Classification of squamous cell carcinoma from FF-OCT images: Data selection and progressive model construction.

We investigate the speed and performance of squamous cell carcinoma (SCC) classification from full-field optical coherence tomography (FF-OCT) images based on the convolutional neural network (CNN). Due to the unique characteristics of SCC features, the high variety of CNN, and the high volume of our 3D FF-OCT dataset, progressive model construction is a time-consuming process. To address the issue, we develop a training strategy for data selection that makes model training 16 times faster by exploiting the dependency between images and the knowledge of SCC feature distribution. The speedup makes progressive model construction computationally feasible. Our approach further refines the regularization, channel attention, and optimization mechanism of SCC classifier and improves the accuracy of SCC classification to 87.12% at the image level and 90.10% at the tomogram level. The results are obtained by testing the proposed approach on an FF-OCT dataset with over one million mouse skin images.

Dermal epidermal junction detection for full-field optical coherence tomography data of human skin by deep learning.

Full-field optical coherence tomography (FF-OCT) has been developed to obtain three-dimensional (3D) OCT data of human skin for early diagnosis of skin cancer. Detection of dermal epidermal junction (DEJ), where melanomas and basal cell carcinomas originate, is an essential step for skin cancer diagnosis. However, most existing DEJ detection methods consider each cross-sectional frame of the 3D OCT data independently, leaving the relationship between neighboring frames unexplored. In this paper, we exploit the continuity of 3D OCT data to enhance DEJ detection. In particular, we propose a method for noise reduction of the training data and a multi-directional convolutional neural network to predict the probability of epidermal pixels in the 3D OCT data, which is more stable than one-directional convolutional neural network for DEJ detection. Our crosscheck refinement method also exploits the domain knowledge to generate a smooth DEJ surface. The average mean error of the entire DEJ detection system is approximately 6 µm.

Detecting mouse squamous cell carcinoma from submicron full-field optical coherence tomography images by deep learning.

The standard medical practice for cancer diagnosis requires histopathology, which is an invasive and time-consuming procedure. Optical coherence tomography (OCT) is an alternative that is relatively fast, noninvasive, and able to capture three-dimensional structures of epithelial tissue. Unlike most previous OCT systems, which cannot capture crucial cellular-level information for squamous cell carcinoma (SCC) diagnosis, the full-field OCT (FF-OCT) technology used in this paper is able to produce images at sub-micron resolution and thereby facilitates the development of a deep learning algorithm for SCC detection. Experimental results show that the SCC detection algorithm can achieve a classification accuracy of 80% for mouse skin. Using the sub-micron FF-OCT imaging system, the proposed SCC detection algorithm has the potential for in-vivo applications.

Segmentation of nucleus and cytoplasm of a single cell in three-dimensional tomogram using optical coherence tomography.

A random rayburst sampling (RRBS) framework was developed to detect the nucleus and cell membrane boundaries in three-dimensional (3-D) space. Raw images were acquired through a full-field optical coherence tomography system with submicron resolution­i.e., 0.8 ?? ? m in lateral and 0.9 ?? ? m in axial directions. The near-isometric resolution enables 3-D segmentation of a nucleus and cell membrane for determining the volumetric nuclear-to-cytoplasmic (N/C) ratio of a single cell. The RRBS framework was insensitive to the selection of seeds and image pixel noise. The robustness of the RRBS framework was verified through the convergence of the N/C ratio searching algorithm. The relative standard deviation of the N/C ratio between different randomly selected seed sets was only 2%. This technique is useful for various in vitro assays on single-cell analyses.

Full-depth epidermis tomography using a Mirau-based full-field optical coherence tomography.

With a Gaussian-like broadband light source from high brightness Ce(3+):YAG single-clad crystal fiber, a full-field optical coherence tomography using a home-designed Mirau objective realized high quality images of in vivo and excised skin tissues. With a 40 × silicone-oil-immersion Mirau objective, the achieved spatial resolutions in axial and lateral directions were 0.9 and 0.51 µm, respectively. Such a high spatial resolution enables the separation of lamellar structure of the full epidermis in both the cross-sectional and en face planes. The number of layers of stratum corneum and its thickness were quantitatively measured. This label free and non-invasive optical probe could be useful for evaluating the water barrier of skin tissue in clinics. As a preliminary in vivo experiment, the blood vessel in dermis was also observed, and the flowing of the red blood cells and location of the melanocyte were traced.

Toward single-mode active crystal fibers for next-generation high-power fiber devices.

We report what we believe to be the first demonstration of a facile approach with controlled geometry for the production of crystal-core ceramic-clad hybrid fibers for scaling fiber devices to high average powers. The process consists of dip coating a solution of polycrystalline alumina onto a high-crystallinity 40-µm-diameter Ti:sapphire single-crystalline core followed by thermal treatments. Comparison of the measured refractive index with high-resolution transmission electron microscopy reveals that a Ca/Si-rich intragranular layer is precipitated at grain boundaries by impurity segregation and liquid-phase formation due to the relief of misfit strain energy in the Al2O3 matrix, slightly perturbing the refractive index and hence the optical properties. Additionally, electron backscatter diffractions supply further evidence that the Ti:sapphire single-crystalline core provides the template for growth into a sacrificial polycrystalline cladding, bringing the core and cladding into a direct bond. The thus-prepared doped crystal core with the undoped crystal cladding was achieved through the abnormal grain-growth process. The presented results provide a general guideline both for controlling crystal growth and for the performance of hybrid materials and provides insights into how one might design single-mode high-power crystal fiber devices.

Investigation of influences of the paraformaldehyde fixation and paraffin embedding removal process on refractive indices and scattering properties of epithelial cells.

The scattering properties and refractive indices (RI) of tissue are important parameters in tissue optics. These parameters can be determined from quantitative phase images of thin slices of tissue blocks. However, the changes in RI and structure of cells due to fixation and paraffin embedding might result in inaccuracies in the estimation of the scattering properties of tissue. In this study, three-dimensional RI distributions of cells were measured using digital holographic microtomography to obtain total scattering cross sections (TSCS) of the cells based on the first-order Born approximation. We investigated the slight loss of dry mass and drastic shrinkage of cells due to paraformaldehyde fixation and paraffin embedding removal processes. We propose a method to compensate for the correlated changes in volume and RI of cells. The results demonstrate that the TSCS of live cells can be estimated using restored cells. The percentage deviation of the TSCS between restored cells and live cells was only −8%. Spatially resolved RI and scattering coefficients of unprocessed oral epithelium ranged from 1.35 to 1.39 and from 100 to 450 cm−1, respectively, estimated from paraffinembedded oral epithelial tissue after restoration of RI and volume.

Simple and efficient defect-tailored fiber-based UV-VIS broadband white light generation.

We propose and demonstrate a facile approach for ultraviolet-visible broadband generation from a sapphire crystal core-borosilicate glass cladding hybrid fiber using a laser-heated pedestal growth technique. Considerable formation of F- and F(2)-type color emitters is effectively facilitated by Ti(4+) ions and Al(3+) vacancies, retaining efficient luminescence and high crystallinity of the sapphire core. These color centers intensify the ultraviolet, blue, and green emissions at 370, 450, and 540 nm, whereas the 650-nm red emission is contributed by Cr(3+) in the octahedral sites of the corundum structure. Over 1-mW white light with an optical-to-optical efficiency of up to nearly 5% and 1931 Commission International de l'Eclairage chromaticity coordinate of (0.287, 0.333) is achieved under 325-nm excitation.

Cell death detection by quantitative three-dimensional single-cell tomography.

Ultrahigh-resolution optical coherence tomography (UR-OCT) has been used for the first time to our knowledge to study single-cell basal cell carcinoma (BCC) in vitro. This noninvasive, in situ, label-free technique with deep imaging depth enables three-dimensional analysis of scattering properties of single cells with cellular spatial resolution. From three-dimensional UR-OCT imaging, live and dead BCC cells can be easily identified based on morphological observation. We developed a novel method to automatically extract characteristic parameters of a single cell from data volume, and quantitative comparison and parametric analysis were performed. The results demonstrate the capability of UR-OCT to detect cell death at the cellular level.

Infiltrating macrophage count: a significant predictor for the progression and prognosis of oral squamous cell carcinomas in Taiwan.

BACKGROUND: Infiltrating macrophage count (IMC) is found to correlate with the progression and prognosis of many human cancers. METHODS: This study used immunohistochemistry to measure the IMC (macrophages/high-power field [HPF]) in 92 specimens of oral squamous cell carcinoma (OSCC). RESULTS: A significantly increased IMC was found in OSCCs with larger tumor size, positive lymph node metastasis, more advanced clinical stages, or recurrence (all ps < .05). Kaplan-Meier survival analysis found that OSCC patients with IMC >196 macrophages/HPF had a significantly shorter disease-free (p = .001, log-rank test) or overall survival (p < .001, log-rank test) than OSCC patients with IMC <196 macrophages/HPF. Multivariate Cox regression analyses showed that IMC >196 macrophages/HPF was an independent predictor for poor disease-free (p = .005) and overall survival of patients with OSCC (p = .015). CONCLUSIONS: The IMC can predict the progression and prognosis of OSCCs in Taiwan.

Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction.

Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, and COX-2 expression in human BCC cells. TAMs also aggregate near COX-2 expressing BCC tumor nests. We hypothesize that TAMs might activate COX-2 in BCC cells and subsequently increase their invasion and angiogenesis. TAMs are a kind of M2 macrophage derived from macrophages exposed to Th2 cytokines. M2-polarized macrophages derived from peripheral blood monocytes were cocultured with BCC cells without direct contact. Coculture with the M2 macrophages induced COX-2-dependent invasion and angiogenesis of BCC cells. Human THP-1 cell line cells, after treated with phorbol myristate acetate (PMA), differentiated to macrophages with M2 functional profiles. Coculture with PMA-treated THP-1 macrophages induced COX-2-dependent release of matrix metalloproteinase-9 and subsequent increased invasion of BCC cells. Macrophages also induced COX-2-dependent secretion of basic fibroblast growth factor and vascular endothelial growth factor-A, and increased angiogenesis in BCC cells.

Prediction of heat-induced collagen shrinkage by use of second harmonic generation microscopy.

Collagen shrinkage associated with denaturation from thermal treatment has a number of important clinical applications. However, individualized treatment is hindered by the lack of reliable noninvasive methods to monitor the process of collagen denaturation. We investigate the serial changes of collagen denaturation from thermal treatment of rat tail tendons at 58 degrees C by use of second harmonic generation (SHG) microscopy. We find that rat tail tendon shrinks progressively from 0 to 9 min of thermal treatment, and remains unchanged in length upon further thermal treatment. The SHG intensity also decreases from 0 to 9 min of thermal treatment and becomes barely detectable from further thermal treatment. Collagen shrinkage and the SHG intensity are well correlated in a linear model. In addition, SHG imaging reveals a tiger-tail-like pattern of collagen denaturation. The bands of denatured collagen progressively widen from increased thermal treatment and completely replace the adjacent bands of normal collagen after 9 min of thermal treatment. Our results show that collagen denaturation in rat tail tendon from thermal treatment is inhomogeneous, and that SHG intensity can be used to predict the degree of thermally induced collagen shrinkage. With additional development, this approach has the potential to be used in biomedical applications.

Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis.

Cyclooxygenase-2 (COX-2) is critical for tumor formation, angiogenesis, metastasis, and prognosis. In this study, the role of COX-2 in antiapoptosis, tumorigenesis, and angiogenesis of human basal cell carcinoma (BCC) cells was investigated. Transfection of COX-2 constitutive expression vector into a BCC cell line yielded several overexpressing clones. All transfectants demonstrated remarkable resistance to ultraviolet B-induced apoptosis (confirmed by flow cytometry analysis, morphological change, and DNA fragmentation). Immunoblot analysis revealed marked increases in apoptosis-regulated genes Mcl-1 and Bcl-2. A 10-fold concentrated conditioned medium from COX-2-overexpressing BCC cells exhibited higher angiogenic activity in Matrigel plug and human umbilical vein endothelial cell tube formation assay. Cells exhibited increased levels of vascular endothelial growth factor-A (VEGF-A) mRNA and protein, and secreted VEGF-A and basic fibroblast growth factor (bFGF). COX-2-specific small interfering RNA markedly reduced the secreted species. After 7 weeks of inoculation, the tumor volume of COX-2-overexpressing cells in severe combined immunodeficient mice was significantly greater than that of vector control cells. Immunohistochemical analysis of CD31-positive vessels revealed a two-fold increase in microvessel density in COX-2 tumors, compared to control vector tumors. Our data indicate that Mcl-1 and Bcl-2, as well as VEGF-A and bFGF, are downstream effectors of COX-2-induced antiapoptosis and angiogenesis, respectively.

1,2-Ethanedithiol-induced erythema multiforme-like contact dermatitis.

Contact dermatitis simulating erythema multiforme can be caused by many allergens. The chemical agent 1,2-ethanedithiol, which serves as a protective group in chemical synthesis, has hitherto only been implicated as an irritant. We report on a 22-year-old female chemistry student who developed widespread erythema multiforme-like lesions after local contact with 1,2-ethanedithiol. Many target lesions were observed bilaterally on her hands, forearms, arms, and on her forehead. One such lesion was histologically compatible with erythema multiforme. The patient had a positive patch test to 1,2-ethanedithiol, whereas none of 30 healthy subjects showed a positive reaction. However, eight of the 30 controls (26.7%) developed irritant reactions to 1,2-ethanedithiol. Cautious handling of the compound is a prudent precaution.