High Frequency Ultrasonic Imaging

High frequency ultrasonic imaging is considered by many to be the next frontier in ultrasound. It has many clinical applications ranging from imaging the eye and skin to small animal imaging. Small animal imaging has recently generated intense interest for the purpose of evaluating the efficacy of drugs and gene therapy. Commercial high frequency scanners often termed “ultrasonic biomicroscope”, or UBM, all use mechanically scanned single element transducers at frequencies between 30 to 60 MHz with a frame rate of 30 frames/second or lower. To alleviate problems with UBMs which include mechanical motion and fixed focusing, high frequency linear arrays and imaging systems in the 20–50 MHz range have been developed. In this paper, current efforts in the development of high frequency ultrasonic imaging will be reviewed and potential biomedical applications discussed

Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.

This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic

Why is the bandwidth of sodium observed to be narrower in photoemission experiments?

The experimentally predicted narrowing in the bandwidth of sodium is interpreted in terms of the non-local self-energy effect on quasi-particle energies of the electron liquid. The calculated self-energy correction is a monotonically increasing function of the wavenumber variable. The usual analysis of photo-emission experiments assumes the final state energies on the nearly-free-electron-like model and hence it incorrectly ascribes the non-local self-energy correction to the final state energies to the occupied state energies, thus leading to a seeming narrowing in the bandwidth.Comment: 9 page

Realtime Photoacoustic Microscopy of Murine Cardiovascular Dynamics

Non-invasive visualization of cardiovascular dynamics in small animals is challenging due to their rapid heart-rates. We present a realtime photoacoustic imaging system consisting of a 30-MHz ultrasound array transducer, receive electronics, a high-repetition-rate laser, and a multicore-computer, and demonstrate its ability to image optically-absorbing structures of the beating hearts of young athymic nude mice at rates of ~50 frames per second with 100 µm×25 µm spatial resolution. To our knowledge this is the first report of realtime photoacoustic imaging of physiological dynamics

Ultrasound array photoacoustic microscopy for dynamic in vivo 3D imaging

Using realtime ultrasound array photoacoustic microscopy (UA-PAM), we demonstrated the feasibility of noninvasive in vivo imaging of human pulsatile dynamics, as well as 3-D dynamic imaging of sentinel lymph nodes (SLNs) in a murine model. The system, capable of realtime B-scan imaging at 50 Hz and high-speed 3-D imaging, was validated by imaging the subcutaneous microvasculature in rats and humans. After the validation, a human superficial palmar was imaged, and its pulsatile dynamics monitored, with 20-ms B-scan imaging temporal resolution. In addition, noninvasive photoacoustic sentinel lymph node (SLN) mapping with high spatial resolution has the potential to reduce the false negative rate and eliminate the use of radioactive tracers. Upon intra-dermal injection of Evans blue, the system maps SLNs accurately in mice and rats. Furthermore, the ~6 s 3-D imaging temporal resolution offers the capability to quantitatively and noninvasively monitor the dye dynamics in SLNs in vivo through sequential 3-D imaging. The demonstrated capability suggests that high-speed 3-D photoacoustic imaging should facilitate the understanding of the dynamics of various dyes in SLNs, and potentially help identify SLNs with high accuracy. With the results shown in this study, we believe that UA-PAM can potentially enable many new possibilities for studying functional and physiological dynamics in both preclinical and clinical imaging settings

Dimensional effects in photoelectron spectra of Ag deposits on GaAs(110) surfaces

It is shown that the peak structure observed in angle-resolved photoelectron spectra of metallic deposits can only be unambiguously associated to single electronic states if the deposit has a two dimensional character (finite along one spatial direction). In one and zero dimensions the density of states shows peaks related to bunches of single electron states (the finer structure associated to the latter may not always be experimentally resolved). The characteristics of the peak structure strongly depend on the band dispersion in the energy region where they appear. Results for the density of states and photoemission yield for Ag crystallites on GaAs(110) are presented and compared with experimental photoelectron spectra.Comment: Uuencoded gz-compressed postcript file including text and three figures; Send comments to [email protected]

Fast 3-D photoacoustic imaging in vivo with a high frequency ultrasound array toward clinical applications

We present an in vivo reflection-mode photoacoustic microscopy system that performs B-scan imaging at 50 Hz with realtime beamforming and 3-D imaging of 166 B-scan frames at 1 Hz with post-beamforming. To our knowledge, this speed is currently the fastest in high frequency photoacoustic imaging. In addition, with a custom fiber based light delivery system, the imaging device is capable of performing handheld operation. Software for image processing and display with clinically user-friendly graphic user interface (GUI) is developed. The system has axial, lateral, and elevational resolutions of 25, 70, and 200 μm, respectively, and can image 3 mm deep in scattering biological tissue. Volumetric images of subcutaneous vasculature in murine are demonstrated in vivo. The system is anticipated to have potential clinical applications in skin melanoma detection due to its unique ability to image in realtime and to image anatomical sites inaccessible to other imaging systems

Fast 3-D dark-field reflection-mode photoacoustic microscopy in vivo with a 30-MHz ultrasound linear array

We present an in vivo dark-field reflection-mode photoacoustic microscopy system that performs cross-sectional (B-scan) imaging at 50Hz with real-time beamforming and 3-D imaging consisting of 166 B-scan frames at 1Hz with postbeamforming. To our knowledge, this speed is currently the fastest in photoacoustic imaging. A custom-designed light delivery system is integrated with a 30-MHz ultrasound linear array to realize dark-field reflection-mode imaging. Linear mechanical scanning of the array produces 3-D images. The system has axial, lateral, and elevational resolutions of 25, 70, and 200μm, respectively, and can image 3mm deep in scattering biological tissues. Volumetric images of subcutaneous vasculature in rats are demonstrated in vivo. Fast 3-D photoacoustic microscopy is anticipated to facilitate applications of photoacoustic imaging in biomedical studies that involve dynamics and clinical procedures that demand immediate diagnosis