Ayache Bouakaz

Ultrasound contrast imaging: Current and new potential methods

For 10 years, it was thought that ultrasound (US) contrast agents could be sufficiently detected and imaged with the conventional imaging techniques, now referred to as fundamental imaging. However, it turned out that fundamental imaging was not sensitive enough to detect the contrast agents in the presence of tissue. New imaging techniques that are based on specific properties of the contrast agents, such as nonlinear and transient scattering, proved to be more sensitive. US contrast imaging modalities used today are fundamental, second harmonic, harmonic power Doppler, and pulse inversion; new modalities, such as release burst and subharmonic imaging are emerging. Second harmonic imaging is still not optimal for perfusion imaging applications. However, in combination with Doppler techniques such as power Doppler, it is one of the most sensitive techniques currently available. A complete understanding of the US-contrast agent interaction is essential for further improvements of current detection methods, and the development of new imaging techniques.

Microbubble spectroscopy of ultrasound contrast agents

A new optical characterization of the behavior of single ultrasound contrast bubbles is presented. The method consists of insonifying individual bubbles several times successively sweeping the applied frequency, and to record movies of the bubble response up to 25 million frames/s with an ultrahigh speed camera operated in a segmented mode. The method, termed microbubble spectroscopy, enables to reconstruct a resonance curve in a single run. The data is analyzed through a linearized model for coated bubbles. The results confirm the significant influence of the shell on the bubble dynamics: shell elasticity increases the resonance frequency by about 50%, and shell viscosity is responsible for about 70% of the total damping. The obtained value for shell elasticity is in quantative agreement with previously reported values. The shell viscosity increases significantly with the radius, revealing a new nonlinear behavior of the phospholipid coating.

Basic acoustic properties of microbubbles.

Small (encapsulated) gas bubbles in a contrast medium react to an external oscillating pressure field with volume pulsations. Depending on the magnitude of the ultrasound wave, the vibrations will be related either linearly or nonlinearly to the applied acoustic pressure. For low acoustic pressures, the instantaneous radius oscillates linearly in relation to the amplitude of the applied external pressure field. The oscillation of the bubble is governed by parameters such as resonance frequency, damping coefficients, and shell properties. For higher amplitudes of the external field, the pulsation of the bubbles becomes nonlinear. The spectrum of the scattered ultrasound wave also contains higher harmonics of the emitted frequency in addition to the fundamental frequency. The emitted frequency, bubble size, and nonlinear propagation effects have significant influence on the harmonic generation. For encapsulated bubbles exposed to even higher acoustic amplitudes, their scattering effectiveness increases dramatically and becomes transient. The scattered frequency spectrum broadens, containing higher harmonics. This consequence is due to rupture, disappearance, change of gas content, etc. Using these specific characteristics of the contrast bubbles will open new perspectives in imaging and analysis for medical diagnosis.

Detection procedures of ultrasound contrast agents.

In the early days, it was believed that ultrasound contrast agents (UCA) could be sufficiently detected and imaged with the conventional imaging methods nowadays referred to as fundamental imaging. Newer imaging techniques proved to be more sensitive and are based on specific properties of the UCA. In general, these new characteristics involve non-linear and transient characteristics of contrast agents that appear at the high end of the diagnostic acoustic intensity. Imaging modalities used today for UCA are, besides fundamental imaging, second harmonic imaging, power Doppler, harmonic power Doppler, pulse inversion and pulse inversion Doppler, multi-pulse imaging and subharmonic imaging. Although the results of conventional second harmonic imaging are still not optimal for perfusion imaging applications, in combination with Doppler techniques (colour Doppler, power Doppler) it is one of the most sensitive techniques currently available in terms of agent-to-tissue ratio. Further improvements in current and future detection methods demand a complete understanding of the ultrasound-UCA interaction.

Comparison of native and contrast-enhanced harmonic echocardiography for visualization of left ventricular endocardial border.

Our study was designed to compare the utility of fundamental and second harmonic imaging (SH) for visualization of the left ventricular (LV) endocardial border. SH is a new imaging modality using nonlinear acoustic response, which may provide better endocardial border delineation. Standard apical views were studied in 42 patients using fundamental frequency (FF), SH without contrast (1.6- to 1.8-MHz and 2.1- to 2.5-MHz transmission frequencies), and SH after an intravenous injection of 2.5 g of Levovist. The quality of endocardial delineation in 16 standard segments was scored from 0 to 2. The endocardial visualization index was calculated as a mean of the scores. SH with and without contrast significantly improved LV endocardial border detection (endocardial visualization index 1.25+/-0.53, 1.64+/-0.67, 1.55+/-0.69, and 1.73+/-0.28 for fundamental, lower, and higher frequency harmonic and contrast-harmonic mode, respectively, p <0.005). Improvement was found in all LV segments. The number of invisible segments decreased from 142 (FF) to 54, 112, and 61 (in lower, higher, and contrast SH mode, respectively, p <0.001). Endocardial delineation in the apical segments using SH was optimal after contrast injection. In the basal LV area, contrast-enhanced images were less informative because of signal attenuation. Thus, SH significantly improves visualization of the LV endocardial border. Contrast enhancement with Levovist improves imaging of the apical segments but has no additional advantage in the basal segments. SH emerges as first-line modality for studies of LV function.

Harmonic chirp imaging method for ultrasound contrast agent

Coded excitation is currently used in medical ultrasound to increase signal-to-noise ratio (SNR) and penetration depth. We propose a chirp excitation method for contrast agents using the second harmonic component of the response. This method is based on a compression filter that selectively compresses and extracts the second harmonic component from the received echo signal. Simulations have shown a clear increase in response for chirp excitation over pulse excitation with the same peak amplitude. This was confirmed by two-dimensional (2-D) optical observations of bubble response with a fast framing camera. To evaluate the harmonic compression method, we applied it to simulated bubble echoes, to measured propagation harmonics, and to B-mode scans of a flow phantom and compared it to regular pulse excitation imaging. An increase of approximately 10 dB in SNR was found for chirp excitation. The compression method was found to perform well in terms of resolution. Axial resolution was in all cases within 10% of the axial resolution from pulse excitation. Range side-lobe levels were 30 dB below the main lobe for the simulated bubble echoes and measured propagation harmonics. However, side-lobes were visible in the B-mode contrast images.

Optical imaging of contrast agent microbubbles in an ultrasound field with a 100-MHz camera

Ultrasound (US) contrast agents, used in the field of medical diagnosis, contain small microbubbles of a mean diameter of about 3 microm. The acoustic behavior of these bubbles in US field has been subject to many investigations. In this study, we propose a method to visualize the behavior of the bubbles in a 0.5-MHz US field under a microscope with a frame rate of 4 MHz. For low acoustic pressures (peak negative pressure of 0.12 MPa), the radius-time curve as measured from the optical images is in agreement with the theory. For higher acoustic pressures (peak negative pressure of 0.6 MPa), the recorded radius is significantly larger than predicted by theory and sudden change in the bubbles shapes has been noticed. The proposed method enables the study and characterization of individual bubbles and their encapsulation. It is expected that this will open new areas for quality control, US contrast imaging and US-guided drug delivery.

Contrast harmonic imaging

The behavior of ultrasound contrast agents depends highly on the acoustic pressure of the insonified ultrasound wave. For low pressure the expansion and compression is linear to the pressure, for medium acoustic pressure nonlinear behavior starts to occur and for high pressures, but still in the diagnostic range transient scattering can be noticed, resulting in an enhanced scattering followed by a disappearance of the bubble. The nonlinear and transient regime can be utilized for imaging of the contrast agent in or nearby tissue. The magnitude of the nonlinear signal from the contrast has to compete with the nonlinear component of the ultrasound wave, which is generated during propagation. It is shown that contrast is superior to tissue when using low frequencies and imaging the third or fourth harmonic of the transmitted frequency.

Contrast superharmonic imaging: A feasibility study

Harmonic imaging provided significant improvement in image quality by taking advantage of the scattered second harmonic (2H) component from contrast bubbles. However, differentiation between contrast and tissue (usually termed contrast-to-tissue ratio, CTR) is sometimes cumbersome and this is mainly due to tissue contamination. We have previously demonstrated, using simulations and in vitro measurements, that CTR increases as a function of the order of the harmonic number. A new contrast imaging method based on the detection of the higher harmonics was developed and termed superharmonic (SH). This technique has been shown to be more sensitive to contrast by increasing the signal from contrast and suppressing that from tissue (high CTR). The purpose of this study was to determine the clinical feasibility and usefulness of SH in patients using a commercially available contrast agent (SonoVue(R)) for quantification of myocardial perfusion. A total of 10 patients with various cardiac diseases were assessed. Apical four-chamber views were acquired using SH in triggered mode before and after contrast injection. The superharmonic was performed with a newly developed probe transmitting at 0.8 MHz with a mechanical index of 0.2. Myocardial perfusion was determined visually and analyzed quantitatively using radiofrequency (RF) processing from different regions of interest. The results showed that, before contrast injection, SH was totally blinded to tissue and no superharmonic components were generated in the image view. After administration of SonoVue(R), myocardial opacification was visualized by SH after contrast entered the myocardium. An increase of more than 15 dB in the myocardial bubbles echo compared to tissue echo was measured. In addition, the technique was used to visualize myocardial perfusion after myocardial septal ablation for hypertrophic cardiomyopathy. The clinical results showed the ability of contrast SH imaging in differentiating low and normal perfusion areas, demonstrating the high sensitivity and specificity of the technique.

Noninvasive measurement of the hydrostatic pressure in a fluid-filled cavity based on the disappearance time of micrometer-sized free gas bubbles

A new method for noninvasive pressure measurement, based on the disappearance time of micrometer-sized free gas bubbles, is described in this article. An ultrasound (US) contrast agent, consisting of encapsulated gas bubbles, is used as a vehicle to transport the free gas bubbles to the desired region where the pressure is to be measured. The small free gas bubbles are generated at the region of interest (e.g., heart chambers), from the encapsulated gas bubbles, which rupture when they are exposed to a single low-frequency (e.g., 0.5 MHz), high acoustic amplitude US burst. The released gas bubbles persist for only a few ms and dissolve in the liquid, depending on their size, the gas, the liquid characteristics and ambient parameters such as temperature, gas concentration and pressure. A pressure-disappearance time relationship is determined using a sequence of high-frequency (e.g., 10 MHz), low acoustic amplitude US pulses. From in vitro experiments, reproducible results show a significant difference between the disappearance time of the bubbles as function of the local pressure, resulting in a quicker disappearance of the bubble for higher values of the pressure. The sensitivity of the method to small pressure changes (50 mmHg) is demonstrated.