Search

Background Patients with chronic kidney disease are at increased risk of cystic kidney disease that requires imaging monitoring in many cases. However, these same patients often have contraindications to contrast-enhanced computed tomography and magnetic resonance imaging. This study evaluates the accuracy of contrast-enhanced ultrasound (CEUS), which is safe for patients with chronic kidney disease, for the characterization of kidney lesions in patients with and without chronic kidney disease. Methods We performed CEUS on 44 patients, both with and without chronic kidney disease, with indeterminate or suspicious kidney lesions (both cystic and solid). Two masked radiologists categorized lesions using CEUS images according to contrast-enhanced ultrasound adapted criteria. CEUS designation was compared to histology or follow-up imaging in cases without available tissue in all patients and the subset with chronic kidney disease to determine sensitivity, specificity and overall accuracy. Results Across all patients, CEUS had a sensitivity of 96% (95% CI: 84%, 99%) and specificity of 50% (95% CI: 32%, 68%) for detecting malignancy. Among patients with chronic kidney disease, CEUS sensitivity was 90% (95% CI: 56%, 98%), and specificity was 55% (95% CI: 36%, 73%). Conclusions CEUS has high sensitivity for identifying malignancy of kidney lesions. However, because specificity is low, modifications to the classification scheme for contrast-enhanced ultrasound could be considered as a way to improve contrast-enhanced ultrasound specificity and thus overall performance. Due to its sensitivity, among patients with chronic kidney disease or other contrast contraindications, CEUS has potential as an imaging test to rule out malignancy. Trial registration This trial was registered in clinicaltrials.gov, NCT01751529. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0681-8) contains supplementary material, which is available to authorized users.

Malignant renal cell carcinoma (RCC) is a diverse set of diseases, which are independently difficult to characterize using conventional MRI and CT protocols due to low temporal resolution to study perfusion characteristics. Because different disease subtypes have different prognoses and involve varying treatment regimens, the ability to determine RCC subtype non-invasively is a clinical need. Contrast-enhanced ultrasound (CEUS) has been assessed as a tool to characterize kidney lesions based on qualitative and quantitative assessment of perfusion patterns, and we hypothesize that this technique might help differentiate disease subtypes. Twelve patients with RCC confirmed pathologically were imaged using contrast-enhanced ultrasound. Time intensity curves were generated and analyzed quantitatively using 10 characteristic metrics. Results showed that peak intensity ( p = 0.001) and time-to-80% on wash-out ( p = 0.004) provided significant differences between clear cell, papillary, and chromophobe RCC subtypes. These results suggest that CEUS may be a feasible test for characterizing RCC subtypes.

Background In adult patients, the consistent use of language to describe dyspnea enhances patient-provider communication and contributes to diagnostic and therapeutic decisions. The objective of this research was to determine whether pediatric patients similarly display consistency in the language used to describe "uncomfortable awareness of breathing." Methods One hundred children between the ages of 8 and 15 years with moderate to severe persistent asthma enrolled in an asthma education research program completed questionnaires regarding descriptors of asthma on each of two occasions. In addition to the breathlessness questionnaires, demographic information, self-reported asthma severity, ED visits, missed school days, anthropometrics, and spirometry were obtained for each participant. Results Children were reliable in their choice of the descriptors that they applied to their breathing discomfort across two occasions, and they selected the same descriptors that were used by adults with asthma in previous studies. Children with greater self-reported asthma severity endorsed more descriptors to characterize breathing discomfort than did children with less severe asthma, but no differences were found among children based on demographic or anthropometric variables. Conclusions Children with moderate to severe persistent asthma are reliable in their choice of descriptors of breathlessness. Knowledge of their experience of symptoms may be helpful clinically in the assessment and management of asthma.

Purpose: Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is on going. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods: The effects of two common anesthesia carrier gas selections - pure oxygen and medical air were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results: A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. Copyright © 2011 John Wiley & Sons, Ltd.

The application of microbubbles and ultrasound to deliver nanoparticle carriers for drug and gene delivery is an area that has expanded greatly in recent years. Under ultrasound exposure, microbubbles can enhance nanoparticle delivery by increasing cellular and vascular permeability. In this review, the underlying mechanisms of enhanced nanoparticle delivery with ultrasound and microbubbles and various proposed delivery techniques are discussed. Additionally, types of nanoparticles currently being investigated in preclinical studies, as well as the general limitations and benefits of a microbubble- based approach to nanoparticle delivery, are reviewed.

Phase-change contrast agents (PCCAs) can be vaporized to the echogenic gas state by acoustic/thermal energy from an ultrasound transducer. Few studies to date have explored the molecular imaging capability of PCCAs. In this study, we generate nanoscale droplets composed of low boiling point perfluorocarbons encapsulated in lipid shells capable of targeting αvβ3. When incubated with HUVEC cells expressing αvβ3, the agents could be activated and imaged with the same transducer, and produced a significant increase in pixel intensity within the cell monolayer. Analysis showed a significant imaging contrast over both baseline and non-targeted controls. Low-boiling point, nanoscale PCCAs may provide new approaches to intravascular and extravascular ultrasound-based molecular imaging.

Recent efforts using perfluorocarbon (PFC) nanoparticles in conjunction with acoustic droplet vaporization has introduced the possibility of expanding the diagnostic and therapeutic capability of ultrasound contrast agents to beyond the vascular space. Our laboratories have developed phase-change nanoparticles (PCNs) from the highly volatile PFCs decafluorobutane (DFB, bp =-2 °C) and octafluoropropane (OFP, bp =-37 °C ) for acoustic droplet vaporization. Studies with commonly used clinical ultrasound scanners have demonstrated the ability to vaporize PCN emulsions with frequencies and mechanical indices that may significantly decrease tissue bioeffects. In addition, these contrast agents can be formulated to be stable at physiological temperatures and the perfluorocarbons can be mixed to modulate the balance between sensitivity to ultrasound and general stability. We herein discuss our recent efforts to develop finely-tuned diagnostic/molecular imaging agents for tissue interrogation. We discuss studies currently under investigation as well as potential diagnostic and therapeutic paradigms that may emerge as a result of formulating PCNs with low boiling point PFCs.

Recently, an interest has developed in designing in biomaterials for medical ultrasonics that can provide the acoustic activity of microbubbles, but with improved stability in vivo and a smaller size distribution for extravascular interrogation. One proposed alternative is the phase-change contrast agent. Phase-change contrast agents (PCCAs) consist of perfluorocarbons (PFCs) that are initially in liquid form, but can then be vaporized with acoustic energy. Crucial parameters for PCCAs include their sensitivity to acoustic energy, their size distribution, and their stability, and this manuscript provides insight into the custom design of PCCAs for balancing these parameters. Specifically, the relationship between size, thermal stability and sensitivity to ultrasound as a function of PFC boiling point and ambient temperature is illustrated. Emulsion stability and sensitivity can be ‘tuned’ by mixing PFCs in the gaseous state prior to condensation. Novel observations illustrate that stable droplets can be generated from PFCs with extremely low boiling points, such as octafluoropropane (b.p. −36.7°C), which can be vaporized with acoustic parameters lower than previously observed. Results demonstrate the potential for low boiling point PFCs as a useful new class of compounds for activatable agents, which can be tailored to the desired application.

We propose that by utilizing acoustically-active delivery vehicles (AADVs), which combine the acoustic activity of an ultrasound contrast agent (UCA) with the high payload and extravasation ability of nanoparticles, we can overcome limitations of current chemotherapy delivery methodologies. AADV were formed by conjugating nanocapsules to the shell of biotinylated UCAs. Ultrasound parameters were optimized with a 2.25 MHz focused transducer using a flow phantom to achieve both acoustic radiation force and microbubble destruction. R3230 cells cultured on a cover slip were exposed to the AADV and sonicated with the focused transducer. Fluorescence microscopy verified binding of nanocapsules to ultrasound contrast agents to form AADVs, and increased delivery of nanocapsules to cells within the focus of the transducer (relative to nanocapsule delivery without ultrasound). An order-of-magnitude increase in particles were delivered to cells exposed to ultrasound compared to unexposed cells.

Both clinical and preclinical ultrasound imaging studies use microbubble contrast agents. Short in-vivo lifetimes limit the diagnostic and therapeutic capabilities of these contrast agents, and currently there is research interest in how to lengthen their circulation times. Differences have been observed in contrast agent circulation times during preclinical studies depending on the type of inhaled anesthesia carrier gas. This paper presents the observations from a controlled experiment that evaluated differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating in rodents as a function of inhaled anesthesia carrier gas. Both pure oxygen and medical air are considered and we discuss the persistence of the contrast agents as determined by ultrasound video intensity. The results show a significantly longer in-vivo contrast agent circulation for animals breathing medical air as compared to breathing pure oxygen. Simulations show enhanced contrast persistence may be explained by classical diffusion and that nitrogen plays a critical role by contributing to the volume and diluting the other gas species in the microbubble gas core.