In this paper, we propose eigendecposition- (ED-) based clutter filtering technique for 3D optical imaging of blood flow. Due to its best mean square approximation of the clutter, eigen-regression filters can theoretically provide maximum clutter suppression. Compared to the existing clutter rejection techniques in the literature used for optical imaging of blood flow, ED-based clutter filtering is less sensitive to tissue motion and can efficiently suppress the clutter while preserving the flow information. Therefore, it creates images with better contrast in the presence of bulk motion. The performance of the proposed ED-based technique is compared with that of phase compensation method and static high-pass filtering. The quantitative and qualitative performances are compared with each other in phantom studies and in vivo imaging, respectively. Also, 3D image of microvascular structures in mouse ear is presented where the clutter has been suppressed with ED-based technique. This technique can be used in applications where involuntary movements due to cardiac and respiratory cycles are inevitable (such as retinal imaging).

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.

Abstract. Optical microangiography based on optical coherence tomography (OCT) is prone to noise that arises from a static tissue region. Here, we propose a method that can significantly reduce this noise. The method is developed based on an approach that uses the magnitude information of OCT signals to produce tissue microangiograms, especially suitable for the case where a swept-source OCT system is deployed. By combined use of two existing OCT microangiography methods-ultrahigh-sensitive optical microangiography (UHS-OMAG) and correlation mapping OCT (cmOCT)-the final tissue microangiogram is generated by masking UHS-OMAG image using the binary representation of cmOCT image. We find that this process masks the residual static artifacts while preserving the vessel structures. The noise rejection capability of the masked approach (termed as mOMAG) is tested on a tissue-like flow phantom as well as an in vivo human skin tissue. Compared to UHS-OMAG and cmOCT, we demonstrate that the proposed method is capable of achieving improved signal-to-noise ratio in providing microcirculation images. Finally, we show its clinical potential by quantitatively assessing the vascular difference between a burn scar and a normal skin of human subject in vivo. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

The proton-acoustic process was simulated using a realistic model and the minimal detection limit was established for proton-acoustic range validation. These limits correspond to a best case scenario with a single large detector with no losses and detector thermal noise as the sensitivity limiting factor. Our study indicated practical proton-acoustic range verification may be feasible with approximately 5 × 10(6) protons/pulse and beam current.

Lymphatic vessels are a part of the circulatory system that collect plasma and other substances that have leaked from the capillaries into interstitial fluid (lymph) and transport lymph back to the circulatory system. Since lymph is transparent, lymphatic vessels appear as dark hallow vessel-like regions in optical coherence tomography (OCT) cross sectional images. We propose an automatic method to segment lymphatic vessel lumen from OCT structural cross sections using eigenvalues of Hessian filters. Compared to the existing method based on intensity threshold, Hessian filters are more selective on vessel shape and less sensitive to intensity variations and noise. Using this segmentation technique along with optical micro-angiography allows label-free noninvasive simultaneous visualization of blood and lymphatic vessels in vivo. Lymphatic vessels play an important role in cancer, immune system response, inflammatory disease, wound healing and tissue regeneration. Development of imaging techniques and visualization tools for lymphatic vessels is valuable in understanding the mechanisms and studying therapeutic methods in related disease and tissue response.

Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies.

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In this paper, we propose a super-resolution spectral estimation technique to quantify microvascular hemodynamics using optical microangiography (OMAG) based on optical coherence tomography (OCT). The proposed OMAG technique uses both amplitude and phase information of the OCT signals which makes it sensitive to the axial and transverse flows. The scanning protocol for the proposed method is identical to three-dimensional ultrahigh sensitive OMAG, and is applicable for in vivo measurements. In contrast to the existing capillary flow quantification methods, the proposed method is less sensitive to tissue motion and does not have aliasing problems due fast flow within large blood vessels. This method is analogous to power Doppler in ultrasonography and estimates the number of red blood cells passing through the beam as opposed to the velocity of the particles. The technique is tested both qualitatively and quantitatively by using OMAG to image microcirculation within mouse ear flap in vivo.