Seungsoo Kim

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.

Prospects of molecular photoacoustic imaging at 1064 nm wavelength

An analysis of the photoacoustic (PA) signal from murine tissue in vivo revealed several benefits of contrast-enhanced PA imaging at a wavelength of 1064nm. Of all the wavelengths tested in a range from 710 to 1064nm, the background PA signal from tissue in vivo was lowest and more homogeneous at 1064nm. For blood-laden tissue, the background PA signal was up to 70% less at 1064nm. Furthermore, when plasmonic nanoparticles, such as silver nanoplates, were introduced in vivo as contrast agents, the contrast in PA images at 1064nm increased 38% compared to 750nm. Therefore, contrast-enhanced PA imaging at 1064nm is advantageous because of the low and homogeneous signal from native tissue, enabling high contrast in PA imaging when exogenous, molecularly targeted agents are employed.

In vivo three-dimensional spectroscopic photoacoustic imaging for monitoring nanoparticle delivery

Abstract In vivo monitoring of nanoparticle delivery is essential to better understand cellular and molecular interactions of nanoparticles with tissue and to better plan nanoparticle-mediated therapies. We developed a three-dimensional ultrasound and photoacoustic (PA) imaging system and a spectroscopic PA imaging algorithm to identify and quantify the presence of nanoparticles and other tissue constituents. Using the developed system and approach, three-dimensional in vivo imaging of a mouse with tumor was performed before and after intravenous injection of gold nanorods. The developed spectroscopic PA imaging algorithm estimated distribution of nanoparticle as well as oxygen saturation of blood. Moreover, silver staining of excised tumor tissue confirmed nanoparticle deposition, and showed good correlation with spectroscopic PA images. The results of our study suggest that three-dimensional ultrasound-guided spectroscopic PA imaging can monitor nanoparticle delivery in vivo.

Multiplex photoacoustic molecular imaging using targeted silica-coated gold nanorods

The establishment of multiplex photoacoustic molecular imaging to characterize heterogeneous tissues requires the use of a tunable, thermally stable contrast agent targeted to specific cell types. We have developed a multiplex photoacoustic imaging technique which uses targeted silica-coated gold nanorods to distinguish cell inclusions in vitro. This paper describes the use of tunable targeted silica-coated gold nanorods (SiO2-AuNRs) as contrast agents for photoacoustic molecular imaging. SiO2-AuNRs with peak absorption wavelengths of 780 nm and 830 nm were targeted to cells expressing different cell receptors. Cells were incubated with the targeted SiO2-AuNRs, incorporated in a tissue phantom, and imaged using multiwavelength photoacoustic imaging. We used photoacoustic imaging and statistical correlation analysis to distinguish between the unique cell inclusions within the tissue phantom.

Advances in Clinical and Biomedical Applications of Photoacoustic Imaging

IMPORTANCE OF THE FIELD: Photoacoustic imaging is an imaging modality that derives image contrast from the optical absorption coefficient of the tissue being imaged. The imaging technique is able to differentiate between healthy and diseased tissue with either deeper penetration or higher resolution than other functional imaging modalities currently available. From a clinical standpoint, photoacoustic imaging has demonstrated safety and effectiveness in diagnosing diseased tissue regions using either endogenous tissue contrast or exogenous contrast agents. Furthermore, the potential of photoacoustic imaging has been demonstrated in various therapeutic interventions ranging from drug delivery and release to image-guided therapy and monitoring. AREAS COVERED IN THIS REVIEW: This article reviews the current state of photoacoustic imaging in biomedicine from a technological perspective, highlights various biomedical and clinical applications of photoacoustic imaging, and gives insights on future directions. WHAT THE READER WILL GAIN: Readers will learn about the various applications of photoacoustic imaging, as well as the various contrast agents that can be used to assist photoacoustic imaging. This review will highlight both pre-clinical and clinical uses for photoacoustic imaging, as well as discuss some of the challenges that must be addressed to move photoacoustic imaging into the clinical realm. TAKE HOME MESSAGE: Photoacoustic imaging offers unique advantages over existing imaging modalities. The imaging field is broad with many exciting applications for detecting and diagnosing diseased tissue or processes. Photoacoustics is also used in therapeutic applications to identify and characterize the pathology and then to monitor the treatment. Although the technology is still in its infancy, much work has been done in the pre-clinical arena, and photoacoustic imaging is fast approaching the clinical setting.

Visualization of molecular composition and functionality of cancer cells using nanoparticle-augmented ultrasound-guided photoacoustics

Assessment of molecular signatures of tumors in addition to their anatomy and morphology is desired for effective diagnostic and therapeutic procedures. Development of in vivo imaging techniques that can identify and monitor molecular composition of tumors remains an important challenge in pre-clinical research and medical practice. Here we present a molecular photoacoustic imaging technique that can visualize the presence and activity of an important cancer biomarker – epidermal growth factor receptor (EGFR), utilizing the effect of plasmon resonance coupling between molecular targeted gold nanoparticles. Specifically, spectral analysis of photoacoustic images revealed profound changes in the optical absorption of systemically delivered EGFR-targeted gold nanospheres due to their molecular interactions with tumor cells overexpressing EGFR. In contrast, no changes in optical properties and, therefore, photoacoustic signal, were observed after systemic delivery of non-targeted gold nanoparticles to the tumors. The results indicate that multi-wavelength photoacoustic imaging augmented with molecularly targeted gold nanoparticles has the ability to monitor molecular specific interactions between nanoparticles and cell-surface receptors, allowing visualization of the presence and functional activity of tumor cells. Furthermore, the approach can be used for other cancer cell-surface receptors such as human epidermal growth factor receptor 2 (HER2). Therefore, ultrasound-guided molecular photoacoustic imaging can potentially aid in tumor diagnosis, selection of customized patient-specific treatment, and monitor the therapeutic progression and outcome in vivo.

An autocorrelation-based method for improvement of sub-pixel displacement estimation in ultrasound strain imaging

In ultrasound strain and elasticity imaging, an accurate and cost-effective sub-pixel displacement estimator is required because strain/elasticity imaging quality relies on the displacement SNR, which can often be higher if more computational resources are provided. In this paper, we introduce an autocorrelation-based method to cost-effectively improve subpixel displacement estimation quality. To quantitatively evaluate the performance of the autocorrelation method, simulated and tissue-mimicking phantom experiments were performed. The computational cost of the autocorrelation method is also discussed. The results of our study suggest the autocorrelation method can be used for a real-time elasticity imaging system.

Ultrasound-based imaging of nanoparticles: From molecular and cellular imaging to therapy guidance

The effectiveness of an imaging technique is often based on the ability to image quantitatively both morphological and physiological functions of the tissue. Here we present several ultrasound-based imaging techniques capable of visualizing both structural and functional properties of living tissue. Each imaging system utilizes custom-made, targeted nanoparticles developed to probe specific molecular events. Therefore, images of these nanoparticles display molecular processes in the body. Furthermore, the developed nanoparticle contrast agents can also be used for image-guided molecular therapy. For each imaging system, the basic physics and principles behind each approach are described. Experimental aspects of each imaging system including fabrication of integrated imaging probes and associated imaging hardware, and design of targeted contrast agents are discussed. Finally, biomedical and clinical applications of the developed imaging approaches ranging from microscopic to macroscopic imaging of cardiovascular diseases, cancer detection, diagnosis, therapy and therapy monitoring are demonstrated and discussed.

Estimation of mechanical properties of a viscoelastic medium using a laser-induced microbubble interrogated by an acoustic radiation force

An approach to assess the mechanical properties of a viscoelastic medium using laser-induced microbubbles is presented. To measure mechanical properties of the medium, dynamics of a laser-induced cavitation microbubble in viscoelastic medium under acoustic radiation force was investigated. An objective lens with a 1.13 numerical aperture and an 8.0 mm working distance was designed to focus a 532 nm wavelength nanosecond pulsed laser beam and to create a microbubble at the desired location. A 3.5 MHz ultrasound transducer was used to generate acoustic radiation force to excite a laser-induced microbubble. Motion of the microbubble was tracked using a 25 MHz imaging transducer. Agreement between a theoretical model of bubble motion in a viscoelastic medium and experimental measurements was demonstrated. Youngs modulii reconstructed using the laser-induced microbubble approach were compared with those measured using a direct uniaxial method over the range from 0.8 to 13 kPa. The results indicate good agreement between methods. Thus, the proposed approach can be used to assess the mechanical properties of a viscoelastic medium.

On stability of molecular therapeutic agents for noninvasive photoacoustic and ultrasound image-guided photothermal therapy

Image-guided molecular photothermal therapy using targeted gold nanoparticles acting as photoabsorbers can be used to noninvasively treat various medical conditions including cancer. Among different types of gold nanoparticles, gold nanorods are an attractive candidate for both photothermal therapy and photoacoustic imaging due to their high and tunable optical absorption cross-section. However, nanorods are not thermodynamically stable; under laser exposure, the nanorods can easily transform to spheres, thus changing their desired optical properties. In this study, gold-silica coreshell nanorods were prepared by coating silica directly onto the surface of PEGylated gold nanorods using a modified Stöber method. The nanorods were exposed to 800 nm wavelength, 7 ns pulses of light at a 10 Hz pulse repetition rate. For different fluences ranging from 0 to 8 mJ/cm2, the optical extinction spectrum was measured before and after the exposure to investigate their photothermal stability. Finally, the effectiveness of gold-silica core-shell nanoparticles as a photoacoustic contrast agent and photothermal nanoabsorber was tested using inclusion-embedded phantoms and a combined ultrasound and photoacoustic imaging system. The results of our study suggest that gold-silica core-shell nanorods are excellent candidates for image-guided molecular photothermal therapy.