Glutathione Protects the Developing Heart from Defects and Global DNA Hypomethylation Induced by Prenatal Alcohol Exposure.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C2 H5 OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant." METHODS/RESULTS: Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts. CONCLUSIONS: GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.

How histological features of basal cell carcinomas influence image quality in optical coherence tomography.

Optical coherence tomography (OCT) has the potential to diagnose and measure the depth of nonmelanoma skin cancer (NMSC) in skin, but some lesions appear blurred in OCT images. The aim of this study is to identify histological characteristics of basal cell carcinomas (BCC) that correlate with good quality OCT images of the same lesions. A total of 34 patients with BCC were OCT scanned. The influence of histology parameters (e.g. inflammation, sun damage of skin, carcinoma cell size) on OCT image quality was studied by comparing 15 BCC lesions easily identified compared to 19 BCC lesions that produced only blurred in OCT images. Inflammation was more pronounced in blurred OCT images, whereas solar elastosis dominated in easily identified lesions. Hyperkeratosis did not impair imaging significantly. OCT image quality of BCC may depend on specific histology parameters.

Improved quality of optical coherence tomography imaging of basal cell carcinomas using speckle reduction.

BACKGROUND: Optical coherence tomography (OCT) is a possible imaging method for delineation of non-melanoma skin cancer. Speckle noise is the dominant noise contribution in OCT images; it limits the ability to identify cellular structures especially skin cancer. QUESTIONS ADDRESSED: This report suggests a method for improving OCT image quality for skin cancer imaging. EXPERIMENTAL DESIGN: OCT is an optical imaging method analogous to ultrasound. Two basal cell carcinomas (BCC) were imaged using an OCT speckle reduction technique (SR-OCT) based on repeated scanning by altering the distance between the probe and the surface of the skin. RESULTS: SR-OCT resulted in improved visualisation and more accurate thickness measurements in BCC lesions. CONCLUSION: This OCT speckle reduction method led to improved visualisation and better defined delineations in two BCC lesions. Thus, OCT was improved to a clinically relevant level when imaging BCC lesions.

Optical coherence tomography imaging of psoriasis vulgaris: correlation with histology and disease severity.

Epidermal thickness (ET) has been suggested as a surrogate measure of psoriasis severity. Optical coherence tomography (OCT) is a recent imaging technology that provides real-time skin images to a depth of 1.8 mm with a micrometre resolution. OCT may provide an accurate in vivo measure of ET. It is, therefore, speculated that OCT may be used in the assessment of psoriasis vulgaris. A total of 23 patients with psoriasis vulgaris were systematically evaluated by OCT imaging and skin biopsy during treatment. Biopsies were graded for disease severity, and additional evaluation was done by the physician via psoriasis area and severity index (PASI) score, and by the patient through measures such as self-administered PASI, psoriasis life stress inventory index and dermatology life quality index. ET was calculated from OCT images. In comparison to normal skin, psoriasis appeared with a more irregular surface with a stronger entrance signal, a serrated dermo-epidermal junction was found and a less signal intensity in the dermis as shown in OCT images. ET measured in untreated plaques was thicker reflecting epidermal hyperproliferation and inflammation. The changes were significantly correlated with the biopsy grading (r (2) = 0.41, p = 0.001) and ET significantly decreased with treatment (p = 0.0001). ET correlated significantly with self-reported measures of disease severity, but not with physician-assessed global PASI. The data suggest that OCT may be used to measure ET in psoriasis and the measurements correlate with several other parameters of disease severity. This implies that OCT assessment of psoriatic plaques may provide a useful method for non-invasive in vivo method to follow the evolution of psoriasis lesions.

OCT imaging of skin cancer and other dermatological diseases.

Optical coherence tomography (OCT) provides clinicians and researchers with micrometer-resolution, in vivo, cross-sectional images of human skin up to several millimeter depth. This review of OCT imaging applied within dermatology covers the application of OCT to normal skin, and reports on a large number of applications in the fields of non-melanoma skin cancer, malignant melanomas, psoriasis and dermatitis, infestations, bullous skin diseases, tattoos, nails, haemangiomas, and other skin diseases.

Assessment of optical coherence tomography imaging in the diagnosis of non-melanoma skin cancer and benign lesions versus normal skin: observer-blinded evaluation by dermatologists and pathologists.

BACKGROUND: Optical coherence tomography (OCT) is an optical imaging technique that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES: To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell carcinoma (BCC) and in benign lesions and to assess the diagnostic accuracy of OCT in differentiating NMSC from benign lesions and normal skin. METHODS AND MATERIALS: OCT and polarization-sensitive (PS) OCT from 104 patients were studied. Observer-blinded evaluation of OCT images from 64 BCCs, 1 baso-squamous carcinoma, 39 AKs, two malignant melanomas, nine benign lesions, and 105 OCT images from perilesional skin was performed; 50 OCT images of NMSC and 50 PS-OCT images of normal skin were evaluated twice. RESULTS: Sensitivity was 79% to 94% and specificity 85% to 96% in differentiating normal skin from lesions. Important features were absence of well-defined layering in OCT and PS-OCT images and dark lobules in BCC. Discrimination of AK from BCC had an error rate of 50% to 52%. CONCLUSION: OCT features in NMSC are identified, but AK and BCC cannot be differentiated. OCT diagnosis is less accurate than clinical diagnosis, but high accuracy in distinguishing lesions from normal skin, crucial for delineating tumor borders, was obtained.

Morphology and epidermal thickness of normal skin imaged by optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is an optical imaging technology with a potential in the non-invasive diagnosis of skin cancer. To identify skin pathologies using OCT, it is of prime importance to establish baseline morphological features of normal skin. AIMS: The aim of this study is to describe normal skin morphology using OCT and polarization-sensitive OCT (PS-OCT), which is a way of representing birefringent tissue such as collagen in OCT images. Anatomical locations in 20 healthy volunteers were imaged, and epidermal thickness (ET) was measured and compared to age, gender and skin colour. METHODS: OCT imaging is based on infrared light reflection/backscatter from tissue. PS-OCT detects birefringence of tissue. Imaging was performed in 12 skin regions. ET was calculated from the OCT images. RESULTS: Normal skin has a layered structure. Layering is less pronounced in adults. In glabrous skin the stratum corneum is visible. Children had larger ET (p < 0.0001). Age had a negative correlation with ET (p < 0.05). No gender- or skin-type-related differences in ET were found. CONCLUSION: This study contributes to understanding OCT and PS-OCT images of normal skin and indicates that OCT can be used for both the qualitative and quantitative assessment of skin.

[Optical coherence tomography]. / Optisk kohaerenstomografi.

Optical coherence tomography (OCT) is a novel technique for two and three-dimensional imaging of tissues at a histological level. The technique is based on optical technology and commercially available fiber-optic components that may be adapted for use in conventional endoscopes or intravascular catheters. OCT is a non-invasive technique, which does not utilize ionizing radiation, and it may within a few seconds provide in vivo images ("optical biopsies") of tissues in cases where excisional biopsy is hazardous or impossible, or when repeated examinations are required. OCT has numerous potential clinical applications, and the technique is currently used in ophthalmology, where it may improve diagnosis and therapeutic control of various eye diseases. Detection and characterization of skin tumors and other dermatological diseases is another area where OCT has tremendous clinical potential. In the field of cardiology, intravascular OCT may be capable to contribute to early diagnosis of vulnerable atherosclerotic lesions. The OCT technique is also being developed in other clinical areas and is expected to become integrated in a range of clinical situations in the future.