Enrico Vannacci

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

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.

Fabrication of fiber-optic broadband ultrasound emitters by micro-opto-mechanical technology

A micro-opto-mechanical system (MOMS) technology for the fabrication of fiber-optic optoacoustic emitters is presented. The described devices are based on the thermoelastic generation of ultrasonic waves from patterned carbon films obtained by the controlled pyrolysis of photoresist layers and fabricated on miniaturized single-crystal silicon frames used to mount the emitters on the tip of an optical fiber. Thanks to the micromachining process adopted, high miniaturization levels are reached in the fabrication of the emitters, and self-standing devices on optical fiber with diameter around 350 µm are demonstrated, potentially suited to minimally invasive medical applications. The functional testing of fiber-optic emitter prototypes in water performed by using a 1064 nm Q-switched Nd-YAG excitation laser source is also presented, yielding broadband emission spectra extended from low frequencies up to more than 40 MHz, and focused emission fields with a maximum peak-to-peak pressure level of about 1.2 MPa at a distance of 1 mm from the devices.

Tissue characterization in echographic spectral hyperspace: Breast pathologies differentiation

Spectral processing procedure on RadioFrequency (RF) echographic signals is proposed for detecting and characterizing mammary pathologies in order to improve echographic diagnosis on breast cancer that is the second leading cause of cancer death among women. The spectral content of each RF track of a frame is decomposed in N-subband obtained by a bank of filters derived from Morlet Wavelet. The proposed processing procedure works in a N-dimensional spectral hyperspace. Different biological structure can be differentiated by their position in the hyperspace. A Clustering technique is employed to detect the typical spatial distributions. The algorithm is developed in two phases: Training step and Classification step. In the first one, a set of patients are selected and only Regions Of Interest (ROI) are processed to define the suitable Clusters. The Classifications phase, which operates on entire frame, is applied over all patients. The method is amplitude independent and moreover it is capable to compensate for different frequency responses of ultrasonic transducers.

Differentiation of Breast Lesions by Use of HyperSPACE: Hyper-Spectral Analysis for Characterization in Echography

Early diagnosis represents the cornerstone in breast cancer control. Ultrasound is still a valid tool because of its low invasiveness, reduced costs and reduced risk of harm, but better exploitation of its potential is necessary to extract information on tissue features. The proposed method, HyperSPACE (hyper-spectral analysis for characterization in echography), which processes the ultrasonic radiofrequency signal in an N-dimension spectral hyperspace to define several characteristic parameters of the tissue under investigation, was used with the aim of differentiating two types of breast lesion: infiltrating ductal carcinoma and fibroadenoma. The analyzed data set consisted of 2000 radiofrequency frames related to 200 sections of pathologic breast nodules: 104 infiltrating ductal carcinomas and 96 fibroadenomas. The algorithm was trained on single radiofrequency frames related to 50 sections (26 carcinomas, 24 fibroadenomas) to recognize the two pathologies considered, and all the radiofrequency frames related to the other 150 sections were classified, yielding a sensitivity of 92.2%, specificity of 93%, positive predictive value of 93.2% and negative predictive value of 91%. The results were compared with those of RULES (radiofrequency ultrasonic local estimators), a processing method set developed by our group and used by other researchers in clinical and laboratory environments.

Study and Characterization of Subharmonic Emissions by Using Shaped Ultrasonic Driving Pulse

Subharmonic emissions from Ultrasound Contrast Agents (UCAs) were studied by a Pulse Inversion method in order to assess the feasibility of implementation of this technique to subharmonic imaging. Interesting results concerning the dependence of the subharmonic emission with respect to initial pulse shape are presented. The experimentation was performed also by varying the acoustic pressure and concentration of the contrast agent (SonoVue®)

Multidimensional spectral analysis of the ultrasonic radiofrequency signal for characterization of media

The importance of the analysis of the radiofrequency signal is by now recognized in the field of tissue characterization via ultrasound. The RF signal contains a wealth of information and structural details that are usually lost in the B-Mode representation. The HyperSPACE (Hyper SPectral Analysis for Characterization in Echography) algorithm presented by the authors in previous papers for clinical applications is based on the radiofrequency ultrasonic signal. The present work describes the method in detail and evaluates its performance in a repeatable and standardized manner, by using two test objects: a commercial test object that simulates the human parenchyma, and a laboratory-made test object consisting of human blood at different dilution values. In particular, the sensitivity and specificity in discriminating different density levels were estimated. In addition, the robustness of the algorithm with respect to the signal-to-noise ratio was also evaluated.

Wide bandwidth fiber-optic ultrasound probe in MOMS technology: Preliminary signal processing results

HighlightsFiber‐optic ultrasonic microprobe is used for in vitro tissue characterization.The wide, flat bandwidth of the probe allows high resolution ultrasonic investigation.Different details are detected by analyzing the received signal at different frequencies.Preliminary results of tissue characterization are performed by HyperSPACE algorithm.A real “virtual biopsy” with minimally invasive ultrasonic probes may be performed. ABSTRACT An ultrasonic probe consisting of two optical fiber‐based miniaturized transducers for wideband ultrasound emission and detection is employed for the characterization of in vitro biological tissues. In the probe, ultrasound generation is obtained by thermoelastic emission from patterned carbon films in Micro‐Opto‐Mechanical‐System (MOMS) devices mounted on the tip of an optical fiber, whereas acousto‐optical detection is performed in a similar way by a miniaturized polymeric interferometer. The microprobe presents a wide, flat bandwidth that is a very attractive feature for ultrasonic investigation, especially for tissue characterization. Thanks to the very high ultrasonic frequencies obtained, the probe is able to reveal different details of the object under investigation by analyzing the ultrasonic signal within different frequencies ranges, as shown by specific experiments performed on a patterned cornstarch flour sample in vitro. This is confirmed by measurements executed to determine the lateral resolution of the microprobe at different frequencies of about 70 &mgr;m at 120 MHz. Moreover, measurements performed with the wideband probe in pulsed‐echo mode on a histological finding of porcine kidney are presented, on which two different spectral signal processing algorithms are applied. After processing, the ultrasonic spectral features show a peculiar spatial distribution on the sample, which is expected to depend on different ultrasonic backscattering properties of the analyzed tissues.

A feasibility study of a novel spectral method using radiofrequency ultrasound data for monitoring laser tissue ablation

HIGHLIGHTSNew spectral ultrasound signal processing is presented for laser ablation monitoring.A pilot study on ex‐vivo prostates has been performed.Spectral parametric images are produced to visualize laser ablation results on tissue.Ablation in parametric image is correlated to the one in the histological sample. ABSTRACT This paper presents preliminary results of a new non‐invasive ultrasound monitoring method called TUV (Thermotherapy Ultrasonic View) able to investigate structural tissue modifications caused by minimally invasive percutaneous laser ablation. The method, based on the spectral analysis of the raw ultrasound radiofrequency signal, develops spectral parameters in a multidimensional space and its N dimensions are represented by the central frequencies of the sub bands the signal spectrum is decomposed into. Signal processing has been performed on the data related to 7 laser treatments performed on 4 samples of removed prostatic glands which underwent laser ablation at power of 3 W, 4 W and 5 W and energy of 1800 J. In this preliminary study, clusters of these parameters, referred to tissue areas at different distances from the light laser source, modified their shape and position in different ways, during ablation treatment. TUV results have been represented by a chromatic code superimposed to the corresponding ultrasound conventional image, in order to highlight the alteration intensities occurred in the ablated tissue. Resulting images of ablated area have been compared to histological specimens to evaluate the degree of similarity between them by means of Dice and Jaccard coefficients.