Yun-Sheng Chen

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.

Environment-Dependent Generation of Photoacoustic Waves from Plasmonic Nanoparticles

Nanoparticle-augmented photoacoustics is an emerging technique for molecular imaging. This study investigates the fundamental process of the photoacoustic signal generation by plasmonic nanoparticles suspended in a weakly absorbing fluid. The photoacoustic signal of gold nanospheres with varying silica shell thicknesses is shown to be dominated by the heat transfer between the nanoparticles and the surrounding environment.

Magneto-photo-acoustic imaging

Magneto-photo-acoustic imaging, a technique based on the synergy of magneto-motive ultrasound, photoacoustic and ultrasound imaging, is introduced. Hybrid nanoconstructs, liposomes encapsulating gold nanorods and iron oxide nanoparticles, were used as a dual-contrast agent for magneto-photo-acoustic imaging. Tissue-mimicking phantom and macrophage cells embedded in ex vivo porcine tissue were used to demonstrate that magneto-photo-acoustic imaging is capable of visualizing the location of cells or tissues labeled with dual-contrast nanoparticles with sufficient contrast, excellent contrast resolution and high spatial resolution in the context of the anatomical structure of the surrounding tissues. Therefore, magneto-photo-acoustic imaging is capable of identifying the nanoparticle-labeled pathological regions from the normal tissue, providing a promising platform to noninvasively diagnose and characterize pathologies.

Capacitor-embedded 0.54 pJ/bit silicon-slot photonic crystal waveguide modulator

A high-speed compact silicon modulator based on the lateral capacitor configuration is experimentally demonstrated with low-power consumption and 3 dB modulation depth. The capacitor layout is introduced to scale down the total modulator capacitance to 30x10(-15) F, which effectively reduces the rf power consumption to 0.54 pJ/bit. Exploiting the slow group velocity of light in the slot photonic crystal waveguides, the device reported herein exhibits higher modulation efficiency than conventional capacitor modulator and provides a V(pi)L figure of merit of 0.18 Vcm at the wavelength of 1548 nm.

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.

Silica-coated gold nanoplates as stable photoacoustic contrast agents for sentinel lymph node imaging

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.

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.

Intravascular Photoacoustics for Image-Guidance and Temperature Monitoring During Plasmonic Photothermal Therapy of Atherosclerotic Plaques: A Feasibility Study

Recently, combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging has been demonstrated as a novel imaging modality capable of visualizing both morphology (via IVUS) and cellular/molecular composition (via IVPA) of atherosclerotic plaques, using both endogenous tissue absorbers and exogenous contrast agents. Plasmonic gold nanoparticles were previously utilized as IVPA contrast agents which co-localize with atherosclerotic plaques, particularly phagocytically active macrophages. The present work demonstrates the use of IVUS/IVPA imaging as a tool for localized temperature monitoring during laser heating. The temperature dependent change in IVPA signal intensity of silica-coated gold nanorod contrast agents absorbing within the near-infrared optical wavelength range is evaluated and shown to have a linear relationship, with a slope greater than that of endogenous tissue. A continuous wave laser was subsequently incorporated into the IVUS/IVPA integrated catheter and utilized to selectively heat the nanoparticles with simultaneous IVPA temperature monitoring. IVUS/IVPA, therefore, provides a platform for detection and temperature monitoring of atherosclerotic plaques through the selective heating of plasmonic gold nanoparticle contrast agents.