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.
Optical coherence tomography (OCT) has emerged as a powerful imaging tool for a variety of biomedical applications. Methods to enhance contrast in OCT images, including gold nanoshells, have been explored recently. Gold nanoshells are a novel type of nanoparticle composed of a silica core and a thin gold shell. By varying the relative dimensions of core and shell, the optical resonance of these nanoshells can be precisely and systematically varied over a broad wavelength region ranging from the near-UV to the mid-infrared. For this study, we designed and constructed nanoshells expected to have low absorption and high scattering for OCT at 1310 nm. We then conducted measurements to elucidate the effects of nanoshell core and shell size, nanoshell concentration, and tissue scattering coefficient on OCT image enhancement (i.e. intensity gain) by nanoshells. These measurements were performed with nanoshells suspended in water and in a variety of tissue phantoms. Increasing nanoshell core and shell size tends to increase the calculated backscattering coefficient, and thus increases OCT intensities by 2-7 dB in a tissue phantom with a biologically relevant scattering coefficient. Increasing nanoshell concentration also increases OCT intensities, however a minimum of 10<sup>9</sup> nanoshells/mL is needed for appreciable enhancement in the tissue phantom. The intensity gain from one size of nanoshells varies between 5 and 9 dB depending on the scattering coefficient, with intensity gains decreasing as scattering increases. These results provide the first quantitative measurements of the effects of nanoshells to enhance OCT imaging at 1310 nm.
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.
Currently, separate diagnostic and therapeutic modalities are required for the diagnosis and treatment of cancer. In many cases, the present standard of care requires invasive surgical procedures and/or other treatments associated with significant side effect profiles, high cost, and poor clinical outcome. A single technology with dual diagnostic/therapeutic capabilities would potentially yield significant savings in the time and cost associated with diagnosing and treating many cancers. In this paper, we discuss gold nanoshell bioconjugates and their role in the development of an integrated cancer imaging and therapy application. Nanoshells are a novel class of nanomaterials that have unique properties including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. Here, we describe the development of an integrated cancer imaging and therapy application using near-infrared (NIR) gold nanoshell bioconjugates.