Emerging Optical Techniques for Detection of Oral, Cervical and Anal Cancer in Low-Resource Settings

Cancers of the oral and anogenital regions are a growing global health problem that disproportionately impact women and men living in developing countries. The high death rate in developing countries is largely due to the fact that these countries do not have the appropriate medical infrastructure and resources to support the organized screening and diagnostic programs that are available in the developed world. Emerging optical diagnostics techniques, such as optical spectroscopy, reflectance imaging, and fluorescence imaging, are noninvasive techniques that are sensitive to multiple cancer biomarkers and have shown the potential as a cost–effective and fast tool for diagnosis of early precancerous changes in the cervix, oral cavity and anus. This paper provides a review of current strategies for prevention, screening and diagnostic tests of oral, cervical and anal cancers and development in optical diagnostic techniques that could potentially be used to improve current practice in resource–limited settings

Morphological Features of Dysplastic Progression in Epithelium: Quantification of Cytological, Microendoscopic, and Second Harmonic Generation Images

Advances in imaging technology have led to a variety of available clinical and investigational systems. In this collection of studies, we tested the relevance of morphological image feature quantification on several imaging systems and epithelial tissues. Quantification carries the benefit of creating numerical baselines and thresholds of healthy and abnormal tissues, to potentially aid clinicians in determining a diagnosis, as well as providing researchers with standardized, unbiased results for future dissemination and comparison. Morphological image features in proflavine stained oral cells were compared qualitatively to traditional Giemsa stained cells, and then we quantified the nuclear to cytoplasm ratio. We determined that quantification of proflavine stained cells matched our hypothesis, as the nuclei in oral carcinoma cells were significantly larger than healthy oral cells. Proflavine has been used in conjunction with translational fluorescence microendoscopy of the gastrointestinal tract, and we demonstrated the ability of our custom algorithm to accurately (up to 85% sensitivity) extract colorectal crypt area and circularity data, which could minimize the burden of training on clinicians. In addition, we proposed fluorescein as an alternative fluorescent dye, providing comparable crypt area and circularity information. In order to investigate the morphological changes of crypts via the supporting collagen structures, we adapted our quantification algorithm to analyze crypt area, circularity, and an additional shape parameter in second harmonic generation images of label-free freshly resected murine epithelium. Murine models of colorectal cancer (CRC) were imaged at early and late stages of tumor progression, and we noted significant differences between the Control groups and the late cancer stages, with some differences between early and late stages of CRC progression

Comparative study on the detection of early dental caries using thermo-photonic lock-in imaging and optical coherence tomography

Early detection of dental caries is known to be the key to the effectiveness of therapeutic and preventive approaches in dentistry. However, existing clinical detection techniques, such as radiographs, are not sufficiently sensitive to detect and monitor the progression of caries at early stages. As such, in recent years, several optics-based imaging modalities have been proposed for the early detection of caries. The majority of these techniques rely on the enhancement of light scattering in early carious lesions, while a few of them are based on the enhancement of light absorption at early caries sites. In this paper, we report on a systemic comparative study on the detection performances of optical coherence tomography (OCT) and thermophotonic lock-in imaging (TPLI) as representative early caries detection modalities based on light scattering and absorption, respectively. Through controlled demineralization studies on extracted human teeth and µCT validation experiments, several detection performance parameters of the two modalities such as detection threshold, sensitivity and specificity have been qualitatively analyzed and discussed. Our experiment results suggests that both modalities have sufficient sensitivity for the detection of well-developed early caries on occlusal and smooth surfaces; however, TPLI provides better sensitivity and detection threshold for detecting very early stages of caries formation, which is deemed to be critical for the effectiveness of therapeutic and preventive approaches in dentistry. Moreover, due to the more specific nature of the light absorption contrast mechanism over light scattering, TPLI exhibits better detection specificity, which results in less false positive readings and thus allows for the proper differentiation of early caries regions from the surrounding intact areas. The major shortcoming of TPLI is its inherent depth-integrated nature, prohibiting the production of depth-resolved/B-mode like images. The outcomes of this research justify the need for a light-absorption based imaging modality with the ability to produce tomographic and depth-resolved images, combining the key advantages of OCT and TPLI.York University Librarie

A protocol for Enhanced imaging and Quantification of Cervical Cell Under Scanning electron Microscope

The application of Field Emission Scanning Electron Microscopy and Energy Dispersive X-Ray (FE-SEM/EDX) for the characterization of biological samples can produce promising results for classification purpose. The limitations of the established sample preparation technique of cervical cells for FE-SEM/EDX study that differentiate between normal and abnormal cells prompted the development of a proposed protocol for the preparation of cervical cells. The proposed protocol was conducted by a McDowell-Trump fixative prepared in 0.1M phosphate buffer without osmium tetroxide at 4°C for 2 h in the fixation process. Morphologically, the cervical cells scanned under the FE-SEM/EDX did not present blackening effects, and the structure of the cells was not broken based on the FE-SEM images. Quantitatively, the possible elemental distributions in the cells, such as carbon, nitrogen, oxygen, and sodium, are detected in samples prepared by the proposed protocol. The analysed elements were validated using the Attenuated Total Reflection and Fourier Transform Infrared (ATR/FTIR) spectroscopy. Moreover, by avoiding osmium tetroxide fixation, the time required for sample preparation decreased significantly. This sample preparation protocol can be used for normal and abnormal cervical cells in achieving better results in terms of morphological, detected elemental distribution, and rapid in time

Histopathological image analysis : a review

Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe

Smart and Functional Interfaces for Sensitive SPR Biosensing Towards Biomedical Applications

The aim of this thesis is to develop Surface Plasmon Resonance (SPR) methods that improve biosensing performance, in particular the sensitivity and selectivity of the analysis and their adaptation for biomedical applications to samples with complex background. This is of significant importance in translating the biosensor technologies to deliver the same results as the conventional methods but in a more accessible, efficient, and economical manner. The first study exploited SPR as a DNA biosensor for the detection of Malaria Plasmodium falciparum parasite with the hybridization chain reaction (HCR), which resulted in the formation of self-assembled target DNA nanostructures for signal enhancement. The sensitivity was further improved by using gold nanoparticles (AuNPs) for additional signal amplification. Tests with human blood plasma indicated the results were comparable to analyses in buffer, despite noticeable non-specific binding from the plasma. The concern of non-specific binding was systematically investigated in the second study where an antifouling surface consists of supported lipid bilayer membranes (SLBs) and protein A was developed for detection of trace amount of proteins in undiluted human serum. Specifically, cholera toxin (CT) spiked into the serum was used as the target, and advanced interface was further extended to immunosensing of immunoglobulin G (IgG). In the third study, SPR biosensor was employed in combination of bright field microscopy to characterize cellular apoptosis. HeLa cells undergoing apoptosis induced by hydrogen peroxide (H2O2) were monitored by SPR and the signals were compared to microscopic analysis of the morphological changes. SPR study revealed a decreased signal as cell confluency decreases, with the rates increasing as H2O2 concentration increases. An abnormality was found at high concentrations when both apoptosis and necrosis were induced. A mathematical model was proposed to explain SPR response where a non- uniform adsorbed layer was partially responsible. The significance of this thesis is that a number of high performing biosensing approaches have been developed and demonstrated. In addition to the advantages of SPR (e.g. label-free, real-time biomolecules binding, and portability), these methods have paved the way towards realizing effective sensing in biomedical research, especially in the early detection of infectious diseases and in the treatment of cancers

Early detection of curable precancerous lesions in the oral cavity using polarized reflectance spectroscopy

textIn 2004, the American Cancer Society estimates that more than 1,500 deaths a day associated with cancer will occur. For all cancers, the five-year survival rate is greater if diagnosis is made at an early stage of cancer development. The focus of this dissertation is on the development of a highly selective and sensitive non-invasive optical device for the early detection of epithelial precancers, which has enormous potential to reduce patient morbidity and mortality. Specifically, this dissertation will concentrate on the assessment of the polarized reflectance spectroscopy (PRS) to detect and diagnose early curable precancerous lesions within the oral cavity. PRS is a variation of elastic scattering spectroscopy which is sensitive to important morphological indicators of early precancer, such as scatterer size and refractive index. In this dissertation I will present a fiber optic probe that combines polarized illumination and detection with an angled distal probe geometry to detect the size dependent scattering within the epithelial layer of tissue, where most cancer originate. This technique allows a simple Mie theory based model to be used to extract the nuclear sizes. Tissue phantoms that mimic the two-layered scattering structure of mucosal tissue were used to test the feasibility of PRS to extract scatter sizes. Results of these studies showed excellent agreement between spectroscopically derived scatter sizes and direct microscopy measurements. In vivo measurements within the oral cavity of normal volunteers also yielded nuclear sizes that corresponded very well to published values. The PRS device was found to be capable of discriminating normal oral mucosa tissue from severe dysplasia in a collaborative pilot clinical trial of 21 patients, at the UT MD Anderson Cancer Center. Nuclear morphology extracted from the polarized spectroscopy measurements compared very well to quantitative histopathology. Overall this dissertation gives a thorough basis for a larger statistically significant clinical trial to be performed to determine the sensitivity and specificity of polarized reflectance spectroscopy as a screening and diagnostic instrument in the oral cavity. The work in this dissertation lays the foundation for future exploration of the optical scattering properties polarized light within tissue for clinical applications.Physic

Breast Cancer Early Detection Comparison with Deep Learning and Machine Learning Models: A Case of Study

Breast cancer is one of the most widespread in the female population, being able to predict its developments and capturing the inputs of the onset of the disease is one of the main objectives that science is pursuing. Clinical Decision Support Systems (CDSS) in recent decades are extensively using these technological tools, such as Machine Learning (ML) and Deep Learning (DL). In this paper, two of the main methods of these subset of AI are compared: an ensemble-type algorithm, XGBoost (or Extreme Gradient Boosting) and a deep neural network (DNN) are applied to the data of a study conducted on an Indonesian population. The results obtained are very interesting as despite being tabular, binary categorical and multiclass data, the DNN model achieves performance and results much higher than the well-known XGB used in literature for data of this type

Rapid and complete paraffin removal from human tissue sections delivers enhanced Raman spectroscopic and histopathological analysis

Incomplete removal of paraffin and organic contaminants from tissues processed for diagnostic histology has been a profound barrier to the introduction of Raman spectroscopic techniques into clinical practice. We report a route to rapid and complete paraffin removal from a range of formalin-fixed paraffin embedded tissues using super mirror stainless steel slides. The method is equally effective on a range of human and animal tissues, performs equally well with archived and new samples and is compatible with standard pathology lab procedures. We describe a general enhancement of the Raman scatter and enhanced staining with antibodies used in immunohistochemistry for clinical diagnosis. We conclude that these novel slide substrates have the power to improve diagnosis through anatomical pathology by facilitating the simultaneous combination of improved, more sensitive immunohistochemical staining and simplified, more reliable Raman spectroscopic imaging, analysis and signal processing