We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name ‘Cy-droplet’, has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a ‘microbubble condensation’ method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical ‘triggerability’ can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release.

The very high frame rate afforded by ultrafast ultrasound, combined with microbubble contrast agents, opens new opportunities for imaging tissue microvasculature. However, new imaging paradigms are required to obtain superior image quality from the large amount of acquired data while allowing real-time implementation. In this paper, we report a technique-acoustic sub-aperture processing (ASAP)-capable of generating very high contrast/signal-to-noise ratio (SNR) images of macro-and microvessels, with similar computational complexity to classical power Doppler (PD) imaging. In ASAP, the received data are split into subgroups. The reconstructed data from each subgroup are temporally correlated over frames to generate the final image. As signals in subgroups are correlated but the noise is not, this substantially reduces the noise floor compared to PD. Using a clinical imaging probe, the method is shown to visualize vessels down to $200~\mu \text{m}$ with a SNR of 10 dB higher than PD and to resolve microvascular flow/perfusion information in rabbit kidneys noninvasively in vivo at multiple centimeter depths. With careful filter design, the technique also allows the estimation of flow direction and the separation of fast flow from tissue perfusion. ASAP can readily be implemented into hardware/firmware for real-time imaging and can be applied to contrast enhanced and potentially noncontrast imaging and 3-D imaging.

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Contrast echocardiography (CE) ultrasound with microbubble contrast agents have significantly advanced our capability in assessing cardiac function, including myocardium perfusion imaging and quantification. However in conventional CE techniques with line by line scanning, the frame rate is limited to tens of frames per second and image quality is low. Recent research works in high frame-rate (HFR) ultrasound have shown significant improvement of the frame rate in noncontrast cardiac imaging. But with a higher frame rate, the coherent compounding of HFR CE images shows some artifacts due to the motion of the microbubbles. In this work we demonstrate the impact of this motion on compounded HFR CE in simulation and then apply a motion correction algorithm on in-vivo data acquired from the left ventricle (LV) chamber of a sheep. It shows that even if with the fast flow found inside the LV, the contrast is improved at least 100%.

Computational models of acoustic wave propagation are frequently used in transcranial ultrasound therapy, for example, to calculate the intracranial pressure field or to calculate phase delays to correct for skull distortions. To allow intercomparison between the different modeling tools and techniques used by the community, an international working group was convened to formulate a set of numerical benchmarks. Here, these benchmarks are presented, along with intercomparison results. Nine different benchmarks of increasing geometric complexity are defined. These include a single-layer planar bone immersed in water, a multi-layer bone, and a whole skull. Two transducer configurations are considered (a focused bowl and a plane piston operating at 500 kHz), giving a total of 18 permutations of the benchmarks. Eleven different modeling tools are used to compute the benchmark results. The models span a wide range of numerical techniques, including the finite-difference time-domain method, angular spectrum method, pseudospectral method, boundary-element method, and spectral-element method. Good agreement is found between the models, particularly for the position, size, and magnitude of the acoustic focus within the skull. When comparing results for each model with every other model in a cross-comparison, the median values for each benchmark for the difference in focal pressure and position are less than 10% and 1 mm, respectively. The benchmark definitions, model results, and intercomparison codes are freely available to facilitate further comparisons.