The Role of Hemodynamics in Intracranial Bifurcation Arteries after Aneurysm Treatment with Flow-Diverter Stents.

BACKGROUND AND PURPOSE: Treatment of intracranial bifurcation aneurysms with flow-diverter stents can lead to caliber changes of the distal vessels in a subacute phase. This study aims to evaluate whether local anatomy and flow disruption induced by flow-diverter stents are associated with vessel caliber changes in intracranial bifurcations. MATERIALS AND METHODS: Radiologic images and demographic data were acquired for 25 patients with bifurcation aneurysms treated with flow-diverter stents. Whisker plots and Mann-Whitney rank sum tests were used to evaluate if anatomic data and caliber changes could be linked. Symmetry/asymmetry were defined as diameter ratio 1 = symmetric and diameter ratio <1 = asymmetric. Computational fluid dynamics was performed on idealized and patient-specific anatomies to evaluate flow changes induced by flow-diverter stents in the jailed vessel. RESULTS: Statistical analysis identified a marked correspondence between asymmetric bifurcation and caliber change. Symmetry ratios were lower for cases showing narrowing or subacute occlusion (medium daughter vessel diameter ratio = 0.59) compared with cases with posttreatment caliber conservation (medium daughter vessel diameter ratio = 0.95). Computational fluid dynamics analysis in idealized and patient-specific anatomies showed that wall shear stress in the jailed vessel was more affected when flow-diverter stents were deployed in asymmetric bifurcations (diameter ratio <0.65) and less affected when deployed in symmetric anatomies (diameter ratio ∼1.00). CONCLUSIONS: Anatomic data analysis showed statistically significant correspondence between caliber changes and bifurcation asymmetry characterized by diameter ratio <0.7 (P < .001). Similarly, computational fluid dynamics results showed the highest impact on hemodynamics when flow-diverter stents are deployed in asymmetric bifurcations (diameter ratio <0.65) with noticeable changes on wall sheer stress fields. Further research and clinical validation are necessary to identify all elements involved in vessel caliber changes after flow-diverter stent procedures.

Linear and nonlinear characterization of microbubbles and tissue using the Nakagami statistical model.

The goal of this work is to exploit the statistical signatures for discrimination between biological tissues and contrast microbubbles in order to develop new strategies for contrast imaging and tissue characterization. For this purpose, the efficiency of the Nakagami statistical model, for describing the ultrasonic echoes of both contrast microbubbles and tissues, was investigated. Experimental measurements have been performed using a linear array probe connected to an open research platform. A commercially available in vitro phantom was used to mimic biological tissue in which SonoVue contrast microbubbles were flowing. Experimental ultrasound echoes have been filtered around the transmitted frequency (fundamental at 2.5MHz) and around twice the transmitted frequency (at 5MHz) for 2nd harmonic analysis, and a logarithmic compression was applied. The signals have been analyzed in order to evaluate the Nakagami parameter m, the scaling parameter Ω and the probability density function at both frequencies. Parametric images based on the Nakagami parameters map (Nakagami-mode images) were reconstructed and compared to B-mode images. Contrary to the B-mode image which is influenced by the system settings and user operations, the Nakagami parametric image is only based on the backscattered statistics of the ultrasonic signals in a local phantom. Such an imaging principle allows the Nakagami image to quantify the local scatterer concentrations in the phantom and to extract the backscattering information from the regions of the weakest echoes that may be lost in the conventional B-mode image. Results show that the tissue and microbubbles characterization is more sensitive in the 2nd harmonic mode when a logarithmic transform is used. These results would be useful for improving the ultrasound image quality and contrast detection in nonlinear mode.

Role of endocytosis in sonoporation-mediated membrane permeabilization and uptake of small molecules: a electron microscopy study.

Sonoporation is a physical method that has been successfully used to deliver drugs into living cells both in vitro and in vivo for experimental and therapeutic purposes. Despite numerous studies on this topic, often reporting successful outcomes, very little is known about the mechanisms involved in the hypothesized membrane permeabilization processes. In this study, electron microscopy was used to investigate the ultra-structural modifications of cell membranes, induced by sonoporation. Here, we demonstrate that sonoporation in the presence of microbubbles induces the formation of a significant number of transient and permeant structures at the membrane level. These structures were transient with a half-life of 10 min and had a heterogeneous size distribution ranging from a few nanometers to 150 nm. We demonstrated that the number and the size of these structures were positively correlated with the enhanced intracellular uptake of small molecules. In addition, we showed that these structures were associated with caveolae-dependent endocytosis for two thirds of the recorded events, with the remaining one third related to non-specific routes such as membrane disruptions as well as caveolae-independent endocytosis. In conclusion, our observations provide direct evidences of the involvement of caveolae-endocytosis in cell membrane permeabilization to small molecules after sonoporation.

Evaluation of chirp reversal power modulation sequence for contrast agent imaging.

Over the last decade, significant research effort has been focused on the use of chirp for contrast agent imaging because chirps are known to significantly increase imaging contrast-to-noise ratio (CNR). New imaging schemes, such as chirp reversal (CR), have been developed to improve contrast detection by increasing non-linear microbubble responses. In this study we evaluated the contrast enhancement efficiency of various chirped imaging sequences in combination with well-established imaging schemes such as power modulation (PM) and pulse inversion (PI). The imaging schemes tested were implemented on a fully programmable open scanner and evaluated by ultrasonically scanning (excitation frequency of 2.5 MHz; amplitude of 350 kPa) a tissue-mimicking flow phantom comprising a 4 mm diameter tube through which aqueous dispersions (dilution fraction of 1/2000) of the commercial ultrasound contrast agent, SonoVue(®) were continuously circulated. The recovery of non-linear microbubble responses after chirp compression requires the development and the optimization of a specific filter. A compression filter was therefore designed and used to compress and extract several non-linear components from the received microbubble responses. The results showed that using chirps increased the image CNR by approximately 10 dB, as compared to conventional Gaussian apodized sine burst excitation but degraded the axial resolution by a factor of 1.4, at -3 dB. We demonstrated that the highest CNR and contrast-to-noise ratio (CTR) were achievable when CR was combined with PM as compared to other imaging schemes such as PI.

Focused ultrasound mediated drug delivery from temperature-sensitive liposomes: in-vitro characterization and validation.

Nanomedicine-based delivery with non-invasive techniques is a promising approach to increase local drug concentration and to reduce systemic side effects. Focused ultrasound (FUS) has become a promising strategy for non-invasive local drug delivery by mild hyperthermia. In this study, traditional temperature-sensitive liposomes (TTSLs) encapsulating doxorubicin (DOX) were evaluated for FUS-mediated drug delivery with an in-vitro FUS setup. In-vitro studies showed quantitative release of the DOX from the lumen of the temperature-sensitive liposomes when heated to 42 °C with FUS using 1 MHz sinusoidal waves at 1.75 MPa for 10 min. No release was observed when heated at 37 °C. Moreover, we showed that DOX released from TTSLs by FUS is as efficiently internalized by glioblastoma cells as free DOX at 37 °C. In-vitro therapeutic evaluation showed that exposure of a cell monolayer to FUS-activated TTSLs induced a 60% and a 50% decrease in cell viability compared to cell medium and to TTSLs preheated at 37 °C, respectively. Using an in-vitro 3D cell culture model, the results showed that after FUS-mediated hyperthermia, preheated liposomes induced a 1.7-fold decrease in U-87 MG spheroid growth in comparison to the preheated liposomes at 37 °C. In conclusion, our results show that in-vitro FUS allows the evaluation of TTSLs and does not modify the cellular uptake of the released DOX nor its cytotoxic activity.

Irinotecan delivery by microbubble-assisted ultrasound: in vitro validation and a pilot preclinical study.

Irinotecan is a powerful anticancer drug with severe systemic side effects that limit its clinical application. Drug-targeted delivery with noninvasive methods is required to enhance the drug concentration locally and to reduce these undesirable events. Microbubble-assisted ultrasound has become a promising method for noninvasive targeted drug delivery. The aim of this study is to evaluate the therapeutic effectiveness of in vitro and in vivo irinotecan delivery based on the combination of ultrasound and microbubbles. In the present study, in vitro results showed that the irinotecan treatment with microbubble-assisted ultrasound induced a significant decrease in cell viability of human glioblastoma cells. Moreover, using subcutaneous glioblastoma xenografts, the in vivo preclinical study in nude mice demonstrated that this therapeutic protocol led to a decrease in tumor growth and perfusion and an increase of tumor necrosis. The conclusions drawn from this study demonstrate the promising potential of this therapeutic approach for the anticancer targeted therapy.

New insights into uteroplacental perfusion: quantitative analysis using Doppler and contrast-enhanced ultrasound imaging.

OBJECTIVE: To monitor and quantify uteroplacental perfusion in rat pregnancies by Doppler ultrasound (DUS) and contrast-enhanced ultrasound (CEUS). METHODS: Fourteen rats were randomized in two groups (the CEUS group and the control group). On days 8, 11, 14, 17, 19 and 20 of gestation, we used DUS to measure the resistance index (RI), pulsatility index and blood velocity in the uterine, arcuate and umbilical arteries in both groups. On days 14, 17 and 20, one group was also examined by CEUS. Quantitative perfusion parameters were calculated in 4 compartments (mesometrial triangle, placenta, umbilical cord and fetus) and compared. RESULTS: The DUS measurement showed that the RI of the uterine and arcuate arteries decreased (p < 0.01) from day 14 to day 17, while velocity increased each of these arteries (p < 0.01 and p < 0.05, respectively). Quantification of uteroplacental perfusion by CEUS in bolus mode revealed that blood volume and local blood flow increased from day 14 to day 20 in the mesometrial triangle (p < 0.01) and the placenta (p < 0.05). In the CEUS destruction-replenishment mode, the perfusion parameters showed trends similar to those observed in bolus mode. No microbubbles were detected in the umbilical vein or fetal compartments. The weights of pups in the two groups did not differ significantly. CONCLUSIONS: CEUS estimates of placental perfusion complement the data provided by DUS.

Bleomycin delivery into cancer cells in vitro with ultrasound and SonoVue® or BR14® microbubbles.

BACKGROUND: Cell exposure to ultrasound (US) in the presence of contrast agent microbubbles (MBs) can result in cell sonoporation that can be exploited for drug or gene delivery. Anticancer drug bleomycin (BLM), used in sonoporation, can effectively eliminate tumor cells in vitro and in vivo. Nevertheless, sonoporation mechanism is not known, thus different US parameters and MB types are used. Recently, we proposed that efficiency of cell sonoporation can be related to the efficiency of MB sonodestruction. PURPOSE: We analyzed human tumor cells viability in response to BLM, US and MB treatment. METHODS: Human glioblastoma astrocytoma (U-87 MG) or colon cancer (HCT-116) cells were exposed to US in the presence of BLM and either SonoVue® or BR14® MBs. MB sonodestruction was evaluated according to US signal attenuation. RESULTS: Both HCT-116 and U-87 MG cell viability following US exposure decreased up to 30%. Decrease in cell viability followed similar tendency as MB sonodestruction, which suggests direct relationship between MB sonodestruction and BLM intracellular delivery. CONCLUSION: Sonoporation is a feasible method to deliver BLM in to several types of human cancer cell lines. Efficiency of cell sonoporation correlated well with MB sonodestruction, providing a possibility to optimize US parameters by measuring MB sonodestruction.

[Tolerance and efficacy of peripheral nerve blocks for carpal tunnel release]. / Tolérance et efficacité des blocs nerveux périphériques pour la chirurgie du canal carpien.

INTRODUCTION: Several peripheral nerve block techniques (PNB) are performed for hand surgery. Their tolerance by patients or their efficacy are poorly described. We evaluated them for blocks at the wrist and at the brachial canal. PATIENTS AND METHODS: Cohort of outpatients undergoing open carpal tunnel release under PNB with arm tourniquet. Various anaesthetic protocols existed in our staff. The primary end points were a moderate to severe pain (greater than 3/10 on a numerical rating scale) felt during needle puncture, nerve stimulation, mepivacaine injection, at the surgical site (intraoperatively) or at the arm tourniquet, an intraoperative lidocaine supplementation, the occurrence of vasovagal events. For each primary end point, a logistic regression analyzed: the effects of gender, age, operated side, Emla(®)application, sedation before PNB (midazolam-sufentanil), wrist or brachial canal approach, musculocutaneous or radial block were using. RESULTS: Between January 2007 and June 2010, 551 consecutive patients were analyzed. Puncture pain, mepivacaine injection pain, pain tourniquet and vasovagal events were associated with wrist block (P=0.003, relative risk=1.86; P<0.001, RR=4.22; P<0.001, RR=4.52; P=0.035, RR=6.40). An intraoperative pain greater than 3/10 at the surgical site, or a supplementation by the surgeon were associated with the absence of musculocutaneous block (P=0.013, RR=2.44; P=0.013, RR=2.51). DISCUSSION: Wrist blocks are less tolerated than brachial canal blocks. The musculocutaneous nerve might often participate in the palm sensitive innervation. For open carpal tunnel release, median, ulnar and musculocutaneous nerves blocks at the brachial canal should be preferred.

Doxorubicin delivery into tumor cells with ultrasound and microbubbles.

Doxorubicin is a potent chemotherapeutic whose severe side effects limit its application. Drug-targeted delivery with noninvasive techniques is required to increase the drug concentration locally and to reduce systemic side effects. Microbubble-assisted ultrasound has become a promising strategy for noninvasive local drug delivery. The aim of this study is to evaluate the applicability and the effectiveness of administration of doxorubicin combined with microbubble-assisted ultrasound in human U-87MG glioblastoma and MDA-MB-231 breast cancer cells. In the present study, the doxorubicin delivery aided by microbubble-assisted ultrasound enhanced the death of breast cancer and glioblastoma cells, including the induction of apoptosis. Various microbubbles were evaluated including Vevo Micromarker, BR14, SonoVue and experimental polymer shelled microbubbles. The results showed that Vevo Micromarker microbubble-assisted ultrasound could induce an enhancement of doxorubicin in glioblastoma and breast cancer cell death. Polylactide-Shelled PEG and Vevo Micromarker microbubbles were the best microbubbles for efficient doxorubicin delivery in the U-87 MG and MDA-MB-231 cells, respectively. Moreover, the induction of apoptosis by doxorubicin and Vevo Micromarker microbubble-assisted ultrasound was examined and results showed a positive increment for acoustic pressures above 600 kPa. The conclusions drawn from in vitro study show the potential of this strategy for an in vivo application.

In vitro microemboli classification using neural network models and RF signals.

Emboli classification is of high clinical importance for selecting appropriate treatment for patients. Several ultrasonic (US) methods using Doppler processing have been used for emboli detection and classification as solid or gaseous matter. We suggest in this experimental study exploiting the Radio-Frequency (RF) signal backscattered by the emboli since they contain additional information on the embolus than the Doppler signal. The aim of the study is the analysis of RF signals using Multilayer Perceptron (MLP) and Radial-Basis Function Network (RBFN) in order to classify emboli. Anthares scanner with RF access was used with a transmit frequency of 1.82MHz at two mechanical indices (MI) 0.2 and 0.6. The mechanical index is given as the peak negative pressure (in MPa) divided by the square root of the frequency (in MHz). A Doppler flow phantom was used containing a 0.8mm diameter vessel surrounded by a tissue mimicking material. To imitate gas emboli US behaviour, Sonovue microbubbles were injected at two different doses (10µl and 5µl) in a nonrecirculating at a constant flow. The surrounding tissue was assumed to behave as a solid emboli. In order to mimic real clinical pathological situations, Sonovue concentration was chosen such that the fundamental scattering from the tissue and from the contrast were identical. The amplitudes and bandwidths of the fundamental and the 2nd harmonic components were selected as input parameters to the MLP and RBFN models. Moreover the frequency bandwidths of the fundamental and the 2nd harmonic echoes were approximated by Gaussian functions and the coefficients were used as a third input parameter to the neural network models. The results show that the Gaussian coefficients provide the highest rate of classification in comparison to the amplitudes and the bandwidths of the fundamental and the 2nd harmonic components. The classification rates reached 89.28% and 92.85% with MLP and RBFN models respectively. This short communication demonstrates the opportunity to classify emboli based on a RF signals and neural network analysis.

In vitro gene transfer by electrosonoporation.

Among the nonviral methods for gene delivery in vitro, electroporation is simple, inexpensive and safe. To upregulate the expression level of transfected gene, we investigated the applicability of electrosonoporation. This approach consists of a combination of electric pulses and ultrasound assisted with gas microbubbles. Cells were first electroporated with plasmid DNA encoding-enhanced green fluorescent protein and then sonoporated in presence of contrast microbubbles. Twenty-four hours later, cells that received electrosonoporation demonstrated a four-fold increase in transfection level and a six-fold increase in transfection efficiency compared with cells having undergone electroporation alone. Although electroporation induced the formation of DNA aggregates into the cell membrane, sonoporation induced its direct propulsion into the cytoplasm. Sonoporation can improve the transfer of electro-induced DNA aggregates by allowing its free and rapid entrance into the cells. These results demonstrated that in vitro gene transfer by electrosonoporation could provide a new potent method for gene transfer.

[Sonopermeabilization: therapeutic alternative with ultrasound and microbubbles]. / Sonoperméabilisation: alternative thérapeutique par ultrasons et microbulles.

Future applications of ultrasound and microbubbles extend to more than imaging applications. Over the last few years, it was reported that sonographic contrast agent effects under ultrasound, modulate transiently cell membrane permeability. This process, named sonoporation and classified as a new physical method to transfer genes or drugs, consists of using a physical energy source to modulate membrane integrity. The possibility to transfer therapeutic genes would be a new tool for gene therapy and could constitute an alternative method. After in vitro and in vivo studies presentation, the therapeutic potential of sonoporation will be investigated in this paper.

Effect of ultrasound-activated microbubbles on the cell electrophysiological properties.

New clinical applications of ultrasound contrast microbubbles extend beyond imaging and diagnosis toward therapeutic applications. Cell membrane permeability and the uptake of substances have been shown to be enhanced by microbubbles under ultrasound stimulation. However, the mechanisms of action of ultrasound-activated microbubbles are still unknown. The aim of our study was to examine how microbubbles and ultrasound interact with cells in an attempt to understand the sonoporation mechanism. The ruptured-patch-clamp whole-cell technique was used to measure membrane potential variations of a single cell. SonoVue microbubbles and mammary breast cancer cell line MDA-MB-231 were used. Ultrasound was applied using single-element transducers of 1 MHz. Microbubbles and cells were simultaneously video monitored during ultrasound exposure. Our results showed that, during sonoporation, a marked cell membrane hyperpolarization occurs (n = 6 cells) at negative pressures above 150 kPa, indicating the activation of specific ion channels while the cell and the microbubbles remain viable. The hyperpolarization was sustained for as long as the microbubbles are in a direct contact with the cell and the ultrasound waves are transmitted. Smaller acoustic amplitudes induced only mild hyperpolarization, whereas shutting off the ultrasound brings the cell membrane potential to its resting value. However, ultrasound alone did not affect the cell membrane potential. A similar hyperpolarization of the cell membrane was observed when a mechanical pressure was applied on the cell through a glass probe. In conclusion, the results demonstrate that microbubbles' oscillations under ultrasound activation entail modifications of the electrophysiologic cell activities by triggering the modulation of ionic transports through the plasmic cell membrane. However, only cells in direct contact with the microbubbles are impacted. The mechanisms involved are likely related to activation of specific channels sensitive to mechanical stresses (stretch-activated channels) and possibly nonspecific ion channels.

Intravascular ultrasound tissue harmonic imaging: a simulation study.

Recently, the in vivo feasibility of tissue harmonic imaging (THI) with a mechanically-rotated intravascular ultrasound (IVUS) catheter was experimentally demonstrated. To isolate the second harmonic signal content, both pulse inversion (PI) and analog filtering were used. In the present paper, we report the development of a simulation tool to investigate nonlinear IVUS beams and the influence of rotation on the efficiency of PI signal processing. Nonlinear 20 MHz beams were simulated in a homogeneous tissue-mimicking medium, resulting in second harmonic pressure fields at 40 MHz. The acoustic response from tissue was simulated by summing radio-frequency (RF) pulse-echo responses from many point-scatterers. When the transducer was rotated with respect to the point-scatterers, the fundamental frequency suppression using PI degraded rapidly with increasing inter-pulse angles. The results of this study will aid in the optimization of harmonic IVUS imaging systems.

Detecting broken struts of a Björk-Shiley heart valve using ultrasound: a feasibility study.

The Björk-Shiley (BScc) mechanical heart valve has extensively been used in surgery from 1979 to 1986. There is, compared with equivalent valve types, increased occurrence of unexpected mechanical failure of the outlet strut of the valve, with a high incidence of mortality, when it occurs. Many approaches have been attempted to noninvasively determine BScc valve integrity. None of the approaches resulted in adequate assessment, mostly due to a lack of either sensitivity or specificity demonstrated in in vitro and/or in vivo studies. In our study we analyze leg movement of the BScc valves outlet strut during the cardiac cycle with ultrasound. For a broken strut, the movement of both legs will be significantly different, whereas the difference will be negligible for an intact strut. BScc valves were mounted in the mitral position in an in vitro pulse duplicator system. A focused single-element transducer was used to direct ultrasound on a leg of the outlet strut. Correlation-based time delay estimation was used to estimate differences in time of flight of the outlet strut echoes to determine outlet strut leg movement. The movement of an intact valve and a valve with a single-leg fracture with both ends grating against each other (SLF), the most difficult fracture to diagnose, has been studied. The results showed no significant difference in movement between both legs of the outlet strut of the intact BScc valve (amplitude of movement 9.2 microm +/- 0.1 microm). Whereas for the defective valve, the amplitude of movement of the broken leg of the SLF valve was 12 microm +/- 1.6 microm vs. 8.6 microm +/- 0.1 microm for the intact leg. In conclusion, the proposed method has shown to be feasible in vitro and has potentials for in vivo detection of BScc valve outlet strut fracture.

Low back pain, the stiffness of the sacroiliac joint: a new method using ultrasound.

Abnormal biomechanical properties of the sacroiliac joints are believed to be related to low back and pelvic pain. Presently, physiotherapists judge the condition of the sacroiliac joints by function and provocation tests, and palpation. No objective measuring device is available. Research is ongoing to identify the biomechanical properties of the sacroiliac joints from the dynamic behaviour of the pelvic bones. A new concept based on ultrasound (US) for the measurement of bone vibration is under investigation. The objective of this study was to validate this concept on a physical model and to assess the applicability in vivo. A model consisting of a piezo shaker covered by a layer of US transmission gel (representing bone and soft tissue) has been used. A packet of US detection signals is directed onto the shaker and correlation-based processing is used to estimate the difference in time-of-flight of their echoes. These variations of time are used to compute the displacement of the shaker at each pulse reflection. To assess the validity of our US technique, we compared the obtained measurements with the readings of the built-in strain gauge sensor. The experimental procedure has been tested on a volunteer where low-frequency excitation was provided through the ilium and vibration detected on the sacrum and ilia. The results demonstrated that the correlation-based approach is capable of reproducing the piezo shaker displacements with high accuracy (+/- 7%). Vibration amplitudes from 0.25 microm to 3 microm could be measured. The US technique was able to detect bone vibration in vivo. In conclusion, the principle based on US waves can be used to develop a new measurement tool, instrumental in studying the relation between the biomechanical properties of the sacroiliac joints and low back pain.

Feasibility of 3D harmonic contrast imaging.

Improved endocardial border delineation with the application of contrast agents should allow for less complex and faster tracing algorithms for left ventricular volume analysis. We developed a fast rotating phased array transducer for 3D imaging of the heart with harmonic capabilities making it suitable for contrast imaging. In this study the feasibility of 3D harmonic contrast imaging is evaluated in vitro. A commercially available tissue mimicking flow phantom was used in combination with Sonovue. Backscatter power spectra from a tissue and contrast region of interest were calculated from recorded radio frequency data. The spectra and the extracted contrast to tissue ratio from these spectra were used to optimize the excitation frequency, the pulse length and the receive filter settings of the transducer. Frequencies ranging from 1.66 to 2.35 MHz and pulse lengths of 1.5, 2 and 2.5 cycles were explored. An increase of more than 15 dB in the contrast to tissue ratio was found around the second harmonic compared with the fundamental level at an optimal excitation frequency of 1.74 MHz and a pulse length of 2.5 cycles. Using the optimal settings for 3D harmonic contrast recordings volume measurements of a left ventricular shaped agar phantom were performed. Without contrast the extracted volume data resulted in a volume error of 1.5%, with contrast an accuracy of 3.8% was achieved. The results show the feasibility of accurate volume measurements from 3D harmonic contrast images. Further investigations will include the clinical evaluation of the presented technique for improved assessment of the heart.

Emboli detection using a new transducer design.

We have presented, in a previous study, a new approach to detect, characterize and estimate the size of gaseous emboli, based on the nonlinear behavior of gaseous bubbles. In this study, a specific transducer design has been developed to be used for such a purpose. It is composed of two separate transmitting and receiving capabilities. The transmit part, consisting of a lead zirconate-titanate (PZT) material, emits at a frequency of 500 kHz and could generate pressures up to 410 kPa. On the top of the transmit surface, a thin polyvinylidene difluoride (PVDF) layer is glued and used for receiving frequencies from 250 kHz (f0/2) up to 2.5 MHz (5 f0). To evaluate this new design, ultrasonic measurements were carried out with gas bubbles with diameters ranging from 10 microm up to 90 microm and solid particles between 350 microm and 550 microm. The experimental results confirmed our previous findings: gaseous emboli with a diameter close to the resonance size scatter significantly at higher harmonic components (from the second harmonic up to the fifth), and bubbles with a diameter around twice the resonance size produce a subharmonic and/or an ultraharmonic component. Meanwhile, solid particles and other bubble sizes behave only linearly and their scattered spectrum appeared without any harmonics. The study demonstrates the utility of this approach in using a single transducer to detect and characterize selective gaseous emboli from other particles using their nonlinear behavior.