Goertz, D.E.

Characterization of Definity™ Ultrasound Contrast Agent at Frequency Range of 5-15 MHz (Article)

2011-02-01T00:00:00Z

The status of vasa vasorum, which can be imaged using ultrasound contrast agents, is an indication for the progression of atherosclerosis. The preferred ultrasound frequency for this purpose is between 5 and 15 MHz. Therefore, it is essential to have knowledge about the acoustic properties of microbubbles such as elasticity and viscosity to be able to implement the current models for lipid encapsulated microbubbles developed for frequencies used in precordial imaging. In this study, the shell parameters, stiffness Spand friction Sf, of Definity™ microbubbles have been calculated at frequency range of 5-15 MHz by comparing the theoretical modeling of acoustic bubble response and experimental measurements. Derived parameters are in good agreement with previous estimations on SonoVue™ and Sonazoid™ contrast agent. However, the value of Sfis higher than previously estimated for Definity™ between 12-28 MHz.

Self-demodulation of high-frequency ultrasound (Article)

2010-04-09T00:00:00Z

High-frequency (>10 MHz) ultrasound is used in, e.g., small animal imaging or intravascular applications. Currently available ultrasound contrast agents (UCAs) have a suboptimal response for high frequencies. This study therefore investigates the nonlinear propagation effects in a high-frequency ultrasound field (25 MHz) and its use for standard UCA and diagnostic frequencies (1-3 MHz). Nonlinear mixing of two high-frequency carrier waves produces a low-frequency wave, known as the self-demodulation or parametric array effect. Hydrophone experiments showed that the self-demodulated field of a focused 25 MHz transducer (850 kPa source pressure) has an amplitude of 45 kPa at 1.5 MHz in water. Such pressure level is sufficient for UCA excitation. Experimental values are confirmed by numerical simulations using the Khokhlov-Zabolotskaya-Kuznetsov equation on a spatially convergent grid.

Pressure-Dependent Attenuation and Scattering of Phospholipid-Coated Microbubbles at Low Acoustic Pressures (Article)

2009-01-01T00:00:00Z

Previous optical studies have shown threshold behavior of single-contrast agent microbubbles. Below the acoustic pressure threshold, phospholipid-coated microbubbles with sizes <5.0 μm in diameter oscillate significantly less than above the threshold pressure. Previous studies also revealed an acoustic pressure-dependent attenuation of ultrasound by microbubble contrast agents. In this study, we investigated whether pressure-dependent acoustic behavior may be explained by threshold behavior. For this purpose, pressure-dependent attenuation and scattering of a phospholipid-coated contrast agent were measured. Transmit frequencies between 1.5 and 6.0 MHz and acoustic pressures between 5 and 200 kPa were applied. Unlike the galactose-based contrast agent Levovist, the phospholipid-coated contrast agent BR14 showed a pressure-dependent attenuation. In addition, it was found that filtered suspensions with only microbubbles <3.0 μm in diameter show more pressure-dependent attenuation behavior than native suspensions of phospholipid-coated microbubbles. For the scattering measurements conducted at 3.0 MHz, the native suspension did not show any pressure-dependent behavior. However, the filtered suspension responded highly nonlinearly. Between 30 and 150 kPa, 16 dB additional scattered power was obtained. We concluded that threshold behavior of phospholipid-coated microbubbles results in pressure-dependent attenuation and scattering. (E-mail: m.emmer@erasmusmc.nl).

Pulse inversion sequences for mechanically scanned transducers (Article)

2008-10-01T00:00:00Z

Mechanically scanned transducers are currently used for tissue harmonic imaging (THI) and nonlinear microbubble imaging at high frequencies. The pulse inversion (PI) technique is widely used for suppressing the fundamental signal, but its effectiveness is reduced by relative tissue/transducer motion. In this paper, we investigate multipulse inversion (MPI) sequences that achieve a significant improvement on the fundamental suppression for mechanically scanned single-element transducers. MPI was subsequently applied on simulated and measured RF-data and relative fundamental suppression was compared with the 2-pulse PI technique. Simulations showed, for example, an increased fundamental suppression of 6 and 10 dB for MPI-sequences that combined 3 and 7 pulses, respectively, for a rotating intravascular ultrasound transducer with an interpulse angle of 0.15°. Initial application of MPI sequences on RF-data from in vivo acquisitions resulted in similar fundamental suppression levels. The investigated MPI technique will help to reduce relative tissue/transducer motion effects and might lead to improved sensitivity and spatial resolution in nonlinear tissue imaging and improved microbubble detection in contrast imaging for mechanically scanned transducers.

High-Frequency Subharmonic Pulsed-Wave Doppler and Color Flow Imaging of Microbubble Contrast Agents (Article)

2008-07-01T00:00:00Z

A recent study has shown the feasibility of subharmonic (SH) flow imaging at a transmit frequency of 20 MHz. This paper builds on these results by examining the performance of SH flow imaging as a function of transmit pressure. Further, we also investigate the feasibility of SH pulsed-wave Doppler (PWD) imaging. In vitro flow experiments were performed with a 1-mm-diameter wall-less vessel cryogel phantom using the ultrasound contrast agent Definity™ and an imaging frequency of 20 MHz. The phantom results show that there is an identifiable pressure range where accurate flow velocity and power estimates can be made with SH imaging at 10 MHz (SH10), above which velocity estimates are biased by radiation force effects and unstable bubble behavior, and below which velocity and power estimates are degraded by poor SNR. In vivo validation of SH PWD was performed in an arteriole of a rabbit ear, and blood velocity estimates compared well with fundamental (F20) mode PWD. The ability to suppress tissue signals using SH signals may enable the use of higher frame rates and improve sensitivity to microvascular flow or slow velocities near large vessel walls by reducing or eliminating the need for clutter filters. (E-mail: aneedles@visualsonics.com).

Clinical relevance of pressure-dependent scattering at low acoustic pressures (Article)

2007-12-01T00:00:00Z

Recent optical and acoustical studies have shown a threshold behaviour in the response of phospholipid-coated contrast agents, for a certain range of sizes. Below the acoustic pressure threshold, the microbubbles' scattering efficacy is significantly reduced compared to that above the threshold. Here we investigate the clinical relevance of the observed threshold behaviour. A cardiac ultrasound scanner system was used to analyse the pressure-dependence of the scatter intensity. The scattering of a native suspension of a phospholipid-coated contrast agent was compared to that of a suspension in which microbubbles with a size larger than 3.0 μm in diameter were extracted. A power modulation scheme at the fundamental frequency was applied. After linearly scaling and subtracting the B-mode images recorded at 70 and 200 kPa, the contrast-to-tissue ratio (CTR) of the native suspension was 3.2 dB, whereas the CTR of the filtered suspension was 20 dB. The 17 dB difference is attributed to the threshold behaviour. Well-established ultrasound imaging techniques such as fundamental power modulation imaging could benefit from the pressure-dependent scattering properties of this type of contrast microbubbles.

Subharmonic Contrast Intravascular Ultrasound for Vasa Vasorum Imaging (Article)

2007-12-01T00:00:00Z

The feasibility of subharmonic contrast intravascular ultrasound (IVUS) imaging was investigated using a prototype nonlinear IVUS system and the commercial contrast agent Definity™. The system employed a mechanically scanned commercial catheter with a custom transducer element fabricated to have sensitivity at both 15 and 30 MHz. Experiments were conducted at a fundamental frequency of 30 MHz (F30; 25% bandwidth), with on-axis pressures ranging from 0.12 to 0.79 MPa, as measured with a needle hydrophone. In vitro characterization experiments demonstrated the detection of 15 MHz subharmonic signals (SH15) when pressure levels reached 360 kPa. The formation of SH15 images was shown, with tissue signals suppressed to near the noise floor and contrast to tissue ratios were improved by up to 30 dB relative to F30. In vivo experiments were performed using the atherosclerotic rabbit aorta model. Following the bolus injection of contrast agent upstream of the imaging catheter, agent was detected within the aorta, vena cava and within the perivascular space. These results provide a first in vivo demonstration of subharmonic contrast IVUS and suggest its potential as a new technique for imaging vasa vasorum. (E-mail: goertz@sri.utoronto.ca).

Attenuation and Size Distribution Measurements of Definity™ and Manipulated Definity™ Populations (Article)

2007-09-01T00:00:00Z

The contrast agent Definity™has recently been shown to have substantial nonlinear activity at high ultrasound frequencies (>10 MHz). In this study, measurements were performed to characterize the frequency dependant attenuation properties of Definity™and populations of Definity™that had been modified to preferentially isolate smaller bubbles through decantation or mechanical filtration. A narrowband pulse-echo substitution method was employed with a series of four transducers covering the frequency range from 2 to 50 MHz. "Native" Definity™has peak in attenuation in the vicinity of 10 MHz and remains high until 50 MHz. This pattern is significantly different from other clinically approved agents and is consistent with recent reports of nonlinear activity at high frequencies. With increasing decantation times, the attenuation peak becomes more diffuse and occurs at progressively higher frequencies. By 3 h for example, attenuation continues to rise until 30 MHz. The bubble size distribution undergoes preferential skewing toward smaller bubbles with increasing decantation time. Between 30 s and 3 h, the mean bubble diameter goes from 3.99 to 0.98 micrometers. Mechanical filtration with 2 and 1 μm pores causes attenuation to rise until 15 and 40 MHz, respectively. Definity™can therefore be manipulated to improve its relative activity at higher frequencies (>10 MHz), which has implications for ultrasound biomicroscopy and intravascular ultrasound applications. Further, these results suggest that agent handling can have a substantial impact on size distributions affecting lower frequency applications. Shell friction estimates derived from these data are lower than those reported for larger bubbles at lower frequencies. (E-mail: goertz@sri.sunnybrook.utoronto.ca).

High frequency ultrasound imaging of a single-species biofilm (Article)

2007-08-01T00:00:00Z

Objective: This study evaluated the feasibility of a high frequency ultrasound scan to examine the 3D morphology of Streptococcus mutans biofilms grown in vitro. Methods: Six 2-day S. mutans biofilms and six 7-day biofilms were grown on tissue culture membranes and on bovine dentine discs. A sterile growth medium on the membrane and disc were used as controls. Surfaces were rinsed and then immersed in sterile saline. High-frequency ultrasound imaging system was used to scan these surfaces at 55 MHz, and a computer program calculated the average thickness of the biofilm layer from the 3D images. Results: 3D pictures of the biofilm layers were obtained. Different cross-sections and plains are easily demonstrated. The average thickness of the 7-day biofilm was significantly bigger than the 2-day on both the membranes and dentinal discs. No structures were observed on the sterile membrane or disc. Conclusion: Three-dimensional structural imaging in situ is possible without damaging the biofilm layer in a quick and easy manner and can therefore be used to evaluate biofilms longitudinally as a function of time.

The Onset of Microbubble Vibration (Article)

2007-06-01T00:00:00Z

A linear relationship between the relative expansion of an off-resonance ultrasound contrast microbubble and low acoustic pressures is expected. In this study, high-speed optical recordings of individual phospholipid-coated microbubbles were used to investigate this relationship for microbubbles ranging from 2 to 11 μm and for acoustic pressures ranging from 20 to 250 kPa at a driving frequency of 1.7 MHz. For microbubbles larger than 5 μm, the relative expansion (ΔD/D0) increased linearly with applied acoustic pressure, starting at the origin. The response of smaller microbubbles (<5 μm) also increased linearly with the applied acoustic pressure. However, linearity started at an acoustic pressure threshold value of 30 to 120 kPa for the different individual microbubbles. Below these pressure values, little or no oscillation was observed. The results may be explained by size-dependent mechanical properties of the phospholipid shells. An imaging technique such as power modulation imaging could profit from the presence of an acoustic pressure threshold in the microbubble response.

Kon-Tiki revisited (Article)

2007-06-01T00:00:00Z

Interframe Clutter Filtering for High Frequency Flow Imaging (Article)

2007-04-01T00:00:00Z

This study investigates 'interframe' clutter filtering with a high frequency (HF) flow imaging system with the objective of improving the performance of HF microvascular imaging at high frame rates. An interframe filter exploits the correlation of tissue signals on the time scale of the frame rate and is, therefore, insensitive to tissue spectral broadening induced by sweeping a single element transducer over a region of tissue. In vitro experiments were conducted in a tissue-mimicking flow phantom over a range of mean flow velocities (0.5 to 70.0 mm/s). Power Doppler (PD) imaging and color flow (CF) imaging were performed for both slow (0.25 fps) and fast (20 fps) scanning acquisitions. Flow data acquired at 20 fps and interframe filtered had similar velocity and mean Doppler power values as the 0.25 fps single-frame filtered data sets. In vivo validation experiments were conducted using a 500 μm blood vessel in a human finger and detected blood flow of 2 to 3 mm/s. Further in vivo experiments examining experimental murine tumors demonstrated the feasibility of performing HF PD and CF imaging at high frame rates using interframe filtering. (E-mail: aneedles@swri.ca).

Intravascular ultrasound tissue harmonic imaging: A simulation study (Article)

2006-12-22T00:00:00Z

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.