Stanislav Emelianov

Internal displacement and strain imaging using ultrasonic speckle tracking

Previous ultrasound speckle tracking methods have been extended, permitting measurement of internal displacement and strain fields over a wide dynamic range of tissue motion. The markedly increased dynamic range of this approach should lead to enhanced contrast resolution in strain and elasticity images. Results of experiments on gelatin-based, tissue equivalent phantoms show the capabilities of the method.<<ETX>>

Speckle tracking methods for ultrasonic elasticity imaging using short-time correlation

In ultrasound elasticity imaging, strain decorrelation is a major source of error in displacements estimated using correlation techniques. This error can be significantly decreased by reducing the correlation kernel. Additional gains in signal-to-noise ratio (SNR) are possible by filtering the correlation functions prior to displacement estimation. Tradeoffs between spatial resolution and estimate variance are discussed, and estimation in elasticity imaging is compared to traditional time-delay estimation. Simulations and experiments on gel-based phantoms are presented. The results demonstrate that high resolution, high SNR strain estimates can be computed using small correlation kernels (on the order of the autocorrelation width of the ultrasound signal) and correlation filtering.

Multiwavelength Photoacoustic Imaging and Plasmon Resonance Coupling of Gold Nanoparticles for Selective Detection of Cancer

Gold nanoparticles targeting epidermal growth factor receptor via antibody conjugation undergo molecular specific aggregation when they bind to receptors on cell surfaces, leading to a red shift in their plasmon resonance frequency. Capitalizing on this effect, we demonstrate the efficacy of the molecular specific photoacoustic imaging technique using subcutaneous tumor-mimicking gelatin implants in ex-vivo mouse tissue. The results of our study suggest that highly selective and sensitive detection of cancer cells is possible using multiwavelength photoacoustic imaging and molecular specific gold nanoparticles.

Tissue elasticity reconstruction based on ultrasonic displacement and strain images

A method is presented to reconstruct the elastic modulus of soft tissue based on ultrasonic displacement and strain images. Incompressible and compressible media are considered separately. Problems arising with this method, as well as applications to real measurements on gel-based, tissue equivalent phantoms, are given. Results show that artifacts present in strain images can be greatly reduced using a hybrid reconstruction procedure based on numerical solution of the partial differential equations describing mechanical equilibrium of a deformed medium.<<ETX>>

Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance

Imaging modalities play an important role in the clinical management of cancer, including screening, diagnosis, treatment planning and therapy monitoring. Owing to increased research efforts during the past two decades, photoacoustic imaging (a non-ionizing, noninvasive technique capable of visualizing optical absorption properties of tissue at reasonable depth, with the spatial resolution of ultrasound) has emerged. Ultrasound-guided photoacoustics is noted for its ability to provide in vivo morphological and functional information about the tumor within the surrounding tissue. With the recent advent of targeted contrast agents, photoacoustics is now also capable of in vivo molecular imaging, thus facilitating further molecular and cellular characterization of cancer. This review examines the role of photoacoustics and photoacoustic-augmented imaging techniques in comprehensive cancer detection, diagnosis and treatment guidance.

Biophysical Bases of Elasticity Imaging

Elasticity imaging is based on two processes. The first is the evaluation of the mechanical response of a stressed tissue using imaging modalities, e.g. ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) scans and Doppler ultrasound. The second step is depiction of the elastic properties of internal tissue structures by mathematical solution of the inverse mechanical problem. The evaluation of elastic properties of tissues has the potential for being an important diagnostic tool in the detection of cancer as well as other injuries and diseases. The success of breast self-examination in conjunction with mammography for detection and continuous monitoring of lesions has resulted in early diagnosis and institution of therapy. Self-examination is based on the manually palpable texture difference of the lesion relative to adjacent tissue and, as such, is limited to lesions located relatively near the skin surface and increased lesion hardness with respect to the surrounding tissue. Imaging of tissue “hardness” should allow more sensitive detection of abnormal structures deeper within tissue. Tissue hardness can actually be quantified in terms of the tissue elastic moduli and may provide good contrast between normal and abnormal tissues based on the large relative variation in shear (or Young’s) elastic modulus.

Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy

Photothermal stability and, therefore, consistency of both optical absorption and photoacoustic response of the plasmonic nanoabsorbers is critical for successful photoacoustic image-guided photothermal therapy. In this study, silica-coated gold nanorods were developed as a multifunctional molecular imaging and therapeutic agent suitable for image-guided photothermal therapy. The optical properties and photothermal stability of silica-coated gold nanorods under intense irradiation with nanosecond laser pulses were investigated by UV-Vis spectroscopy and transmission electron microscopy. Silica-coated gold nanorods showed increased photothermal stability and retained their superior optical properties under much higher fluences. The changes in photoacoustic response of PEGylated and silica-coated nanorods under laser pulses of various fluences were compared. The silica-coated gold nanorods provide a stable photoacoustic signal, which implies better imaging capabilities and make silica-coated gold nanorods a promising imaging and therapeutic nano-agent for photoacoustic imaging and image-guided photothermal therapy.

Photoacoustic imaging and temperature measurement for photothermal cancer therapy.

Photothermal therapy is a noninvasive, targeted, laser-based technique for cancer treatment. During photothermal therapy, light energy is converted to heat by tumor-specific photoabsorbers. The corresponding temperature rise causes localized cancer destruction. For effective treatment, however, the presence of photoabsorbers in the tumor must be ascertained before therapy and thermal imaging must be performed during therapy. This study investigates the feasibility of guiding photothermal therapy by using photoacoustic imaging to detect photoabsorbers and to monitor temperature elevation. Photothermal therapy is carried out by utilizing a continuous wave laser and metal nanocomposites broadly absorbing in the near-infrared optical range. A linear array-based ultrasound imaging system is interfaced with a nanosecond pulsed laser to image tissue-mimicking phantoms and ex-vivo animal tissue before and during photothermal therapy. Before commencing therapy, photoacoustic imaging identifies the presence and spatial location of nanoparticles. Thermal maps are computed by monitoring temperature-induced changes in the photoacoustic signal during the therapeutic procedure and are compared with temperature estimates obtained from ultrasound imaging. The results of our study suggest that photoacoustic imaging, augmented by ultrasound imaging, is a viable candidate to guide photoabsorber-enhanced photothermal therapy.

Strain rate imaging using two-dimensional speckle tracking

Strain rate images (SRI) of the beating heart have been proposed to identify non-contracting regions of myocardium. Initial attempts used spatial derivatives of tissue velocity (Doppler) signals. Here, an alternate method is proposed based on two-dimensional phase-sensitive speckle tracking applied to very high frame rate, real-time images. This processing can produce high resolution maps of the time derivative of the strain magnitude (i.e., square root of the strain intensity). Such images complement traditional tissue velocity images (TVI), providing a more complete description of cardiac mechanics. To test the proposed approach, SRI were both simulated and measured on a thick-walled, cylindrical, tissue-equivalent phantom modeling cardiac deformations. Real-time ultrasound images were captured during periodic phantom deformation, where the period was matched to the data capture rate of a commercial scanner mimicking high frame rate imaging of the heart. Simulation results show that SRI with spatial resolution between 1 and 2 mm are possible with an array system operating at 5 MHz. Moreover, these images are virtually free of angle-dependent artifacts present in TVI and simple strain rate maps derived from these images. Measured results clearly show that phantom regions of low deformation, which are difficult to identify on tissue velocity-derived SRI, are readily apparent with SRI generated from two-dimensional phase-sensitive speckle tracking.

Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging

Since being discovered by Alexander Bell, photoacoustics may again be seeing major resurgence in biomedical imaging. Photoacoustics is a non-ionizing, functional imaging modality capable of high contrast images of optical absorption at depths significantly greater than traditional optical imaging techniques. Optical contrast agents have been used to extend photoacoustics to molecular imaging. Here we introduce an exogenous contrast agent that utilizes vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. Our agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles, entitled photoacoustic nanodroplets. Upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. Once triggered, the gaseous phase provides ultrasound contrast enhancement. We demonstrate in phantom and animal studies that photoacoustic nanodroplets act as dual-contrast agents for both photoacoustic and ultrasound imaging through optically triggered vaporization.