Luca Breschi

Stable and transient subharmonic emissions from isolated contrast agent microbubbles

Ultrasound contrast agents (UCAs) have been widely studied in recent years in order to improve and develop new, sophisticated imaging techniques for clinical applications. In order to improve the understanding of microbubble-ultrasound interactions, an acoustic dynamic characterization of UCA microbubble behavior was performed in this work using a high frame-rate acquiring and processing system. This equipment is connected to a commercial scanner that provides RF beam-formed data with a frame-rate of 30 Hz. Acquired RF sequences allows us to follow the dynamics of cavitation mechanisms in its temporal evolution during different insonifying conditions. The experimental setup allowed us to keep the bubbles free in a spatial region of the supporting medium, thus avoiding boundary effects that can alter the ultrasound field and the scattered echo from bubbles. The work focuses on the study of subharmonic emission from an isolated bubble of contrast agent. In particular, the acoustic pressure threshold for a subharmonic stable emission was evaluated for a subset of 50 microbubbles at 3.3 MHz and at 5 MHz of insonation frequencies. An unexpected second pressure threshold, which caused the standstill of the subharmonic emission, was detected at 3.3 MHz and 5 MHz excitation frequencies. A transient subharmonic emission, which is hypothesized as being related to the formation of new free gas bubbles, was detected during the ultrasound-induced destruction of microbubbles. An experimental procedure was devised in order to investigate these behaviors and several sequences of RF echo signals and the related spectra, acquired from an isolated bubble in different insonation conditions, are presented and discussed in this paper

US-guided application of Nd:YAG laser in porcine pancreatic tissue: an ex vivo study and numerical simulation

BACKGROUND Laser ablation (LA) with a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser is a minimally invasive approach able to achieve a high rate of complete tissue necrosis. In a previous study we described the feasibility of EUS-guided Nd:YAG pancreas LA performed in vivo in a porcine model. OBJECTIVE To establish the best laser setting of Nd:YAG lasers for pancreatic tissue ablation. A secondary aim was to investigate the prediction capability of a mathematical model on ablation volume. DESIGN Ex vivo animal study. SETTING Hospital animal laboratory. SUBJECTS Explanted pancreatic glands from 60 healthy farm pigs. INTERVENTION Laser output powers (OP) of 1.5, 3, 6, 10, 15, and 20 W were supplied. Ten trials for each OP were performed under US guidance on ex vivo healthy porcine pancreatic tissue. MAIN OUTCOME MEASUREMENTS Ablation volume (Va) and central carbonization volume (Vc) were measured on histologic specimens as the sum of the lesion areas multiplied by the thickness of each slide. The theoretical model of the laser-tissue interaction was based on the Pennes equation. RESULTS A circumscribed ablation zone was observed in all histologic specimens. Va values grow with the increase of the OP up to 10 W and reach a plateau between 10 and 20 W. The trend of Vc values rises constantly until 20 W. The theoretical model shows a good agreement with experimental Va and Vc for OP between 1.5 and 10 W. LIMITATIONS Ex vivo study. CONCLUSION Volumes recorded suggest that the best laser OP could be the lowest one to obtain similar Va with smaller Vc in order to avoid the risk of thermal injury to the surrounding tissue. The good agreement between the two models demonstrates the prediction capability of the theoretical model on laser-induced ablation volume in an ex vivo animal model and supports its potential use for estimating the ablation size at different laser OPs.

Subharmonic emissions from microbubbles: effect of the driving pulse shape

The aims of this work are to investigate the response of the ultrasonic contrast agents (UCA) insonified by different arbitrary-shaped pulses at different acoustic pressures and concentration of the contrast agent focusing on subharmonic emission. A transmission setup was developed in order to insonify the contrast agent contained in a measurement chamber. The transmitted ultrasonic signals were generated by an arbitrary wave generator connected to a linear power amplifier able to drive a single-element transducer. The transmitted ultrasonic pulses that passed through the contrast agent-filled chamber were received by a second transducer or a hydrophone aligned with the first one. The radio frequency (RF) signals were acquired by fast echographic multiparameters multi-image novel apparatus (FEMMINA) which is an echographic platform able to acquire ultrasonic signals in a real-time modality. Three sets of ultrasonic signals were devised in order to evaluate subharmonic response of the contrast agent with respect to sinusoidal burst signals used as reference pulses. A decreasing up to 30 dB in subharmonic response was detected for a Gaussian-shaped pulse; differences in subharmonic emission up to 21 dB were detected for a composite pulse (two-tone burst) for different acoustic pressures and concentrations. Results from this experimentation demonstrated that the transmitted pulse shape strongly affects subharmonic emission in spite of a second harmonic one. In particular, the smoothness of the initial portion of the shaped pulses can inhibit subharmonic generation from the contrast agents with respect to a reference sinusoidal burst signal. It was also shown that subharmonic generation is influenced by the amplitude and the concentration of the contrast agent for each set of the shaped pulses. Subharmonic emissions that derive from a nonlinear mechanism involving nonlinear coupling among different oscillation modes are strongly affected by the shape of the ultrasonic driving pulse

Multipulse technique exploiting the intermodulation of ultrasound waves in a nonlinear medium

In recent years, the nonlinear properties of materials have attracted much interest in nondestructive testing and in ultrasound diagnostic applications. Acoustic nonlinear parameters represent an opportunity to improve the information that can be extracted from a medium such as structural organization and pathologic status of tissue. In this paper, a method called pulse subtraction intermodulation (PSI), based on a multipulse technique, is presented and investigated both theoretically and experimentally. This method allows separation of the intermodulation products, which arise when 2 separate frequencies are transmitted in a nonlinear medium, from fundamental and second harmonic components, making them available for improved imaging techniques or signal processing algorithms devoted to tissue characterization. The theory of intermodulation product generation was developed according the Khokhlov-Zabolotskaya-Kuznetsov (KZK) nonlinear propagation equation, which is consistent with experimental results. The description of the proposed method, characterization of the intermodulation spectral contents, and quantitative results coming from in vitro experimentation are reported and discussed in this paper.

Transient subharmonic and ultraharmonic acoustic emission during dissolution of free gas bubbles

This work concerns the study of free gas bubble behavior, a basic step in contrast agent study. In order to improve the understanding of microbubble-ultrasound interaction, we propose an acoustic dynamic observation of microbubble behavior performed by a high frame-rate acquiring and processing system. Results from ultrasonic observations of free gas microbubbles are discussed and compared with theoretical simulation. Peculiar radio frequency (RF) echo signals back-propagated from bubbles during dissolution tip to their destruction are shown and their behavior is discussed. In particular, the different orders of subharmonic emissions related to changes in bubble sized; during dissolution were observed.

RADIOFREQUENCY REAL TIME PROCESSING: ULTRASONIC SPECTRAL IMAGES AND VECTOR DOPPLER INVESTIGATION

Novel radio frequency processing techniques for biological tissue characterization with ultrasound are presented in order to improve the diagnostic power of ultrasonic echographic systems. Spectral images of biological “in-vitro” and “in-vivo” tissue, obtained through the Discrete Wavelet Packet Transform (DWPT) are presented, as well as velocity vector maps of blood flow obtained with 2-D Doppler investigation. The implementation of the Discrete Wavelet Packet Transform through a digital filter produces, for each acquired frame, real time spectral maps, in different frequency bands. Multi-parametric images are composed by merging these maps using a dedicated “balance image fusion” algorithm. New blood images, obtained without using the Doppler effect, for “in-vivo” and “in-vitro” experiments are presented based on the exploitation of non-linear ultrasound-medium interaction effects [1,2,3,4]. The proposed spectral processing procedure seems to be suitable to perform tissue characterization. Pathological portions inside tissue could be detected thanks to their different echo frequency content which in turns is determined by linear and non-linear ultrasonicmedium interaction. The target of future clinical applications is to investigate the potential of the procedure as a “virtual biopsy”. Vector Doppler multi parametric images are obtained with compound measurements of Doppler shifts along different directions, and superimposing the resulting 2-D velocity vector maps to the conventional morphological B-mode representation [5,6,7] The results, here presented, were produced by employing a hardware and software platform dedicated to ultrasonic signal and image processing [8,9,10]. The radiofrequency signal for multi parametric calculation and presentation with a multiprocessing digital architecture was used. This platform provides a multi analysis and

Clinical test of RULES (RULES: radiofrequency ultrasonic local estimators)

An echographic method for differentiating pathological regions in biological tissue was proposed previously (Masotti, L. et al., Proc. IEEE Ultrason. Symp., p.1030-3, 2003). The method, named RULES (Biagi, E. et al., Italian Patent FI2003A000254, 2003; Italian Patent FI2002A34, 2002; European Patent 03425118.1, 2003; US Patent 10/383674, 2003), is based on radiofrequency (RF) echographic signal processing. It permits spectral parameters related to the organization and mechanical properties of investigated tissue to be extracted. Spectral images are produced through a processing procedure, based on the discrete wavelet packet transform. A hardware-software platform, FEMMINA (fast echographic multiparameter multi image novel apparatus) (Scabia, M. et al., IEEE Trans. UFFC, vol.49, no.10, p.1444-51, 2002), for real-time signal and image processing was employed in order to test the diagnostic applicability of the method. The results for breast tumor detection and characterization are presented together with the results from a clinical investigation on the prostate, where the RULES features are employed for localizing pathological zones in order to guide bioptical sampling.

Real Time Images of Local Ultrasonic Spectral Parameters for Tissue Differentation Through Wavelet Transform

In this work we propose a novel echographic method to investigate biological tissue internal organization and consequently to differentiate pathological regions. The method is based on time-frequency processing of the radiofrequency echographic signal. Our analysis correlates spectral parameters to actual organization and mechanical properties of investigated tissue and, clinically, to physical properties of tissue derived from histology.

Ultrasonic Images of Tissue Local Power Spectrum by Means of Wavelet Packets for Prostate Cancer Detection

The aim of this work is to present a novel apparatus for experimental activity in research where a high frequency signal must be acquired and processed in real-time, and represented through a multi-image visualization tool. The proposed apparatus is a hardware and software platform dedicated to signal and/or image processing and fast data visualization. Currently the system is employed for studying new algorithms for biological tissue ultrasound investigation 1,2. Real-time operation mode designates clinical environment as its elective application because fast data processing is a necessary prerequisite in order to evaluate the on-line diagnostic performance of different investigation methods. Furthermore, for research purposes, the possibility to have simultaneous views of different ultrasonic parameters is essential for an efficient analysis, verification and modelling of the specific ultrasound-media interaction phenomenon .

Carotid plaque tissue differentiation based on radiofrequency echographic signal local spectral content (RULES: Radiofrequency Ultrasonic Local Estimators)

An echographic method is proposed in order to detect and differentiate carotid vessel plaques. The method based on a novel spectral processing procedure for the radiofrequency echo signal is named RULES (radiofrequency ultrasonic local estimators). It allows the extraction of local spectral parameters related to the organization and mechanical properties of an investigated tissue region. Spectral images are produced through a processing procedure, based on a statistical analysis of radiofrequency signal spectral coefficients, calculated with the discrete wavelet packet transform. For each organ, the regions of the investigated tissue, which exhibit the same distribution of the spectral coefficients, were considered homogeneous and were put in correspondence with local tissue condition (healthy or with pathology), as derived from histological analysis.