Nanoshell-enhanced optical coherence tomography (OCT) is a novel technique with the potential for molecular imaging and improved disease detection. However, optimization of this approach will require a quantitative understanding of the influence of nanoshell parameters on detected OCT signals. In this study, OCT was performed at 1310 nm in water and turbid tissue-simulating phantoms to which nanoshells were added. The effect of nanoshell concentration, core diameter, and shell thickness on signal enhancement was characterized. Experimental results indicated trends that were consistent with predicted optical properties—a monotonic increase in signal intensity and attenuation with increasing shell and core size. Threshold concentrations for a 2-dB OCT signal intensity gain were determined for several nanoshell geometries. For the most highly backscattering nanoshells tested—291-nm core diameter, 25-nm shell thickness—a concentration of 109 nanoshells/mL was needed to produce this signal increase. Based on these results, we discuss various practical considerations for optimizing nanoshell-enhanced OCT. Quantitative experimental data presented here will facilitate optimization of OCT-based diagnostics and may also be relevant to other reflectance-based approaches as well.
Current optical technologies utilize changes in optical properties of tissue to distinguish diseased from normal tissue. This poses an important challenge to enhance this subtle intrinsic contrast with the use of novel nanoparticle based contrast agents. Gold nanoshells are a novel type of spherical concentric nanoparticle that possesses high optical efficiencies well into the near infrared. Gold nanoshells are typically made of a dielectric silica core and a thin metallic gold outer layer and a wide range of sizes are easily fabricated using current chemistries. Gold nanoshells can scatter and/or absorb light with optical cross-sections often several times larger than the geometric cross-section. To elucidate the effectiveness of gold nanoshells as a contrast agent for reflectance, it is important to understand how different optical properties of nanoshells affect reflectance, and ultimately provide insight into how reflectance is affected by gold nanoshells embedded in biological tissue. A fiber-probe based spectrometer was used to measure diffuse reflectance of gold nanoshells suspensions from 500nm to 900nm. We further characterize diffuse reflectance of gold nanoshell suspensions using Monte Carlo based computational tools. Our results show that gold nanoshells are capable of producing large changes in diffuse reflectance, and computer modeling results agreed well with the experimental observations. From the study, we also show that it may be feasible to use Monte Carlo based modeling to simulate biological medium embedded with gold nanoshells.
Many optical diagnostic approaches rely on changes in scattering and absorption properties to generate optical contrast between normal and diseased tissue. Recently, there has been increasing interest in using exogenous agents to enhance this intrinsic contrast with particular emphasis on the development for targeting specific molecular features of disease. Gold nanoshells are a class of core-shell nanoparticles with an extremely tunable peak optical resonance ranging from the near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a wide variety of core and shell sizes can easily be fabricated to scatter and/or absorb light with optical cross sections often several times larger than the geometric cross section. Using gold nanoshells of different size and optical parameters, we employ Monte Carlo models to predict the effect of varying concentrations of nanoshells on tissue reflectance. The models demonstrate the importance of absorption from the nanoshells on remitted signals even when the optical extinction is dominated by scattering. Furthermore, because of the strong optical response of nanoshells, a considerable change in reflectance is observed with only a very small concentration of nanoshells. Characterizing the optical behavior of gold nanoshells in tissue will aid in developing nanoshells as contrast agents for optical diagnostics.
Metal nanoshells are a novel type of composite nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad wavelength region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) region where tissue transmissivity peaks. In addition, nanoshells offer other advantages over conventional organic dye imaging agents, including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. We first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.
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