Polarization Sensitive Optical Coherence Tomography (PS-OCT) measures the intensity and polarization state of backscattered light to provide information about tissue structure, retardation and depolarization. Developing molecular contrast agents for PS-OCT could also provide physiological, cellular, and molecular information. In this study, we utilize the depolarization and spectral signature of anisotropic gold nanobipyramids (GNBPs) and demonstrate how the optical properties of these nanostructures can be used as contrast agents for PS-OCT in living tissue.
Polarization Sensitive Optical Coherence Tomography (PS-OCT) measures the polarization state of backscattered light and provides information regarding its retardation and depolarization caused by propagation through tissue microstructure. Developing molecular contrast agents could enhance the utility of OCT for physiological, cellular, and molecular imaging. In this study, we characterize for the first time the depolarization signature of gold nanobipyramids (GNBPs) and demonstrate how depolarization can be used to enhance Spectral Contrast OCT based detection of GNBPs for multiplexed contrast agent detection.
Developing suitable contrast agents is essential for multiplexed optical coherence tomography (OCT), which allows simultaneous imaging of different biomarkers, cells and flows in living subjects. However, few OCT contrast agents have shown multiplexing capability, especially in the second near infrared (NIR-II) window. Here we demonstrate that using gold nanobipyramds as OCT contrast agents, two separate lymph flows can be visualized simultaneously in a live mouse in the NIR-II window. We concurrently traced lymph flows draining from a melanoma tumor and peritumoral tissue upstream of the melanoma, showing these flows exhibit distinct drainage patterns and merge into the same lymph node.
KEYWORDS: Optical coherence tomography, Lymphatic system, Scattering, Gold, Nanoparticles, Capillaries, In vivo imaging, Multiplexing, Particles, RGB color model
The ability to detect multiple contrast agents simultaneously would greatly enhance Optical Coherence Tomography (OCT) images, providing nuanced biological context to physiological structures. However, previous OCT contrast agent work has been limited to scenarios where only a single contrast agent could be robustly detected within each voxel. We present a novel spectroscopic technique for de-mixing the spectral signal from multiple OCT contrast agents within a single voxel. We validate our technique in vitro and also demonstrate in vivo imaging of three spectrally distinct gold nanobipyramids, trafficking within the lymphatic system of a live mouse. This approach opens the door to a much broader range of pre-clinical and clinical OCT applications where multiplexed labeling is desirable.
Optical coherence tomography angiography (OCTA) is an important tool for investigating vascular networks and microcirculation in living tissue. Traditional OCTA detects blood vessels via intravascular dynamic scattering signals derived from the movements of red blood cells (RBCs). However, the low hematocrit and long latency between RBCs in capillaries make these OCTA signals discontinuous, leading to incomplete mapping of the vascular networks. OCTA imaging of microvascular circulation is particularly challenging in tumors due to the abnormally slow blood flow in angiogenic tumor vessels and strong attenuation of light by tumor tissue. Here we demonstrate in vivo that gold nanoprisms (GNPRs) can be used as OCT contrast agents working in the second near infrared window, significantly enhancing the dynamic scattering signals in microvessels and improving the sensitivity of OCTA in skin tissue and melanoma tumors in live mice. This is the first demonstration that nanoparticle-based OCT contrast agent works in vivo in the second near infrared window, which allows deeper imaging depth by OCT. With GNPRs as contrast agents, the post-injection OCT angiograms showed 41% and 59% more microvasculature than pre-injection angiograms in healthy mouse skin and melanoma tumors, respectively. By enabling better characterization of microvascular circulation in vivo, GNPR-enhanced OCTA could lead to better understanding of vascular functions during pathological conditions, more accurate measurements of therapeutic response, and improved patient prognoses.
Optical Coherence Tomography (OCT) imaging of living subjects offers millimeters depth of penetration into tissue while maintaining high spatial resolution. However, because most molecular biomarkers do not produce inherent OCT contrast signals, exogenous contrast agents must be employed to achieve molecular imaging. Here we demonstrate that microbeads (μBs) can be used as effective contrast agents to target cellular biomarkers in lymphatic vessels and can be detected by OCT using a phase variance algorithm. We applied this technique to image the molecular dynamics of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in vivo, which showed significant down-regulation during tissue inflammation.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.