54 results found
Koruk H, Choi JJ, 2019, Displacement of a bubble located at a fluid-viscoelastic medium interface, Journal of the Acoustical Society of America, Vol: 145, ISSN: 0001-4966
A model for estimating the displacement of a bubble located at a fluid-viscoelastic medium interface in response to acoustic radiation force is presented by extending the model for a spherical object embedded in a bulk material. The effects of the stiffness and viscosity of the viscoelastic medium and the amplitude and duration of the excitation force on bubble displacement were investigated using the proposed model. The results show that bubble displacement has a nonlinear relationship with excitation duration and viscosity. The time at which the steady state is reached increases with increasing medium viscosity and decreasing medium stiffness.
Morse SV, Pouliopoulos AN, Chan TG, et al., 2019, Rapid short-pulse ultrasound delivers drugs uniformly across the murine blood-brain barrier with negligible disruption, Radiology, Vol: 291, Pages: 459-466, ISSN: 0033-8419
Background Previous work has demonstrated that drugs can be delivered across the blood-brain barrier by exposing circulating microbubbles to a sequence of long ultrasound pulses. Although this sequence has successfully delivered drugs to the brain, concerns remain regarding potentially harmful effects from disrupting the brain vasculature. Purpose To determine whether a low-energy, rapid, short-pulse ultrasound sequence can efficiently and safely deliver drugs to the murine brain. Materials and Methods Twenty-eight female wild-type mice underwent focused ultrasound treatment after injections of microbubbles and a labeled model drug, while three control mice were not treated (May-November 2017). The left hippocampus of 14 mice was exposed to low-energy short pulses (1 MHz; five cycles; peak negative pressure, 0.35 MPa) of ultrasound emitted at a rapid rate (1.25 kHz) in bursts (0.5 Hz), and another 14 mice were exposed to standard long pulses (10 msec, 0.5 Hz) containing 150 times more acoustic energy. Mice were humanely killed at 0 (n = 5), 10 (n = 3), or 20 minutes (n = 3) after ultrasound treatment. Hematoxylin-eosin (H-E) staining was performed on three mice. The delivered drug dose and distribution were quantified with the normalized optical density and coefficient of variation. Safety was assessed by H-E staining, the amount of albumin released, and the duration of permeability change in the blood-brain barrier. Statistical analysis was performed by using the Student t test. Results The rapid short-pulse sequence delivered drugs uniformly throughout the parenchyma. The acoustic energy emitted from the microbubbles also predicted the delivered dose (r = 0.97). Disruption in the blood-brain barrier lasted less than 10 minutes and 3.4-fold less albumin was released into the brain than with long pulses. No vascular or tissue damage from rapid short-pulse exposure was observable using H-E staining. Conclusion The rapid short-pulse ultrasound sequence is a minimally
El Ghamrawy A, de Comtes F, Koruk H, et al., 2019, Acoustic streaming in a soft tissue microenvironment, Ultrasound in Medicine and Biology, Vol: 45, Pages: 208-217, ISSN: 0301-5629
We demonstrated that sound can push fluid through a tissue-mimicking material. Although acoustic streaming in tissue has been proposed as a mechanism for biomedical ultrasound applications, such as neuromodulation and enhanced drug penetration, streaming in tissue or acoustic phantoms has not been directly observed. We developed a material that mimics the porous structure of tissue and used a dye and a video camera to track fluid movement. When applied above an acoustic intensity threshold, a continuous focused ultrasound beam (spatial peak time average intensity: 238 W/cm2, centre frequency: 5 MHz) was found to push the dye axially, that is, in the direction of wave propagation and in the radial direction. Dye clearance increased with ultrasound intensity and was modelled using an adapted version of Eckart's acoustic streaming velocity equation. No microstructural changes were observed in the sonicated region when assessed using scanning electron microscopy. Our study indicates that acoustic streaming can occur in soft porous materials and provides a mechanistic basis for future use of streaming for therapeutic or diagnostic purposes.
Saharkhiz N, Koruk H, Choi JJ, 2018, The effects of ultrasound parameters and microbubble concentration on acoustic particle palpation, Journal of the Acoustical Society of America, Vol: 144, Pages: 796-805, ISSN: 0001-4966
The elasticity of tissue-an indicator of disease progression-can be imaged by ultrasound elasticity imaging technologies. An acoustic particle palpation (APP) has recently been developed-the use of ultrasonically driven acoustic particles (e.g., microbubbles)-as an alternative method of tissue deformation. APP has the potential to improve the resolution, contrast, and depth of ultrasound elasticity imaging; but the tissue displacement dynamics and its dependence on acoustic pressure, center frequency, and microbubble concentration remains unknown. Here, displacements of at least 1 μm were produced by applying ultrasound onto a microbubble solution (concentration: 10 × 106 microbubbles ml-1) placed within a tunnel surrounded by a 5% gelatin phantom. Displacements of more than 10 μm were produced using a 1, 3.5, or 5 MHz center frequency pulse with peak-rarefactional pressures of 470, 785, and 1210 kPa, respectively. The deformation of the distal wall varied spatially and temporally according to the different parameters investigated. At low pressures, the deformation increased over several milliseconds until it was held at a nearly constant value. At high pressures, a large deformation occurred within a millisecond followed by a sharp decrease and long stabilization. Ultrasound exposure in the presence of microbubbles produced tissue deformation (p < 0.05) while without microbubbles, no deformation was observed.
Chan T, Morse S, Copping M, et al., 2018, Targeted delivery of DNA-Au nanoparticles across the blood-brain barrier using focused ultrasound, ChemMedChem, Vol: 13, Pages: 1311-1314, ISSN: 1860-7187
Nanoparticles have been widely studied as versatile platforms for in vivo imaging and therapy. However, their use to image and/or treat the brain is limited, as they are often unable to cross the blood–brain barrier (BBB). To overcome this problem, herein we report the use of focused ultrasound in vivo to successfully deliver DNA‐coated gold nanoparticles to specific locations in the brains of mice.
Koruk H, Choi JJ, 2018, Displacement of a bubble by acoustic radiation force into a fluid-tissue interface., Journal of the Acoustical Society of America, Vol: 143, Pages: 2535-2540, ISSN: 0001-4966
Microbubbles in an ultrasound beam experience a primary Bjerknes force, which pushes the microbubbles against a fluid-tissue interface and deforms the tissue. This interaction has been used to measure tissue elasticity and is a common interaction in many therapeutic and diagnostic applications, but the mechanisms of deformation, and how the deformation dynamic depends on the bubble and ultrasound parameters, remain unknown. In this study, a mathematical model is proposed for the displacement of a bubble onto a fluid-tissue interface and the tissue deformation in response to the primary Bjerknes force. First, a model was derived for static loading and the model's prediction of bubble-mediated tissue displacement and stresses in tissue were explored. Second, the model was updated for dynamic loading. The results showed that the bubble is both displaced by the applied force and changes its shape. The bubble displacement changes nonlinearly with the applied force. The stress values in tissue are quite high for a distance within one radius of the bubble from the bubble surface. The model proposed here is permissible in human tissue and can be used for biomedical ultrasound applications, including material characterization.
Lazarus C, Pouliopoulos AN, Tinguely M, et al., 2017, Clustering dynamics of microbubbles exposed to low-pressure 1-MHz ultrasound, Journal of the Acoustical Society of America, Vol: 142, Pages: 3135-3146, ISSN: 0001-4966
Ultrasound-driven microbubbles have been used in therapeutic applications to deliver drugs acrosscapillaries and into cells or to dissolve blood clots. Yet the performance and safety of these applica-tions have been difficult to control. Microbubbles exposed to ultrasound not only volumetricallyoscillate, but also move due to acoustic radiation, or Bjerknes, forces. The purpose of this work wasto understand the extent to which microbubbles moved and clustered due to secondary Bjerknesforces. A microbubble population was exposed to a 1-MHz ultrasound pulse with apeak-rarefactional pressure of 50–100 kPa and a pulse length of 20 ms. Microbubbles exposed tolow-pressure therapeutic ultrasound were observed to cluster at clustering rates of 0.01–0.02 micro-bubbles per duration (in ms) per initial average inter-bubble distance (inlm), resulting in 1 to 3clustered microbubbles per initial average inter-bubble distance (inlm). Higher pressures causedfaster clustering rates and a larger number of clustered microbubbles. Experimental data revealedclustering time scales, cluster localizations, and cluster sizes that were in reasonable agreementwith simulations using a time-averaged model at low pressures. This study demonstrates that clus-tering of microbubbles occurs within a few milliseconds and is likely to influence the distributionof stimuli produced in therapeutic applications.
Morse SV, Pouliopoulos AN, Chan T, et al., 2017, Rapid short-pulse (RaSP) sequences improve the distribution of drug delivery to the brain in vivo, IEEE UFFC, Publisher: IEEE, ISSN: 1948-5719
Focused ultrasound and microbubbles have been shown to locally and noninvasively open the blood-brain barrier. Despite encouraging results in human patients, several performance and safety features, such as poor drug distribution, high drug accumulation along vessels and small sites of red blood cell extravasation, have been unavoidable. We have recently developed a new ultrasound sequence - rapid short-pulse (RaSP) sequence - designed to suppress these adverse features by promoting safer modes of cavitation activity throughout capillaries. In our RaSP sequences, low-pressure short ultrasonic pulses are emitted at kHz pulse repetition frequencies (PRF) and grouped into bursts. We have shown in vitro that RaSP sequences prolong microbubble lifetime and increase their mobility, enhancing the distribution of acoustic cavitation activity. Here we evaluate the ability of RaSP sequences to improve the in vivo performance and safety of ultrasound-mediated drug delivery to the brain.
Zhang C, Yao Z-C, Ding Q, et al., 2017, Tri-needle coaxial electrospray engineering of magnetic polymer yolk-shell particles possessing dual-imaging modality, multiagent compartments, and trigger release potential, ACS Applied Materials and Interfaces, Vol: 9, Pages: 21485-21495, ISSN: 1944-8244
Particulate platforms capable of delivering multiple actives as well as providing diagnostic features have gained considerable interest over the last few years. In this study, magnetic polymer yolk–shell particles (YSPs) were engineered using a tri-needle coaxial electrospraying technique enabling dual-mode (ultrasonic and magnetic resonance) imaging capability with specific multidrug compartments via an advanced single-step encapsulation process. YSPs comprised magnetic Fe3O4 nanoparticles (MNPs) embedded in the polymeric shell, an interfacing oil layer, and a polymeric core (i.e., composite shell–oil interface–polymeric core). The frequency of the ultrasound backscatter signal was modulated through YSP loading dosage, and both T1- and T2-weighted magnetic resonance imaging signal intensities were shown to decrease with increasing MNP content (YSP outer shell). Three fluorescent dyes (selected as model probes with varying hydrophobicities) were coencapsulated separately to confirm the YSP structure. Probe release profiles were tuned by varying power or frequency of an external auxiliary magnetic field (AMF, 0.7 mT (LAMF) or 1.4 mT (HAMF)). In addition, an “inversion” phenomenon for the AMF-enhanced drug release process was studied and is reported. A low YSP cytotoxicity (5 mg/mL) and biocompatibility (murine, L929) was confirmed. In summary, magnetic YSPs demonstrate timely potential as multifunctional theranostic agents for dual-imaging modality and magnetically controlled coactive delivery.
Heymans SV, Martindale CF, Suler A, et al., 2017, Simultaneous Ultrasound Therapy and Monitoring of Microbubble-Seeded Acoustic Cavitation Using a Single-Element Transducer, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 64, Pages: 1234-1244, ISSN: 0885-3010
Ultrasound-driven microbubble (MB) activity is used in therapeutic applications such as blood clot dissolution and targeted drug delivery. The safety and performance of these technologies are linked to the type and distribution of MB activities produced within the targeted area, but controlling and monitoring these activities in vivo and in real time has proven to be difficult. As therapeutic pulses are often milliseconds long, MB monitoring currently requires a separate transducer used in a passive reception mode. Here, we present a simple, inexpensive, integrated setup, in which a focused single-element transducer can perform ultrasound therapy and monitoring simultaneously. MBs were made to flow through a vesselmimicking tube, placed within the transducer's focus, and were sonicated with therapeutic pulses (peak rarefactional pressure: 75-827 kPa, pulse lengths: 200 μs and 20 ms). The MB-seeded acoustic emissions were captured using the same transducer. The received signals were separated from the therapeutic signal with a hybrid coupler and a high-pass filter. We discriminated the MB-generated cavitation signal from the primary acoustic field and characterized MB behavior in real time. The simplicity and versatility of our circuit could make existing single-element therapeutic transducers also act as cavitation detectors, allowing the production of compact therapeutic systems with real time monitoring capabilities.
Pouliopoulos A, Caiqin L, Tinguely M, et al., 2016, Rapid short-pulse sequences enhance the spatiotemporal uniformity of acoustically driven microbubble activity during flow conditions, Journal of the Acoustical Society of America, Vol: 140, ISSN: 0001-4966
Despite the promise of microbubble-mediated focused ultrasound therapies, in vivo findings have revealed over-treated and under-treated regions distributed throughout the focal volume. This poor distribution cannot be improved by conventional pulse shapes and sequences, due to their limited ability to control acoustic cavitation dynamics within the ultrasonic focus. This paper describes the design of a rapid short-pulse (RaSP) sequence which is comprised of short pulses separated by μs off-time intervals. Improved acoustic cavitation distribution was based on the hypothesis that microbubbles can freely move during the pulse off-times. Flowing SonoVue® microbubbles (flow velocity: 10 mm/s) were sonicated with a 0.5 MHz focused ultrasound transducer using RaSP sequences (peak-rarefactional pressures: 146–900 kPa, pulse repetition frequency: 1.25 kHz, and pulse lengths: 5–50 cycles). The distribution of cavitation activity was evaluated using passive acoustic mapping. RaSP sequences generated uniform distributions within the focus in contrast to long pulses (50 000 cycles) that produced non-uniform distributions. Fast microbubble destruction occurred for long pulses, whereas microbubble activity was sustained for longer durations for shorter pulses. High-speed microscopy revealed increased mobility in the direction of flow during RaSP sonication. In conclusion, RaSP sequences produced spatiotemporally uniform cavitation distributions and could result in efficient therapies by spreading cavitation throughout the treatment area.
Pouliopoulos A, Choi JJ, 2016, Superharmonic microbubble Doppler effect in ultrasound therapy, Physics in Medicine and Biology, Vol: 61, ISSN: 1361-6560
The introduction of microbubbles in focused ultrasound therapies has enabled a diverse range of non-invasive technologies: sonoporation to deliver drugs into cells, sonothrombolysis to dissolve blood clots, and blood-brain barrier opening to deliver drugs into the brain. Current methods for passively monitoringthe microbubble dynamics responsible for these therapeutic effects can identify the cavitation position by passive acoustic mapping and cavitation mode by spectral analysis. Here, we introduce a new feature that can be monitored: microbubble effective velocity. Previous studies have shown that echoes from short imaging pulses had a Doppler shift that was produced by the movement of microbubbles. Therapeutic pulses are longer (>1,000 cycles) and thus produce a larger alteration of microbubble distribution due to primary and secondary acoustic radiation force effects which cannot be monitored using pulse-echo techniques.In our experiments, we captured and analysed the Doppler shift during long therapeutic pulses using a passive cavitation detector. A population of microbubbles (5×104-5×107 microbubbles ml-1) was embedded in a vessel (inner diameter: 4mm) and sonicated using a 0.5 megahertz focused ultrasound transducer (peak-rarefactional pressure: 75-366 kPa, pulse length: 50,000 cycles or 100 milliseconds) within a water tank. Microbubble acoustic emissions were captured with a coaxially aligned 7.5 megahertz passive cavitation detector and spectrally analysed to measure the Doppler shift for multiple harmonics above the 10th harmonic (i.e., superharmonics). A Doppler shift was observed on the order of tens of kilohertz with respect to the primary superharmonic peak and is due to the axial movement of the microbubbles. The position, amplitude and width of the Doppler peaks depended on the acoustic pressure and the microbubble concentration. Higher pressures increased the effective velocity of the microbubblesup to 3m/s, prior to the onset of bro
Koruk H, El Ghamrawy A, Pouliopoulos AN, et al., 2015, Acoustic Particle Palpation for Measuring Tissue Elasticity, Applied Physics Letters, Vol: 107, ISSN: 1077-3118
We propose acoustic particle palpation – the use of sound to press a population of acoustic particles against an interface – as a method for measuring the qualitative and quantitative mechanical properties of materials. We tested the feasibility of this method by emitting ultrasound pulses across a tunnel of an elastic material filled with microbubbles. Ultrasound stimulated the microbubble cloud to move in the direction of wave propagation, press against the distal surface, and cause deformations relevant for elasticity measurements. Shear waves propagated away from the palpation site with a velocity that was used to estimate the material’s Young’s modulus.
Shamout FE, Pouliopoulos AN, Lee P, et al., 2015, Enhancement of non-invasive trans-membrane drug delivery using ultrasound and microbubbles during physiologically relevant flow, Ultrasound in Medicine and Biology, Vol: 41, Pages: 2435-2448, ISSN: 0301-5629
Coviello C, Kozick R, Choi J, et al., 2015, Passive acoustic mapping utilizing optimal beamforming in ultrasound therapy monitoring, JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA, Vol: 137, Pages: 2573-2585, ISSN: 0001-4966
Pouliopoulos AN, Bonaccorsi S, Choi JJ, 2014, Exploiting flow to control the in vitro spatiotemporal distribution of microbubble-seeded acoustic cavitation activity in ultrasound therapy, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 59, Pages: 6941-6957, ISSN: 0031-9155
Choi JJ, Carlisle RC, Coviello C, et al., 2014, Non-invasive and real-time passive acoustic mapping of ultrasound-mediated drug delivery, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 59, Pages: 4861-4877, ISSN: 0031-9155
Graham SM, Carlisle R, Choi JJ, et al., 2014, Inertial cavitation to non-invasively trigger and monitor intratumoral release of drug from intravenously delivered liposomes, JOURNAL OF CONTROLLED RELEASE, Vol: 178, Pages: 101-107, ISSN: 0168-3659
Carlisle R, Choi J, Bazan-Peregrino M, et al., 2013, Enhanced Tumor Uptake and Penetration of Virotherapy Using Polymer Stealthing and Focused Ultrasound, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 105, Pages: 1701-1710, ISSN: 0027-8874
Graham SM, Myers RS, Choi J, et al., 2013, Use of micro- and nano-sized inertial cavitation nuclei to trigger and map drug release from cavitation-sensitive liposomes.
Encapsulation of cytotoxic drugs into liposomes enhances pharmacokinetics and improves passive accumulation in tumors. However, stable liposomes have limited drug release, and thus action, at the target site. This inefficient and unpredictable drug release is compounded by a lack of low-cost, non-invasive methods to map release in real time. We present a new liposomal vehicle that is exclusively triggered by inertial cavitation. Ultrasound exposure of these liposomes in the absence of SonoVue® provided no increase in drug release, whilst with SonoVue® at inertial cavitation pressure levels a substantial (30%) and significant (p < 0.001) increase was observed in vitro. A 16-fold increase in the level of drug release within tumors was similarly observed in the presence of inertial cavitation following intravenous delivery. Passive acoustic mapping of inertial cavitation sources during delivery was also found to correlate strongly with the presence of release. However, variability in tumor perfusion indicated that uneven distribution of micron-sized SonoVue® may limit this approach. Nano-scale cavitation nuclei, which may more readily co-localize with 140 nm liposomes, were thus developed and showed similar cavitation energies to SonoVue® in vitro. These nano-nuclei may ultimately provide a more reliable and uniform way to trigger drug release in vivo.
Bazan-Peregrino M, Rifai B, Carlisle RC, et al., 2013, Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound, JOURNAL OF CONTROLLED RELEASE, Vol: 169, Pages: 40-47, ISSN: 0168-3659
Coviello C, Kozick RJ, Choi JJ, et al., 2013, Passive acoustic mapping using optimal beamforming for real-time monitoring of ultrasound therapy, ISSN: 1939-800X
In ultrasound therapy, passive acoustic mapping (PAM) has been shown to be an effective method for imaging the acoustic emissions generated during treatment providing the potential for real-time therapy monitoring. In both high intensity ultrasound (HIFU) ablative surgery and targeted drug delivery, imaging artefacts at higher amplitude exposure conditions have been observed which make the localization and dosimetry of therapeutically relevant cavitation activity a challenge. Due to these artefacts, correlating drug release or lesion volumes to the PAMs is hindered for many exposures. It is proposed that incorporating optimal beamforming techniques into the PAM framework can reduce and remove these artefacts allowing determination of the extent of cavitation activity during ultrasound therapy. Additionally, optimal beaforming is found to yield improved resolution, good interference suppression, and robustness against steering vector errors. A description of the origin of the artefacts as well as reduction of them by implementing optimal beamforming within PAM will be demonstrated in the context of targeted drug delivery. © 2013 Acoustical Society of America.
Choi JJ, Coussios C-C, 2012, Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure, JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA, Vol: 132, Pages: 3538-3549, ISSN: 0001-4966
Konofagou EE, Tung Y-S, Choi J, et al., 2012, Ultrasound-Induced Blood-Brain Barrier Opening, CURRENT PHARMACEUTICAL BIOTECHNOLOGY, Vol: 13, Pages: 1332-1345, ISSN: 1389-2010
Baseri B, Choi JJ, Deffieux T, et al., 2012, Activation of signaling pathways following localized delivery of systemically administered neurotrophic factors across the blood-brain barrier using focused ultrasound and microbubbles, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 57, Pages: N65-N81, ISSN: 0031-9155
Choi J, Konofagou E, Borden M, 2011, Systems and methods for opening a tissue, US20110295105 A1
Systems and methods for opening a tissue to a target value are disclosed herein. In an exemplary method, a region of the tissue is targeted for opening, a size range of microbubbles corresponding to the target value is determined, microbubbles of the size range are positioned in proximity to the targeted region, and an ultrasound beam is applied to the targeted region such that the tissue is opened with the assistance of the microbubbles to the target value.
Choi JJ, Selert K, Vlachos F, et al., 2011, Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 16539-16544, ISSN: 0027-8424
Carlisle R, Choi J, Kostka L, et al., 2011, Ultrasound-enhanced delivery of polymer-coated oncolytic adenovirus for tumour growth inhibition, Publisher: MARY ANN LIEBERT INC, Pages: A36-A36, ISSN: 1043-0342
Choi JJ, Selert K, Gao Z, et al., 2011, Noninvasive and localized blood-brain barrier disruption using focused ultrasound can be achieved at short pulse lengths and low pulse repetition frequencies, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 31, Pages: 725-737, ISSN: 0271-678X
Tung YS, Vlachos F, Choi JJ, et al., 2010, In vivo transcranial cavitation detection during ultrasound-inducedblood- brain barrier opening, Pages: 1518-1521, ISSN: 1051-0117
The blood-brain barrier (BBB) has been shown capable being openednoninvasively through the combined application of focused ultrasound (FUS) andmicrobubbles. In order to better identify the underlying mechanism responsiblefor BBB opening as well as associated safety, the in vivo noninvasive andtranscranial cavitation detection associated with FUS-induced BBB opening wasstudied. A cylindrically focused hydrophone, confocal with the FUS transducer,was used as a passive cavitation detector (PCD) to identify the threshold ofinertial cavitation (IC) in the presence of Definity microbubbles. AfterDefinity were injected intravenously, pulsed FUS was applied (frequency: 1.525and 1.5 MHz, peak-negative pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz,duration: 1 min with 30s interval) on the right hippocampus in twenty-six micein vivo through their intact scalp and skull. T1-weighted MRI was used to verifythe BBB opening. A spectrogram was generated at each pressure in order todetect the inertial cavitation onset and duration. The bubble behavior was showndetectable in vivo through the intact scalp and skull. We demonstrated that: 1)the inertial cavitation response could be detected transcranially during BBBopening; 2) the inertial cavitation pressure threshold lied at 0.45 MPa but theBBB was opened at 0.30 MPa so the BBB can be opened without requiring inertialcavitation; 3) the BBB could be opened without any cellular damage. © 2010IEEE.
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