In vivo imaging of nanoparticle delivery and tumor microvasculature with multimodal optical coherence tomography

Abstract

Current imaging techniques capable of tracking nanoparticles in vivo supply either a large field of view or cellular resolution, but not both. Here, we demonstrate a multimodality imaging platform of optical coherence tomography (OCT) techniques for high resolution, wide field of view in vivo imaging of nanoparticles. This platform includes the first in vivo images of nanoparticle pharmacokinetics acquired with photothermal OCT (PTOCT), along with overlaying images of microvascular and tissue morphology. Gold nanorods (51.8 ± 8.1 nm by 15.2 ± 3.3 nm) were intravenously injected into mice, and their accumulation into mammary tumors was non-invasively imaged in vivo in three dimensions over 24 hours using PTOCT. Spatial frequency analysis of PTOCT images indicated that gold nanorods reached peak distribution throughout the tumors by 16 hours, and remained well-dispersed up to 24 hours post-injection. In contrast, the overall accumulation of gold nanorods within the tumors peaked around 16 hours post-injection. The accumulation of gold nanorods within the tumors was validated post-mortem with multiphoton microscopy. This shows the utility of PTOCT as part of a powerful multimodality imaging platform for the development of nanomedicines and drug delivery technologies.

Depth-resolved analytical model and correction algorithm for photothermal optical coherence tomography

“…The mouse was imaged again 17h post-injection with PT-OCT while under anesthesia (isofluorane mixed with air, 1.5-2%). The full protocol, including AuNRs synthesis and surgical procedure is described in detail in [12]. For this experiment, the photothermal laser was set to λ PT = 740 nm, with 70 mW of power at the sample.…”

“…This causes a local variation in optical path length that is then detected by a phase-sensitive OCT system. PT-OCT thus offers similar sources of contrast as photoacoustic imaging, while allowing multiplexing with other functional OCT modalities (such as speckle variance OCT [12]). Additionally this method does not require the instrument to be in contact with the sample.…”

“…PT-OCT has been demonstrated in vitro [10], ex vivo [13] and in vivo [14] on a multitude of contrast agents, such as gold nanospheres [10], gold nanoshells [13,15], gold nanorods [12,14,16, 17], carbon nanotubes [18], indocyanine green [19,20] and blood [21,22]. However, PT-OCT images are still affected by two artifacts: phase-accumulation (signal becoming brighter with depth) and shadowing below high intensity regions.…”

Photothermal Behaviors of Flowing Media Caused by Localized Surface Plasmon Resonance of Au Nanorings

“…By extracting the oscillating phase information of OCT signal at the laser modulation frequency, the distributions of metal NPs and their linked subjects in a background medium can be identified. Such an OCT technique is usually named as photothermal (PT) OCT [6][7][8][9][10][11][12][13][14][15].…”

“…A widely developed example is the detection of cancer cells in a tissue through the linkage of bioconjugated Au NPs. The widely used Au NPs include Au sphere-like NP [7,9,11], nanorod [6,[12][13][14], nanoshell [8], nanocage [10], etc. However, the LSPR wavelengths of those Au NPs are usually shorter than 900 nm such that they can be used only for OCT scan around 800 nm in operation wavelength.…”