Preclinical assessment of a mathematical model for ablation zone prediction in thyroid laser ablation.

To develop and validate a 3D simulation model to calculate laser ablation (LA) zone size and estimate the volume of treated tissue for thyroid applications, a model was developed, taking into account dynamic optical and thermal properties of tissue change. For validation, ten Yorkshire swines were equally divided into two cohorts and underwent thyroid LA at 3 W/1,400 J and 3 W/1,800 J respectively with a 1064-nm multi-source laser (Echolaser X4 with Orblaze™ technology; ElEn SpA, Calenzano, Italy). The dataset was analyzed employing key statistical measures such as mean and standard deviation (SD). Model simulation data were compared with animal gross histology. Experimental data for longitudinal length, width (transverse length), ablation volume and sphericity were 11.0 mm, 10.0 mm, 0.6 mL and 0.91, respectively at 1,400 J and 14.6 mm, 12.4 mm, 1.12 mL and 0.83, respectively at 1,800 J. Gross histology data showed excellent reproducibility of the ablation zone among same laser settings; for both 1,400 J and 1,800 J, the SD of the in vivo parameters was ≤ 0.7 mm, except for width at 1,800 J, for which the SD was 1.1 mm. Simulated data for longitudinal length, width, ablation volume and sphericity were 11.6 mm, 10.0 mm, 0.62 mL and 0.88, respectively at 1,400 J and 14.2 mm, 12.0 mm, 1.06 mL and 0.84, respectively at 1,800 J. Experimental data for ablation volume, sphericity coefficient, and longitudinal and transverse lengths of thermal damaged area showed good agreement with the simulation data. Simulation datasets were successfully incorporated into proprietary planning software (Echolaser Smart Interface, Elesta SpA, Calenzano, Italy) to provide guidance for LA of papillary thyroid microcarcinomas. Our mathematical model showed good predictability of coagulative necrosis when compared with data from in vivo animal experiments.

Advantages of cooled fiber for monitoring laser tissue ablation through temporal and spectral analysis of RF ultrasound signal: A case study.

The promising minimally invasive laser thermal therapy technique may be improved if thermal lesions induced into the tissue can be carefully monitored in extension and morphology during the treatment. According to results obtained in several recent experimentations, solutions that avoid tissue carbonization during the treatment have been proposed, in order to allow deeper and longer lasting light penetration in treated tissue and to reduce failures of the applicator tip and fiber optic, dangerous for patients. In the work the advantages in using a cooled fiber are shown, in order not only to induce efficient lesions but also in performing an accurate monitoring by ultrasound. Indeed, one important limit of the ultrasound control is caused by the gas bubbles generation, which represent an acoustic barrier that invalidate the ultrasonic image representation of the treated tissue. Ultrasonic radiofrequency signals were acquired from the same bovine liver ex vivo sample by using both bare and cooled fiber and processed to produce B-mode and spectral parametric images by implementing TUV (Thermotherapy Ultrasonic View) algorithm. Radiofrequency signals, B-mode and TUV images were analysed and compared in order to evaluate the different tissue heating processes during ablation and the different lesion extensions induced into the tissue after the treatment. Cooled fiber avoided carbonization and strongly reduced gas bubbles generation inducing a larger lesion and allowing a more effective ultrasound monitoring. Moreover by correlating optical images of the lesions and the corresponding Integral TUV images, by using Dice and Jaccard coefficients, it was proven that TUV algorithm is able to characterize the tissue portions differently modified by ablation exhibiting better performances in the case of cooled fiber and revealing to be a potential tool capable to improve the laser delivery settings control.

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

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 3W, 4W and 5W and energy of 1800J. 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.

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.

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.

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 stand still 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 respect with 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 respect with a reference sinusoidal burst signal. It also was 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.

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 up to their destruction are shown and their behavior is discussed. In particular, the different orders of subharmonic emissions related to changes in bubble sizes during dissolution were observed.

A novel spectral ultrasonic differentiation method for marking regions of interest in biological tissue: in vitro results for prostate.

OBJECTIVE: The aim of the present study was to evaluate the effectiveness of a new method of spectral analysis of the radiofrequency (RF) ultrasonic echo signal in discriminating neoplastic from non-neoplastic tissue of the prostate gland. MATERIAL AND METHODS: The proposed method was previously set up on ten prostatic glands where cancer had been detected by histology in order to correlate the tumour areas with specific spectral parameters. In the present study sixty prostate specimens of patients undergoing radical retropubic prostatectomy for clinically localized prostate cancer were examined. The surgically removed prostate glands were scanned using an echo signal acquisition apparatus and the spectral parameters were obtained by the wavelet transform. The echographic scans of all cases were then compared with the whole-mount histological sections of the prostate in order to evaluate sensitivity and specificity of the proposed method. RESULTS: The sensitivity and specificity for cancer detection were 93% and 91%, respectively. The specificity was invalidated by the fact that in some of the cases studied, the tumour was located in areas of benign prostatic hyperplasia (BPH). As for the sensitivity, of the three false negative cases two were due to the coexistence of cancer foci and BPH. CONCLUSIONS: Our proposed method, named WAMBLE (Wavelet Analysis Multi Band Local Estimator), is accurate in detecting prostate cancer. Further in vivo studies are warranted to confirm the clinical value of this technique.