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 makes 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 work 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, GNPRenhanced OCTA could lead to better understanding of vascular functions during pathological conditions, more accurate measurements of therapeutic response, and improved patient prognoses.
KEYWORDS:gold nanoprisms, optical coherence tomography angiography, microvessels, melanoma, in vivo imaging, second near infrared window, contrast agents All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/322545 doi: bioRxiv preprint first posted online May. 16, 2018; Real-time imaging of vascular networks and microcirculation in living tissue plays a crucial role in better understanding pathological conditions. 1 In particular, better characterization of tumor vasculature in vivo could provide significant prognostic value for cancer patients 2 and improved measurements of their therapeutic responses, 3-6 since tumor vessels are critical sites for drug delivery, angiogenic therapy, chemotherapy, and immunotherapy. 7 The variety of imaging tools currently available for in vivo angiography can mostly be classified into two categories: macroscopic and microscopic. Macroscopic imaging tools, such as computed tomography, positron emission tomography, ultrasound imaging, and magnetic resonance imaging, provide full body penetration but lack the spatial resolution to resolve small blood vessels in tissue.
8Microscopic imaging modalities, such as confocal and multiphoton microscopy, provide subcellular imaging resolution but have suboptimal tissue penetration depth and small fields of...