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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.

Weakly supervised conversion from in vivo OCT images on human skin to H&E-stain-like images is developed. The dermis-epidermis junction, stratum corneum boundary, and nuclei distribution match well between the OCT and converted H&E-stain-liked images.

The detection of skin cancers has been studied using the full-field optical coherence tomography. High-speed CMOS camera with high brightness light source were employed to achieve real-time imaging with cellular resolution for the detection of cellular atypia and structural derangement. Animal model on squamous cell carcinoma shows greater than 90% accuracy.

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.

Convolutional neural networks were applied to sub-micron-resolution optical coherence tomography images of the human skin for anatomical segmentation. The main layers of skin were discerned with an average 90% accuracy, which we believe to possess potential in the assessment of skin health.

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.

Summary Background Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. Objectives To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. Methods Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. Results PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 μg mL−1 recombinant human SLURP-1 protein. Conclusions Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.

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.

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.

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 resolution—i.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.

With silicone-oil-immersion Mirau objective utilizing high brightness Ce3+:YAG crystal fiber light source through multi-mode fiber, this system respectively images in vivo tomographic cellular structure of tissue and flowing pathway of red blood cell in dynamics.

Non-invasive, label free, and high-speed imaging of cells and tissues with sub-micron resolution could help unveil functions of living organisms, and facilitate early disease/cancer diagnosis. Single cell analyses and in-vivo epidermis/dermis evaluation are discussed.

Based on single-objective construction utilizing high brightness Ce3+:YAG single-clad crystal fiber light source, this Mirau-based full-field time-domain optical coherence tomography with circular polarization incident light represents deeper penetration in scattering medium. Using objective-changeable ability of home-designed Mirau objective, this system provides different applications, like biological tissue and single cells, by different spatial resolution with corresponding dynamics. High quality image relying on less ghost image and near common-path interference was demonstrated under this compact and power-stable system.

This study reports a facile approach for the emission of ultraviolet-visible broadband from a Ti:sapphire crystalline-core fiber, using a laser-heated pedestal growth technique. White light with CIE (0.287, 0.333) is obtained via the F-Ti centers.

Via Mirau-based full-field optical coherence tomography using Gaussian-like spectrum light source from Ce3+:YAG single-clad crystal fiber, melanocytes and keratinocytes are successfully classified with their shape dissimilarity and nucleus-cytoplasm ratio from epidermal primary cell culture.

Non-invasive single cell tomography on keratinocyte and fiberblast were demonstrated in-vitro using a crystalline fiber based broadband light source at visible wavelength. Nuclear-cytoplasmic ratio and other characteristic parameters of single cell were extracted and analyzed.

We report using ultrahigh-resolution optical coherence tomography for distinguishing keratinocytes and fibroblasts at the single-cell level. Linear discriminant analysis based on characteristic parameters extracted from volume data was applied for the prediction of cell types.

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.

In a hospital, a medical summary is indispensable for both a clinician and a patient. However, it is written in English in some non-English native countries and becomes a barrier for a patient to read. In this paper we propose a framework for rapid acquisition of bilingual medical summaries using machine translation (MT) techniques. We describe a medical summary corpus and some terminological databases prepared for the framework. We then touch on the challenging issues of MT adapted from generic to specific domains, and propose a pattern translation scheme to achieve domain adaptation based on a background statistical MT system. We identify the significant patterns to capture the specific writing styles in a medical summary. The patterns are then translated with the involvements of doctors. Our major concern is to reduce the cost of translation and better allocate the efforts made by the domain experts. The experimental results show the proposed methods are effective in terms of the significance and diversity of the patterns. The approaches to integrate the mined patterns into background MT are also discussed.

Single-cell imaging by ultrahigh-resolution optical coherence tomography was demonstrated for the first time to our knowledge. Three-dimensional volume data analysis was applied to identify controlled samples of apoptotic and normal basal cell carcinoma cell lines.

Broadband emissions centered at 560 nm, 770 nm, and 1380 nm from glass-clad crystal fibers with 3-dB bandwidths of 98, 180, and 240 nm were used for various biomedical and in-vivo optical tomography applications with cellular resolution. The adjacent image pixel cross talks are less than −20 dB due to the near Gaussian spectral shapes of the broadband emissions.

Infiltrating macrophage count (IMC) is found to correlate with the progression and prognosis of many human cancers.This study used immunohistochemistry to measure the IMC (macrophages/high-power field [HPF]) in 92 specimens of oral squamous cell carcinoma (OSCC).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 IMC196 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 IMC196 macrophages/HPF. Multivariate Cox regression analyses showed that IMC196 macrophages/HPF was an independent predictor for poor disease-free (p = .005) and overall survival of patients with OSCC (p = .015).The IMC can predict the progression and prognosis of OSCCs in Taiwan.

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.

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.

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 paraffin-embedded oral epithelial tissue after restoration of RI and volume.

Auteur(s) : Cheng-Han Lee1, Hsing-Chuan Lee1, Chia-Fang Lu2,3, Cheng-Hsiang Hsiao4, Shiou-Hwa Jee1, Jeng-Wei Tjiu1 1Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan 2Department of Periodontics, Chang-Gung Memorial Hospital, Taipei, Taiwan 3Graduate Institute of Dental and Craniofacial Science, Chang-Gung University, Taoyuan, Taiwan 4Departments of Pathology, [...]

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.

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.

Blastic natural killer (NK)-cell lymphoma is a clinically aggressive hemato-logic neoplasm with a high incidence of cutaneous involvement. We report a 19-year-old man who presented with asymptomatic, erythematous, infiltrated bean plaques and nodules of various sizes, scattered over the face, trunk and extremities. A skin biopsy specimen revealed diffuse dermal infiltration of medium-sized pleomorphic cells with a blastic appearance. Immunohistochemical studies showed that the tumor cells were positive for CD56, CD43, CD123, and terminal deoxynucleotidyl trans-ferase (TdT). The neoplastic cells were negative for B-cell, T-cell, and myeloid cell markers. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) gave a negative result. Flow cytometric analysis of bone marrow aspirate demonstrated a CD56 positive population of blastic cells. A diagnosis of blastic NK-cell lymphoma was made and the skin lesions regressed after treatment with L-asparaginase-based chemotherapy (L-asparaginase, cyclophosphamide, etoposide). The skin lesions regressed after two sessions of chemotherapy.