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) is a powerful biomedical imaging technology that relies on the coherent detection of backscattered light to image tissue morphology in vivo. As a consequence, OCT is susceptible to coherent noise, known as speckle noise, which imposes significant limitations on its diagnostic capabilities. Here we show Speckle- Modulating OCT (SM-OCT), a method based purely on light manipulation, which can remove speckle noise, including noise originating from sample multiple back-scattering. SM-OCT accomplishes this by creating and averaging an unlimited number of scans with uncorrelated speckle patterns, without compromising spatial resolution. The uncorrelated speckle patterns are created by scrambling the phase of the light with sub-resolution features using a moving ground-glass diffuser in the optical path of the sample arm. This method can be implemented in existing OCTs as a relatively low-cost add-on. SM-OCT speckle statistics follow the expected decrease in speckle contrast as the number of averaged scans increases. Within a scattering phantom, SM-OCT provides a 2.5-fold increase in effective resolution compared to conventional OCT. Using SM-OCT, we reveal small structures in the tissues of living animals, such as the inner stromal structure of a live mouse cornea, the fine structures inside the mouse pinna, and sweat ducts and Meissner’s corpuscle in the human fingertip skin – features that are otherwise obscured by speckle noise when using conventional OCT or OCT with current state of the art speckle reduction methods. Our results indicate that SM-OCT has the potential to improve the current diagnostic and intra-operative capabilities of OCT.
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) <i>in vivo</i>, which showed significant down-regulation during tissue inflammation.