Publications by authors named "Paul Sheeran"

The neuromuscular blocking drugs rocuronium and vecuronium are often used during general anesthesia. These drugs temporarily paralyze the patient and thus both facilitate placement of an endotracheal tube and prevent any patient movement during surgery. Reversal of neuromuscular blockade is necessary at the end of surgery to avoid postoperative weakness and adverse respiratory events in the recovery room.

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Phase-change droplets are a class of ultrasound contrast agents that can convert into echogenic microbubbles in situ with the application of sufficient acoustic energy. Droplets are smaller and more stable than their microbubble counterparts. However, traditional ultrasound contrast agents are not trackable beyond acoustic feedback measurements, which makes quantifying contrast agent bio-distribution or accumulation ex vivo difficult.

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Background: Pediatric patients with a mediastinal mass can experience severe complications while undergoing anesthesia. Nearly, all published reviews involve either patients with an anterior mediastinal mass or patients with an oncologic disease.

Aim: The identification of risk factors for anesthetic-related complications in pediatric patients with any type of mediastinal mass.

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Ultrasound (US) is known to stimulate endogenous shear-dependent pathways, and can lower microvascular resistance through mediators that are conducted downstream from US exposure. We hypothesized that endovascular US, already in use for thrombolysis in humans, can improve tissue perfusion in the setting of acute limb ischemia through downstream-conducted effects. Models of severe peripheral arterial disease were developed in mice and in rhesus macaques.

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Background: Cavitation of microbubble contrast agents with ultrasound produces shear-mediated vasodilation and an increase in tissue perfusion. We investigated the influence of the size of the cavitation volume by comparing flow augmentation produced by two-dimensional (2D) versus three-dimensional (3D) therapeutic ultrasound. We also hypothesized that cavitation could augment flow beyond the ultrasound field through release of vasodilators that are carried downstream.

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The ability to monitor cavitation activity during ultrasound and microbubble-mediated procedures is of high clinical value. However, there has been little reported literature comparing the cavitation characteristics of different clinical microbubbles, nor have current clinical scanners been used to perform passive cavitation detection in real time. The goal of this work was to investigate and characterize standard microbubble formulations (Optison, Sonovue, Sonazoid, and a custom microbubble made with similar components as Definity) with a custom passive cavitation detector (two confocal single-element focused transducers) and with a Philips EPIQ scanner with a C5-1 curvilinear probe passively listening.

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Submicron phase-change droplets are an emerging class of ultrasound contrast agent. Compared with microbubbles, their relatively small size and increased stability offer the potential to passively extravasate and accumulate in solid tumors through the enhanced permeability and retention effect. Under exposure to sufficiently powerful ultrasound, these droplets can convert into in situ gas microbubbles and thus be used as an extravascular-specific contrast agent.

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Microbubble contrast agents were introduced more than 25 years ago with the objective of enhancing blood echoes and enabling diagnostic ultrasound to image the microcirculation. Cardiology and oncology waited anxiously for the fulfillment of that objective with one clinical application each: myocardial perfusion, tumor perfusion and angiogenesis imaging. What was necessary though at first was the scientific understanding of microbubble behavior in vivo and the development of imaging technology to deliver the original objective.

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Objectives: The authors investigated ideal acoustic conditions on a clinical scanner custom-programmed for ultrasound (US) cavitation-mediated flow augmentation in preclinical models. We then applied these conditions in a first-in-human study to test the hypothesis that contrast US can increase limb perfusion in normal subjects and patients with peripheral artery disease (PAD).

Background: US-induced cavitation of microbubble contrast agents augments tissue perfusion by convective shear and secondary purinergic signaling that mediates release of endogenous vasodilators.

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Breast cancer remains a leading cause of death for women throughout the world. Recent advances in medical imaging technologies and tumor targeting agents signify vast potential for progress toward improved management of this global problem. Phase-change contrast agents (PCCAs) are dynamic imaging agents with practical applications in both the research and clinical settings.

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Three-dimensional contrast-enhanced ultrasound (CEUS) imaging presents a clear advantage over its 2-D counterpart in detecting and characterizing suspicious lesions as it properly surveys the inherent heterogeneity of tumors. However, 3-D CEUS is also slow compared to 2-D CEUS and tends to undersample the microbubble wash-in. This makes it difficult to resolve the feeding vessels, an important oncogenic marker, from the background perfusion cloud.

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In this paper, we assess the importance of microbubble shell composition for contrast-enhanced imaging sequences commonly used on clinical scanners. While the gas core dynamics are primarily responsible for the nonlinear harmonic response of microbubbles at diagnostic pressures, it is now understood that the shell rheology plays a dominant role in the nonlinear response of microbubbles subjected to low acoustic pressures. Of particular interest here, acoustic pressures of tens of kilopascal can cause a reversible phase transition of the phospholipid coatings from a stiff elastic organized state to a less stiff disorganized buckled state.

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Phase-shift droplets can be converted by sound from low-echogenicity, liquid-core agents into highly echogenic microbubbles. Many proposed applications in imaging and therapy take advantage of the high spatiotemporal control over this dynamic transition. Although some studies have reported increased circulation time of the droplets compared with microbubbles, few have directly explored the impact of encapsulation on droplet performance.

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While plane-wave imaging can improve the performance of power Doppler by enabling much longer ensembles than systems using focused beams, the long-ensemble averaging of the zero-lag autocorrelation R(0) estimates does not directly decrease the mean noise level, but only decreases its variance. Spatial variation of the noise due to the time-gain compensation and the received beamforming aperture ultimately limits sensitivity. In this paper, we demonstrate that the performance of power Doppler imaging can be improved by leveraging the higher lags of the autocorrelation [e.

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While long Doppler ensembles are, in principle, beneficial for velocity estimates, short acoustic pulses must be used in microbubble contrast-enhanced (CE) Doppler to mitigate microbubble destruction. This introduces inherent tradeoffs in velocity estimates with autocorrelators, which are studied here. A model of the autocorrelation function adapted to the microbubble Doppler signal accounting for transit time, the echo frequency uncertainty, and contrast-agent destruction is derived and validated in vitro.

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Breast cancer is a diverse and complex disease that remains one of the leading causes of death among women. Novel, outside-of-the-box imaging and treatment methods are needed to supplement currently available technologies. In this study, we present evidence for the intracellular delivery and ultrasound-stimulated activation of folate receptor (FR)-targeted phase-change contrast agents (PCCAs) in MDA-MB-231 and MCF-7 breast cancer cells in vitro.

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Continued advances in the field of ultrasound and ultrasound contrast agents have created new approaches to imaging and medical intervention. Phase-shift perfluorocarbon droplets, which can be vaporized by ultrasound energy to transition from the liquid to the vapor state, are one of the most highly researched alternatives to clinical ultrasound contrast agents (i.e.

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Phase-shift perfluorocarbon droplets have been investigated for over 20 years as pre-clinical ultrasound contrast agents with distinctive advantages in imaging and therapy. A number of formulation strategies exist, each with inherent advantages and limitations. In this note, we demonstrate a unique opportunity: that phase-shift droplets can be generated directly from commercially available microbubbles.

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Phase-shift perfluorocarbon droplets are designed to convert from the liquid to the gas state by the external application of acoustic or optical energy. Although droplet vaporization has been investigated extensively at ultrasonic frequencies between 1 and 10 MHz, few studies have characterized performance at the higher frequencies commonly used in small animal imaging. In this study, we use standard B-mode imaging sequences on a pre-clinical ultrasound platform to both image and activate sub-micron decafluorobutane droplet populations in vitro and in vivo at center frequencies in the range of 20-40 MHz.

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Liquid-filled perfluorocarbon droplets emit a unique acoustic signature when vaporized into gas-filled microbubbles using ultrasound. Here, we conducted a pilot study in a tissue-mimicking flow phantom to explore the spatial aspects of droplet vaporization and investigate the effects of applied pressure and droplet concentration on image contrast and axial and lateral resolution. Control microbubble contrast agents were used for comparison.

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Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular.

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Background: During high-intensity focused ultrasound (HIFU) surgical procedures, there is a need to rapidly ablate pathological tissue while minimizing damage to healthy tissue. Current techniques are limited by relatively long procedure times and risks of off-target heating of healthy tissue. One possible solution is the use of microbubbles, which can improve the efficiency of thermal energy delivery during HIFU procedures.

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Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published on the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare data with those for conventional microbubbles with respect to contrast generation and circulation properties.

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Purpose: Perfluorocarbon (PFC) microdroplets, called phase-change contrast agents (PCCAs), are a promising tool in ultrasound imaging and therapy. Interest in PCCAs is motivated by the fact that they can be triggered to transition from the liquid state to the gas state by an externally applied acoustic pulse. This property opens up new approaches to applications in ultrasound medicine.

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