David Li

Acoustic micro-tapping for non-contact 4D imaging of tissue elasticity

Elastography plays a key role in characterizing soft media such as biological tissue. Although this technology has found widespread use in both clinical diagnostics and basic science research, nearly all methods require direct physical contact with the object of interest and can even be invasive. For a number of applications, such as diagnostic measurements on the anterior segment of the eye, physical contact is not desired and may even be prohibited. Here we present a fundamentally new approach to dynamic elastography using non-contact mechanical stimulation of soft media with precise spatial and temporal shaping. We call it acoustic micro-tapping (AμT) because it employs focused, air-coupled ultrasound to induce significant mechanical displacement at the boundary of a soft material using reflection-based radiation force. Combining it with high-speed, four-dimensional (three space dimensions plus time) phase-sensitive optical coherence tomography creates a non-contact tool for high-resolution and quantitative dynamic elastography of soft tissue at near real-time imaging rates. The overall approach is demonstrated in ex-vivo porcine cornea.

Polypyrrole Coated Perfluorocarbon Nanoemulsions as a Sono-Photoacoustic Contrast Agent

A new contrast agent for combined photoacoustic and ultrasound imaging is presented. It has a liquid perfluorocarbon (PFC) core of about 250 nm diameter coated by a 30 nm thin polypyrrole (PPy) doped polymer shell emulsion that represents a broadband absorber covering the visible and near-infrared ranges (peak optical extinction at 1050 nm). When exposed to a sufficiently high intensity optical or acoustic pulse, the droplets vaporize to form microbubbles providing a strong increase in imaging sensitivity and specificity. The threshold for contrast agent activation can further drastically be reduced by up to 2 orders of magnitude if simultaneously exposing them with optical and acoustic pulses. The selection of PFC core liquids with low boiling points (i.e., perfluorohexane (56 °C), perfluoropentane (29 °C), and perfluorobutane (-2 °C)) facilitates activation and reduces the activation threshold of PPy-coated emulsion contrast agents to levels well within clinical safety limits (as low as 0.2 MPa at 1 mJ/cm2). Finally, the potential use of these nanoemulsions as a contrast agent is demonstrated in a series of phantom imaging studies.

Air-coupled acoustic radiation force for non-contact generation of broadband mechanical waves in soft media.

A non-contact method for efficient, non-invasive excitation of mechanical waves in soft media is proposed, in which we focus an ultrasound (US) signal through air onto the surface of a medium under study. The US wave reflected from the air/medium interface provides radiation force to the medium surface that launches a transient mechanical wave in the transverse (lateral) direction. The type of mechanical wave is determined by boundary conditions. To prove this concept, a home-made 1 MHz piezo-ceramic transducer with a matching layer to air sends a chirped US signal centered at 1 MHz to a 1.6 mm thick gelatin phantom mimicking soft biological tissue. A phase-sensitive (PhS)-optical coherence tomography system is used to track/image the mechanical wave. The reconstructed transient displacement of the mechanical wave in space and time demonstrates highly efficient generation, thus offering great promise for non-contact, non-invasive characterization of soft media, in general, and for elasticity measurements in delicate soft tissues and organs in bio-medicine, in particular.

Optical coherence elastography in ophthalmology

Abstract. Optical coherence elastography (OCE) can provide clinically valuable information based on local measurements of tissue stiffness. Improved light sources and scanning methods in optical coherence tomography (OCT) have led to rapid growth in systems for high-resolution, quantitative elastography using imaged displacements and strains within soft tissue to infer local mechanical properties. We describe in some detail the physical processes underlying tissue mechanical response based on static and dynamic displacement methods. Namely, the assumptions commonly used to interpret displacement and strain measurements in terms of tissue elasticity for static OCE and propagating wave modes in dynamic OCE are discussed with the ultimate focus on OCT system design for ophthalmic applications. Practical OCT motion-tracking methods used to map tissue elasticity are also presented to fully describe technical developments in OCE, particularly noting those focused on the anterior segment of the eye. Clinical issues and future directions are discussed in the hope that OCE techniques will rapidly move forward to translational studies and clinical applications.

Ultrasound-based formation of nano-Pickering emulsions investigated via in-situ SAXS

Sonication is one of the most commonly used methods to synthesize Pickering emulsions. Yet, the process of emulsion sonication is rarely characterized in detail and acoustic conditions are largely determined by experimenters personal experience. In this study, the role of sonication in the formation of Pickering emulsions from amphiphilic gold nanoparticles was investigated using a new sample environment combining ultrasound delivery with ultra-small-angle X-ray scattering (USAXS) measurements. The detection of acoustic cavitation and the simultaneous analysis of structural data via USAXS demonstrated direct correlation between Pickering emulsion formation and cavitation events. There was no evidence of spontaneous adsorption of particles onto the oil-water interface without ultrasound, which suggests the presence of a stabilizing force. Acoustically detected cavitation events could originate in the bulk solvent and/or inside the emulsion droplets. These events helped overcome energy barriers to induce particle adsorption.

Air-coupled ARF-based excitation of broadband mechanical waves for dynamic elastography

Recently we demonstrated non-contact excitation of broadband mechanical waves in soft media for transient elastography. Using US from an air-coupled transducer focused on an air/medium interface, this method (called “acoustic micro-tapping”, or AμT) provides sufficient radiation force to launch a transient displacement. Combined with ultrafast phase sensitive OCT, AμT-OCT can track propagating mechanical waves with a fully non-contact system appropriate for many applications. Complementary methods are now needed to properly reconstruct the elastic modulus from imaged wavefields. Here we explore the different modes launched by an AμT source that can be tracked efficiently with OCT. The motivation is an optimal method to reconstruct the elastic modulus from complex displacement fields given the highly dispersive nature of waves in bounded media such as the cornea.

Gold pickering emulsions as a phase-change contrast agent for photoacoustic imaging

Photoacoustic (PA) imaging is an emerging technique used with ultrasound imaging to provide molecular specificity. Even with contrast agents, PA imaging suffers from poor penetration depth due to strong light attenuation in tissue. Recently, Phase-change contrast agents (PCCAs) have been proposed as an alternative agent since volume expansion during the vaporization process results in significantly larger signals than those from traditional photo-thermal expansion based contrast agents. Our PCCA is a Pickering emulsion featuring a low boiling point liquid perfluorocarbon (PFC) core decorated by 12 nm diameter gold nanoparticles (GNP). The agents can undergo a reversible phase change with the application of either optical or acoustic energy. Photo-thermal heating of the GNP shell or acoustic cavitation causes vaporization of the PFC core. The non-bonded shell can easily recover after vaporization and condensation for multiple activation events. In this study, the synthesis and imaging contrast performance of gold stabilized Pickering is presented.

Sono-photoacoustic imaging using polypyrrole coated phase-change contrast agents

Photoacoustic (PA) imaging is an emerging molecular imaging modality. Image contrast, however, strongly decreases with depth due to light attenuation in tissue. Recently, PA phase-change contrast agents (PCCAs) have been proposed as alternative PA agents because the rapid expansion from droplet vaporization provides contrast orders of magnitude higher than that of conventional PA agents. Current PA PCCAs still require a minimum of 10 mJ/cm2 to activate, making them unsuitable for deep tissue imaging.

Combination of air-coupled acoustic micro-tapping and phase sensitive OCT for 4-D real-time, non-contact imaging of soft tissue elastic moduli

Elastography plays a key role in characterizing soft tissue. Although it has found widespread use in clinical diagnostics, nearly all methods require direct physical contact with tissue and can even be invasive. However, for a number of applications (ophthalmic, for instance) physical contact is not desired and may not even be allowed. Recently, we proposed a fundamentally new approach to 4-D dynamic elastography using non-contact mechanical stimulation (e.g. from air) of soft media with an air-coupled focused US transducer (we call it acoustic micro-tapping, AμT) combined with ultrafast phase sensitive (PhS) OCT [1]. Here, we report on new AμT-OCT system developments and new results obtained in ex-vivo and in-vivo studies on eye and skin.

Acoustic wave directed assembly of conjugated polymers

Conjugated polymers (CP) have attracted a great deal of attention because they are flexible, light weight, economical, and highly scalable. They are widely used in organic electronics, such as organic field effect transistors, photovoltaics, thermoelectrics, spintronics and electronic skins. However, the electrical performance of CP is still limited due to the inefficient charge hopping between polymer chains.