of this study was to evaluate in vitro the amplitude variation of cavitation signals that can be expected for an excised porcine skull model. The variation caused by the relative positioning of the PCD with respect to the cavitation site was quantified. A position-based correction of the signal amplitude was evaluated. Pig skull samples were used to assess variation in signal amplitude caused by bone. The overall coefficient of variation of the signals owing to these measurement biases was estimated at 30.8%.

Real-Time Passive Acoustic Mapping Using Sparse Matrix Multiplication.

Passive acoustic mapping enables the spatiotemporal monitoring of cavitation with circulating microbubbles during focused ultrasound (FUS)-mediated blood-brain barrier opening. However, the computational load for processing large data sets of cavitation maps or more complex algorithms limit the visualization in real-time for treatment monitoring and adjustment. In this study, we implemented a graphical processing unit (GPU)-accelerated sparse matrix-based beamforming and time exposure acoustics in a neuronavigation-guided ultrasound system for real-time spatiotemporal monitoring of cavitation. The system performance was tested in silico through benchmarking, in vitro using nonhuman primate (NHP) and human skull specimens, and demonstrated in vivo in NHPs. We demonstrated the stability of the cavitation map for integration times longer than 62.5 [Formula: see text]. A compromise between real-time displaying and cavitation map quality obtained from beamformed RF data sets with a size of 2000 ×128 ×30 (axial [Formula: see text]) was achieved for an integration time of [Formula: see text], which required a computational time of 0.27 s (frame rate of 3.7 Hz) and could be displayed in real-time between pulses at PRF = 2 Hz. Our benchmarking tests show that the GPU sparse-matrix algorithm processed the RF data set at a computational rate of [Formula: see text]/pixel/sample, which enables adjusting the frame rate and the integration time as needed. The neuronavigation system with real-time implementation of cavitation mapping facilitated the localization of the cavitation activity and helped to identify distortions due to FUS phase aberration. The in vivo test of the method demonstrated the feasibility of GPU-accelerated sparse matrix computing in a close to a clinical condition, where focus distortions exemplify problems during treatment. These experimental conditions show the need for spatiotemporal monitoring of cavitation with real-time capability that enables the operator to correct or halt the sonication in case substantial aberrations are observed.

A new safety index based on intrapulse monitoring of ultra-harmonic cavitation during ultrasound-induced blood-brain barrier opening procedures

Ultrasound-induced blood-brain barrier (BBB) opening using microbubbles is a promising technique for local delivery of therapeutic molecules into the brain. The real-time control of the ultrasound dose delivered through the skull is necessary as the range of pressure for efficient and safe BBB opening is very narrow. Passive cavitation detection (PCD) is a method proposed to monitor the microbubble activity during ultrasound exposure. However, there is still no consensus on a reliable safety indicator able to predict potential damage in the brain. Current approaches for the control of the beam intensity based on PCD employ a full-pulse analysis and may suffer from a lack of sensitivity and poor reaction time. To overcome these limitations, we propose an intra-pulse analysis to monitor the evolution of the frequency content during ultrasound bursts. We hypothesized that the destabilization of microbubbles exposed to a critical level of ultrasound would result in the instantaneous generation of subharmonic and ultra-harmonic components. This specific signature was exploited to define a new sensitive indicator of the safety of the ultrasound protocol. The approach was validated in vivo in rats and non-human primates using a retrospective analysis. Our results demonstrate that intra-pulse monitoring was able to exhibit a sudden appearance of ultra-harmonics during the ultrasound excitation pulse. The repeated detection of such a signature within the excitation pulse was highly correlated with the occurrence of side effects such as hemorrhage and edema. Keeping the acoustic pressure at levels where no such sign of microbubble destabilization occurred resulted in safe BBB openings, as shown by MR images and gross pathology. This new indicator should be more sensitive than conventional full-pulse analysis and can be used to distinguish between potentially harmful and safe ultrasound conditions in the brain with very short reaction time.

Internal flow structure, fault detection, and performance optimization of centrifugal pumps

This review mainly summarizes the latest developments in the internal flow field and external characteristics of centrifugal pumps. In particular, the latest findings of centrifugal pumps focused on turbulence and cavitation models, flow visualization methods, and fault detection based on noise and vibration. The external characteristics, cavitation, and vibration of the centrifugal pump were extensively discussed. In addition, advanced multi-objective optimization methods for improving impeller’s efficiency and reducing net positive suction head (NPSH) were briefed. Although some progress was made in this field, there remain many unsolved problems, such as monitoring and modeling of cavitation, rotational stall phenomenon, and discrepancies between simulation and measurement. In the future, researchers are encouraged to employ multi-dimensional flow visualization technologies and high-performance computing facilities to advance existing understandings on these issues and create new research directions.

Real-time visualization of instantaneous frequency from bubble cavitation using color Doppler ultrasound imaging

Time-resolved observations of acoustic cavitation emission signals are important in understanding bubble cavitation dynamics and monitoring sonoporation efficiencies of ultrasound-assisted drug delivery systems. Previous methods using back propagation of such signals measure frequencies with high time resolutions but require post-processing. We propose a method using color Doppler ultrasound to obtain instantaneous frequencies of these signals from the phase differences with an external reference signal. Standard color Doppler processing is applied to both emissions and reference signals to enable real-time observations of bubble cavitation generated by high-intensity ultrasound wave irradiation. A sinusoidal wave signal was used to confirm the accuracy of our method with an estimation error of 8.59%. Experiments were performed using Sonazoid suspensions of two different concentrations. With a sound pressure of 1.0 MPa for the ultrasound wave, the type of bubble cavitation that is dominant is different before and after irradiation of about ten pulses.

A new frequency domain passive acoustic mapping method using passive Hilbert beamforming to reduce the computational complexity of fast Fourier transform

Passive acoustic mapping (PAM) is the current state-of-the-art imaging tool for monitoring cavitation activity during focused ultrasound therapy such as blood-brain barrier opening. However, PAM incurs huge computational complexity. To address this issue, frequency-domain PAM (FD-PAM) was proposed. Nevertheless, FD-PAM still requires a large number of fast Fourier transforms (FFTs) to produce the frequency components utilized for cavitation monitoring with PAM. Hence, in this paper, we proposes a frequency domain PAM method using passive Hilbert beamforming (PHB-PAM), which can significantly reduce the number of input samples for FFT by down-sampling the analytic signal of the received RF samples at each channel at a rate equal to the bandwidth of the frequency components of interest. The experimental results show that the proposed PHB-PAM provides comparable image quality to that of FD-PAM (correlation coefficient > 0.98). Additionally, the study experimentally verifies that the pre-processing block for generating the decimated analytic signal and FFT in PHB-PAM can be realized using lesser logic resources than FFT in FD-PAM when implemented in an FPGA. Especially, with 128-fold decimation, PHB-PAM reduces the amount of LUTs and DSP slices to implement the pre-processing block by 72.16% and 53.4%, respectively, compared to those of FD-PAM, which allows the 64-channel implementation of the pre-processing block in a low-cost single FPGA. Finally, a hardware-efficient architecture for the pre-processing block of PHB-PAM is described, which can be implemented by replacing the two lowpass filters of an off-the-shelf analog front-end component for ultrasound imaging with a pair of band-pass filters. If PHB-PAM is realized using such a component, it can truly minimize the computational complexity of FD-PAM.

Correlation Between Brain Tissue Damage and Inertial Cavitation Dose Quantified Using Passive Cavitation Imaging

Focused ultrasound (FUS)-induced cavitation-mediated brain therapies have become emerging therapeutic modalities for neurologic diseases. Cavitation monitoring is essential to ensure the safety of all cavitation-mediated therapeutic techniques as inertial cavitation can be associated with tissue damage. The objective of this study was to reveal the correlation between the inertial cavitation dose, quantified by passive cavitation imaging (PCI), and brain tissue histologic-level damage induced by FUS in combination with microbubbles. An ultrasound image-guided FUS system consisting of a single-element FUS transducer (1.5 MHz) and a co-axially aligned 128-element linear ultrasound imaging array was used to perform FUS treatment of mice. Mice were sonicated by FUS with different peak negative pressures (0.5 MPa, 1.1 MPa, 4.0 MPa and 6.5 MPa) in the presence of systemically injected microbubbles. The acoustic emissions from the FUS-activated microbubbles were passively detected by the imaging array. The pre-beamformed channel data were acquired and processed offline using the frequency-domain delay, sum and integration algorithm to generate inertial cavitation maps. All the mice were sacrificed after the FUS treatment, and their brains were harvested and processed for hematoxylin and eosin staining. The obtained inertial cavitation maps revealed the dynamic changes of microbubble behaviors during FUS treatment at different pressure levels. It was found that the inertial cavitation dose quantified based on PCI had a linear correlation with the scale of histologic-level tissue damage. Findings from this study suggested that PCI can be used to predict histologic-level tissue damage associated with the FUS-induced cavitation.

Compensation of array lens effects for improved co-registration of passive acoustic mapping and B-mode images for cavitation monitoring.

Passive acoustic mapping (PAM) techniques offer a simple means of spatio-temporal cavitation monitoring during therapeutic ultrasound procedures. Implementation with a conventional diagnostic ultrasound system allows natural integration of PAM with B-mode imaging. However, the refracting properties of diagnostic array lenses may introduce PAM image registration errors that could lead to inaccuracies in treatment monitoring and guidance. To address these concerns, this paper presents lens characterization of two different array designs, analytical estimation of lens-induced source mapping errors in simple media, and experimental demonstration and correction of lens effects, reducing the depth-averaged image co-registration errors to no more than 0.52 mm.

Monitoring of acoustic cavitation in microbubble-presented focused ultrasound exposure using gradient-echo MRI.

Gadolinium-based contrast agents can be used to identify the blood-brain barrier (BBB) opening after inducing a focused ultrasound (FUS) cavitation effect in the presence of microbubbles. However, the use of gadolinium may be limited for frequent routine monitoring of the BBB opening in clinical applications. To use a gradient-echo sequence without contrast agent administration for monitoring of acoustic cavitation. Animal and phantom prospective. Static and flowing gel phantoms; six normal adult male Sprague-Dawley rats. 3T, 7T; fast low-angle shot sequence. Burst FUS with acoustic pressures = 1.5, 2.2, 2.8 MPa; pulse repetition frequencies = 1, 10,100 Hz; and duty cycles = 2%, 5%, 10% were transmitted to the chamber of a static phantom with microbubble concentrations = 10%, 1%, 0.1%. MR slice thicknesses = 3, 6, 8 mm were acquired. In flowing phantom experiments, 0.1%, 0.25%, 0.5%, 0.75%, and 1% microbubbles were infused and transmitted by burst FUS with an acoustic pressure = 0.4 and 1 MPa. In in vivo experiments, 0.25% microbubbles was infused and 0.8 MPa burst FUS was transmitted to targeted brain tissue beneath the superior sagittal sinus. The mean signal intensity (SI) was normalized using the mean SI from pre-FUS. Two-tailed Student's t-test. P < 0.05 was considered statistically significant. In the static phantom, the time courses of normalized SI decreases to minimum SI levels of 70-80%. In the flowing phantom, substantial normalized SI of 160-230% was present with variant acoustic pressures and microbubble concentrations. Compared with in vivo control rats, the brain tissue of experimental rats with transmission of FUS pulses exhibited considerable decreases of normalized SI (P < 0.001) because of the cavitation-induced perturbation of flow. Observing gradient-echo SI changes can help monitor the targeted location of microbubble-enhanced FUS, which in turn assists the monitoring of the BBB opening. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:311-318.

A Review of Experimental Detection Methods of Cavitation in Centrifugal Pumps and Inducers

An important flow mechanism that affects the performance and efficiency of centrifugal pumps is cavitation. In recent years, many researchers have studied the physics of cavitation in order to create appropriate detection methodologies. The aim of this paper is to review the various experimental tools that have been developed so far and enlighten the area of future research on the field of cavitation monitoring. According to the results, cavitation detection is possible, but a large number of sensors have to be used and permanent changes in the machine need to be made for increasing the results reliability. Therefore, future research steps are proposed towards the development of reliable, accurate but also easy to install and low cost experimental set ups.

Closed-loop cavitation control for focused ultrasound-mediated blood–brain barrier opening by long-circulating microbubbles

Focused ultrasound (FUS) exposure in the presence of microbubbles (MBs) has been successfully used in the delivery of various sizes of therapeutic molecules across the blood–brain barrier (BBB). While acoustic pressure is correlated with the BBB opening size, real-time control of BBB opening to avoid vascular and neural damage is still a challenge. This arises mainly from the variability of FUS-MB interactions due to the variations of animal-specific metabolic environment and specific experimental setup. In this study, we demonstrate a closed-loop cavitation control framework to induce BBB opening for delivering large therapeutic molecules without causing macro tissue damages. To this end, we performed in mice long-term (5 min) cavitation monitoring facilitated by using long-circulating MBs. Monitoring the long-term temporal kinetics of the MBs under varying level of FUS pressure allowed to identify in situ, animal specific activity regimes forming pressure-dependent activity bands. This enables to determine the boundaries of each activity band (i.e. steady oscillation, transition, inertial cavitation) independent from the physical and physiological dynamics of the experiment. However, such a calibration approach is time consuming and to speed up characterization of the in situ, animal specific FUS-MB dynamics, we tested a novel method called ‘pre-calibration’ that closely reproduces the results of long-term monitoring but with a much shorter duration. Once the activity bands are determined from the pre-calibration method, an operation band can be selected around the desired cavitation dose. To drive cavitation in the selected operation band, we developed an adaptive, closed-loop controller that updates the acoustic pressure between each sonication based on measured cavitation dose. Finally, we quantitatively assessed the safety of different activity bands and validated the proposed methods and controller framework. The proposed framework serves to optimize the FUS pressure instantly to maintain the targeted cavitation level while improving safety control.

Microbubble-assisted MRI-guided focused ultrasound for hyperthermia at reduced power levels

Purpose: Ultrasound contrast agent microbubbles were combined with magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) as a means to achieve mild hyperthermia at reduced power levels.Methods: MRgFUS hyperthermia (42°C for 20 min) was evaluated in rabbit thigh muscle or Vx2 tumors using infusions of microbubbles (Definity, 20 µL/kg) or saline (sham) administered over 5 min. The impact of treatments on drug uptake was assessed with liposomal doxorubicin (Caelyx, 2.5 mg/kg). Applied power levels before and after the injection of microbubbles or saline were compared, and drug uptake was evaluated with fluorometry of tissues harvested 24 hr post-treatment.Results: MRgFUS hyperthermia in muscle and tumors resulted in accurate temperature control (mean =42.0°C, root mean square error (RMSE) = 0.3°C). The power dropped significantly following the injection of microbubbles in muscle and tumors compared to exposures without microbubbles (–21.9% ± 12.5% vs –5.9% ± 7.8%, p = .009 in muscle; –33.8% ± 9.9% vs –3.0% ± 7.2%, p < .001 in tumors). Cavitation monitoring indicated emission of subharmonic, ultraharmonic, and elevated levels of fourth to sixth harmonic frequencies following microbubble injection. The drug delivery was elevated significantly in muscle with the use of microbubble-assisted relative to conventional heating (0.5 ± 0.5 ng/mg vs 0.20 ± 0.04 ng/mg, p = .05), whereas in tumors similar levels were found (11 ± 3 ng/mg vs 16 ± 4 ng/mg, p = .13).Conclusions: The finding that microbubbles reduce the applied power requirements for hyperthermia has considerable clinical implications. The elevated levels of drug found in muscle but not tumor tissue suggest a complex interplay between the heating effects of microbubbles with those of enhanced permeabilization and possible vascular damage.

Impact of stone characteristics on cavitation in burst wave lithotripsy

Non-invasive kidney stone treatments such as shock wave lithotripsy (SWL) and burst wave lithotripsy (BWL) rely on the delivery of pressure waves through tissue to the stone. In both SWL and BWL, the potential to hinder comminution by exciting cavitation proximal to the stone has been reported. To elucidate how different stones alter prefocal cavitation in BWL, different natural and synthetic stones were treated in vitro using a therapy transducer operating at 350 kHz (peak negative pressure 7 MPa, pulse length 20 cycles, pulse repetition frequency 10 Hz). Stones were held in a confined volume of water designed to mimic the geometry of a kidney calyx, with the water filtered and degassed to maintain conditions for which the cavitation threshold (in the absence of a stone) matches that from in vivo observations. Stone targeting and cavitation monitoring were performed via ultrasound imaging using a diagnostic probe aligned coaxially with the therapy transducer. Quantitative differences in the extent and location of cavitation activity were observed for different stone types—e.g., “softer” stones (natural and synthetic) that disintegrate into dusty fragments produced larger prefocal cavitation clouds. Future work will focus on correlation of such cavitation metrics with stone fragmentation. [Funding support by NIH P01-DK043881, K01-DK104854.]