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 0.8-1.2 µm and depths of 1 µm were etched into a silicon wafer and crevice bubbles were driven at 0.75, 2.5, and 5.0 MHz while monitoring with high-speed photography. Experimental results were compared to a derived crevice bubble model. On three separate wafers, cylindrical crevices (10 or 100) with diameters of 1, 10, or 100 µm and depths of 10 µm were etched and imaged with a research ultrasound system in Doppler mode at 5, 7.8, and 18.5 MHz. Within the pressure ranges studied here (∼1MPa), no bubble oscillation was observed for the 0.8-1.2 µm crevice bubbles which matched computational results. Crevices with 1 and 10 µm diameters produced more twinkling than 100 µm crevices at 5 and 7.8 MHz. In contrast, 100 µm crevices produced more twinkling than 1 or 10 µm crevices at 18.5 MHz (p < 0.001 in all cases). These results provide better insight into how crevice bubbles cause twinkling on pathological mineralizations.

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. These results support the crevice microbubble theory of twinkling and suggest gases may be varied to enhance twinkling on some mineralizations.

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

Objective.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.Approach.In this study, five cholesterol, calcium phosphate, and uric acid crystals were grownin vitroand imaged in Doppler mode with a research ultrasound system and L7-4 transducer in water. To evaluate the influence of pressure on twinkling, the same crystals were imaged in a high-pressure chamber. Then, the effect of surface tension on twinkling was evaluated by imaging crystals in different concentrations of surfactant (1%, 2%, 3%, 4%) and ethanol (10%, 30%, 50%, 70%), artificial urine, bovine blood, and a tissue-mimicking phantom.Main results. Results showed that all crystals twinkled in water, with cholesterol twinkling significantly more than calcium phosphate and uric acid. When the ambient pressure was increased, twinkling disappeared for all tested crystals when pressures reached 7 MPa (absolute) and reappeared when returned to ambient pressure (0.1 MPa). Similarly, twinkling across all crystals decreased with surface tension when imaged in the surfactant and ethanol (statistically significant when surface tension <22 mN m-1) and decreased in blood (surface tension = 52.7 mN m-1) but was unaffected by artificial urine (similar surface tension to water). In the tissue-mimicking phantom, twinkling increased for cholesterol and calcium phosphate crystals with no change observed in uric acid crystals.Significance.Overall, these results support the theory that bubbles are present on crystals and cause twinkling, which could be leveraged to improve twinkling for the detection of other pathological mineralizations.

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. Here, we rationally design fibrinogen-mimicking fluoropeptide nanoemulsions, or nanopeptisomes (NPeps), that allow contrast-enhanced ultrasound imaging of thrombi and synchronous inhibition of clot growth. The theranostic duality of NPeps is imparted via their intrinsic binding to integrins overexpressed on platelets activated during coagulation. The platelet-bound nanoemulsions can be vaporized and oscillate in an applied acoustic field to enable contrast-enhanced Doppler ultrasound detection of thrombi. Concurrently, nanoemulsions bound to platelets competitively inhibit secondary platelet-fibrinogen binding to disrupt further clot growth. Continued development of this synchronous theranostic platform may open new opportunities for image-guided, non-invasive, interventions for DVT and other vascular diseases.

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 0.41-1.13 MPa (approximately 0.5-1 times diagnostic ultrasound pressure and 5-10 times ambient pressure) reduced twinkling. However, it is unclear what external and internal stone features support bubbles. Thirteen ex vivo kidney stones were scanned with color Doppler ultrasound at 2.5, 5 and 18.5 MHz. Select stones were imaged with environmental scanning electron microscopy or underwater micro-computed tomography to evaluate features that may cause twinkling. Results revealed that the lower frequencies produced larger volumes of twinkling. Condensation first occurred in the smallest (∼1 µm diameter) surface pores and may be indicative of where bubbles form. Gas pockets were seen inside two of three tested stones that may contribute to twinkling. Overall, these results provide evidence of cavity structures both externally and internally and their correlation to the twinkling artifact. This indicates that microbubbles may be present on and within kidney stones and may contribute to the twinkling artifact.

Structural contributions to phantom partial generation in the piano.

The results of experiments designed to determine the origin of the anomalous frequency components in the sound of the piano commonly referred to as phantom partials are reported. It is shown that these overtones, which occur at the sum and difference frequencies associated with the transverse string motion, are produced by nonlinearities in both the string and the wooden components of the piano. However, the contribution from the string is significantly smaller than the contributions from other components.

The production of phantom partials due to nonlinearities in the structural components of the piano.

Phantom partials are anomalous overtones in the spectrum of the piano sound that occur at sum and difference frequencies of the natural overtones of the string. Although they are commonly assumed to be produced by forced longitudinal waves in the string, analysis of the sound of a piano produced by mechanically vibrating the soundboard while all the strings are damped indicates that phantom partials can occur in the absence of string motion. The magnitude of the effect leads to the conclusion that nonlinearity in the non-string components may be responsible for some of the power in the phantom partials.