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The feasibility of identifying cancer cells by measuring the refractive index (RI) distribution across a single live cell with ultrahigh resolution full-field optical coherence microscopy (FF-OCM) is presented. The FF-OCM is utilized to quantify integral RI distributions of unmodified cells without any cell treatments and used as a biophysical indicator for diagnosing cell malignancy. Firstly, the physical thickness distribution of the cell adherent to a culture dish is measured by taking a series of 0.6 µm resolved en-face tomograms. Subsequently, from the en-face image of the bottom surface of the cell or the top surface of the dish, the phase gain image of the cell is extracted. Then, from these two measurements the axially averaged RI map of the cell is extracted. The implemented FF-OCM system had a 0.8 µm axial resolution and the phase measurement sensitivity of the system was around 124 mrad. With the system, RI maps of several living cell lines of normal and cancer cells were constructed and quantitatively analyzed. The experiments showed that cancer cells had higher RI than normal ones. This approach using the FF-OCM has significant potential for cancer diagnosis and dynamic cell analysis as in situ label-free biophysical assay.

Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats’ eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.

Background and Objective Acne is a common skin disease that often leads to scarring. Collagen and other tissue damage from the inflammation of acne give rise to permanent skin texture and microvascular changes. In this study, we demonstrate the capabilities of optical coherence tomography based microangiography in detecting high-resolution, three-dimensional structural and microvascular features of in vivo human facial skin during acne lesion initiation and scar development. Materials and Methods A real time swept source optical coherence tomography system is used in this study to acquire volumetric images of human skin. The system operates on a central wavelength of 1310 nm with an A-line rate of 100 kHz, and with an extended imaging range (~12 mm in air). The system uses a handheld imaging probe to image acne lesion on a facial skin of a volunteer. We utilize optical microangiography (OMAG) technique to evaluate the changes in microvasculature and tissue structure. Results Thanks to the high sensitivity of OMAG, we are able to image microvasculature up to capillary level and visualize the remodeled vessels around the acne lesion. Moreover, vascular density change derived from OMAG measurement is provided as an alternative biomarker for the assessment of human skin diseases. In contrast to other techniques like histology or microscopy, our technique made it possible to image 3D tissue structure and microvasculature up to 1.5 mm depth in vivo without the need of exogenous contrast agents. Conclusion The presented results are promising to facilitate clinical trials aiming to treat acne lesion scarring, as well as other prevalent skin diseases, by detecting cutaneous blood flow and structural changes within human skin in vivo.

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.

Optical microangiography (OMAG) is a powerful optical angiographic tool to visualize micro-vascular flow in vivo. Despite numerous demonstrations for the past several years of the qualitative relationship between OMAG and flow, no convincing quantitative relationship has been proven. In this paper, we attempt to quantitatively correlate the OMAG signal with flow. Specifically, we develop a simplified analytical model of the complex OMAG, suggesting that the OMAG signal is a product of the number of particles in an imaging voxel and the decorrelation of OCT (optical coherence tomography) signal, determined by flow velocity, interframe time interval, and wavelength of the light source. Numerical simulation with the proposed model reveals that if the OCT amplitudes are correlated, the OMAG signal is related to a total number of particles across the imaging voxel cross-section per unit time (flux); otherwise it would be saturated but its strength is proportional to the number of particles in the imaging voxel (concentration). The relationship is validated using microfluidic flow phantoms with various preset flow metrics. This work suggests OMAG is a promising quantitative tool for the assessment of vascular flow. Chen, and R. K. Wang, "Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography," J. Biomed. Opt. 21(6), 065002 (2016). 42. Z. Chu, J. Lin, C. Gao, C. Xin, Q. Zhang, C. L. Chen, L. Roisman, G. Gregori, P. J. Rosenfeld, and R. K. Wang, "Quantitative assessment of the retinal microvasculature using optical coherence tomography angiography," J.

Normal aging is associated with significant alterations in brain's vascular structure and function, which can lead to compromised cerebral circulation and increased risk of neurodegeneration. The in vivo examination of cerebral blood flow (CBF), including capillary beds, in aging brains with sufficient spatial detail remains challenging with current imaging modalities. In the present study, we use 3-dimensional (3-D) quantitative optical coherence tomography angiography (OCTA) to examine characteristic differences of the cerebral vasculatures and hemodynamics at the somatosensory cortex between old (16 months old) and young mice (2 months old) in vivo. The quantitative metrics include cortical vascular morphology, CBF, and capillary flow velocity. We show that compared with young mice, the pial arterial tortuosity increases by 14%, the capillary vessel density decreases by 15%, and the CBF reduces by 33% in the old mice. Most importantly, changes in capillary velocity and heterogeneity with aging are quantified for the first time with sufficiently high statistical power between young and old populations, with a 21% (p < 0.05) increase in capillary mean velocity and 19% (p ≤ 0.05) increase in velocity heterogeneity in the latter. Our findings through noninvasive imaging are in line with previous studies of vascular structure modification with aging, with additional quantitative assessment in capillary velocity enabled by advanced OCTA algorithms on a single imaging platform. The results offer OCTA as a promising neuroimaging tool to study vascular aging, which may shed new light on the investigations of vascular factors contributing to the pathophysiology of age-related neurodegenerative disorders.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. Although the increasing numbers of cases and deaths is of great concern, an effective treatment strategy for SFTS has not been established. We present the cases of two patients with rapidly progressing SFTS who were successfully treated with plasma exchange and ribavirin.