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We present an intravascular ultrasound (IVUS) transducer array designed to enable shear wave elasticity imaging (SWEI) of arteries for the detection and characterization of atherosclerotic soft plaques. Using a custom dicing fixture, we have fabricated single-element and axially-segmented array transducer prototypes from 4.6-Fr to 7.6-Fr piezoceramic tubes, respectively. Focused excitation of the array prototype at 4 MHz yielded a focal gain of 5× in intensity, for an estimated 60 mW/cm2 [Formula: see text] and 1.6-MPa negative peak pressure at 4.5-mm range in water. The single-element transducer generated a peak radial displacement of [Formula: see text] in a uniform elasticity phantom, with axial shear waves detectable by an external linear array probe up to 5 mm away from the excitation plane. In a vessel phantom with a soft inclusion, the array prototype generated peak displacements of 2.2 and [Formula: see text] in the soft inclusion and vessel wall regions, respectively. A SWEI image of the vessel phantom was reconstructed, with measured shear wave speed (SWS) of 1.66 ± 0.91 m/s and 0.97 ± 0.59 m/s for the soft inclusion and vessel wall regions, respectively. The array prototype was also used to obtain a SWEI image of an ex vivo porcine artery, with a mean SWS of 3.97 ± 1.12 m/s. These results suggest that a cylindrical intravascular ultrasound (IVUS) transducer array could be made capable of SWEI for atherosclerotic plaque detection in coronary arteries.

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Our previous methodology in local sound speed estimation utilized time delays measured by the cross correlation of delayed full-synthetic aperture channel data to estimate the average speed of sound. However, focal distortions in this methodology lead to biased estimates of the average speed of sound, which, in turn, leads to biased estimates of the local speed of sound. Here, we demonstrate the bias in the previous methodology and introduce a coherence-based average sound speed estimator that eliminates this bias and is computationally much cheaper in practice. Because this coherence-based approach estimates the average sound speed in the medium over an equally spaced grid in depth rather than time, we derive a refined model that relates the local and average speeds of sound as a function of depth in layered media. A fast, closed-form inversion of this model yields highly accurate local sound speed estimates. The root-mean-square (rms) error of local sound speed reconstruction in simulations of two-layer media is 4.6 and 2.5 m/s at 4 and 8 MHz, respectively. This work examines the impact of frequency, f -number, aberration, and reverberation on sound speed estimation. Phantom and in vivo experiments in rats further validate the coherence-based sound speed estimator.

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Objective. Speed of sound has previously been demonstrated to correlate with fat concentration in the liver. However, estimating speed of sound in the liver noninvasively can be biased by the speed of sound of the tissue layers overlying the liver. Here, we demonstrate a noninvasive local speed of sound estimator, which is based on a layered media assumption, that can accurately capture the speed of sound in the liver. We validate the estimator using an obese Zucker rat model of non-alcoholic fatty liver disease and correlate the local speed of sound with liver steatosis.Approach.We estimated the local and global average speed of sound noninvasively in 4 lean Zucker rats fed a normal diet and 16 obese Zucker rats fed a high fat diet for up to 8 weeks. The ground truth speed of sound and fat concentration were measured from the excised liver using established techniques.Main Results. The noninvasive, local speed of sound estimates of the livers were similar in value to their corresponding 'ground truth' measurements, having a slope ± standard error of the regression of 0.82 ± 0.15 (R2= 0.74 andp< 0.001). Measurement of the noninvasive global average speed of sound did not reliably capture the 'ground truth' speed of sound in the liver, having a slope of 0.35 ± 0.07 (R2= 0.74 andp< 0.001). Decreasing local speed of sound was observed with increasing hepatic fat accumulation (approximately -1.7 m s-1per 1% increase in hepatic fat) and histopathology steatosis grading (approximately -10 to -13 m s-1per unit increase in steatosis grade). Local speed of sound estimates were highly correlated with steatosis grade, having Pearson and Spearman correlation coefficients both ranging from -0.87 to -0.78. In addition, a lobe-dependent speed of sound in the liver was observed by theex vivomeasurements, with speed of sound differences of up to 25 m s-1(p< 0.003) observed between lobes in the liver of the same animal.Significance.The findings of this study suggest that local speed of sound estimation has the potential to be used to predict or assist in the measurement of hepatic fat concentration and that the global average speed of sound should be avoided in hepatic fat estimation due to significant bias in the speed of sound estimate.

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Passive cavitation mapping (PCM) algorithms for diagnostic ultrasound arrays based on time exposure acoustics (TEA) exhibit poor axial resolution, which is in part due to the diffraction-limited point spread function of the imaging system and poor rejection by the delay-and-sum beamformer. In this article, we adapt a method for speed of sound estimation to be utilized as a cavitation source localization (CSL) approach. This method utilizes a hyperbolic fit to the arrival times of the cavitation signals in the aperture domain, and the coefficients of the fit are related to the position of the cavitation source. Wavefronts exhibiting poor fit to the hyperbolic function are corrected to yield improved source localization. We demonstrate through simulations that this method is capable of accurate estimation of the origin of coherent spherical waves radiating from cavitation/point sources. The average localization error from simulated microbubble sources was 0.12 ± 0.12mm ( 0.15 ± 0.14λ0 for a 1.78-MHz transmit frequency). In simulations of two simultaneous cavitation sources, the proposed technique had an average localization error of 0.2mm ( 0.23λ0 ), whereas conventional TEA had an average localization error of 0.81mm ( 0.97λ0 ). The reconstructed PCM-CSL image showed a significant improvement in resolution compared with the PCM-TEA approach.

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Passive cavitation mapping (PCM) techniques typically utilize a time-exposure acoustic (TEA) approach, where the received radio frequency data are beamformed, squared, and integrated over time. Such PCM-TEA cavitation maps typically suffer from long-tail artifacts and poor axial resolution with pulse-echo diagnostic arrays. Here, we utilize a recently developed PCM technique based on cavitation source localization (CSL), which fits a hyperbolic function to the received cavitation wavefront. A filtering method based on the root-mean-square error (rmse) of the hyperbolic fit is utilized to filter out spurious signals. We apply a wavefront correction technique to the signals with poor fit quality to recover additional cavitation signals and improve cavitation localization. Validation of the PCM-CSL technique with rmse filtering and wavefront correction was conducted in experiments with a tissue-mimicking flow phantom and an in vivo mouse model of cancer. It is shown that the quality of the hyperbolic fit, necessary for the PCM-CSL, requires an rmse < 0.05 mm2 in order to accurately localize the cavitation sources. A detailed study of the wavefront correction technique was carried out, and it was shown that, when applied to experiments with high noise and interference from multiple cavitating microbubbles, it was capable of effectively correcting noisy wavefronts without introducing spurious cavitation sources, thereby improving the quality of the PCM-CSL images. In phantom experiments, the PCM-CSL was capable of precisely localizing sources on the therapy beam axis and off-axis sources. In vivo cavitation experiments showed that PMC-CSL showed a significant improvement over PCM-TEA and yielded acceptable localization of cavitation signals in mice.

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Ultrasound and microbubble (USMB)-mediated drug delivery is a valuable tool for increasing the efficiency of the delivery of therapeutic agents to cancer while maintaining low systemic toxicity. Typically, selection of USMB drug delivery parameters used in current research settings are either based on previous studies described in the literature or optimized using tissue-mimicking phantoms. However, phantoms rarely mimic in vivo tumor environments, and the selection of parameters should be based on the application or experiment. In the following study, we optimized the therapeutic parameters of the ultrasound drug delivery system to achieve the most efficient in vivo drug delivery using fluorescent semiconducting polymer nanoparticles as a model nanocarrier. We illustrate that voltage, pulse repetition frequency and treatment time (i.e., number of ultrasound pulses per therapy area) delivered to the tumor can successfully be optimized in vivo to ensure effective delivery of the semiconducting polymer nanoparticles to models of hepatocellular carcinoma. The optimal in vivo parameters for USMB drug delivery in this study were 70 V (peak negative pressure = 3.4 MPa, mechanical index = 1.22), 1-Hz pulse repetition frequency and 100-s therapy time. USMB-mediated drug delivery using in vivo optimized ultrasound parameters caused an up to 2.2-fold (p < 0.01) increase in drug delivery to solid tumors compared with that using phantom-optimized ultrasound parameters.

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Intravascular acoustic radiation force impulse (IV-ARFI) imaging has the potential to identify vulnerable atherosclerotic plaques and improve clinical treatment decisions and outcomes for patients with coronary heart disease. Our long-term goal is to develop a thin, flexible catheter probe that does not require mechanical rotation to achieve high-resolution IV-ARFI imaging. In this work, we propose a novel cylindrical transducer array design for IV-ARFI imaging and investigate the feasibility of this approach. We present the construction of a 2.2-mm-long, 4.6-Fr cylindrical prototype transducer to demonstrate generating large ARFI displacements from a small toroidal beam, and we also present simulations of the proposed IV-ARFI cylindrical array design using Field II and a cylindrical finite-element model of vascular tissues and soft plaques. The prototype transducer was found to generate peak radial displacements of over [Formula: see text] in soft gelatin phantoms, and simulations demonstrate the ability of the array design to obtain ARFI images and distinguish soft plaque targets from surrounding, stiffer vessel wall tissue. These results suggest that high-resolution IV-ARFI imaging is possible using a cylindrical transducer array.

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Spatially localized microbubble cavitation by ultrasound offers an effective means of altering permeability of natural barriers (i.e. blood vessel and cell membrane) in favor of nanomaterials accumulation in the target site. In this study, a clinically relevant, minimally invasive ultrasound guided therapeutic approach is investigated for targeted delivery of anticancer microRNA loaded PLGA-b-PEG nanoparticles to spontaneous hepatocellular neoplasia in a canine model. Quantitative assessment of the delivered microRNAs revealed prominent and consistent increase in miRNAs levels (1.5-to 2.3-fold increase (p<0.001)) in ultrasound treated tumor regions compared to untreated control regions. Immunohistology of ultrasound treated tumor tissue presented a clear evidence for higher amount of nanoparticles extravasation from the blood vessels. A distinct pattern of cytokine expression supporting CD8+ T cells mediated "cold-to-hot" tumor transition was evident in all patients. On the outset, proposed platform can enhance delivery of miRNA-loaded nanoparticles to deep seated tumors in large animals to enhance chemotherapy.