Poor prognosis of cancers, including hepatocellular carcinoma (HCC), is mainly associated with metastasis; however, the underlying mechanisms remain poorly understood. This article investigates the role of lysyl oxidase-like 2 (LOXL-2) in the biology of HCC metastasis. First, we showed that HCC metastasis relies on a collagen-modifying enzyme, LOXL2, which was significantly overexpressed in tumorous tissues and sera of HCC patients, indicating that LOXL2 may be a good diagnostic marker for HCC patients. Second, we delineated a complex, interlinked signaling network that involves multiple regulators, including hypoxia, transforming growth factor beta (TGF-β), and microRNAs (miRNAs), converging to control the expression of LOXL2. We found not only that LOXL2 was regulated by hypoxia/hypoxia-inducible factor 1 alpha (HIF-1α), but also that TGF-β activated LOXL2 transcription through mothers against decapentaplegic homolog 4 (Smad4), whereas two frequently underexpressed miRNA families, miR-26 and miR-29, cooperatively suppressed LOXL2 transcription through interacting with the 3' untranslated region of LOXL2. Third, we demonstrated the imperative roles of LOXL2 in modifying the extracellular matrix components in the tumor microenvironment and metastatic niche of HCC. LOXL2 promoted intrahepatic metastasis by increasing tissue stiffness, thereby enhancing the cytoskeletal reorganization of HCC cells. Furthermore, LOXL2 facilitated extrahepatic metastasis by enhancing recruitment of bone-marrow–derived cells to the metastatic site. Conclusion : These findings integrate the clinical relevance, molecular regulation, and functional implications of LOXL2 in HCC metastasis. (Hepatology 2014;60:1645–1658)

BACKGROUND AND OBJECTIVE: To demonstrate the feasibility of using a 1,050-nm swept-source optical coherence tomography (SS-OCT) system to achieve noninvasive retinal vasculature imaging in human eyes. MATERIALS AND METHODS: Volumetric data sets were acquired using a 1-µm SS-OCT prototype that operated at a 100-kHz A-line rate. A scanning protocol designed to allow for motion contrast processing, referred to as OCT angiography or optical microangiography (OMAG), was used to scan an approximately 3 × 3–mm area in the central macular region of the retina within approximately 4.5 seconds. An intensity differentiation-based OMAG algorithm was used to extract three-dimensional retinal functional microvasculature information. RESULTS: Intensity signal differentiation generated capillary-level resolution en face OMAG images of the retina. The parafoveal capillaries were clearly visible, thereby allowing visualization of the foveal avascular zone in healthy subjects. CONCLUSION: The capability of OMAG to produce retinal vascular images was demonstrated using the 1-µm SS-OCT prototype. This technique has potential clinical value for studying retinal vasculature abnormalities. [ Ophthalmic Surg Lasers Imaging Retina. 2014;45:382–389.]

Optical coherence tomography (OCT)-based optical microangiography (OMAG) is a high-resolution, noninvasive imaging technique capable of providing three-dimensional in vivo blood flow visualization within microcirculatory tissue beds in the eye. Although the technique has demonstrated early clinical utility by imaging diseased eyes, its limited field of view (FOV) and the sensitivity to eye motion remain the two biggest challenges for the widespread clinical use of the technology. Here, we report the results of retinal OMAG imaging obtained from a Zeiss Cirrus 5000 spectral domain OCT system with motion tracking capability achieved by a line scan ophthalmoscope (LSO). The tracking LSO is able to guide the OCT scanning, which minimizes the effect of eye motion in the final results. We show that the tracking can effectively correct the motion artifacts and remove the discontinuities and distortions of vascular appearance due to microsaccade, leading to almost motion-free OMAG angiograms with good repeatability and reliability. Due to the robustness of the tracking LSO, we also show the montage scan protocol to provide unprecedented wide field retinal OMAG angiograms. We experimentally demonstrate a $12×16mm2$ retinal OMAG angiogram acquired from a volunteer, which is the widest FOV retinal vasculature imaging up to now in the community.

BACKGROUND AND OBJECTIVE: To evaluate the central macular microvascular network in patients with macular telangiectasia type 2 (MacTel2) using optical coherence tomography (OCT)-based microangiography (OMAG). PATIENTS AND METHODS: Prospective, observational study of patients with MacTel2 evaluated using a swept-source OCT (SS-OCT) prototype. OMAG was performed using a 3 mm × 3 mm central foveal raster scan. The algorithm segmented the retina into three layers. Microvascular distribution was depicted as en face images, and qualitative information was compared to fluorescein angiography (FA) images. RESULTS: OMAG detected abnormal microvasculature in all MacTel2 eyes, predominantly in the middle retinal layers with neovascularization in the outer retina. These vessels correlated well with the FA alterations. The abnormal temporal, juxtafoveal microvasculature in MacTel2 became apparent as the disease progressed and in later stages tended to extend circumferentially, with anastomotic vessels temporally. CONCLUSION: OMAG provided detailed, depth- resolved information about the perifoveal macular microvasculature in MacTel2. In most cases, images were better using OMAG than FA. The OMAG images demonstrated that most of the leakage seen on FA appeared to arise from the abnormal perifoveal microvasculature in the middle retinal layer. [ Ophthalmic Surg Lasers Imaging Retina . 2014; 45:369–380.]

A novel noncontact indentation system with the combination of an air jet and optical coherence tomography (OCT) was presented in this paper for the quantitative measurement of the mechanical properties of soft tissues. The key idea of this method is to use a pressure-controlled air jet as an indenter to compress the soft tissue in a noncontact way and utilize the OCT signals to extract the deformation induced. This indentation system provides measurement and mapping of tissue elasticity for small specimens with high scanning speed. Experiments were performed on 27 silicone tissue-mimicking phantoms with different Young’s moduli, which were also measured by uniaxial compression tests. The regression coefficient of the indentation force to the indentation depth (N mm−1) was used as an indicator of the stiffness of tissue under air jet indentation. Results showed that the stiffness coefficients measured by the current system correlated well with the corresponding Young’s moduli obtained by conventional mechanical testing (r = 0.89, p < 0.001). Preliminary in vivo tests also showed that the change of soft tissue stiffness with and without the contraction of the underlying muscles in the hand could be differentiated by the current measurement. This system may have broad applications in tissue assessment and characterization where alterations of mechanical properties are involved, in particular with the potential of noncontact micro-indentation for tissues.