A Spectral Demixing Model for Triplex In Vivo Imaging of Optical Coherence Tomography Contrast Agents

Abstract

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 demixing 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.

Gold nanomaterials for optical biosensing and bioimaging

“…Due to their highly tunable plasmonic resonances and scattering coefficient, AuNPs of different shapes and dimensions have been extensively investigated as OCT contrast agents in recent years. AuNSh, 5-10 AuNR, 3,4,[68][69][70][71][72][73][74] AuNSt, 75 AuNC, [20][21][22] AuNRg, 26,28 AuND, 21,22 AuNPr 14,15,76,77 and AuNBP 18,19 have been demonstrated to be promising contrast agents to improve OCT signals in tissue and blood vessels (Table 1). Among them, AuNSt, AuNC and AuND have plasmonic resonance peaks mainly in the rst near infrared window (NIR-I, 700-1000 nm) so they are used as contrast agents for OCT with a light source in the NIR-I region; while AuNR, AuNSh, AuNRg, AuNPr and AuNBP can be employed as OCT contrast agents in both NIR-I and NIR-II windows.…”

“…By engineering the shape and size of AuNPs, one can tune many optical properties of AuNPs including localized surface plasmon resonance (LSPR), ratio between light absorption and scattering coefficients, surface enhanced Raman scattering (SERS), uorescence, etc. To date, researchers have fabricated dozens of Au nanostructures, including nanospheres (AuNS), 1 nanorods (AuNR), [2][3][4] nanoshells (AuNSh), [5][6][7][8][9][10][11][12] nanoprisms (AuNPr), [13][14][15] nanopyramids (AuNPy), 16 nanobipyramids (AuNBP), [17][18][19] nanocages (AuNC), [20][21][22][23][24][25] nanorings (AuNRg), [26][27][28][29] nanodisks (AuND), 22,30 nanostars (AuNSt), 31,32 nanorice, 33 nanobowls, 34 nanocrescents (AuNCr), 35,36 etc. (Fig.…”

Multiple forward scattering reduces the measured scattering coefficient of blood in visible-light optical coherence tomography

“…We systemically investigated measuring optical scattering properties of blood detected by vis-OCT. First, we performed Monte Carlo (MC) simulations of a retinal blood vessel and photon detection by vis-OCT. MC simulation is not susceptible to systemic biases present in practical OCT detection or image reconstruction [37][38][39] and, therefore, provides a fundamental understanding of light-tissue interaction. For each photon packet exiting the tissue, we monitored the number of scattering events and optical pathlength traveled in tissue to investigate the impact of multiple scattering on the vis-OCT signal.…”

Adaptive spectroscopic visible-light optical coherence tomography for human retinal oximetry

“…Recently, we showed how SDR (27) and SDBG (28) contaminate spectroscopic measurements of ex vivo blood samples and in vivo humans, respectively, in vis-OCT. LCA (illustrated by the axial displacements of green, yellow, and red wavelengths in the scanning beam in Fig. 1) has also been considered a contaminant for structural and spectroscopic OCT (29)(30)(31). Please also refer to Supplementary Materials -Accounting for LCA.…”