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In this study, nanoparticles of pure zinc oxide (ZnO) and ZnO doped with iron of various doping concentrations (Zn1- xFexO) are analyzed using fluorescence spectroscopy. Excitation and emission spectra using various operating wavelengths were collected. Individual spectra and excitation emission matrix were analyzed. Various peaks including strong ultraviolet (UV) emission peaks and strong blue emission peaks that are corresponding to the near-band-edge emission (NBE) and defect emission (DE) peaks were studied based on the peak intensities, peak wavelengths, and NBE peak to defect peak ratios. The Zn1-xFexO materials were also analyzed using X-ray diffraction and optical absorption spectroscopy. The variation in the band gap energy and in the NBE emission energy with dopant concentration was analyzed. A red-shift was observed with the NBE emission peak. The NBE to DE ratio initially increases from pure ZnO to Zn0.97Fe0.03O and then decreases as the dopant concentration increases.
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Convolutional neural networks (CNN) are a class of machine learning model that are especially well suited for imagebased tasks. In this study, we design and train a CNN on tissue samples imaged using Multi-Photon Microscopy (MPM) and show that the model can distinguish between chromophobe renal cell carcinoma (chRCC) and oncocytoma. We demonstrate the method to train a model using simple max-pooling vote fusion, and use the model to highlight regions of the input that cause a positive classification. The model can be tuned for higher sensitivity at the cost of specificity with a constant threshold and little impact to accuracy overall. Several numerical experiments were run to measure the model’s accuracy on both image and patient level analysis. Our models were designed with a dropout parameter that biases the model towards higher sensitivity or specificity. Our best performance model, as measured by area under the receiver operating characteristic curve (AUC of ROC, or AUROC) on patient level classification, is measured with a 94% AUROC and 88% accuracy, along with 100% sensitivity and 75% specificity.
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This chapter first reviews the research and applications of nonresonance and resonance Raman spectroscopy for analysis of human brain normal and abnormal tissues. Next, special emphasis is made on our recent achievements of visible resonance Raman (VRR) technique in primary human brain tumor disease investigation and diagnosis. Visible resonance Raman (VRR) spectroscopy technique uses excitation of visible light (532 nm) to evaluate the resonant and nonresonant molecular vibrational modes in biological tissues. The VRR signal intensities are enhanced by two to three orders of magnitude for faster use in medical applications in quasi real time. VRR opens up a new stainless “molecular optics based histopathology” diagnosis approach. © 2019 Elsevier Ltd. All rights reserved.
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The purpose of this study is to examine optical spatial frequency spectroscopy analysis (SFSA) combined with visible resonance Raman (VRR) spectroscopic method, for the first time, to discriminate human brain metastases of lung cancers adenocarcinoma (ADC) and squamous cell carcinoma (SCC) from normal tissues. A total of 31 label-free micrographic images of three types of brain tissues were obtained using a confocal micro-Raman spectroscopic system. VRR spectra of the corresponding samples were synchronously collected using excitation wavelength of 532[Formula: see text]nm from the same sites of the tissues. Using SFSA method, the difference in the randomness of spatial frequency structures in the micrograph images was analyzed using Gaussian function fitting. The standard deviations, [Formula: see text] calculated from the spatial frequencies of the micrograph images were then analyzed using support vector machine (SVM) classifier. The key VRR biomolecular fingerprints of carotenoids, tryptophan, amide II, lipids and proteins (methylene/methyl groups) were also analyzed using SVM classifier. All three types of brain tissues were identified with high accuracy in the two approaches with high correlation. The results show that SFSA–VRR can potentially be a dual-modal method to provide new criteria for identifying the three types of human brain tissues, which are on-site, real-time and label-free and may improve the accuracy of brain biopsy.
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Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins.
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