Abstract
Optical Coherence Tomography (OCT) enables real-time imaging of living tissues at cell-scale resolution over millimeters in three dimensions. Despite these advantages, functional biological studies with OCT have been limited by a lack of exogenous contrast agents that can be distinguished from tissue. Here we report an approach to functional OCT imaging that implements custom algorithms to spectrally identify unique contrast agents: large gold nanorods (LGNRs). LGNRs exhibit 110-fold greater spectral signal per particle than conventional GNRs, which enables detection of individual LGNRs in water and concentrations as low as 250 pM in the circulation of living mice. This translates to ~40 particles per imaging voxel in vivo. Unlike previous implementations of OCT spectral detection, the methods described herein adaptively compensate for depth and processing artifacts on a per sample basis. Collectively, these methods enable high-quality noninvasive contrast-enhanced imaging of OCT in living subjects, including detection of tumor microvasculature at twice the depth achievable with conventional OCT. Additionally, multiplexed detection of spectrally-distinct LGNRs was demonstrated to observe discrete patterns of lymphatic drainage and identify individual lymphangions and lymphatic valve functional states. These capabilities provide a powerful platform for molecular imaging and characterization of tissue noninvasively at cellular resolution, called MOZART.
Highlights
Modality for molecular imaging is to achieve signal from exogenous agents that can overcome the intrinsic signal of living tissues
MOZART is based on a spectral domain OCT (SD-OCT) with a broad superluminescent diode (SLD) source and a spectrometer imaging at wavelengths from 800–1000 nm
We enhanced the contrast of this Spectral Domain OCT (SD-OCT) by using larger GNRs (LGNRs) with tuned resonance peaks and post-processing algorithms that were tailored to detect LGNRs in living tissue
Summary
Modality for molecular imaging is to achieve signal from exogenous agents that can overcome the intrinsic signal of living tissues. Larger GNRs with greatly enhanced scattering cross-sections[17,18] could potentially achieve the signal-to-background ratio necessary to realize the advantages of OCT with molecular contrast. Such particles have only recently been explored for biological applications, such as mapping constrained diffusion in 3D cell culture[19]. We demonstrate functional imaging with contrast-enhanced OCT in vivo To achieve this goal, we implemented large GNRs (~100 × 30 nm, called LGNRs) that were adapted for biological use as OCT contrast agents as recently reported[20]. Based on its current capabilities, our contrast-enhanced OCT method, which we call MOZART, provides an ideal platform for in vivo targeted molecular imaging studies
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