Xinmai Yang

Nanoparticles for photoacoustic imaging

Nanoparticles have been designed and applied as contrast enhancers in various optical imaging techniques, such as optical coherence tomography, fluorescence imaging, and optical reflectance microscopy. As an emerging hybrid imaging modality, photoacoustic imaging (PAI) has also benefited from the application of these nanoparticle-based contrast agents. We review this rapidly growing field and describe the applications of nanoparticles in PAI. Particular focus is given to nanoparticles whose absorption mechanism is based on surface plasmon resonance, including gold nanoshells, nanorods, and nanocages. Dye-embedded nanoparticles are also reviewed. Specifically, the design and application of each nanoparticle-based contrast agent in relation to the field of PAI are detailed.

A model for the dynamics of gas bubbles in soft tissue

Understanding the behavior of cavitation bubbles driven by ultrasonic fields is an important problem in biomedical acoustics. Keller-Miksis equation, which can account for the large amplitude oscillations of bubbles, is rederived in this paper and combined with a viscoelastic model to account for the strain-stress relation. The viscoelastic model used in this study is the Voigt model. It is shown that only the viscous damping term in the original equation needs to be modified to account for the effect of elasticity. With experiment determined viscoelastic properties, the effects of elasticity on bubble oscillations are studied. Specifically, the inertial cavitation thresholds are determined using R(max)/R(0), and subharmonic signals from the emission of an oscillating bubble are estimated. The results show that the presence of the elasticity increases the threshold pressure for a bubble to oscillate inertially, and subharmonic signals may only be detectable in certain ranges of radius and pressure amplitude. These results should be easy to verify experimentally, and they may also be useful in cavitation detection and bubble-enhanced imaging.

Molecular Photoacoustic Tomography with Colloidal Nanobeacons

Spotting clots: Vascularly constrained colloidal gold nanobeacons (GNBs; see picture) can be used as exogenous photoacoustic contrast agents for the targeted detection of fibrin, a major biochemical feature of thrombus. Fibrin-targeted GNBs provide a more than tenfold signal enhancement in photoacoustic tomography in the near-IR wavelength window, indicating their potential for diagnostic imaging.

Time domain simulation of nonlinear acoustic beams generated by rectangular pistons with application to harmonic imaging

A time-domain numerical code (the so-called Texas code) that solves the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation has been extended from an axis-symmetric coordinate system to a three-dimensional (3D) Cartesian coordinate system. The code accounts for diffraction (in the parabolic approximation), nonlinearity and absorption and dispersion associated with thermoviscous and relaxation processes. The 3D time domain code was shown to be in agreement with benchmark solutions for circular and rectangular sources, focused and unfocused beams, and linear and nonlinear propagation. The 3D code was used to model the nonlinear propagation of diagnostic ultrasound pulses through tissue. The prediction of the second-harmonic field was sensitive to the choice of frequency-dependent absorption: a frequency squared f2 dependence produced a second-harmonic field which peaked closer to the transducer and had a lower amplitude than that computed for an f1.1 dependence. In comparing spatial maps of the harmonics we found that the second harmonic had dramatically reduced amplitude in the near field and also lower amplitude side lobes in the focal region than the fundamental. These findings were consistent for both uniform and apodized sources and could be contributing factors in the improved imaging reported with clinical scanners using tissue harmonic imaging.

Monkey brain cortex imaging by photoacoustic tomography

Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultrasound signal attenuation and distortion caused by a relatively thick skull.

Bubble dynamics and size distributions during focused ultrasound insonation

The deposition of ultrasonic energy in tissue can cause tissue damage due to local heating. For pressures above a critical threshold, cavitation will occur, inducing a much larger thermal energy deposition in a local region. The present work develops a nonlinear bubble dynamics model to numerically investigate bubble oscillations and bubble-enhanced heating during focused ultrasound (HIFU) insonation. The model is applied to calculate two threshold-dependent phenomena occurring for nonlinearly oscillating bubbles: Shape instability and growth by rectified diffusion. These instabilities in turn are shown to place physical boundaries on the time-dependent bubble size distribution, and thus the thermal energy deposition.

Growth of melanoma brain tumors monitored by photoacoustic microscopy

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

Nonlinear dynamics of gas bubbles in viscoelastic media

Understanding the behavior of cavitation bubbles driven by ultrasonic fields is an important problem in biomedical acoustics. The Keller–Miksis equation for nonlinear bubble dynamics is combined with the Voigt model for viscoelastic media. Using experimentally determined values, the effects of elasticity on bubble oscillations are studied. Inertial cavitation thresholds are determined using Rmax/R0=2, and subharmonic emissions are also estimated. The elasticity increases the threshold pressure for inertial cavitation, and subharmonic signals are significant only in a certain region of radii and driving pressures at a given frequency. These results should prove useful in cavitation detection and bubble-enhanced imaging work.

Ultrathin gold nanowire-functionalized carbon nanotubes for hybrid molecular sensing.

Carbon nanotubes (CNTs) have shown great potential as sensing component in the electrochemical field effect transistor and optical sensors, because of their extraordinary one-dimensional electronic structure, thermal conductivity, and tunable and stable near-infrared emission. However, the insolubility of CNTs due to strong van der Waals interactions limits their use in the field of nanotechnology. In this study, we demonstrate that noncovalent ultrathin gold nanowires functionalized multiwalled carbon nanotube (GNW-CNT) hybrid sensing agents show highly efficient and selective immune molecular sensing in electrochemical and near-infrared photoacoustic imaging methods. A detection limit of 0.01 ng/mL for the alpha-fetoprotein (AFP) antigen with high selectivity is shown. The extraordinary optical absorption, thermal, and electric conductivity of hybrid GNW-CNTs presented in this study could be an effective tactic to integrate imaging, sensing, and treatment functionalities.

Ring-based ultrasonic virtual point detector with applications to photoacoustic tomography

An ultrasonic virtual point detector is constructed using the center of a ring transducer. The virtual point detector provides ideal omnidirectional detection free of any aperture effect. Compared with a real point detector, the virtual one has lower thermal noise and can be scanned with its center inside a physically inaccessible medium. When applied to photoacoustictomography, the virtual point detector provides both high spatial resolution and high signal-to-noise ratio. It can also be potentially applied to other ultrasound-related technologies.