Ultrasound imaging using a matrix array allows real-time multi-planar volumetric imaging. To enhance image quality, the matrix array should provide fast volumetric ultrasound imaging with spatially consistent focusing in the lateral and elevational directions. However, because of the significantly increased data size, dealing with massive and continuous data acquisition is a significant challenge. We have designed an imaging acquisition sequence that handles volumetric data efficiently using a single 256-channel Verasonics ultrasound research platform multiplexed with a 1024-element matrix array. The developed sequence has been applied for building an ultrasonic pupilometer. Our results demonstrate the capability of the developed approach for structural visualization of an ex vivo porcine eye and the temporal response of the modeled eye pupil with moving iris at the volume rate of 30 Hz. Our study provides a fundamental ground for researchers to establish their own volumetric ultrasound imaging platform and could stimulate the development of new volumetric ultrasound approaches and applications.

Super-resolution imaging with moving microbubbles has shown potential in identifying fine details of deep-lying vascular compartments. To image the extravascular targets, the current study has employed nanometer-sized, optically triggered perfluorohexane nanodroplets (PFHnDs). In response to pulsed laser irradiation, the PFHnDs repeatedly vaporize and stochastically recondense, resulting in random changes of ultrasound signals. Our previous study has shown that the stochastic recondensation of the PFHnDs can be used to isolate individual PFHnDs for super-resolution imaging. This study introduces an improved method for super-resolution imaging with ultrafast ultrasound imaging of PFHnDs. The previous method was based on subtraction of two consecutive ultrasound images to detect signals from recondensed, isolated droplets whereas our current method compounds respective multiple pre- and post-recondensation ultrafast ultrasound images prior to subtraction to improve the spatial resolution further. To evaluate the axial and lateral resolutions of our method, we repeatedly imaged a phantom containing PFHnDs using a programmable ultrasound system synchronized with a pulsed laser system. As a result, our method improved the lateral and axial resolutions by 54% and 68%, respectively, over the previous super-resolution imaging approach, indicating that it can be used for localizing extravascular molecular targets with superior accuracy.

Photoacoustic (PA) imaging^{1 – 6} is an emergent area of research in biomedical imaging. The technique uses nanosecond pulses of light to induce ultrasonic waves from imaging targets in tissue, which can then be detected by an ultrasound (US) transducer. The ultrasonic wave is induced by rapid expansion of the target as a result of heat generated from the absorbed laser light. The strength of the ultrasonic wave is dependent on the quantity of light delivered, a set of physical properties referred together as the Gruneisen coefficient, and the optical absorption coefficient of the imaging target.⁵ Since the optical absorption coefficient is wavelength dependent and has been characterized for a wide variety of tissue types, imaging targets can be identified by imaging a single region at multiple wavelengths and then comparing the changes in PA signal intensity with what would be predicted based on the known optical absorption coefficients.

Laser-activated perfluorocarbon nanodroplets (PFCnDs) are emerging phase-change contrast agents that showed promising potential in ultrasound and photoacoustic (US/PA) imaging. Unlike monophase gaseous microbubbles, PFCnDs shift their state from liquid to gas via optical activation and can provide high US/PA contrast on demand. Depending on the choice of perfluorocarbon core, the vaporization and condensation dynamics of the PFCnDs are controllable. Therefore, these configurable properties of activation and deactivation of PFCnDs are employed to enable various imaging approaches, including contrast-enhanced imaging and super-resolution imaging. In addition, synchronous application of both acoustic and optical pulses showed a promising outcome vaporizing PFCnDs with lower activation thresholds. Furthermore, due to their sub-micrometer size, PFCnDs can be used for molecular imaging of extravascular tissue. PFCnDs can also be an effective therapeutic tool. As PFCnDs can carry therapeutic drugs or other particles, they can be used for drug delivery, as well as photothermal and photodynamic therapies. Blood barrier opening for neurological applications was recently demonstrated with optically-triggered PFCnDs. This paper specifically focuses on the activation and deactivation properties of laser-activated PFCnDs and associated US/PA imaging approaches, and briefly discusses their theranostic potential and future directions.

This paper introduces a configurable combined laser, ultrasound, and elasticity (CLUE) imaging platform. The CLUE platform enables imaging sequences capable of simultaneously providing quantitative acoustic, optical, and mechanical contrast for comprehensive diagnosis and monitoring of complex diseases, such as cancer. The CLUE imaging platform was developed on a Verasonics ultrasound scanner integrated with a pulsed laser, and it was designed to be modular and scalable to allow researchers to create their own specific imaging sequences efficiently. The CLUE imaging platform and sequence were demonstrated in a tissue-mimicking phantom containing a stiff inclusion labeled with optically-activated nanodroplets and in an ex vivo mouse spleen. We have shown that CLUE imaging can simultaneously capture multi-functional imaging signals providing quantitative information on tissue.

Perfluorocarbon nanodroplets (PFCnDs) are sub-micrometer emulsions composed of a surfactant-encased perfluorocarbon (PFC) liquid and can be formulated to transiently vaporize through optical stimulation. However, the factors governing repeated optical droplet vaporization (ODV) have not been investigated. In this study, we employ high-frame-rate ultrasound (US) to characterize the ODV thresholds of various formulations and imaging parameters and identify those that exhibit low vaporization thresholds and repeatable vaporization. We observe a phenomenon termed “preconditioning”, where initial laser pulses generate reduced US contrast that appears linked with an increase in nanodroplet size. Variation in laser pulse repetition frequency is found not to change the vaporization threshold, suggesting that “preconditioning” is not related to residual heat. Surfactants (bovine serum albumin, lipids, and zonyl) impact the vaporization threshold and imaging lifetime, with lipid shells demonstrating the best performance with relatively low thresholds (21.6 ± 3.7 mJ/cm²) and long lifetimes (t_1/2 = 104 ± 21.5 pulses at 75 mJ/cm²). Physiological stiffness does not affect the ODV threshold and may enhance nanodroplet stability. Furthermore, PFC critical temperatures are found to correlate with vaporization thresholds. These observations enhance our understanding of ODV behavior and pave the way for improved nanodroplet performance in biomedical applications.