2007 IEEE International Workshop on Imaging Systems and Techniques, 2007
One of the most important issues in the field of contrast agents-based echographic imaging is the... more One of the most important issues in the field of contrast agents-based echographic imaging is the development of techniques able to separate the echoes of such contrast media from the echoes of the biological tissue: in particular in literature could be found various solutions concerning the use of multiple transmitted signals and the combination of related echoes. These techniques may
Over the past decade, ultrasound contrast agents (UCA) in the form of tiny gas bubbles were intro... more Over the past decade, ultrasound contrast agents (UCA) in the form of tiny gas bubbles were introduced to improve the echographic image quality. The recent research is devoted to exploit the potentiality of new UCA, known as targeted UCA. This contrast agent is able to selectively adhere to cancer cells, as a consequence, the number of attached microbubbles that composes
Abstract. One of the most important issues in the field of ultrasound medical imaging using contr... more Abstract. One of the most important issues in the field of ultrasound medical imaging using contrast agents is the development of techniques able to separate the response of contrast media from the response of biological tissues. In the literature, one can find various solutions ...
Next-generation ultrasound contrast agents, in the form of tiny gas bubbles, can be targeted to s... more Next-generation ultrasound contrast agents, in the form of tiny gas bubbles, can be targeted to selectively adhere to cancer cells. The number of attached microbubbles could be correlated with the status of the cancer. Consequently, the estimation of bubble concentration can provide useful medical information in addition to ultrasound molecular imaging. In this paper, a method to obtain the ultrasound image of a region of interest and the estimation of the related microbubble volumetric concentration is proposed. The mentioned tasks are performed in an unique investigation, working on the signals remotely acquired by means of an ultrasound scanner. The algorithm is divided into two steps. Firstly, a signal processing technique, based on multi-pulse transmission and recombination of the received signals, is used to obtain an image of the scene and to detect the bubble echoes abating surrounding tissue contribution. Then, the residual bubble echo, remained after the application of the technique, is processed in order to estimate the concentration. The concentration estimation method is based on a nonlinear regression approach, carried out by a support vector machine. Preliminary in vitro experiments provided encouraging results.
The quantification of contrast agent concentration is an ongoing research area to improve the ult... more The quantification of contrast agent concentration is an ongoing research area to improve the ultrasound medical diagnosis capability. The accurate evaluation of local blood perfusion in a tissue and the detection of a tumor at early stage could be the main applications. The intensity of an ultrasound image is not directly correlated with the volumetric contrast agent concentration. The qualitative
Recently, polymer-shelled microbubbles have been proposed, showing some important advantages. The... more Recently, polymer-shelled microbubbles have been proposed, showing some important advantages. They offer both a mechanical stability and a distinctive feature to be easily targeted to a specific address within the body. This paper focuses on the opportunity of use polymeric microbubbles as contrast agent in medical imaging applications, where the nonlinear response is exploited and the destruction of bubbles is avoided. The major drawback of polymer-shelled microbubbles is related to the lower elasticity of their shell. Lower echoes are then expected. As a consequence, it is evident the risk that, for low/moderate pressure values, the response of these microbubbles is not sufficiently nonlinear to allow a good detection of the contrast agent presence. A non-conventional method, based on the transmission in temporal succession of three chirp pulses, is employed to detect polymeric bubbles at different acoustic pressures. The results reveal that this signal processing technique is particularly adapted for the detection of polymer-shelled microbubbles even at low acoustic pressures and low concentrations, where conventional techniques, as pulse inversion and contrast pulse sequence imaging, fail.
ABSTRACT A multimodality contrast agent able to be detected with ultrasound and MRI can combine t... more ABSTRACT A multimodality contrast agent able to be detected with ultrasound and MRI can combine the advantages of the two diagnostic techniques. In this paper, a preliminary ultrasound assessment of two different types of innovative magnetic microbubbles is presented. In both cases, the combination of superparamagnetic iron oxide nanoparticles with polymeric microbubbles is used to produce the contrast agent. The only difference is the structure of the magnetic bubble: the nanoparticles are attached on the polymeric shell in the first case, while in the second case they are physically trapped into the membrane. After a preliminary comparison with polymer-shelled bubbles without magnetic nanoparticles, the performance of the two types of magnetic bubbles are compared through in vitro experiments. A non-conventional signal processing technique, particularly adapted to detect polymeric bubbles and based on the combination of multi-pulse excitation and chirp coding, is applied. The measurement of the contrast-to-tissue ratio reveals that the detection sensitivity of the signal processing technique depends on the structure of the magnetic microbubbles.
ABSTRACT The estimation of the contrast agent concentration is important for the introduction of ... more ABSTRACT The estimation of the contrast agent concentration is important for the introduction of effective quantification in ultrasound medical diagnoses. This paper focuses on the comparison of three methods for estimating the number of microbubbles in a small volume. An energy-based linear regression approach and a nonlinear regression approach are applied to estimate the microbubble concentration working from the signals backscattered by a contrast agent population. The nonlinear regression approach, based on the support vector machine, is employed assuming either only one feature, the signal energy, or a set of significant features. Synthetic data are used for the training phase and the test of the methods. The results demonstrate that, although the energy-based methods allows to achieve good results in terms of mean estimated values, the adoption of a vector of features significantly reduces the mean square error. The nonlinear regression approach with multidimensional feature vector allows to improve the measurement precision of the bubble concentration.
One of the important issues in the field of ultrasound medical imaging using contrast agents is t... more One of the important issues in the field of ultrasound medical imaging using contrast agents is the development of techniques able to separate the response of the contrast media from that of the biological tissues. In the literature, one can find various solutions involving the use of multiple transmitted signals and the combination of related echoes. However, the quality of these techniques may be reduced due to some undesired effects that are seldom considered, despite the fact that they are always present in real systems. These effects are the signal distortions introduced by the hardware equipment, the thermal noise in the electronic circuitry, and body motion between successive pulses. In this paper we propose a simulation tool that will allow the calculation of the backscattered echo from a population of contrast agents immersed in a biological tissue, considering all the mentioned effects. With this tool, an assessment of the comparative robustness of three well-known multi-pulse techniques has been carried out under realistic working conditions and the performance of the three techniques has been evaluated in terms of contrastto-tissue ratio and signal-to-noise ratio. The results show that the undesired effects have a strong impact on these techniques and that there are notable differences in their robustness. Finally, some suggestions on the choice of the particular technique to be applied are provided on the basis of the specific work conditions.
The development of techniques to separate the response of the contrast agent from that of the bio... more The development of techniques to separate the response of the contrast agent from that of the biological tissues is of great importance in ultrasound medical imaging. In the literature, one can find various solutions involving the use of multiple transmitted signals and the weighted sum of related echoes. In this paper, the combination of one of these multi-pulse techniques with a coded excitation is proposed and assessed. Coded excitation has been used mainly to increase the signal-to-noise ratio (SNR) and the penetration depth, provided that a matched filtering is applied in the reception chain. However, it has been shown that a signal with a long duration time also increases the backscattered echoes produced by the microbubbles and, consequently, the contrast-to-tissue ratio. Therefore, the implementation of a multi-pulse technique using a long coded pulse can yield a better contrast-to-tissue ratio and SNR. This paper investigates the combination of the linear chirp pulse with a multi-pulse technique based on the transmission of three pulses. The performance was evaluated using both simulated and real signals, assessing the improvement in the contrast-to-tissue ratio and SNR, the visual quality of the images obtained and the axial accuracy. A comparison with the same multi-pulse technique implemented using a traditional amplitude-modulated pulse revealed that the deployment of a chirp pulse produces several noticeable advantages and only a minor drawback.
The estimation of the contrast agent concentration can provide useful information in medical diag... more The estimation of the contrast agent concentration can provide useful information in medical diagnostics. Because the intensity of an ultrasound image is not directly correlated with the volumetric concentration of a contrast agent, a method that can estimate the concentration, working only from the signals acquired by the ultrasound scanner, could be particularly useful in terms of precision, time consumption and cost. In this paper, a method to obtain the ultrasound image of a region of interest and the estimation of the related microbubble concentration is proposed. The mentioned tasks are performed in a unique investigation, working from the signals remotely acquired by means of an ultrasound scanner equipped with a grabber board, which is able to collect radio-frequency data. The algorithm is divided into two steps. Firstly, a signal-processing technique, based on multi-pulse transmission and recombination of the received signals, is used to obtain an image of the scene, emphasizing the bubble echoes and abating the contributions of surrounding tissue. Then, the concentration estimation method, based on a nonlinear regression approach carried out by a support vector machine, is applied. Because the training phase requires precise knowledge of the bubble concentration, a completely synthetic training set is assumed, whereas the test set is derived from real signals. In this paper, both non-specific and targeted microbubbles (able to selectively adhere to cancer cells) are considered. The results are encouraging and reveal that the proposed method can provide an accurate estimation in a small volume, which can be useful for diagnostic purposes.
The Journal of the Acoustical Society of America, 2013
This letter describes an ultrasound imaging assessment of novel contrast agents that are detectab... more This letter describes an ultrasound imaging assessment of novel contrast agents that are detectable by both medical ultrasound and magnetic resonance imaging. Such agents are created by including superparamagnetic particles in polymer-shelled microbubbles through two different approaches. The reduced echogenicity and nonlinearity of the microbubbles are observed, depending on the strategy used to include the particles and the resulting density. The best results are obtained using imaging techniques that exploit the third-order nonlinear term, which is especially true when the microbubbles are excited by means of chirp pulses.
The Journal of the Acoustical Society of America, 2013
The combination of superparamagnetic iron oxide nanoparticles with polymeric air-filled microbubb... more The combination of superparamagnetic iron oxide nanoparticles with polymeric air-filled microbubbles is used to produce two types of multimodal contrast agents to enhance medical ultrasound and magnetic resonance imaging. The nanoparticles are either covalently linked to the shell or physically entrapped into the shell. In this paper, the characterization of the acoustic properties (backscattered power, fracturing pressure, attenuation and dispersion of the ultrasonic wave) and ultrasound imaging of the two types of magnetic microbubbles are presented. In vitro B-mode images are generated using a medical ultrasound scanner by applying a nonconventional signal processing technique that is suitable to detect polymeric bubbles and based on the combination of multipulse excitation and chirp coding. Even if both types of microbubbles can be considered to be effective ultrasound contrast agents, the different structure of the shell loaded with nanoparticles has a pronounced effect on the echogenicity and the detection sensitivity of the imaging technique. The best results are obtained using microbubbles that are externally coated with nanoparticles. A backscattered power of 20 dB was achieved at lower concentration, and an increment of 8 dB in the contrast-to-tissue ratio was observed with respect to the more rigid microbubbles with particles entrapped into the shell.
This paper focuses on the use of poly (vinyl alcohol)-shelled microbubbles as a contrast agent in... more This paper focuses on the use of poly (vinyl alcohol)-shelled microbubbles as a contrast agent in ultrasound medical imaging. The objective was an in vitro assessment of the different working conditions and signal processing methods for the visual detection (especially in small vessels) of such microbubbles, while avoiding their destruction. Polymer-shelled microbubbles have recently been proposed as ultrasound contrast agents with some important advantages. The major drawback is a shell that is less elastic than that of the traditional lipidic microbubbles. Weaker echoes are expected, and their detection at low concentrations may be critical. In vitro experiments were performed with a commercial ultrasound scanner equipped with a dedicated acquisition board. A concentration of 100bubbles/mm(3), excitation pressure amplitudes from 120kPa to 320kPa, and a central frequency of 3MHz or 4.5MHz were used. Three multi-pulse techniques (i.e., pulse inversion, contrast pulse sequence based on three transmitted signals, and contrast pulse sequence in combination with the chirp pulse) were compared. The results confirmed that these microbubbles produce a weaker ultrasound response than lipidic bubbles with a reduced second-order nonlinear component. Nevertheless, these microbubbles can be detected by the contrast pulse sequence technique, especially when the chirp pulse is adopted. The best value of the contrast-to-tissue ratio was obtained at an excitation pressure amplitude of 230kPa: although this pressure amplitude is higher than what is typically used for lipidic microbubbles, it does not cause the rupture of the polymeric contrast agent.
2007 IEEE International Workshop on Imaging Systems and Techniques, 2007
One of the most important issues in the field of contrast agents-based echographic imaging is the... more One of the most important issues in the field of contrast agents-based echographic imaging is the development of techniques able to separate the echoes of such contrast media from the echoes of the biological tissue: in particular in literature could be found various solutions concerning the use of multiple transmitted signals and the combination of related echoes. These techniques may
Over the past decade, ultrasound contrast agents (UCA) in the form of tiny gas bubbles were intro... more Over the past decade, ultrasound contrast agents (UCA) in the form of tiny gas bubbles were introduced to improve the echographic image quality. The recent research is devoted to exploit the potentiality of new UCA, known as targeted UCA. This contrast agent is able to selectively adhere to cancer cells, as a consequence, the number of attached microbubbles that composes
Abstract. One of the most important issues in the field of ultrasound medical imaging using contr... more Abstract. One of the most important issues in the field of ultrasound medical imaging using contrast agents is the development of techniques able to separate the response of contrast media from the response of biological tissues. In the literature, one can find various solutions ...
Next-generation ultrasound contrast agents, in the form of tiny gas bubbles, can be targeted to s... more Next-generation ultrasound contrast agents, in the form of tiny gas bubbles, can be targeted to selectively adhere to cancer cells. The number of attached microbubbles could be correlated with the status of the cancer. Consequently, the estimation of bubble concentration can provide useful medical information in addition to ultrasound molecular imaging. In this paper, a method to obtain the ultrasound image of a region of interest and the estimation of the related microbubble volumetric concentration is proposed. The mentioned tasks are performed in an unique investigation, working on the signals remotely acquired by means of an ultrasound scanner. The algorithm is divided into two steps. Firstly, a signal processing technique, based on multi-pulse transmission and recombination of the received signals, is used to obtain an image of the scene and to detect the bubble echoes abating surrounding tissue contribution. Then, the residual bubble echo, remained after the application of the technique, is processed in order to estimate the concentration. The concentration estimation method is based on a nonlinear regression approach, carried out by a support vector machine. Preliminary in vitro experiments provided encouraging results.
The quantification of contrast agent concentration is an ongoing research area to improve the ult... more The quantification of contrast agent concentration is an ongoing research area to improve the ultrasound medical diagnosis capability. The accurate evaluation of local blood perfusion in a tissue and the detection of a tumor at early stage could be the main applications. The intensity of an ultrasound image is not directly correlated with the volumetric contrast agent concentration. The qualitative
Recently, polymer-shelled microbubbles have been proposed, showing some important advantages. The... more Recently, polymer-shelled microbubbles have been proposed, showing some important advantages. They offer both a mechanical stability and a distinctive feature to be easily targeted to a specific address within the body. This paper focuses on the opportunity of use polymeric microbubbles as contrast agent in medical imaging applications, where the nonlinear response is exploited and the destruction of bubbles is avoided. The major drawback of polymer-shelled microbubbles is related to the lower elasticity of their shell. Lower echoes are then expected. As a consequence, it is evident the risk that, for low/moderate pressure values, the response of these microbubbles is not sufficiently nonlinear to allow a good detection of the contrast agent presence. A non-conventional method, based on the transmission in temporal succession of three chirp pulses, is employed to detect polymeric bubbles at different acoustic pressures. The results reveal that this signal processing technique is particularly adapted for the detection of polymer-shelled microbubbles even at low acoustic pressures and low concentrations, where conventional techniques, as pulse inversion and contrast pulse sequence imaging, fail.
ABSTRACT A multimodality contrast agent able to be detected with ultrasound and MRI can combine t... more ABSTRACT A multimodality contrast agent able to be detected with ultrasound and MRI can combine the advantages of the two diagnostic techniques. In this paper, a preliminary ultrasound assessment of two different types of innovative magnetic microbubbles is presented. In both cases, the combination of superparamagnetic iron oxide nanoparticles with polymeric microbubbles is used to produce the contrast agent. The only difference is the structure of the magnetic bubble: the nanoparticles are attached on the polymeric shell in the first case, while in the second case they are physically trapped into the membrane. After a preliminary comparison with polymer-shelled bubbles without magnetic nanoparticles, the performance of the two types of magnetic bubbles are compared through in vitro experiments. A non-conventional signal processing technique, particularly adapted to detect polymeric bubbles and based on the combination of multi-pulse excitation and chirp coding, is applied. The measurement of the contrast-to-tissue ratio reveals that the detection sensitivity of the signal processing technique depends on the structure of the magnetic microbubbles.
ABSTRACT The estimation of the contrast agent concentration is important for the introduction of ... more ABSTRACT The estimation of the contrast agent concentration is important for the introduction of effective quantification in ultrasound medical diagnoses. This paper focuses on the comparison of three methods for estimating the number of microbubbles in a small volume. An energy-based linear regression approach and a nonlinear regression approach are applied to estimate the microbubble concentration working from the signals backscattered by a contrast agent population. The nonlinear regression approach, based on the support vector machine, is employed assuming either only one feature, the signal energy, or a set of significant features. Synthetic data are used for the training phase and the test of the methods. The results demonstrate that, although the energy-based methods allows to achieve good results in terms of mean estimated values, the adoption of a vector of features significantly reduces the mean square error. The nonlinear regression approach with multidimensional feature vector allows to improve the measurement precision of the bubble concentration.
One of the important issues in the field of ultrasound medical imaging using contrast agents is t... more One of the important issues in the field of ultrasound medical imaging using contrast agents is the development of techniques able to separate the response of the contrast media from that of the biological tissues. In the literature, one can find various solutions involving the use of multiple transmitted signals and the combination of related echoes. However, the quality of these techniques may be reduced due to some undesired effects that are seldom considered, despite the fact that they are always present in real systems. These effects are the signal distortions introduced by the hardware equipment, the thermal noise in the electronic circuitry, and body motion between successive pulses. In this paper we propose a simulation tool that will allow the calculation of the backscattered echo from a population of contrast agents immersed in a biological tissue, considering all the mentioned effects. With this tool, an assessment of the comparative robustness of three well-known multi-pulse techniques has been carried out under realistic working conditions and the performance of the three techniques has been evaluated in terms of contrastto-tissue ratio and signal-to-noise ratio. The results show that the undesired effects have a strong impact on these techniques and that there are notable differences in their robustness. Finally, some suggestions on the choice of the particular technique to be applied are provided on the basis of the specific work conditions.
The development of techniques to separate the response of the contrast agent from that of the bio... more The development of techniques to separate the response of the contrast agent from that of the biological tissues is of great importance in ultrasound medical imaging. In the literature, one can find various solutions involving the use of multiple transmitted signals and the weighted sum of related echoes. In this paper, the combination of one of these multi-pulse techniques with a coded excitation is proposed and assessed. Coded excitation has been used mainly to increase the signal-to-noise ratio (SNR) and the penetration depth, provided that a matched filtering is applied in the reception chain. However, it has been shown that a signal with a long duration time also increases the backscattered echoes produced by the microbubbles and, consequently, the contrast-to-tissue ratio. Therefore, the implementation of a multi-pulse technique using a long coded pulse can yield a better contrast-to-tissue ratio and SNR. This paper investigates the combination of the linear chirp pulse with a multi-pulse technique based on the transmission of three pulses. The performance was evaluated using both simulated and real signals, assessing the improvement in the contrast-to-tissue ratio and SNR, the visual quality of the images obtained and the axial accuracy. A comparison with the same multi-pulse technique implemented using a traditional amplitude-modulated pulse revealed that the deployment of a chirp pulse produces several noticeable advantages and only a minor drawback.
The estimation of the contrast agent concentration can provide useful information in medical diag... more The estimation of the contrast agent concentration can provide useful information in medical diagnostics. Because the intensity of an ultrasound image is not directly correlated with the volumetric concentration of a contrast agent, a method that can estimate the concentration, working only from the signals acquired by the ultrasound scanner, could be particularly useful in terms of precision, time consumption and cost. In this paper, a method to obtain the ultrasound image of a region of interest and the estimation of the related microbubble concentration is proposed. The mentioned tasks are performed in a unique investigation, working from the signals remotely acquired by means of an ultrasound scanner equipped with a grabber board, which is able to collect radio-frequency data. The algorithm is divided into two steps. Firstly, a signal-processing technique, based on multi-pulse transmission and recombination of the received signals, is used to obtain an image of the scene, emphasizing the bubble echoes and abating the contributions of surrounding tissue. Then, the concentration estimation method, based on a nonlinear regression approach carried out by a support vector machine, is applied. Because the training phase requires precise knowledge of the bubble concentration, a completely synthetic training set is assumed, whereas the test set is derived from real signals. In this paper, both non-specific and targeted microbubbles (able to selectively adhere to cancer cells) are considered. The results are encouraging and reveal that the proposed method can provide an accurate estimation in a small volume, which can be useful for diagnostic purposes.
The Journal of the Acoustical Society of America, 2013
This letter describes an ultrasound imaging assessment of novel contrast agents that are detectab... more This letter describes an ultrasound imaging assessment of novel contrast agents that are detectable by both medical ultrasound and magnetic resonance imaging. Such agents are created by including superparamagnetic particles in polymer-shelled microbubbles through two different approaches. The reduced echogenicity and nonlinearity of the microbubbles are observed, depending on the strategy used to include the particles and the resulting density. The best results are obtained using imaging techniques that exploit the third-order nonlinear term, which is especially true when the microbubbles are excited by means of chirp pulses.
The Journal of the Acoustical Society of America, 2013
The combination of superparamagnetic iron oxide nanoparticles with polymeric air-filled microbubb... more The combination of superparamagnetic iron oxide nanoparticles with polymeric air-filled microbubbles is used to produce two types of multimodal contrast agents to enhance medical ultrasound and magnetic resonance imaging. The nanoparticles are either covalently linked to the shell or physically entrapped into the shell. In this paper, the characterization of the acoustic properties (backscattered power, fracturing pressure, attenuation and dispersion of the ultrasonic wave) and ultrasound imaging of the two types of magnetic microbubbles are presented. In vitro B-mode images are generated using a medical ultrasound scanner by applying a nonconventional signal processing technique that is suitable to detect polymeric bubbles and based on the combination of multipulse excitation and chirp coding. Even if both types of microbubbles can be considered to be effective ultrasound contrast agents, the different structure of the shell loaded with nanoparticles has a pronounced effect on the echogenicity and the detection sensitivity of the imaging technique. The best results are obtained using microbubbles that are externally coated with nanoparticles. A backscattered power of 20 dB was achieved at lower concentration, and an increment of 8 dB in the contrast-to-tissue ratio was observed with respect to the more rigid microbubbles with particles entrapped into the shell.
This paper focuses on the use of poly (vinyl alcohol)-shelled microbubbles as a contrast agent in... more This paper focuses on the use of poly (vinyl alcohol)-shelled microbubbles as a contrast agent in ultrasound medical imaging. The objective was an in vitro assessment of the different working conditions and signal processing methods for the visual detection (especially in small vessels) of such microbubbles, while avoiding their destruction. Polymer-shelled microbubbles have recently been proposed as ultrasound contrast agents with some important advantages. The major drawback is a shell that is less elastic than that of the traditional lipidic microbubbles. Weaker echoes are expected, and their detection at low concentrations may be critical. In vitro experiments were performed with a commercial ultrasound scanner equipped with a dedicated acquisition board. A concentration of 100bubbles/mm(3), excitation pressure amplitudes from 120kPa to 320kPa, and a central frequency of 3MHz or 4.5MHz were used. Three multi-pulse techniques (i.e., pulse inversion, contrast pulse sequence based on three transmitted signals, and contrast pulse sequence in combination with the chirp pulse) were compared. The results confirmed that these microbubbles produce a weaker ultrasound response than lipidic bubbles with a reduced second-order nonlinear component. Nevertheless, these microbubbles can be detected by the contrast pulse sequence technique, especially when the chirp pulse is adopted. The best value of the contrast-to-tissue ratio was obtained at an excitation pressure amplitude of 230kPa: although this pressure amplitude is higher than what is typically used for lipidic microbubbles, it does not cause the rupture of the polymeric contrast agent.
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Papers by C. Sciallero