Dynamics of crevice microbubbles that cause the twinkling artifact.

The Doppler ultrasound twinkling artifact, a rapid color shift, appears on pathological mineralizations and is theorized to arise from scattering off micron-sized crevice microbubbles. However, the influence of crevice number and size as well as the bubble dynamics on twinkling is not well-understood. Cylinders with diameters of 0.

Effect of ambient gas and crystal features on Doppler ultrasound twinkling of pathological mineralizations.

Color Doppler twinkling on kidney stones and other pathological mineralizations is theorized to arise from stable microbubbles, which suggests twinkling will be sensitive to ambient gas. Here, lab-grown cholesterol, calcium phosphate, and uric acid crystals were imaged with ultrasound in water while varying oxygen, carbon dioxide, and nitrogen levels. Twinkling was found to increase on cholesterol in elevated oxygen, cholesterol and calcium phosphate in elevated carbon dioxide, and no crystals in elevated nitrogen.

Focused ultrasound as an alternative to dry needling for the treatment of tendinopathies: A murine model.

Tendinopathies account for 30% of 102 million annual musculoskeletal injuries occurring annually in the United States. Current treatments, like dry needling, induce microdamage to promote healing but produce mixed success rates. Previously, we showed focused ultrasound can noninvasively create microdamage while preserving mechanical properties in ex vivo murine tendons.

The histotripsy spectrum: differences and similarities in techniques and instrumentation.

Since its inception about two decades ago, histotripsy - a non-thermal mechanical tissue ablation technique - has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity.

Real-Time, In Situ Imaging of Macrophages via Phase-Change Peptide Nanoemulsions.

Macrophages are specialized phagocytes that play central roles in immunity and tissue repair. Their diverse functionalities have led to an evolution of new allogenic and autologous macrophage products. However, realizing the full therapeutic potential of these cell-based therapies requires development of imaging technologies that can track immune cell migration within tissues in real-time.

Controlled Degradation of Polycaprolactone Polymers through Ultrasound Stimulation.

This study describes the development of an ultrasound-responsive polymer system that provides on-demand degradation when exposed to high-intensity focused ultrasound (HIFU). Diels-Alder cycloadducts were used to crosslink polycaprolactone (PCL) polymers and underwent a retro Diels-Alder reaction when stimulated with HIFU. Two Diels-Alder polymer compositions were explored to evaluate the link between reverse reaction energy barriers and polymer degradation rates.

Dual-frequency boiling histotripsy in an ex vivo bovine tendinopathy model.

Histotripsy fractionates most soft tissues; however, healthy tendons have shown resistance to histotripsy fractionation. Prior work has shown that pre-heating tendons increases susceptibility to histotripsy fractionation; combining multiple driving frequencies may also allow successful fractionation of tendons. Here, we evaluate single- and dual-frequency histotripsy in four healthy and eight tendinopathic ex vivo bovine tendons.

The effect of crystal composition and environment on the color Doppler ultrasound twinkling artifact.

Pathological mineralizations form throughout the body and can be difficult to detect using conventional imaging methods. Color Doppler ultrasound twinkling highlights ∼60% of kidney stones with a rapid color shift and is theorized to arise from crevice microbubbles as twinkling disappears on kidney stones at elevated pressures and scratched acrylic balls in ethanol. Twinkling also sometimes appears on other pathological mineralizations; however, it is unclear whether the etiology of twinkling is the same as for kidney stones.

High intensity focused ultrasound atomization and erosion in healthy and tendinopathic tendons.

High-intensity focused ultrasound (HIFU) can induce thermal and mechanical mechanisms in a well-defined focal volume of tissues. Histotripsy is a form of mechanical HIFU that can initiate and interact with bubble(s) to cause shock scattering and perhaps atomization within the bubble(s) to fractionate most soft tissues. Ultrasonic atomization, or the ejection of fine droplets from an acoustically-excited liquid exposed to air, has been shown to erode planar soft tissue surfaces, which has led to theories that atomization is a mechanism in histotripsy.

The effects of elastic modulus and impurities on bubble nuclei available for acoustic cavitation in polyacrylamide hydrogels.

Safety of biomedical ultrasound largely depends on controlling cavitation bubbles in vivo, yet bubble nuclei in biological tissues remain unexplored compared to water. This study evaluates the effects of elastic modulus (E) and impurities on bubble nuclei available for cavitation in tissue-mimicking polyacrylamide (PA) hydrogels. A 1.

Histotripsy Bubble Dynamics in Elastic, Anisotropic Tissue-Mimicking Phantoms.

Elastic, anisotropic tissue such as tendon has proven resistant to mechanical fractionation by histotripsy, a subset of focused ultrasound that uses the creation, oscillation and collapse of cavitation bubbles to fractionate tissue. Our objective was to fabricate an optically transparent hydrogel that mimics tendon for evaluation of histotripsy bubble dynamics. Ex vivo bovine deep digital flexor tendons were obtained (n = 4), and varying formulations of polyacrylamide (PA), collagen and fibrin hydrogels (n = 3 each) were fabricated.

Therapeutic Ultrasound and Shockwave Therapy for Tendinopathy: A Narrative Review.

Tendon injury is prevalent and costly in the United States, comprising 45% of the 66 million musculoskeletal injuries and costing $114 billion annually. Surgical and therapeutic methods, such as arthroscopic surgery, dry needling, and physical therapy, produce mixed success in reintroducing a healing response in tendinopathy due in part to inconsistent dosing and monitoring. Ultrasound is one therapeutic modality that has been shown to noninvasively induce bioeffects in tendon that may help promote healing.

Ultrasound-Responsive Hydrogels for On-Demand Protein Release.

The development of tunable, ultrasound-responsive hydrogels that can deliver protein payload on-demand when exposed to focused ultrasound is described in this study. Reversible Diels-Alder linkers, which undergo a retro reaction when stimulated with ultrasound, were used to cross-link chitosan hydrogels with entrapped FITC-BSA as a model protein therapeutic payload. Two Diels-Alder linkage compositions with large differences in the reverse reaction energy barriers were compared to explore the influence of linker composition on ultrasound response.

Automated Tissue Strain Calculations Using Harris Corner Detection.

The elastic modulus, or slope of the stress-strain curve, is an important metric for evaluating tissue functionality, particularly for load-bearing tissues such as tendon. The applied force can be tracked directly from a mechanical testing system and converted to stress using the tissue cross-sectional area; however, strain can only be calculated in post-processing by tracking tissue displacement from video collected during mechanical testing. Manual tracking of Verhoeff stain lines pre-marked on the tissue is time-consuming and highly dependent upon the user.

Effects of focused ultrasound and dry needling on tendon mechanical properties.

Tendon injuries are extremely common, resulting in mechanically weaker tendons that could lead to tendon rupture. Dry needling (DN) is widely used to manage pain and function after injury. However, DN is invasive and high inter-practitioner variability has led to mixed success rates.

Ultrasound-Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis.

Deep vein thrombosis (DVT) is a life-threatening blood clotting condition that, if undetected, can cause deadly pulmonary embolisms. Critical to its clinical management is the ability to rapidly detect, monitor, and treat thrombosis. However, current diagnostic imaging modalities lack the resolution required to precisely localize vessel occlusions and enable clot monitoring in real time.

Comparison between dry needling and focused ultrasound on the mechanical properties of the rat Achilles tendon: A pilot study.

In the U.S., approximately 14 million tendon and ligament injuries are reported each year.

Evaluation of Stone Features That Cause the Color Doppler Ultrasound Twinkling Artifact.

The color Doppler ultrasound twinkling artifact is a rapid color shift that appears on 43%-96% of kidney stones. Surface microbubbles on kidney stones are theorized to cause twinkling as exposure to elevated static pressures of 0.41-1.

Evidence of Microbubbles on Kidney Stones in Humans.

The color Doppler ultrasound twinkling artifact has been found to improve detection of kidney stones with ultrasound; however, it appears on only ∼60% of stones. Evidence from ex vivo kidney stones suggests twinkling arises from microbubbles stabilized in crevices on the stone surface. Yet it is unknown whether these bubbles are present on stones in humans.

Ultrasound-Guided Cytosolic Protein Delivery Transient Fluorous Masks.

The inability to spatiotemporally guide proteins in tissues and efficiently deliver them into cells remains a key barrier to realizing their full potential in precision medicine. Here, we report ultrasound-sensitive fluoro-protein nanoemulsions which can be acoustically tracked, guided, and activated for on-demand cytosolic delivery of proteins, including antibodies, using clinically relevant diagnostic ultrasound. This advance is accessed through the discovery of a family of fluorous tags, or FTags, that transiently mask proteins to mediate their efficient dispersion into ultrasound-sensitive liquid perfluorocarbons, a phenomenon akin to dissolving an egg in liquid Teflon.

Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney.

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals.

Histotripsy in collagenous tendons.

Tendon injuries comprise 45% of the 66 million musculoskeletal injuries each year with annual costs of $114 billion. Conservative therapies to treat injured tendon produce mixed success rates. Histotripsy is a high intensity focused ultrasound modality that creates and oscillates bubbles to fractionate soft tissues in a well-defined focal volume; however, highly collagenous tissues like tendon have proven resistant to histotripsy.

Summary of "Biomedical Acoustics and Physical Acoustics: Shock Waves and Ultrasound for Calculus Fragmentation".

This paper summarizes the special session, "Shock Waves and Ultrasound for Calculus Fragmentation," that took place during the 176th Meeting of the Acoustical Society of America and 2018 Acoustics Week in Canada. The sessions were cosponsored by the Biomedical Acoustics and Physical Acoustics Technical Committees and consisted of ten talks by industry and academic researchers from institutions in the United States, France, and the Russian Federation. The sessions described basic and applied acoustic research to manage urinary stones.

The role of trapped bubbles in kidney stone detection with the color Doppler ultrasound twinkling artifact.

The color Doppler ultrasound twinkling artifact, which highlights kidney stones with rapidly changing color, has the potential to improve stone detection; however, its inconsistent appearance has limited its clinical utility. Recently, it was proposed stable crevice bubbles on the kidney stone surface cause twinkling; however, the hypothesis is not fully accepted because the bubbles have not been directly observed. In this paper, the micron or submicron-sized bubbles predicted by the crevice bubble hypothesis are enlarged in kidney stones of five primary compositions by exposure to acoustic rarefaction pulses or hypobaric static pressures in order to simultaneously capture their appearance by high-speed photography and ultrasound imaging.