Cavitation Imaging Research Articles

Treatment monitoring for sonothrombolysis in deep vein thrombosis: Receiver array design

The current treatment standard for deep vein thrombosis (DVT) is anticoagulation therapy, which does little to address long term morbidity compared to clot removal approaches. High intensity ultrasound can resolve clots by generating bubble clouds that erode thrombi. However, lack of appropriate treatment monitoring is a limiting factor in its widespread adoption. Passive cavitation imaging is capable of high frame rate, volumetric imaging, the combination of which has been shown to be important for monitoring the onset and development of bubble clouds inducing clot erosion (Acconcia et al. 2017). The results from our previous work motivated development of a device tailored to DVT with a relevant geometry (e.g., semi-cylindrical). Transmit simulations for such a device were conducted in a human thigh model (Smirnov and Hynynen 2017) with a design based on the modular transducer technology developed in our lab (Ellens et al. 2015). Here, we examine the integration of a sparse, randomly distributed receiver array within a semi-cylindrical arrangement of transmit modules for acoustic-based monitoring. Using a multi-layered propagation model, cavitation sources were localized to the femoral vessel, the accuracy of which depended on the inclusion of phase corrections. The receiver size was shown to be an important consideration with implicit trade-offs between directivity and channel SNR. Volumetric rates of ~1 MHz should be achievable with a modest number of receivers (128) in the presence of experimentally derived noise conditions.

Frequency-sum beamforming for passive cavitation imaging.

Beamforming includes a variety of spatial filtering techniques that may be used for determining sound source locations from near-field sensor array recordings. For this scenario, beamforming resolution depends on the acoustic frequency, array geometry, and target location. Random scattering in the medium between the source and the array may degrade beamforming resolution with higher frequencies being more susceptible to degradation. The performance of frequency-sum (FS) beamforming for reducing such sensitivity to mild scattering while increasing resolution is reported here. FS beamforming was used with a data-dependent [minimum variance (MV)] or data-independent (delay-and-sum, DAS) weight vector to produce higher frequency information from lower frequency signal components via a quadratic product of complex signal amplitudes. The current findings and comparisons are based on simulations and passive cavitation imaging experiments using 3 MHz and 6 MHz emissions recorded by a 128-element linear array. FS beamforming results are compared to conventional DAS and MV beamforming using four metrics: point spread function (PSF) size, axial and lateral contrast, and computation time. FS beamforming produces a smaller PSF than conventional DAS beamforming with less computation time than MV beamforming in free space and mild scattering environments. However, it may fail when multiple unknown sound sources are present.

Experimental study on the effect of nozzle geometry on string cavitation in real-size optical diesel nozzles and spray characteristics

Cavitation is quite important for the diesel spray atomization and the combustion of air–fuel mixture. In this study, a high-speed CMOS camera equipped with a long-distance microscope was utilized to capture the transient cavitating flow and spray characteristics in real-size optical nozzles with needle motion. The transient cavitation images, including geometry-induced cavitation and vortex-induced string cavitation, were captured clearly in cylindrical-orifice nozzles and tapered-orifice nozzles, respectively. Besides, the agglomerated phenomenon of geometry-induced cavitation was visually captured and analyzed for the first time. It was found that the string cavitation in nozzle excites the instability of spray cone angle and it is synchronized with increase of spray cone angle. In addition, it is the string cavitation but not geometry-induced cavitation has a much larger contribution to the increase of spray cone angle. It is interesting that the influence of agglomerated geometry-induced cavitation on spray cone angle was prominent. Furthermore, both the nozzle orifice L/D ratio and sac types have significant influences on string cavitation and spray characteristics. The smaller L/D ratio and VCO-type nozzles are prone to incur the stronger string cavitation, and then spray cone angle is obviously larger.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

Transcranial acoustic cavitation localization with ultrafast power cavitation imaging in non-human primates

Acoustic cavitation-guided blood-brain barrier (BBB) opening with focused ultrasound (FUS) and microbubbles is a promising technique for safe and controlled opening of the BBB. Passive cavitation imaging has the ability to monitor the spatial intensity of acoustic cavitation for targeting verification and treatment monitoring. However, isolating acoustic cavitation emissions from tissue and skull reflections is a major challenge. In this study, we perform transcranial passive cavitation imaging with a 1.5D imaging array (M5Sc-D, bandwidth: 1.5–4 MHz, GE Medical Systems) placed in the central opening of a 0.5 MHz FUS transducer (H204, Sonic Concepts) in non-human primates. Broadband FUS pulses were used along with synchronous transmit and receive sequences to perform delay and sum beamforming with absolute time delays. Image sets were acquired at ultrafast frame rates (>1000 frames per second) for calculation of mean intensity images, i.e., power cavitation images. Spatiotemporal clutter filtering of image...

A dual-mode hemispherical sparse array for 3D passive acoustic mapping and skull localization within a clinical MRI guided focused ultrasound device

Previous work has demonstrated that passive acoustic imaging may be used alongside MRI for monitoring of focused ultrasound therapy. However, past implementations have generally made use of either linear arrays originally designed for diagnostic imaging or custom narrowband arrays specific to in-house therapeutic transducer designs, neither of which is fully compatible with clinical MR-guided focused ultrasound (MRgFUS) devices. Here we have designed an array which is suitable for use within an FDA-approved MR-guided transcranial focused ultrasound device, within the bore of a 3 Tesla clinical MRI scanner. The array is constructed from 5 × 0.4 mm piezoceramic disc elements arranged in pseudorandom fashion on a low-profile laser-cut acrylic frame designed to fit between the therapeutic elements of a 230 kHz InSightec ExAblate 4000 transducer. By exploiting thickness and radial resonance modes of the piezo discs the array is capable of both B-mode imaging at 5 MHz for skull localization, as well as passive reception at the second harmonic of the therapy array for detection of cavitation and 3D passive acoustic imaging. In active mode, the array was able to perform B-mode imaging of a human skull, showing the outer skull surface with good qualitative agreement with MR imaging. Extension to 3D showed the array was able to locate the skull within ±2 mm/2° of reference points derived from MRI, which could potentially allow registration of a patient to the therapy system without the expense of real-time MRI. In passive mode, the array was able to resolve a point source in 3D within a ±10 mm region about each axis from the focus, detect cavitation (SNR ~ 12 dB) at burst lengths from 10 cycles to continuous wave, and produce 3D acoustic maps in a flow phantom. Finally, the array was used to detect and map cavitation associated with microbubble activity in the brain in nonhuman primates.

Diffusion Tensor Imaging of Scarring, Necrosis, and Cavitation Based on Histopathological Findings in Dogs with Chronic Spinal Cord Injury: Evaluation of Multiple Diffusion Parameters and Their Correlations with Histopathological Findings.

The use of diffusion tensor imaging (DTI) for the characterization of various lesion types in dogs with spinal cord injury (SCI) has not been investigated. The aim of this study was to characterize scarring (loose immature scarring [LIMS], intermediate mature scarring [IMS], and dense mature scarring [DMS]), necrosis, cavitation, and acute hemorrhage using multiple DTI parameters and determine the correlations between the DTI parameters and histopathological finding in dogs with controlled SCI. All imaging data were obtained from the lumbar spinal cord (from L1 to L3) of normal and SCI dogs using a 3-Tesla magnetic resonance imaging scanner. Transverse multi-shot echo planar imaging (EPI) sequences (12 directions; b-value, 0 and 800 s/mm2) were used for DTI. Regions of interest on DTI maps were selected according to the areas of normal white matter (NWM), normal gray matter (NGM), LIMS, IMS, DMS, necrosis, and cavitation on histopathological images and the area of acute hemorrhage with a hypointense signal on T2*-weighted images obtained 24 h post-SCI. There were statistically significant differences in DTI parameters among NWM, NGM, multi-grade scarring, necrosis, and cavitation and between mature scarring and acute hemorrhage. The maturation grade of scarring demonstrated a positive linear correlation with fractional anisotropy and the planar index and a negative linear correlation with the spherical index and the radial, mean, and axial diffusivities. These results suggest the feasibility of using DTI for detailed noninvasive monitoring of SCI. DTI can provide critical information for guiding therapeutic strategies and determining the prognosis of SCI patients.

Passive acoustic mapping of cavitation using eigenspace-based robust Capon beamformer in ultrasound therapy

Pulse-echo imaging technique can only play a role when high intensity focused ultrasound (HIFU) is turned off due to the interference between the primary HIFU signal and the transmission pulse. Passive acoustic mapping (PAM) has been proposed as a tool for true real-time monitoring of HIFU therapy. However, the most-used PAM algorithm based on time exposure acoustic (TEA) limits the quality of cavitation image. Recently, robust Capon beamformer (RCB) has been used in PAM to provide improved resolution and reduced artifacts over TEA-based PAM, but the presented results have not been satisfactory. In the present study, we applied an eigenspace-based RCB (EISRCB) method to further improve the PAM image quality. The optimal weighting vector of the proposed method was found by projecting the RCB weighting vector onto the desired vector subspace constructed from the eigenstructure of the covariance matrix. The performance of the proposed PAM was validated by both simulations and in vitro histotripsy experiments. The results suggested that the proposed PAM significantly outperformed the conventionally used TEA and RCB-based PAM. The comparison results between pulse-echo images of the residual bubbles and cavitation images showed the potential of our proposed PAM in accurate localization of cavitation activity during HIFU therapy.

Research progress in the pathogenesis and imaging of peripapillary intrachoroidal cavitation

Peripapillary intrachoroidal cavitation (PICC) is a common pathological change observed in high myopia. The exact pathogenesis of PICC is still unclear. Expansion and mechanical stretching of the peripapillary sclera, breakage and defect in the retina near the border of the myopic conus and communication between intrachoroidal cavity and the vitreous space may be important segments during the development of PICC. Color fundus photography shows a localized and well-circumscribed peripapillary lesion with yellow- orange colour, often accompanied by fundus changes, such as myopic conus excavation, optic disc tilting and inferotemporal retinal vein bending at the transition from the PICC to the myopic conus. However, the PICC lesion is not easy to be recognized in the fundus photography. Fluorescein angiography shows early hypofluorescence and later progressively staining in the lesion. Indocyanine green angiography shows hypofluorescence throughout the examination. Optical coherence tomography (OCT) is vital in diagnosing PICC. Hyporeflective cavities inside the choroid, sometimes communicating with the vitreous chamber, can be observed in OCT images. OCT angiography indicates lower vessel density or even absence of choriocapillary network inside or around PICC lesions. Key words: Choroid diseases/diagnosis; Myopia, degenerative/complications; Fluorescein angiography; Tomography, optical coherence; Review

Megahertz rate, volumetric imaging of bubble clouds in sonothrombolysis using a sparse hemispherical receiver array

It is well established that high intensity focused ultrasound can be used to disintegrate clots. This approach has the potential to rapidly and noninvasively resolve clot causing occlusions in cardiovascular diseases such as deep vein thrombosis (DVT). However, lack of an appropriate treatment monitoring tool is currently a limiting factor in its widespread adoption. Here we conduct cavitation imaging with a large aperture, sparse hemispherical receiver array during sonothrombolysis with multi-cycle burst exposures (0.1 or 1 ms burst lengths) at 1.51 MHz. It was found that bubble cloud generation on imaging correlated with the locations of clot degradation, as identified with high frequency (30 MHz) ultrasound following exposures. 3D images could be formed at integration times as short as 1 µs, revealing the initiation and rapid development of cavitation clouds. Equating to megahertz frame rates, this is an order of magnitude faster than any other imaging technique available for in vivo application. Collectively, these results suggest that the development of a device to perform DVT therapy procedures would benefit greatly from the integration of receivers tailored to bubble activity imaging.

Differential PI-Based Subharmonic Cavitation Imaging During Pulsed High Intensity Focused Ultrasound Exposures

Differential PI-Based Subharmonic Cavitation Imaging During Pulsed High Intensity Focused Ultrasound Exposures

Dissolved Oxygen Scavenging by Acoustic Droplet Vaporization using Intravascular Ultrasound.

Modification of dissolved gas content by acoustic droplet vaporization (ADV) has been proposed for several therapeutic applications. Reducing dissolved oxygen (DO) during reperfusion of ischemic tissue during coronary interventions could inhibit reactive oxygen species production and rescue myocardium. The objective of this study was to determine whether intravascular ultrasound (IVUS) can trigger ADV and reduce DO. Perfluoropentane emulsions were created using high-speed shaking and microfluidic manufacturing. High-speed shaking resulted in a polydisperse droplet distribution ranging from less than 1 micron to greater than 16 microns in diameter. Microfluidic manufacturing produced a narrower size range of droplets with diameters between 8.0 microns and 9.6 microns. The DO content of the fluids was measured before and after ADV triggered by IVUS exposure. Duplex B-mode and passive cavitation imaging was performed to assess nucleation of ADV. An increase in echogenicity indicative of ADV was observed after exposure with a clinical IVUS system. In a flow phantom, a 20% decrease in DO was measured distal to the IVUS transducer when droplets, formed via high-speed shaking, were infused. In a static fluid system, the DO content was reduced by 11% when droplets manufactured with a microfluidic chip were exposed to IVUS. These results demonstrate that a reduction of DO by ADV is feasible using a clinical IVUS system. Future studies will assess the potential therapeutic efficacy of IVUS-nucleated ADV and methods to increase the magnitude of DO scavenging.

Post Hoc Analysis of Passive Cavitation Imaging for Classification of Histotripsy-Induced Liquefaction in Vitro.

Histotripsy utilizes focused ultrasound to generate bubble clouds for transcutaneous tissue liquefaction. Bubble activity maps are under development to provide image guidance and monitor treatment progress. The aim of this paper was to investigate the feasibility of using plane wave B-mode and passive cavitation images to be used as binary classifiers of histotripsy-induced liquefaction. Prostate tissue phantoms were exposed to histotripsy pulses over a range of pulse durations (5- ) and peak negative pressures (12-23 MPa). Acoustic emissions were recorded during the insonation and beamformed to form passive cavitation images. Plane wave B-mode images were acquired following the insonation to detect the hyperechoic bubble cloud. Phantom samples were sectioned and stained to delineate the liquefaction zone. Correlation between passive cavitation and plane wave B-mode images and the liquefaction zone was assessed using receiver operating characteristic (ROC) curve analysis. Liquefaction of the phantom was observed for all the insonation conditions. The area under the ROC (0.94 versus 0.82), accuracy (0.90 versus 0.83), and sensitivity (0.81 versus 0.49) was greater for passive cavitation images relative to B-mode images ( ) along the azimuth of the liquefaction zone. The specificity was greater than 0.9 for both imaging modalities. These results demonstrate a stronger correlation between histotripsy-induced liquefaction and passive cavitation imaging compared with the plane wave B-mode imaging, albeit with limited passive cavitation image range resolution.

Pulse-Inversion Subharmonic Ultrafast Active Cavitation Imaging in Tissue Using Fast Eigenspace-Based Adaptive Beamforming and Cavitation Deconvolution.

Pulse-inversion subharmonic (PISH) imaging can display information relating to pure cavitation bubbles while excluding that of tissue. Although plane-wave-based ultrafast active cavitation imaging (UACI) can monitor the transient activities of cavitation bubbles, its resolution and cavitation-to-tissue ratio (CTR) are barely satisfactory but can be significantly improved by introducing eigenspace-based (ESB) adaptive beamforming. PISH and UACI are a natural combination for imaging of pure cavitation activity in tissue; however, it raises two problems: 1) the ESB beamforming is hard to implement in real time due to the enormous amount of computation associated with the covariance matrix inversion and eigendecomposition and 2) the narrowband characteristic of the subharmonic filter will incur a drastic degradation in resolution. Thus, in order to jointly address these two problems, we propose a new PISH-UACI method using novel fast ESB (F-ESB) beamforming and cavitation deconvolution for nonlinear signals. This method greatly reduces the computational complexity by using F-ESB beamforming through dimensionality reduction based on principal component analysis, while maintaining the high quality of ESB beamforming. The degraded resolution is recovered using cavitation deconvolution through a modified convolution model and compressive deconvolution. Both simulations and in vitro experiments were performed to verify the effectiveness of the proposed method. Compared with the ESB-based PISH-UACI, the entire computation of our proposed approach was reduced by 99%, while the axial resolution gain and CTR were increased by 3 times and 2 dB, respectively, confirming that satisfactory performance can be obtained for monitoring pure cavitation bubbles in tissue erosion.

Effect of fuel temperature on cavitation flow inside vertical multi-hole nozzles and spray characteristics with different nozzle geometries

The effects of the fuel temperature on diesel nozzle internal flow and the subsequent atomization were analyzed experimentally. Flow visualization was studied using a 10-times scaled-up transparent acrylic model nozzle with different geometries. A high-speed digital camera was used to capture the flow pattern in the region of the sac chamber and the nozzle. The energy loss in the occurrence of the hydraulic flip was also analyzed. In addition, cavitation images obtained in the multi-hole tapered nozzle with different fuel temperatures had revealed that although the conical shape of the converging tapered holes suppresses formation of geometry-induced cavitation, string cavitation has been clearly observed anyway. Afterward, the experimental method was used to analyze the effects of the nozzle sac volume structure on the cavitation flow inside the nozzle and subsequent spray. It was found that the in-nozzle flow stage and spray formation were sensitive to the fuel temperature. The visual experiment is helpful to understand the nozzle flow and optimize the diesel injectors eventually.

Are flowers vulnerable to xylem cavitation during drought?

Water stress is known to cause xylem cavitation in the leaves, roots and stems of plants, but little is known about the vulnerability of flowers to xylem damage during drought. This is an important gap in our understanding of how and when plants become damaged by water stress. Here we address fundamental questions about if and when flowers suffer cavitation damage, using a new technique of cavitation imaging to resolve the timing of cavitation in water-stressed flower petals compared with neighbouring leaves. Leaves and flowers from a sample of two herbaceous and two woody eudicots were exposed to a severe water stress while the spatial and temporal propagation of embolism through veins was recorded. Although in most cases water potentials inducing 50% embolism of herbaceous flower veins were more negative than neighbouring leaves, there was no significant difference between the average vulnerability of leaves and petals of herbaceous species. In both woody species, petals were more vulnerable to cavitation than leaves, in one case by more than 3 MPa. Early cavitation and subsequent damage of flowers in the two woody species would thus be expected to precede leaf damage during drought. Similar cavitation thresholds of flowers and leaves in the herb sample suggest that cavitation during water shortage in these species will occur simultaneously among aerial tissues. Species-specific differences in the cavitation thresholds of petals provide a new axis of variation that may explain contrasting flowering ecology among plant species.

Real-time acoustic-based feedback for histotripsy therapy

Histotripsy uses high-pressure microsecond ultrasound pulses to generate cavitation to fractionate cells in target tissues. Two acoustic-based feedback mechanisms are being investigated to monitor histotripsy therapy in real-time. First, bubble-induced color Doppler (BICD) is received by an ultrasound probe co-aligned with the histotripsy transducer to monitor the cavitation-induced motion of residual cavitation nuclei in tissue throughout treatment. Second, acoustic backscatter of the histotripsy pulse from the cavitation bubbles is received by directly probing elements of histotripsy transducer to monitor acoustic emissions from the cavitation bubbles during treatment. In these experiments, histotripsy was applied to agarose phantoms and ex vivo tissue by a 112-element, 500 kHz semi-hemispherical ultrasound array with a 15 cm focal distance. The BICD signals were collected on a Verasonics system by an L7-4 probe. The BICD and backscatter signals were compared to high-speed optical images of cavitation in phantoms and histology of tissue. A consistent trend was observed in both the BICD and backscatter waveforms throughout treatment in both tissue and agarose phantoms that correlated with high-speed imaging and histological analysis. These results suggest that BICD and acoustic backscatter can provide non-invasive, real-time, quantitative feedback of tissue treatment progression during histotripsy, thus improving treatment efficiency and accuracy.

Using frequency-sum beamforming in passive cavitation imaging

Passive Cavitation Imaging (PCI) is a method for locating cavitation emissions to study biological effects of ultrasound on tissues. In this method, an image is formed by beamforming passively recorded acoustic emissions with an array. The image resolution depends on the ultrasound frequency and array geometry. Acoustic emissions can be scattered due to tissue inhomogeneity, which may degrade the image resolution. Emissions at higher frequencies are more susceptible to such degradation. Frequency-sum beamforming is a nonlinear technique that alters this sensitivity to scattering by manufacturing higher frequency information from lower frequency components via a quadratic product of complex signal amplitudes. This presentation evaluates the performance of frequency-sum beamforming in a scattering environment using simulations and experiments, conducted in the kHz and MHz frequency regimes. First, 50 and 100 kHz signals were broadcasted from a single source to an array of 16 hydrophones in a water tank with and without discrete scatterers. Second, a tissue-mimicking phantom perfused with microbubbles was insonified at 2 MHz, and the emissions were received by a 128-element linear array. The performance of frequency-sum beamforming was compared to conventional delay-and-sum and minimum variance beamforming in mild and strong scattering environments. [Work partially supported by NAVSEA through the NEEC.]

Frequency-domain passive cavitation imaging

Apfel’s three golden rules (know thy sound field, know thy liquid, and know when something happens) should be considered when monitoring acoustic cavitation-based ultrasound therapies. The third rule is often followed using passive cavitation detection with a single-element transducer. However, therapy guidance demands monitoring cavitation activity in the entire tissue volume of interest. Using array-based passive cavitation detection with appropriate beamforming, maps of cavitation activity can be superimposed on pulse-echo, grayscale images of tissue anatomy. In this talk, we will discuss one approach for generating cavitation activity maps, frequency-domain passive cavitation imaging (FD-PCI). FD-PCI implements a delay, sum, and integrate algorithm, which will be described conceptually and mathematically. The advantages and limitations of the algorithm will be discussed in the context of examples. Advantages of FD-PCI include the innate frequency selectivity of the algorithm, the ability to use parallel computing for increased processing speed, the independence of the image resolution from the therapy insonation pulse shape, and the ability to quantify the acoustic power of emissions detected by the array. Challenges of the algorithm will also be discussed, including poor axial resolution and limitations of estimating the emitted acoustic power.

Image-based measurements for examining model predictability of cavitation on a marine propeller surface

Because of its complex nature, cavitation associated with marine propellers poses a challenge to numerical simulations for predicting it. This paper experimentally examines the predictions of vapor volume fraction (VVF) done by RANS simulations with three cavitation models for a propeller whose design is to suppress sheet cavitation. The equality of VVF and cavitation occurrence probability (COP), whose distribution can be measured with cavitation images acquired using the phase-locked imaging technique in an open-water test, is found and becomes the base of a methodology developed for examining model predictability of cavitation. By comparing and correlating the distributions of VVF computed using different cavitation models with that of measured COP, predictabilities of cavitation models can be quantified to elucidate modeling issues and possible remedies for them.