Training With Uncertain Annotations for Semantic Segmentation of Basal Cell Carcinoma From Full-Field OCT Images.

Semantic segmentation of basal cell carcinoma (BCC) from full-field optical coherence tomography (FF-OCT) images of human skin has received considerable attention in medical imaging. However, it is challenging for dermatopathologists to annotate the training data due to OCT's lack of color specificity. Very often, they are uncertain about the correctness of the annotations they made. In practice, annotations fraught with uncertainty profoundly impact the effectiveness of model training and hence the performance of BCC segmentation. To address this issue, we propose an approach to model training with uncertain annotations. The proposed approach includes a data selection strategy to mitigate the uncertainty of training data, a class expansion to consider sebaceous gland and hair follicle as additional classes to enhance the performance of BCC segmentation, and a self-supervised pre-training procedure to improve the initial weights of the segmentation model parameters. Furthermore, we develop three post-processing techniques to reduce the impact of speckle noise and image discontinuities on BCC segmentation. The mean Dice score of BCC of our model reaches 0.503±0.003, which, to the best of our knowledge, is the best performance to date for semantic segmentation of BCC from FF-OCT images.

Assessing the effects of prenatal poly-drug exposure on fetal brain vasculature using optical coherence angiography.

Significance: Maternal exposure to drugs during pregnancy is known to have detrimental effects on the fetus. Alcohol (ethanol) and nicotine are two of the most commonly co-abused substances during pregnancy, and prenatal poly-drug exposure is common due, in part, to the prevalence of unplanned pregnancies. The second trimester is a critical period for fetal neurogenesis and angiogenesis. When drug exposure occurs during this time, fetal brain development is affected. Several behavioral, morphological, and functional studies have evaluated the changes in fetal brain development due to exposure to these drugs individually. However, research on the combined effects of ethanol and nicotine is far more limited, specifically on fetal vasculature changes and development. Aim: We use correlation mapping optical coherence angiography (cm-OCA) to evaluate acute changes in fetal brain vasculature caused by maternal exposure to a combination of ethanol and nicotine. Approach: Ethanol (16.6% v/v, at a dose of 0.75g/kg) and nicotine (at a dose of 0.1 mg/kg) were administered to pregnant mice after initial cm-OCA measurements in utero. Subsequent measurements were taken at 5-min intervals for a total period of 45 min. Results from these experiments were compared to results from our previous studies in which the mother was exposed to only ethanol (dose: 0.75 g/kg) or nicotine (dose: 0.1 mg/kg). Results: While results from exposure to ethanol or nicotine independently showed vasoconstriction, no significant change in vasculature was observed with combined exposure. Conclusion: Results suggested antagonistic effects of ethanol and nicotine on fetal brain vasculature.

Optical coherence tomography angiography to evaluate murine fetal brain vasculature changes caused by prenatal exposure to nicotine.

Maternal smoking causes several defects ranging from intrauterine growth restriction to sudden infant death syndrome and spontaneous abortion. While several studies have documented the effects of prenatal nicotine exposure in development and behavior, acute vasculature changes in the fetal brain due to prenatal nicotine exposure have not been evaluated yet. This study uses correlation mapping optical coherence angiography to evaluate changes in fetal brain vasculature flow caused by maternal exposure to nicotine during the second trimester-equivalent of gestation in a mouse model. The effects of two different doses of nicotine were evaluated. Results showed a decrease in the vasculature for both doses of nicotine, which was not seen in the case of the sham group.

Assessing colitis ex vivo using optical coherence elastography in a murine model.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes regions of ulceration within the interior of the colon. UC is estimated to afflict hundreds of thousands of people in the United States alone. In addition to traditional colonoscopy, ultrasonic techniques can detect colitis, but have limited spatial resolution, which frequently results in underdiagnoses. Nevertheless, clinical diagnosis of colitis is still generally performed via colonoscopy. Optical techniques such as confocal microscopy and optical coherence tomography (OCT) have been proposed to detect UC with higher resolution. However, UC can potentially alter tissue biomechanical properties, providing additional contrast for earlier and potentially more accurate detection. Although clinically available elastography techniques have been immensely useful, they do not have the resolution for imaging small tissues, such as in small mammalian disease models. However, OCT-based elastography, optical coherence elastography (OCE), is well-suited for imaging the biomechanical properties of small mammal colon tissue. METHODS: In this work, we induced elastic waves in ex vivo mouse colon tissue using a focused air-pulse. The elastic waves were detected using a phase-stabilized swept source OCE system, and the wave velocity was translated into stiffness. Measurements were taken at six positions for each sample to assess regional sample elasticity. Additional contrast between the control and diseased tissue was detected by analyzing the dispersion of the elastic wave and tissue optical properties obtained from the OCT structural image. RESULTS: The results show distinct differences (P<0.05) in the stiffness between control and colitis disease samples, with a Young's modulus of 11.8±8.0 and 5.1±1.5 kPa, respectively. The OCT signal standard deviations for control and diseased samples were 5.8±0.3 and 5.5±0.2 dB, respectively. The slope of the OCT signal spatial frequency decay in the control samples was 92.7±10.0 and 87.3±4.7 dB∙µm in the colitis samples. The slope of the linearly fitted dispersion curve in the control samples was 1.5 mm, and 0.8 mm in the colitis samples. CONCLUSIONS: Our results show that OCE can be utilized to distinguish tissue based on stiffness and optical properties. Our estimates of tissue stiffness suggest that the healthy colon tissue was stiffer than diseased tissue. Furthermore, structural analysis of the tissue indicates a distinct difference in tissue optical properties between the healthy and UC-like diseased tissue.

Detecting murine Inflammatory Bowel Disease using Optical Coherence Elastography.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes regions of ulceration within the interior of the colon. UC is estimated to afflict hundreds of thousands of people in the United States alone. Ultrasonic techniques can detect colitis, but have limited spatial resolution, which frequently results in underdiagnoses. Nevertheless, clinical diagnosis of colitis is still generally performed via colonoscopy. Optical techniques such as confocal microscopy and optical coherence tomography (OCT) have been proposed as higher resolution alternative imaging modalities to detect colitis. Additionally, IBD can potentially alter tissue biomechanical properties, which cannot be quantified from structural imaging alone. Elastography is a potential method to assess colon biomechanical properties to provide additional contrast for distinguishing healthy and diseased colon tissue. In this work, we induced elastic waves in ex vivo mouse colon tissue using a focused air-pulse. The elastic waves were detected using a phase-stabilized swept source optical coherence elastography system, and the wave velocity was translated into stiffness. Measurements were taken at six random positions for each sample in order to assess regional sample elasticity. The results show distinct differences ($p \lt 0.05$) in the stiffness between healthy and IBD-diseased samples, with a Young's Modulus of $10.2 \pm 3.7$ kPa and $4.9 \pm 0.3$ kPa, respectively. Dispersion analysis presents another parameter to distinguish tissue health. The high frequency components of the phase velocity dispersion curve indicate a variation between healthy and IBD colonic tissue. Our results show that OCE may be useful for detecting IBD noninvasively.

Lorentz force optical coherence elastography.

Quantifying tissue biomechanical properties can assist in detection of abnormalities and monitoring disease progression and/or response to a therapy. Optical coherence elastography (OCE) has emerged as a promising technique for noninvasively characterizing tissue biomechanical properties. Several mechanical loading techniques have been proposed to induce static or transient deformations in tissues, but each has its own areas of applications and limitations. This study demonstrates the combination of Lorentz force excitation and phase-sensitive OCE at ?1.5??million A-lines per second to quantify the elasticity of tissue by directly imaging Lorentz force-induced elastic waves. This method of tissue excitation opens the possibility of a wide range of investigations using tissue biocurrents and conductivity for biomechanical analysis.

Classifying murine glomerulonephritis using optical coherence tomography and optical coherence elastography.

Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys.

Three-dimensional computational analysis of optical coherence tomography images for the detection of soft tissue sarcomas.

We present a three-dimensional (3-D) computational method to detect soft tissue sarcomas with the goal of automatic surgical margin assessment based on optical coherence tomography (OCT) images. Three parameters are investigated and quantified from OCT images as the indicators for the tissue diagnosis including the signal attenuation (A-line slope), the standard deviation of the signal fluctuations (speckles), and the exponential decay coefficient of its spatial frequency spectrum. The detection of soft tissue sarcomas relies on the combination of these three parameters, which are related to the optical attenuation characteristics and the structural features of the tissue. Pilot experiments were performed on ex vivo human tissue samples with homogeneous pieces (both normal and abnormal) and tumor margins. Our results demonstrate the feasibility of this computational method in the differentiation of soft tissue sarcomas from normal tissues. The features of A-line-based detection and 3-D quantitative analysis yield promise for a computer-aided technique capable of accurately and automatically identifying resection margins of soft tissue sarcomas during surgical treatment.

Ching-fang-pai-tu-san inhibits the release of influenza virus.

ETHNOPHARMACOLOGICAL RELEVANCE: Ching-fang-pai-tu-san (CFPTS) is a Chinese herbal decoction that is used as a cure for the common cold, fever, headache, and poor circulation. However, no previous studies have investigated the mode of action of CFPTS against influenza virus infections. To investigate the antiviral mechanism of CFPTS, we examined viral entry, transcription, translation, viral glycoprotein hemagglutinin (HA) transport, and budding of the influenza virus. MATERIALS AND METHODS: The antiviral activity of nontoxic concentrations of CFPTS against influenza virus A/WSN/33 was examined by assaying (neutralization assay) its inhibition of the virus-induced cytopathic effects. The mode of CFPTS action was first examined with a time-of-addition assay of synchronized infections, followed by monitoring HA transport by immunofluorescence microscopy. Viral endocytosis was evaluated with attachment and penetration assays. The inhibition of viral replication was measured by quantitative real-time PCR, immunoblotting, and immunofluorescence microscopy. We also performed assays related to the inhibition of viral entry, such as neuraminidase activity and hemagglutinin activity assays. RESULTS: Based on the inhibition of the virus-induced cytopathic effect in Madin-Darby canine kidney cells, the EC(50) of CFPTS was about 1.44 ± 0.22 mg/mL against influenza virus A/WSN/33. CFPTS displayed a broad spectrum of inhibitory activities against different strains of influenza A virus, as well as some enteroviruses. However, this extract proved less effective against clinical oseltamivir-resistant strains and influenza B viruses. CFPTS did not suppress viral RNA or protein synthesis. According to a time-of-addition assay, the antiviral mechanism of CFPTS may involve viral budding or intracellular viral glycoprotein transport. A plaque reduction assay showed that CFPTS reduced both the plaque size and plaque quantity. The intracellular transport of viral glycoprotein hemagglutinin was blocked by CFPTS by immunofluorescence microscopic analysis. Thus, it is possible that the antiviral mechanism of CFPTS might inhibit the assembly of progeny virions and/or their subsequent release. CONCLUSIONS: Our results give scientific support to the use of CFPTS in the treatment of influenza virus infections. CFPTS has potential utility in the management of seasonal pandemics of influenza virus infections, like other clinically available drugs.