Non-invasive detection of oral cancer using reflectance and fluorescence spectroscopy

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references.In vivo reflectance and fluorescence spectra were collected from patients with oral lesions, as well as healthy volunteers, in order to evaluate the potential of spectroscopy to serve as a non-invasive tool for the detection oral cancer. A total of 710 spectra were analyzed from 79 healthy volunteers, and 87 spectra from 67 patients. Physical models were applied to the measured spectral data in order to extract quantitative parameters relating to the structural and biochemical properties of the tissue. Data collected from healthy volunteers were used to characterize the relationship between the spectral parameters and tissue anatomy. Diagnostic algorithms for distinguishing various lesion categories were then developed using data collected from patients. The healthy volunteer study demonstrated that tissue anatomy has a strong influence on the spectral parameters. Anatomic sites could be easily distinguished from each other despite the apparent overlap in their parameter distributions. In particular, keratinized sites (gingiva and hard palate) were significantly distinct from other anatomic sites. The results of this study provide strong evidence that a robust and accurate spectroscopic based diagnostic algorithm for oral cancer needs to be applied in a site specific manner. Spectral diagnostic algorithms were developed using the data collected from patients, in combination with the data collected from healthy volunteers. The diagnostic performance of the algorithms was evaluated using the area under a receiver operator characteristic curve (ROC-AUC) and the sensitivity and specificity. The diagnostic algorithms were most successful when developed and applied to data collected from a single anatomic site or spectrally similar sites, and when distinguishing visibly normal mucosa from lesions.(cont.) ROC-AUC values of >0.90 could be achieved for this classification. Spectral algorithms for distinguishing benign lesions from dysplastic/malignant lesions were successfully created for the lateral surface of the tongue (ROC-AUC =0.75) and for the combination of the floor of the mouth and ventral tongue (ROC-AUC =0.71).by Sasha Alanda McGee.Ph.D

Shigellosis and giardiasis among people living with HIV in Washington, DC, 2012-2016

Background: Shigellosis and giardiasis are transmitted via food, water, and fecal-oral contact. CDC has recently reported increased shigellosis among men who have sex with men (MSM) and among people living with HIV (PLWH), particularly stage 3. Our goal was to characterize the incidence and risk factors associated with shigellosis and giardiasis among PLWH in Washington, DC, in an era of robust availability of antiretroviral treatment. Methods: We conducted a retrospective analysis of HIV, shigellosis and giardiasis cases reported to the District of Columbia Department of Health from 2012 to 2016. We used LinkPlus to probabilistically match individuals with reported HIV and Shigella or Giardia. We conducted bivariate analysis on gender, race/ethnicity, and age for Shigella-HIV, Giardia-HIV and HIV alone. Among men, we conducted bivariate analysis for HIV transmission risk factors. Among those with Shigella-HIV or Giardia-HIV, we compared CD4 cell count, HIV stage, HIV viral load, and viral suppression (VS) using laboratory data within 8 weeks before or after the incident enteric infection. We compared the incidence of shigellosis and giardiasis in the general population versus among those living with HIV in 2016. Results: During 2012-2016, 250 DC residents were reported with shigellosis (2.1 per 100,000 in 2016) and 412 with giardiasis (7.3 per 100,000 in 2016). The proportion with HIV coinfection was 20.4% for shigellosis and 10.6% for giardiasis. Incidence rate ratio (PLWH versus general population) was 25.8 for shigellosis and 9.6 for giardiasis. 40.9% of coinfection cases, versus 15.9% HIV alone, were ages 25-34 at the end of 2016 (p Conclusion: PLWH in DC disproportionately acquired shigellosis and giardiasis in 2012-2016. Factors associated with shigellosis and giardiasis among PLWH include male gender, white race, being in the 25-34 age group, and MSM. Among the Shigella-HIV and Giardia-HIV cases, most did not have stage 3 HIV, but we found low viral suppression rates. Our data supports the need for obtaining a thorough sexual history, focused HIV prevention and antiretroviral adherence counseling, and provides information to target high risk groups in DC

Determinants of Breast Cancer Treatment Delay Differ for African American and White Women

Timeliness of care may contribute to racial disparities in breast cancer mortality. African American women experience greater treatment delay than White women in most, but not all studies. Understanding these disparities is challenging since many studies lack patient-reported data and use administrative data sources that collect limited types of information. We used interview and medical record data from the Carolina Breast Cancer Study (CBCS) to identify determinants of delay and assess whether disparities exist between White and African American women (n=601)

Anatomy-Based Algorithms for Detecting Oral Cancer Using Reflectance and Fluorescence Spectroscopy

OBJECTIVES: We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc). METHODS: In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed. RESULTS: Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC],0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71. CONCLUSIONS: Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined.National Institutes of Health (U.S) (R0I-CA097966)National Institutes of Health (U.S) (P4I-RR02594- 21

Volume 06

Introduction from Dean Dr. Charles Ross Caught Between Folklore and the Cold War: The Americanization of Russian Children\u27s Literature by Kristen Gains Graphic Design by Amanda Willis Graphic Design by Holly Backer Prejudices in Swiss German Accents by Monika Gutierrez Photography by Cara O\u27Neal Photography by Sara Nelson Edmund Tyrone\u27s Long Journey through Night by Sasha Silberman Photography by Jessica Beardsley Photography by Jamie Gardner and Edward Peeples The Republican Razor: The Guillotine as a Symbol of Equality by Jamie Clift Graphic Design by Matthew Sakach Genocide: The Lasting Effects of Gender Stratification in Rwanda By Tess Lione and Emily Wilkins Photography by Kelsey Holt and Jessica Page Morocco and the 20 February Movement by Charles Vancampen, Gilbert Hall, Jenny Nehrt, Kasey Dye, Amanda Tharp, Jamie Leeawrik, & Ashley McGee Photography by Emily Poulin Photography by Michael Kropf Improving Performance of Arbitrary Precision Arithmetic Using SIMD Assembly Code Instructions by Nick Pastore Art by Austin Polasky and Morgan Glasco Art by Laura L. Kahler The Effects of the Neutral Response Option on the Extremeness of Participant Responses by Melinda L. Edwards and Brandon C. Smith Graphic Design by Mariah Asbell Graphic Design by Cabell Edmunds College Bullying: An Exploratory Analysis by Amelia D. Perry Photography by Alyssa Hayes Death-Related Crime: Applying Bryant\u27s Conceptual Paradigm of Thanatological Crime to Military Settings by Irina Boothe Graphic Design by Perry Bason Graphic Design by James Earl

Raman spectroscopic sensing of carbonate intercalation in breast microcalcifications at stereotactic biopsy.

Microcalcifications are an early mammographic sign of breast cancer and frequent target for stereotactic biopsy. Despite their indisputable value, microcalcifications, particularly of the type II variety that are comprised of calcium hydroxyapatite deposits, remain one of the least understood disease markers. Here we employed Raman spectroscopy to elucidate the relationship between pathogenicity of breast lesions in fresh biopsy cores and composition of type II microcalcifications. Using a chemometric model of chemical-morphological constituents, acquired Raman spectra were translated to characterize chemical makeup of the lesions. We find that increase in carbonate intercalation in the hydroxyapatite lattice can be reliably employed to differentiate benign from malignant lesions, with algorithms based only on carbonate and cytoplasmic protein content exhibiting excellent negative predictive value (93?98%). Our findings highlight the importance of calcium carbonate, an underrated constituent of microcalcifications, as a spectroscopic marker in breast pathology evaluation and pave the way for improved biopsy guidance

Re-evaluation of model-based light-scattering spectroscopy for tissue spectroscopy

Model-based light scattering spectroscopy (LSS) seemed a promising technique for in-vivo diagnosis of dysplasia in multiple organs. In the studies, the residual spectrum, the difference between the observed and modeled diffuse reflectance spectra, was attributed to single elastic light scattering from epithelial nuclei, and diagnostic information due to nuclear changes was extracted from it. We show that this picture is incorrect. The actual single scattering signal arising from epithelial nuclei is much smaller than the previously computed residual spectrum, and does not have the wavelength dependence characteristic of Mie scattering. Rather, the residual spectrum largely arises from assuming a uniform hemoglobin distribution. In fact, hemoglobin is packaged in blood vessels, which alters the reflectance. When we include vessel packaging, which accounts for an inhomogeneous hemoglobin distribution, in the diffuse reflectance model, the reflectance is modeled more accurately, greatly reducing the amplitude of the residual spectrum. These findings are verified via numerical estimates based on light propagation and Mie theory, tissue phantom experiments, and analysis of published data measured from Barrett's esophagus. In future studies, vessel packaging should be included in the model of diffuse reflectance and use of model-based LSS should be discontinued.National Institutes of Health (grant P41-RR02594

Determinants of Breast Cancer Treatment Delay Differ for African American and White Women

BACKGROUND: Timeliness of care may contribute to racial disparities in breast cancer mortality. African American women experience greater treatment delay than White women in most, but not all studies. Understanding these disparities is challenging since many studies lack patient-reported data and use administrative data sources that collect limited types of information. We used interview and medical record data from the Carolina Breast Cancer Study (CBCS) to identify determinants of delay and assess whether disparities exist between White and African American women (n=601). METHODS: The CBCS is a population-based study of North Carolina women. We investigated the association of demographic and socioeconomic characteristics, healthcare access, clinical factors, and measures of emotional and functional well-being with treatment delay. The association of race and selected characteristics with delays of >30 days were assessed using logistic regression. RESULTS: Household size, losing a job due to one’s diagnosis, and immediate reconstruction were associated with delay in the overall population and among White women. Immediate reconstruction and treatment type were associated with delay among African American women. Racial disparities in treatment delay were not evident in the overall population. In the adjusted models, African American women experienced greater delay than White women for younger age groups: odds ratio (OR), 3.34; 95% confidence interval (CI), 1.07–10.38 for ages 20–39, and OR, 3.40; 95% CI, 1.76–6.54 for ages 40–49. CONCLUSIONS: Determinants of treatment delay vary by race. Racial disparities in treatment delay exist among women <50 years old. IMPACT: Specific populations need to be targeted when identifying and addressing determinants of treatment delay