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In this study the dynamic behavior of a layered viscoelastic medium in response to the harmonic and impulsive acoustic radiation force applied to its surface was investigated both theoretically and experimentally. An analytical solution for a layered viscoelastic compressible medium in frequency and time domains was obtained using the Hankel transform. A special incompressible case was considered to model soft biological tissues. To verify our theoretical model, experiments were performed using tissue-like gel-based phantoms with varying mechanical properties. A 3.5 MHz single-element focused ultrasound transducer was used to apply the radiation force at the surface of the phantoms. A phase-sensitive optical coherence tomography (OCT) system was used to track the displacements of the phantom surface. Theoretically predicted displacements were compared with experimental measurements. The role of the depth dependence of the elastic properties of a medium in its response to an acoustic pulse at the surface was studied. It was shown that the low-frequency vibrations at the surface are more sensitive to the deep layers than high-frequency ones. Therefore, the proposed model in combination with spectral analysis can be used to evaluate depth-dependent distribution of the mechanical properties based on the measurements of the surface deformation.

A high pulse repetition frequency ultrasound system for an ex vivo measurement of mechanical properties of an animal crystalline lens was developed and validated. We measured the bulk displacement of laser-induced microbubbles created at different positions within the lens using nanosecond laser pulses. An impulsive acoustic radiation force was applied to the microbubble, and spatio-temporal measurements of the microbubble displacement were assessed using a custom-made high pulse repetition frequency ultrasound system consisting of two 25 MHz focused ultrasound transducers. One of these transducers was used to emit a train of ultrasound pulses and another transducer was used to receive the ultrasound echoes reflected from the microbubble. The developed system was operating at 1 MHz pulse repetition frequency. Based on the measured motion of the microbubble, Young's moduli of surrounding tissue were reconstructed and the values were compared with those measured using the indentation test. Measured values of Young's moduli of four bovine lenses ranged from 2.6 ± 0.1 to 26 ± 1.4 kPa, and there was good agreement between the two methods. Therefore, our studies, utilizing the high pulse repetition frequency ultrasound system, suggest that the developed approach can be used to assess the mechanical properties of ex vivo crystalline lenses. Furthermore, the potential of the presented approach for in vivo measurements is discussed.

We propose a real-time technique based on phase-sensitive swept source optical coherence tomography (PhS-SSOCT) modality for noninvasive quantification of very small optical path length changes produced on the surface of a mouse crystalline lens. Propagation of submicron mechanical waves on the surface of the lens was induced by periodic mechanical stimulation. Obtained results demonstrate that the described method is capable of detecting minute damped vibrations with amplitudes as small as 30 nanometers on the lens surface and hence, PhS-SSOCT could be potentially used to assess biomechanical properties of a crystalline lens with high accuracy and sensitivity.

Intravascular photoacoustic (IVPA) imaging has been developed in recent years as a viable imaging modality for the assessment of atherosclerotic plaques. Exogenous imaging contrast and therapeutic agents further enhance this imaging modality and provide significant benefits. Imaging contrast agents can significantly increase photoacoustic signal, resulting in enhanced plaque detection and characterization. The ability to use these particles to molecularly target markers of disease progression makes it possible to determine patient-specific levels of risk and plan treatments accordingly. With improved diagnosis, clinicians will be able to use therapeutic agents that are synergistic with IVPA imaging to treat atherosclerotic patients. Pre-clinical and clinical studies with relevance to IVPA imaging have shown promise in the area of diagnosis and therapeutics. In this review, we present a variety of imaging contrast agents that are either designed for or are compatible with IVPA imaging, cover uses of therapeutic agents that compliment this imaging modality, and discuss future directions of research in the field.

The purpose of this study was to demonstrate the magneto-motive ultrasonic detection of superparamagnetic iron oxide (SPIO) nanoparticles as a marker of macrophage recruitment in tissue. The capability of ultrasound to detect SPIO nanoparticles (core diameter ∼20 nm) taken up by murine liver macrophages was investigated. Eight mice were sacrificed two days after the intravenous administration of four SPIO doses (1.5, 1.0, 0.5, and 0.1 mmol Fe/kg body weight). In the iron-laden livers, ultrasound Doppler measurements showed a frequency shift in response to an applied time-varying magnetic field. M-mode scan and colour power Doppler images of the iron-laden livers also demonstrated nanoparticle movement under focused magnetic field excitation. In the livers of two saline injected control mice, no movement was observed using any ultrasound imaging modes. The results of our experiments indicate that ultrasound imaging of magneto-motive excitation is a candidate imaging modality to identify tissue-based macrophages containing SPIO nanoparticles.

This article presents a method for measuring three-dimensional mechanical displacement and strain fields using stimulated echo MRI. Additional gradient pulses encode internal displacements in response to an externally applied deformation. By limiting the mechanical transition to the stimulated echo mixing time, a more accurate static displacement measurement is obtained. A three-dimensional elasticity reconstruction within a region of interest having a uniform shear modulus along its boundary is performed by numerically solving discretized elasticity equilibrium equations. Data acquisition, strain measurements and reconstruction were performed using a silicone gel phantom containing an inclusion of known elastic properties. A comparison between two-dimensional and three-dimensional reconstructions from simulated and experimental displacement data shows higher accuracy from the three-dimensional reconstruction. The long-term objective of this work is to provide a method for remotely palpating and elastically quantitating manually inaccessible tissues.

A biopsy of the first lymph node to which a tumor drains – the sentinel lymph node (SLN) – is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit high photothermal stability when exposed to pulsed and continuous wave laser irradiation. This makes them well-suited for in vivo photoacoustic imaging. Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs for SLN mapping in a mouse model where they exhibited a strong, sustained photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed that the Si-AuNPs quickly drain to the SLN gradually spreading throughout a large portion of the node.

As applications of nanoparticles in medical imaging and biomedicine rapidly expand, the interactions of nanoparticles with living cells have become an area of active interest. For example, intracellular accumulation of nanoparticles—an important part of cell‐nanoparticle interaction—has been well studied using plasmonic nanoparticles and optical or optics-based techniques due to the change in optical properties of the nanoparticle aggregates. However, magnetic nanoparticles, despite their wide range of clinical applications, do not exhibit plasmonic-resonant properties and therefore their intracellular aggregation cannot be detected by optics-based imaging techniques. In this study, we investigated the feasibility of a novel imaging technique—pulsed magneto-motive ultrasound (pMMUS)—to identify intracellular accumulation of endocytosed magnetic nanoparticles. In pMMUS imaging a focused, high intensity, pulsed magnetic field is used to excite the cells labeled with magnetic nanoparticles, and ultrasound imaging is then used to monitor the mechanical response of the tissue. We demonstrated previously that clusters of magnetic nanoparticles amplify the pMMUS signal in comparison to the signal from individual nanoparticles. Here we further demonstrate that pMMUS imaging can identify interaction between magnetic nanoparticles and living cells, i.e. intracellular accumulation of nanoparticles within the cells. The results of our study suggest that pMMUS imaging can not only detect the presence of magnetic nanoparticles but also provides information about their intracellular accumulation non-invasively and in real-time. (Some figures in this article are in colour only in the electronic version)