Axial superresolution in optical coherence tomography (OCT) by a three-zone annular phase filter is demonstrated. In the proposed probe of a spectral domain OCT system, the width of the central lobe of the axial intensity point spread function is apodized by the filter to be within the coherence gate determined by the light source, while its sidelobes are lying outside the coherence gate without contributing to the coherence imaging. By measurement of the depth response of the OCT system before and after inserting the filter, an improvement of about 20% in axial resolution is confirmed. OCT imaging on biological sample of orange fresh is also conducted, demonstrating increased depth discrimination without the negative contribution from sidelobes realized by the phase filter in combination with the coherence gate intrinsic to OCT. It comes to a conclusion that we can obtain axial superresolution by filter in OCT system without the degrading influence of large sidelobes.

We have developed a noninvasive imaging method to quantify in vivo drug delivery pharmacokinetics without the need for blood or tissue collection to determine drug concentration. By combining the techniques of hyperspectral imaging and a dorsal skinfold window chamber, this method enabled the real-time monitoring of vascular transport and tissue deposition of nanoparticles labeled with near-infrared (NIR) dye. Using this imaging method, we quantified the delivery pharmacokinetics of the native high-density lipoprotein (HDL) and epidermal growth factor receptor (EGFR)-targeted HDL nanoparticles and demonstrated these HDLs had long circulation time in blood stream (half-life >12 h). These HDL nanoparticles could efficiently carry cargo DiR-BOA to extravasate from blood vessels, diffuse through extracellular matrix, and penetrate and be retained in the tumor site. The EGFR targeting specificity of EGFR-targeted HDL (EGFR-specific peptide conjugated HDL) was also visualized in vivo by competitive inhibition with excess EGFR-specific peptide. In summary, this imaging technology may help point the way toward the development of novel imaging-based pharmacokinetic assays for preclinical drugs and evaluation of drug delivery efficiency, providing a dynamic window into the development and application of novel drug delivery systems.

Published 9 October 2012 In conventional polarization-sensitive optical coherence tomography (PS-OCT), phase retardation is obtained by the amplitude of P and S polarization only, and the fast axis angle is obtained by the phase difference in P and S polarizations via Hilbert transformation. In this paper, we proposed a modified PS-OCT setup in which the phase retardation and fast axis angle are simply expressed as the function of the amplitude of P and S polarization and their differential signal. Due to the common-path feature between the two channels of P and S polarization, the fluctuation in the measurement of phase retardation and fast axis angle caused by excess noise and phase noise from the laser source can be reduced by the differential signal of P and S polarization via a modified balance detector. Thus, the signal of phase retardation and fast angle axis in the deep layer of a porcine sample can be improved.

A wide range of techniques has been developed to image biological samples at high spatial and temporal resolution. In this paper, we report recent results from deep-UV confocal fluorescence microscopy to image inherent emission from fluorophores such as tryptophan, and structured illumination microscopy (SIM) of biological materials. One motivation for developing deep-UV fluorescence imaging and SIM is to provide methods to complement our measurements in the emerging field of X-ray coherent diffractive imaging.

Real-time in vivo microscopic imaging has become a reality with the advent of confocal and nonlinear endomicroscopy. These devices are best utilized in conjunction with standard white light endoscopy. We evaluated the use of fluorescence endomicroscopy in detecting microscopic abnormalities in colonic tissues. Mice of C57bl/6 strain had intraperitoneal injection with azoxymethane once every week for five weeks and littermates, not exposed to azoxymethane served as controls. After 14 weeks, intestines were imaged by fluorescence endomicroscopy. The images show obvious cellular structural differences between those two groups of mice. The difference in endomicroscopy imaging can be used for identifying tissues suspicious for neoplasia or other changes, leading to early diagnosis of gastrointestinal track of cancer.

Metastasis is a very complicated multi-step process and accounts for the low survival rate of the cancerous patients. To metastasize, the malignant cells must detach from the primary tumor and migrate to secondary sites in the body through either blood or lymph circulation. Macrophages appear to be directly involved in tumor progression and metastasis. However, the role of macrophages in affecting cancer metastasis has not been fully elucidated. Here, we have utilized an emerging technique, namely in vivo flow cytometry (IVFC) to study the depletion kinetics of circulating prostate cancer cells in mice and determine how depletion of macrophages by the liposome-encapsulated clodronate affects the depletion kinetics. Our results show different depletion kinetics of PC-3 cells between the macrophage-deficient group and the control group. The number of circulating tumor cells (CTCs) in the macrophage-deficient group decreases in a slower manner compared to the control mice group. The differences in depletion kinetics indicate that the absence of macrophages facilitates the stay of prostate cancer cells in circulation. In addition, our imaging data suggest that macrophages might be able to arrest, phagocytose and digest PC-3 cells. Therefore, phagocytosis may mainly contribute to the depletion kinetic differences. The developed methods elaborated here would be useful to study the relationship between macrophages and tumor metastasis in small animal cancer models.

The development of experimental animal models for head and neck tumors generally rely on the bioluminescence imaging to achieve the dynamic monitoring of the tumor growth and metastasis due to the complicated anatomical structures. Since the bioluminescence imaging is largely affected by the intracellular luciferase expression level and external D-luciferin concentrations, its imaging accuracy requires further confirmation. Here, a new triple fusion reporter gene, which consists of a herpes simplex virus type 1 thymidine kinase (TK) gene for radioactive imaging, a far-red fluorescent protein (mLumin) gene for fluorescent imaging, and a firefly luciferase gene for bioluminescence imaging, was introduced for in vivo observation of the head and neck tumors through multi-modality imaging. Results show that fluorescence and bioluminescence signals from mLumin and luciferase, respectively, were clearly observed in tumor cells, and TK could activate suicide pathway of the cells in the presence of nucleotide analog-ganciclovir (GCV), demonstrating the effectiveness of individual functions of each gene. Moreover, subcutaneous and metastasis animal models for head and neck tumors using the fusion reporter gene-expressing cell lines were established, allowing multi-modality imaging in vivo. Together, the established tumor models of head and neck cancer based on the newly developed triple fusion reporter gene are ideal for monitoring tumor growth, assessing the drug therapeutic efficacy and verifying the effectiveness of new treatments.

The subtle color distinction is the important function of electronic endoscope imaging diagnosis. However, after image acquisition, transmission and display, color distortions of intracorporeal organs or tissues occur inevitably, which are adverse to analyze image features accurately or to diagnose early pathological changes. A real-time color correction algorithm based on fourneighborhood and polynomial regression in YUV color space is proposed. Based on polynomial regression the color correction matrix is calculated in YUV color space according to the differences between standard values of color checker and measured values of that imaged by the endoscope. As the correction is only executed on U and V components in YUV color space, the defect that the color of corrected images in RGB color space will change along with luminance can be avoided, and then the stability of image color is improved. Owing to four-neighborhood processing, the signal-to-noise ratio of corrected images is enhanced and the processing speed of correction algorithm is accelerated. The average color difference is reduced from 0.3944 to 0.2850 by application of the proposed algorithm in high-definition electronic endoscope. A total of 17 frames per second can be achieved at the resolution of 1280 × 800, and the color characteristics of the image after processing match that of human visual system.

Manual analysis of anterior segment optical coherence tomography (AS-OCT) images is fairly time consuming, and inter-observer reproducibility cannot be guaranteed. Therefore, automated analysis methods of AS-OCT images are necessary in clinical applications. This paper presents a novel approach to extract the inner contour of the anterior chamber automatically from AS-OCT images using a \divide-and-conquer" strategy. We first find the anchor points in an image and these points are used to divide the image into subimages where the iris, lens and cornea are located. Then the endothelial surface of the cornea, lens surface and iris surface are obtained from these subimages with different schemes, and they are merged together to obtain the complete inner contour. In our method, the endothelial surface of the cornea is fitted by using three circular arcs under continuity constraints. Experiments show that the proposed algorithm can extract the inner contour of the anterior chamber from AS-OCT images accurately in real time.