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

Oblique Polarized Reflectance Spectroscopy for Depth Sensitive Measurements in the Epithelial Tissue

Optical spectroscopy has shown potential as a tool for precancer detection by discriminating alterations in the optical properties within epithelial tissues. Identifying depth-dependent alterations associated with the progression of epithelial cancerous lesions can be especially challenging in the oral cavity due to the variable thickness of the epithelium and the presence of keratinization. Optical spectroscopy of epithelial tissue with improved depth resolution would greatly assist in the isolation of optical properties associated with cancer progression. Here, we report a fiber optic probe for oblique polarized reflectance spectroscopy (OPRS) that is capable of depth sensitive detection by combining the following three approaches: multiple beveled fibers, oblique collection geometry, and polarization gating. We analyze how probe design parameters are related to improvements in collection efficiency of scattered photons from superficial tissue layers and to increased depth discrimination within epithelium. We have demonstrated that obliquely-oriented collection fibers increase both depth selectivity and collection efficiency of scattering signal. Currently, we evaluate this technology in a clinical trial of patients presenting lesions suspicious for dysplasia or carcinoma in the oral cavity. We use depth sensitive spectroscopic data to develop automated algorithms for analysis of morphological and architectural changes in the context of the multilayer oral epithelial tissue. Our initial results show that OPRS has the potential to improve the detection and monitoring of epithelial precancers in the oral cavity.Biomedical Engineerin

Health related quality of life in pregeriatric patients with chronic diseases at urban, public supported clinics

BACKGROUND: Understanding health-related quality of life (HRQOL) leads to more effective and focused healthcare. America's growing health disparities makes it is increasingly necessary to understand the HRQOL of pregeriatric individuals who are now 55–64 years old, i.e. before they are eligible for federally mandated health care at age 65. Our study measured the self-perceived HRQOL of pregeriatric, poor patients with multiple chronic diseases treated at 2 public clinics. METHODS: Consecutive patients aged 55–64 years, many with multiple chronic diseases, responded in an interview to the 36-Item Short-Form Health Survey (SF–36) as a general measure of HRQOL during a regular visit to one of two university-staffed urban public clinics. RESULTS: The perceived physical and mental functioning of 316 pregeriatric patients was tabulated from SF–36 scores to yield their HRQOL. Their scores were statistically significantly lower than those of the general US pregeriatric population and lower than averages for US patients with multiple chronic diseases. All eight subscale scores of SF–36 were 16% to 36% lower compared with the averages of the general US pregeriatric population. Further, as the number of chronic diseases increased, the lower was the HRQOL. Lower physical and mental scores were associated with a lower income, unemployment, and higher numbers of multiple chronic diseases. CONCLUSION: Chronic diseases have a powerful negative impact on perceived mental and physical functioning in pregeriatric patients. HRQOL information can assist health care providers to gain a more complete picture of their pregeriatric patients' health

Teaching First-year Medical Students to Apply Evidence-based Practices to Patient Care

Evidence-based medicine (EBM) is the integration of individual clinical expertise with the best available evidence from systematic research. 1-2 Most teaching of EBM for medical students currently takes place in classroom settings that feature teacher-centered didactic activities. When EBM is taught in this manner, the teaching appears not to influence patient care or to ensure that medical students are prepared to apply EBM at the point of care. 7 It is not surprising, then, that there is a continuing need to introduce and sharpen EBM skills among faculty who teach medical students in ambulatory clinical settings while managing the care of patients. 8 Earlier studies of EBM suggest that even at the preclinical level of training, medical students can learn EBM principles, formulate clinical questions, and receive evidence-based feedback from their teachers. Methods This EBM module is the third in a series of educational interventions that we implemented in the Texas Statewide Family Medicine Preceptorship Program (TSFMPP) between years one and two of medical training. Internal Review Board approval was obtained for the interventions used in this study. During the first year of each intervention, the educational materials were tested, and the students' participation was voluntary. In the following two summers

3D optical sectioning with a new hyperspectral confocal fluorescence imaging system.

A novel hyperspectral fluorescence microscope for high-resolution 3D optical sectioning of cells and other structures has been designed, constructed, and used to investigate a number of different problems. We have significantly extended new multivariate curve resolution (MCR) data analysis methods to deconvolve the hyperspectral image data and to rapidly extract quantitative 3D concentration distribution maps of all emitting species. The imaging system has many advantages over current confocal imaging systems including simultaneous monitoring of numerous highly overlapped fluorophores, immunity to autofluorescence or impurity fluorescence, enhanced sensitivity, and dramatically improved accuracy, reliability, and dynamic range. Efficient data compression in the spectral dimension has allowed personal computers to perform quantitative analysis of hyperspectral images of large size without loss of image quality. We have also developed and tested software to perform analysis of time resolved hyperspectral images using trilinear multivariate analysis methods. The new imaging system is an enabling technology for numerous applications including (1) 3D composition mapping analysis of multicomponent processes occurring during host-pathogen interactions, (2) monitoring microfluidic processes, (3) imaging of molecular motors and (4) understanding photosynthetic processes in wild type and mutant Synechocystis cyanobacteria

Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model

Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects

Watch on the Rhine

Typescript (photocopy).Digitized by Kansas Correctional Industrie

INDIVIDUALIZED INSTRUCTION: ITS EFFECTS UPON ACHIEVEMENT AND INTEREST INBEGINNING COLLEGE SPANISH.

Abstract not availabl

Development and integration of Raman imaging capabilities to Sandia National Laboratories hyperspectral fluorescence imaging instrument.

Raman spectroscopic imaging is a powerful technique for visualizing chemical differences within a variety of samples based on the interaction of a substance's molecular vibrations with laser light. While Raman imaging can provide a unique view of samples such as residual stress within silicon devices, chemical degradation, material aging, and sample heterogeneity, the Raman scattering process is often weak and thus requires very sensitive collection optics and detectors. Many commercial instruments (including ones owned here at Sandia National Laboratories) generate Raman images by raster scanning a point focused laser beam across a sample--a process which can expose a sample to extreme levels of laser light and requires lengthy acquisition times. Our previous research efforts have led to the development of a state-of-the-art two-dimensional hyperspectral imager for fluorescence imaging applications such as microarray scanning. This report details the design, integration, and characterization of a line-scan Raman imaging module added to this efficient hyperspectral fluorescence microscope. The original hyperspectral fluorescence instrument serves as the framework for excitation and sample manipulation for the Raman imaging system, while a more appropriate axial transmissive Raman imaging spectrometer and detector are utilized for collection of the Raman scatter. The result is a unique and flexible dual-modality fluorescence and Raman imaging system capable of high-speed imaging at high spatial and spectral resolutions. Care was taken throughout the design and integration process not to hinder any of the fluorescence imaging capabilities. For example, an operator can switch between the fluorescence and Raman modalities without need for extensive optical realignment. The instrument performance has been characterized and sample data is presented

Adaptive spectral window sizes for extraction of diagnostic features from optical spectra

We present an approach to adaptively adjust the spectral window sizes for optical spectra feature extraction. Previous studies extracted features from spectral windows of a fixed width. In our algorithm, piecewise linear regression is used to adaptively adjust the window sizes to find the maximum window size with reasonable linear fit with the spectrum. This adaptive windowing technique ensures the signal linearity in defined windows; hence, the adaptive windowing technique retains more diagnostic information while using fewer windows. This method was tested on a data set of diffuse reflectance spectra of oral mucosa lesions. Eight features were extracted from each window. We performed classifications using linear discriminant analysis with cross-validation. Using windowing techniques results in better classification performance than not using windowing. The area under the receiver-operating-characteristics curve for windowing techniques was greater than a nonwindowing technique for both normal versus mild dysplasia (MD) plus severe high-grade dysplasia or carcinama (SD) (MD+SD) and benign versus MD+SD. Although adaptive and fixed-size windowing perform similarly, adaptive windowing utilizes significantly fewer windows than fixed-size windows (number of windows per spectrum: 8 versus 16). Because adaptive windows retain most diagnostic information while reducing the number of windows needed for feature extraction, our results suggest that it isolates unique diagnostic features in optical spectra