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Publications (12)19.05 Total impact

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    ABSTRACT: Ultrasound (US) scanners typically apply lossy, non-linear modifications to the US data for visualization purposes. The resulting images are then stored as compressed video data. Some system manufacturers provide dedicated software for quantification purposes to eliminate such processing distortions, at least partially. This is currently the recommended approach for quantitatively assessing changes in contrast-agent concentration from clinical data. However, the machine-specific access to US data and the limited set of analysis functionalities offered by each dedicated-software package make it difficult to perform comparable analyses with different US systems. The objective of this work was to establish if linearization of compressed video images obtained with an arbitrary US system can provide an alternative to dedicated-software analysis of machine-specific files for the estimation of echo-power. For this purpose, an Aplio 50 system (Toshiba Medical Systems, Tochigi, Japan), coupled with dedicated CHI-Q (Contrast Harmonic Imaging Quantification) software by Toshiba Medical Systems, was used. Results were compared with two approaches that apply algorithms to estimate relative echo-power from compressed video images: commercially available VueBox software by Bracco Suisse SA (Geneva, Switzerland) and in-laboratory software called PixPower. The echo-power estimated by CHI-Q analysis indicated a strong linear relationship versus agent concentration in vitro (R(2) ≥ 0.9996) for dynamic range (DR) settings of DR60 and DR80, with slopes between 9.22 and 9.57 dB/decade (p = 0.05). These values approach the theoretically predicted dependence of 10.0 dB/decade (equivalent to 3 dB for each concentration doubling). Echo-power estimations obtained from compressed video images with VueBox and PixPower also exhibited strong linear proportionality with concentration (R(2) ≥ 0.9996), with slopes between 9.30 and 9.68 dB/decade (p = 0.05). On an independent in vivo data set (N = 24), the difference in echo-power estimation between CHI-Q and each of the other two approaches was calculated after excluding regions that contain pixels affected by saturated or thresholded pixel values. The mean difference in estimates (expressed in decibels) was -0.25 dB between VueBox and CHI-Q (95% confidence interval: -0.75 to 0.26 dB) and -0.17 dB between PixPower and CHI-Q (95% confidence interval: -0.67 to 0.13 dB). To achieve linearization of data, one of the approaches (VueBox) requires calibration files provided by the software manufacturer for each machine type and setting. The other (PixPower) requires empirical correction of the imaging dynamic range based on ground truth data. These requirements could potentially be removed if US system manufacturers were willing to make relevant information on the applied processing publically available. Reliable echo-power estimation from linearized data would facilitate inclusion of different US systems in multicentric studies and more widespread implementation of emerging techniques for quantitative analysis of contrast ultrasound.
    Ultrasound in medicine & biology 07/2013; · 2.46 Impact Factor
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    ABSTRACT: With contrast-enhanced ultrasound (CEUS) now established as a valuable imaging modality for many applications, a more specific demand has recently emerged for quantifying perfusion and using measured parameters as objective indicators for various disease states. However, CEUS perfusion quantification remains challenging and is not well integrated in daily clinical practice. The development of VueBox™ alleviates existing limitations and enables quantification in a standardized way. VueBox™ operates as an off-line software application, after dynamic contrast-enhanced ultrasound (DCE-US) is performed. It enables linearization of DICOM clips, assessment of perfusion using patented curve-fitting models, and generation of parametric images by synthesizing perfusion information at the pixel level using color coding. VueBox™ is compatible with most of the available ultrasound platforms (nonlinear contrast-enabled), has the ability to process both bolus and disruption-replenishment kinetics loops, allows analysis results and their context to be saved, and generates analysis reports automatically. Specific features have been added to VueBox™, such as fully automatic in-plane motion compensation and an easy-to-use clip editor. Processing time has been reduced as a result of parallel programming optimized for multi-core processors. A long list of perfusion parameters is available for each of the two administration modes to address all possible demands currently reported in the literature for diagnosis or treatment monitoring. In conclusion, VueBox™ is a valid and robust quantification tool to be used for standardizing perfusion quantification and to improve the reproducibility of results across centers.
    Ultraschall in der Medizin 07/2012; 33 Suppl 1:S31-8. · 4.12 Impact Factor
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    ABSTRACT: Microbubble-mediated sonothrombolysis is a promising approach for ischemic stroke treatment. The aim of this in vitro study was to evaluate a new microbubble (MB) formulation (BR38) for sonothrombolysis and to investigate the involved mechanisms. Human whole-blood clots were exposed to different combinations of recombinant tissue plasminogen activator (rtPA), ultrasound (US) and MB. Ultrasound at 1.6 MHz was used at 150, 300, 600 and 1000 kPa (peak-negative pressure). Thrombolysis efficacy was assessed by measuring clot diameter changes during 60-min US exposure. The rate of clot diameter loss (RDL) in μm/min was determined and clot lysis profiles were analyzed. The most efficient clot lysis (5.9 μm/min) was obtained at acoustic pressures of 600 and 1000 kPa in combination with MB and a low concentration of rtPA (0.3 μg/mL). This is comparable with the rate obtained with rtPA at 3 μg/mL alone (6.6 μm/min, p > 0.05). Clot lysis profiles were shown to be related to US beam profiles and microbubble cavitation.
    Ultrasound in medicine & biology 04/2012; 38(7):1222-33. · 2.46 Impact Factor
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    ABSTRACT: Subharmonic scattering of phospholipid-shell microbubbles excited at very low acoustic pressure amplitudes has been associated with echo responses from compression-only bubbles. These bubbles are near a tension-free buckling state at rest and have initial surface tension values close to zero. In this work, subharmonic scattering of phospholipid microbubbles was investigated as a function of the initial surface tension, which was controlled by changing the hydrostatic pressure through the application of an ambient overpressure. Echo responses from a dilution of an experimental contrast agent were measured as a function of ambient overpressure ranging between 0 to 140 mmHg. The microbubbles were excited using a 64-cycle Tukey-windowed transmit burst with a center frequency of 4 MHz and peak-negative pressure of 50 kPa. Echo-power spectra were calculated, and the subharmonic response was determined for each overpressure value; the subharmonic amplitude increased by 20 dB after applying 140 mmHg overpressure (for which the initial surface tension was assumed to be near zero). In this study, an increase in subharmonic amplitude, instead of a decrease as reported by others [Shi et al., UMB 1999], was measured as a function of ambient overpressure. This observation may be exploited in a new method for noninvasive pressure measurement.
    The Journal of the Acoustical Society of America 04/2012; 131(4):3322. · 1.65 Impact Factor
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    ABSTRACT: This work aims at understanding some of the mechanisms involved in the combined effects of microbubbles, ultrasound exposure and recombinant tissue plasminogen activator (rtPA) on sonothrombolysis. It is based on a combination of experimental observations and a simple model to represent bubble destruction and lysis efficacy. Using an in vitro clot model and a single focused ultrasound beam, complex lysis patterns were observed following static exposure. It was hypothesized that these patterns reflect the role of the beam pressure profile in the presence of a flow of microbubbles subject to destruction/dissolution; separate parametric models for bubble destruction, clot lysis and flow profile were thus combined to represent the observed lysis profiles. Using parameter optimization, a reasonable agreement was found with the observed profiles during exposure, yielding at the same time estimates of bubble destruction parameters, lysis efficacy vs. pressure and bubble displacement during exposure. It is hoped that insight gained in this work may provide useful indications for optimizing schemes to achieve successful sonothrombolysis in vivo.
    Ultrasonics Symposium (IUS), 2011 IEEE International; 01/2011
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    ABSTRACT: The main goal of this study was to determine the optimal strategy for a real-time nonlinear contrast mode for small-animal imaging at high frequencies, on a new array-based micro-ultrasound system. Previously reported contrast imaging at frequencies above 15 MHz has primarily relied on subtraction schemes involving B-mode image data. These approaches provide insufficient contrast to tissue ratios under many imaging conditions. In this work, pulse inversion, amplitude modulation and combinations of these were systematically investigated for the detection of nonlinear fundamental and subharmonic signal components to maximize contrast-to-tissue ratio (CTR) in the 18-24 MHz range. From in vitro and in vivo measurements, nonlinear fundamental detection with amplitude modulation provided optimal results, allowing an improvement in CTR of 13 dB compared with fundamental imaging. Based on this detection scheme, in vivo parametric images of murine kidneys were generated using sequences of nonlinear contrast images after intravenous bolus injections of microbubble suspensions. Initial parametric images of peak enhancement (PE), wash-in rate (WiR) and rise time (RT) are presented. The parametric images are indicative of blood perfusion kinetics, which, in the context of preclinical imaging with small animals, are anticipated to provide valuable insights into the progression of human disease models, where blood perfusion plays a critical role in either the diagnosis or treatment of the disease.
    Ultrasound in medicine & biology 12/2010; 36(12):2097-106. · 2.46 Impact Factor
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    ABSTRACT: Subharmonic scattering of phospholipid-shell microbubbles excited at relatively low acoustic pressure amplitudes (<;30 kPa) has been associated with echo responses from compression-only bubbles having initial surface tension values close to zero. In this work, the relation between subharmonics and compression-only behavior of phospholipid-shell microbubbles was investigated, experimentally and by simulation, as a function of the initial surface tension by applying ambient overpressures of 0 and 180 mmHg. The microbubbles were excited using a 64-cycle transmit burst with a center frequency of 4 MHz and peak-negative pressure amplitudes ranging from 20 of 150 kPa. In these conditions, an increase in subharmonic response of 28.9 dB (P <; 0.05) was measured at 50 kPa after applying an overpressure of 180 mmHg. Simulations using the Marmottant model, taking into account the effect of ambient overpressure on bubble size and initial surface tension, confirmed the relation between subharmonics observed in the pressure-time curves and compression-only behavior observed in the radius-time curves. The trend of an increase in subharmonic response as a function of ambient overpressure, i.e., as a function of the initial surface tension, was predicted by the model. Subharmonics present in the echo responses of phospholipid-shell microbubbles excited at low acoustic pressure amplitudes are indeed related to the echo responses from compression-only bubbles. The increase in subharmonics as a function of ambient overpressure may be exploited for improving methods for noninvasive pressure measurement in heart cavities or big vessels in the human body.
    IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control 09/2010; · 1.82 Impact Factor
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    ABSTRACT: Recently, a linear array based micro-ultrasound system with a 64 channel beamformer has been developed. This study will focus on the implementation of a real-time nonlinear contrast mode on this array based system, and the challenges faced in high-frequency contrast imaging, namely nonlinear propagation in tissue. The array transducer, beamforming techniques, digital sampling and signal processing will be described, along with in vitro and in vivo results.
    Ultrasonics Symposium (IUS), 2009 IEEE International; 10/2009
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    ABSTRACT: Subharmonic scattering of phospholipid-shell microbubbles excited at very low acoustic pressure amplitudes (¿30 kPa) has been associated with echo responses from compression-only bubbles, having initial surface tension values close to zero. In this work, the relation between subharmonics and compression-only behavior of phospholipid-shell microbubbles was investigated as a function of the initial surface tension by applying an ambient overpressure ranging from 0 to 140 mmHg. The microbubbles were excited using a 64-cycle Hanning-apodized transmit burst with a center frequency of 4 MHz and peak-negative pressure amplitude of 50 kPa. An increase in subharmonic response of 10-20 dB was measured after applying an overpressure of 140 mmHg. Simulations using the Marmottant model, taking into account the effect of ambient overpressure on bubble size and initial surface tension, confirmed the relation between subharmonics observed in the pressure-time curves and compression-only behavior observed in the radius-time curves. The increase in subharmonic response as a function of ambient overpressure, i.e. as a function of the initial surface tension, was correctly predicted by the model. Subharmonics present in the echo responses of phospholipid-shell microbubbles excited at very low acoustic pressure amplitudes are indeed related to the echo responses from compression-only bubbles. The increase in subharmonics as a function of ambient overpressure may be exploited for improving methods for noninvasive pressure measurement.
    Ultrasonics Symposium (IUS), 2009 IEEE International; 10/2009
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    ABSTRACT: Individual ultrasound contrast agent microbubbles (BR14) were characterized acoustically. The bubbles were excited at a frequency of 2 MHz and at peak-negative pressure amplitudes of 60 and 100 kPa. By measuring the transmit and receive transfer functions of both the transmit and receive transducers, echoes of individual bubbles were recorded quantitatively and compared to simulated data. At 100 kPa driving pressure, a second harmonic response was observed for bubbles with a size close to their resonance size. Power spectra were derived from the echo waveforms of bubbles of different sizes. These spectra were in good agreement with those calculated from a Rayleigh-Plesset-type model, incorporating the viscoelastic properties of the phospholipid shell. Small bubbles excited below their resonance frequency have a response dominated by the characteristics of their phospholipid shell, whereas larger bubbles, excited above resonance, have a response identical to those of uncoated bubbles of similar size.
    The Journal of the Acoustical Society of America 01/2009; 124(6):4091-7. · 1.65 Impact Factor
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    ABSTRACT: A quantitative acoustical study of individual ultrasound contrast agent microbubbles, excited at low acoustic pressure amplitudes, is presented. A total of 76 microbubbles were studied. Sound pressure amplitudes as low as 1 Pa, collected from the smallest bubbles (radius of 1.4 micrometer), were recorded with a signal-to-noise ratio of 17 dB. Higher signal-to-noise ratios of 31 dB were obtained for bubbles with radii larger than 2 micrometer. The results were compared to a model derived from the Rayleigh-Plesset equation. Two methods are presented to extract the viscoelastic shell parameters, i.e. bubble shell elasticity and bubble shell viscosity. Firstly, the individual time responses were fitted to the modified Rayleigh-Plesset equation, by adjusting the viscoelastic shell parameters through a best-fit optimization procedure. The second method uses a similar best-fit optimization procedure to fit a linearized analytical expression of the model to the scattered pressure amplitude in the fundamental frequency band as a function of initial bubble radius. The shell parameters found with both methods are in close agreement and a good correspondence with the shell parameters found in other studies on similar bubbles was found. The characterization of single bubbles provided more detailed information about the viscoelastic shell parameters as a function of bubble size, which confirms a size dependency of these parameters
    Ultrasonics Symposium, 2006. IEEE; 11/2006
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    ABSTRACT: Microbubble-enhanced sonothrombolysis (MEST) may be an alternative therapeutic option in ischemic stroke. Clinical study of the efficacy of MEST as an adjunct stroke therapy, before imaging with CT or MRI, requires experimental data on the safety of this approach in the presence of hemorrhagic stroke. We, therefore, investigated the effect of diagnostic transcranial ultrasound combined with microbubbles (US + MB) in an experimental animal model of intracerebral hemorrhage (ICH). ICH was induced in anesthetized rats by intracerebral collagenase injection. Transcranial ultrasound (2 MHz, mechanical index 1.3, 1051 kPa) was applied 3 h after ICH induction to rat brains for 30 min during a continuous IV infusion of sulfur hexafluoride microbubbles (SonoVue). The size of cerebral hemorrhage, the extent of brain edema, and the amount of apoptosis were compared with those from control rats with ICH but without US + MB. Results showed no significant effect of US + MB on hemorrhage size (control 23.3 +/- 10.7 mm(3), US + MB 20.3 +/- 5.8 mm(3)), on the extent of brain edema (control 3.3 +/- 2.0%, US +MB 3.5 +/- 1.9%), or on the rate of apoptosis (control 5.2 +/- 1.5%, US + MB 5.2 +/- 1.0%). We conclude that diagnostic ultrasound in combination with microbubbles does not cause additional damage to the rat brain during ICH in our experimental set-up. This finding provides support for the use of MEST as an early stroke therapy.
    Ultrasound in Medicine & Biology 10/2006; 32(9):1377-82. · 2.46 Impact Factor