Controlling the stability of monodisperse phospholipid-coated microbubbles by tuning their buckling pressure.

Hypothesis: Monodisperse phospholipid-coated microbubbles, with a size and resonance frequency tuned to the ultrasound driving frequency, have strong potential to enhance sensitivity, efficiency, and control in emerging diagnostic and therapeutic applications involving bubbles and ultrasound. A key requirement is that they retain their gas volume and shell material during physiologic pressure changes and withstand the overpressure during intravenous injection. The shell typically comprises a mixture of a phospholipid (e.

Additive manufacturing of 3D flow-focusing millifluidics for the production of curable microdroplets.

Microfluidics plays a crucial role in the generation of mono-sized microdroplet emulsions. Traditional glass microfluidic chips typically lack versatility in generating curable droplets of arbitrary liquids due to the inherent hydrophilic nature of glass and to fabrication constraints. To overcome this, we designed a microdroplet generator with 3D flow-focusing capabilities that can be 3D-printed.

Second order and transverse flow visualization through three-dimensional particle image velocimetry in millimetric ducts.

Despite recent advances in 3D particle image velocimetry (PIV), challenges remain in measuring small-scale 3D flows, in particular flows with large dynamic range. This study presents a scanning 3D-PIV system tailored for oscillatory flows, capable of resolving transverse flows less than a percent of the axial flow amplitude. The system was applied to visualize transverse flows in millimetric straight, toroidal, and twisted ducts.

Optimizing high-intensity focused ultrasound-induced immunogenic cell-death using passive cavitation mapping as a monitoring tool.

Over the past decade, ultrasound (US) has gathered significant attention and research focus in the realm of medical treatments, particularly within the domain of anti-cancer therapies. This growing interest can be attributed to its non-invasive nature, precision in delivery, availability, and safety. While the conventional objective of US-based treatments to treat breast, prostate, and liver cancer is the ablation of target tissues, the introduction of the concept of immunogenic cell death (ICD) has made clear that inducing cell death can take different non-binary pathways through the activation of the patient's anti-tumor immunity.

Transverse flow under oscillating stimulation in helical square ducts with cochlea-like geometrical curvature and torsion.

The cochlea, situated within the inner ear, is a spiral-shaped, liquid-filled organ responsible for hearing. The physiological significance of its shape remains uncertain. Previous research has scarcely addressed the occurrence of transverse flow within the cochlea, particularly in relation to its unique shape.

PROTEUS: A Physically Realistic Contrast-Enhanced Ultrasound Simulator-Part I: Numerical Methods.

Ultrasound contrast agents have been used as vascular reporters for the past 40 years. The ability to enhance vascular features in ultrasound images with engineered lipid-shelled microbubbles has enabled break-throughs such as the detection of tissue perfusion or super-resolution imaging of the microvasculature. However, advances in the field of contrast-enhanced ultra-sound are hindered by experimental variables that are difficult to control in a laboratory setting, such as complex vascular geometries, the lack of ground truth, and tissue nonlinearities.

High-Speed Optical Characterization of Protein-and-Nanoparticle-Stabilized Microbubbles for Ultrasound-Triggered Drug Release.

Objective: Ultrasound-triggered bubble-mediated local drug delivery has shown potential to increase therapeutic efficacy and reduce systemic side effects, by loading drugs into the microbubble shell and triggering delivery of the payload on demand using ultrasound. Understanding the behavior of the microbubbles in response to ultrasound is crucial for efficient and controlled release.

Methods: In this work, the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein was characterized.

Validation of ultrasound velocimetry and computational fluid dynamics for flow assessment in femoral artery stenotic disease.

Purpose: To investigate the accuracy of high-framerate echo particle image velocimetry (ePIV) and computational fluid dynamics (CFD) for determining velocity vectors in femoral bifurcation models through comparison with optical particle image velocimetry (oPIV).

Approach: Separate femoral bifurcation models were built for oPIV and ePIV measurements of a non-stenosed (control) and a 75%-area stenosed common femoral artery. A flow loop was used to create triphasic pulsatile flow.

A unifying Rayleigh-Plesset-type equation for bubbles in viscoelastic media.

Understanding the ultrasound pressure-driven dynamics of microbubbles confined in viscoelastic materials is relevant for multiple biomedical applications, ranging from contrast-enhanced ultrasound imaging to ultrasound-assisted drug delivery. The volumetric oscillations of spherical bubbles are analyzed using the Rayleigh-Plesset equation, which describes the conservation of mass and momentum in the surrounding medium. Several studies have considered an extension of the Rayleigh-Plesset equation for bubbles embedded into viscoelastic media, but these are restricted to a particular choice of constitutive model and/or to small deformations.

Wall Shear Stress and Pressure Fluctuations under Oscillating Stimulation in Helical Square Ducts with Cochlea-like Geometrical Curvature and Torsion.

Our study aims to provide basic insights on the impact of the spiral shape of the cochlea, i.e., of geometric torsion and curvature, on wall pressure and wall shear stress.

Dependence of sonoporation efficiency on microbubble size: An in vitro monodisperse microbubble study.

Sonoporation is the process where intracellular drug delivery is facilitated by ultrasound-driven microbubble oscillations. Several mechanisms have been proposed to relate microbubble dynamics to sonoporation including shear and normal stress. The present work aims to gain insight into the role of microbubble size on sonoporation and thereby into the relevant mechanism(s) of sonoporation.

Time-resolved absolute radius estimation of vibrating contrast microbubbles using an acoustical camera.

Ultrasound (US) contrast agents consist of microbubbles ranging from 1 to 10 μm in size. The acoustical response of individual microbubbles can be studied with high-frame-rate optics or an "acoustical camera" (AC). The AC measures the relative microbubble oscillation while the optical camera measures the absolute oscillation.

Blood Flow Quantification with High-Frame-Rate, Contrast-Enhanced Ultrasound Velocimetry in Stented Aortoiliac Arteries: In Vivo Feasibility.

Local flow patterns influence stent patency, while blood flow quantification in stents is challenging. The aim of this study was to investigate the feasibility of 2-D blood flow quantification using high-frame-rate, contrast-enhanced ultrasound (HFR-CEUS) and particle image velocimetry (PIV), or echoPIV, in patients with aortoiliac stents. HFR-CEUS measurements were performed at 129 locations in 62 patients.

Super-Resolved Microbubble Localization in Single-Channel Ultrasound RF Signals Using Deep Learning.

Recently, super-resolution ultrasound imaging with ultrasound localization microscopy (ULM) has received much attention. However, ULM relies on low concentrations of microbubbles in the blood vessels, ultimately resulting in long acquisition times. Here, we present an alternative super-resolution approach, based on direct deconvolution of single-channel ultrasound radio-frequency (RF) signals with a one-dimensional dilated convolutional neural network (CNN).

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: Evaluation.

Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs and , through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice.

US Velocimetry in Participants with Aortoiliac Occlusive Disease.

Background The accurate quantification of blood flow in aortoiliac arteries is challenging but clinically relevant because local flow patterns can influence atherosclerotic disease. Purpose To investigate the feasibility and clinical application of two-dimensional blood flow quantification using high-frame-rate contrast-enhanced US (HFR-CEUS) and particle image velocimetry (PIV), or US velocimetry, in participants with aortoiliac stenosis. Materials and Methods In this prospective study, participants with a recently diagnosed aortoiliac stenosis underwent HFR-CEUS measurements of the pre- and poststenotic vessel segments (August 2018 to July 2019).

Multi-timescale Microscopy Methods for the Characterization of Fluorescently-labeled Microbubbles for Ultrasound-Triggered Drug Release.

Microbubble contrast agents hold great promise for drug delivery applications with ultrasound. Encapsulating drugs in nanoparticles reduces systemic toxicity and increases circulation time of the drugs. In a novel approach to microbubble-assisted drug delivery, nanoparticles are incorporated in or on microbubble shells, enabling local and triggered release of the nanoparticle payload with ultrasound.

Feedback-controlled microbubble generator producing one million monodisperse bubbles per second.

Monodisperse lipid-coated microbubbles are a promising route to unlock the full potential of ultrasound contrast agents for medical diagnosis and therapy. Here, we present a stand-alone lab-on-a-chip instrument that allows microbubbles to be formed with high monodispersity at high production rates. Key to maintaining a long-term stable, controlled, and safe operation of the microfluidic device with full control over the output size distribution is an optical transmission-based measurement technique that provides real-time information on the production rate and bubble size.

Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery.

Apart from its clinical use in imaging, ultrasound has been thoroughly investigated as a tool to enhance drug delivery in a wide variety of applications. Therapeutic ultrasound, as such or combined with cavitating nuclei or microbubbles, has been explored to cross or permeabilize different biological barriers. This ability to access otherwise impermeable tissues in the body makes the combination of ultrasound and therapeutics very appealing to enhance drug delivery in situ.

High-Frequency Acoustic Droplet Vaporization is Initiated by Resonance.

Vaporization of low-boiling point droplets has numerous applications in combustion, process engineering, and in recent years, in clinical medicine. However, the physical mechanisms governing the phase conversion are only partly explained. Here, we show that an acoustic resonance can arise from the large speed of sound mismatch between a perfluorocarbon microdroplet and its surroundings.

Three-phase vaporization theory for laser-activated microcapsules.

Precision control of vaporization, both in space and time, is critical for numerous applications, including medical imaging and therapy, catalysis and energy conversion, and it can be greatly improved through the use of micro- or nano-sized light absorbers. Ultimately, optimization of these applications also requires a fundamental understanding of the vaporization process. Upon laser irradiation, polymeric microcapsules containing a dye can vaporize, leading to the growth of a vapor bubble that emits a strong acoustic signature.

Ultrasound Contrast Agent Modeling: A Review.

Ultrasound is extensively used in medical imaging, being safe and inexpensive and operating in real time. Its scope of applications has been widely broadened by the use of ultrasound contrast agents (UCAs) in the form of microscopic bubbles coated by a biocompatible shell. Their increased use has motivated a large amount of research to understand and characterize their physical properties as well as their interaction with the ultrasound field and their surrounding environment.

Inverse leidenfrost drop manipulation using menisci.

Drops deposited on an evaporating liquid bath can be maintained in an inverse Leidenfrost state by the vapor emanating from the bath, making them levitate and hover without effective friction. These perfectly non-wetting droplets create a depression in the liquid interface that sustains their weight, which generates repellent forces when they approach a meniscus rising against a wall. Here, we study this reflection in detail, and show that frictionless Leidenfrost drops are a simple and efficient tool to probe the shape of an unknown interface.

Microbubble Agents: New Directions.

Microbubble ultrasound contrast agents have now been in use for several decades and their safety and efficacy in a wide range of diagnostic applications have been well established. Recent progress in imaging technology is facilitating exciting developments in techniques such as molecular, 3-D and super resolution imaging and new agents are now being developed to meet their specific requirements. In parallel, there have been significant advances in the therapeutic applications of microbubbles, with recent clinical trials demonstrating drug delivery across the blood-brain barrier and into solid tumours.

Multicore Liquid Perfluorocarbon-Loaded Multimodal Nanoparticles for Stable Ultrasound and F MRI Applied to In Vivo Cell Tracking.

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described.