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  1. Home
  2. Browse by Author

Browsing by Author "Tan, Melody T."

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    Deep learning extended depth-of-field microscope for fast and slide-free histology
    (PNAS, 2020) Jin, Lingbo; Tang, Yubo; Wu, Yicheng; Coole, Jackson B.; Tan, Melody T.; Zhao, Xuan; Badaoui, Hawraa; Robinson, Jacob T.; Williams, Michelle D.; Gillenwater, Ann M.; Richards-Kortum, Rebecca R.; Veeraraghavan, Ashok; Bioengineering; Electrical and Computer Engineering
    Microscopic evaluation of resected tissue plays a central role in the surgical management of cancer. Because optical microscopes have a limited depth-of-field (DOF), resected tissue is either frozen or preserved with chemical fixatives, sliced into thin sections placed on microscope slides, stained, and imaged to determine whether surgical margins are free of tumor cells—a costly and time- and labor-intensive procedure. Here, we introduce a deep-learning extended DOF (DeepDOF) microscope to quickly image large areas of freshly resected tissue to provide histologic-quality images of surgical margins without physical sectioning. The DeepDOF microscope consists of a conventional fluorescence microscope with the simple addition of an inexpensive (less than $10) phase mask inserted in the pupil plane to encode the light field and enhance the depth-invariance of the point-spread function. When used with a jointly optimized image-reconstruction algorithm, diffraction-limited optical performance to resolve subcellular features can be maintained while significantly extending the DOF (200 µm). Data from resected oral surgical specimens show that the DeepDOF microscope can consistently visualize nuclear morphology and other important diagnostic features across highly irregular resected tissue surfaces without serial refocusing. With the capability to quickly scan intact samples with subcellular detail, the DeepDOF microscope can improve tissue sampling during intraoperative tumor-margin assessment, while offering an affordable tool to provide histological information from resected tissue specimens in resource-limited settings.
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    DeepDOF-SE: affordable deep-learning microscopy platform for slide-free histology
    (Springer Nature, 2024) Jin, Lingbo; Tang, Yubo; Coole, Jackson B.; Tan, Melody T.; Zhao, Xuan; Badaoui, Hawraa; Robinson, Jacob T.; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Richards-Kortum, Rebecca R.; Veeraraghavan, Ashok; Bioengineering; Electrical and Computer Engineering
    Histopathology plays a critical role in the diagnosis and surgical management of cancer. However, access to histopathology services, especially frozen section pathology during surgery, is limited in resource-constrained settings because preparing slides from resected tissue is time-consuming, labor-intensive, and requires expensive infrastructure. Here, we report a deep-learning-enabled microscope, named DeepDOF-SE, to rapidly scan intact tissue at cellular resolution without the need for physical sectioning. Three key features jointly make DeepDOF-SE practical. First, tissue specimens are stained directly with inexpensive vital fluorescent dyes and optically sectioned with ultra-violet excitation that localizes fluorescent emission to a thin surface layer. Second, a deep-learning algorithm extends the depth-of-field, allowing rapid acquisition of in-focus images from large areas of tissue even when the tissue surface is highly irregular. Finally, a semi-supervised generative adversarial network virtually stains DeepDOF-SE fluorescence images with hematoxylin-and-eosin appearance, facilitating image interpretation by pathologists without significant additional training. We developed the DeepDOF-SE platform using a data-driven approach and validated its performance by imaging surgical resections of suspected oral tumors. Our results show that DeepDOF-SE provides histological information of diagnostic importance, offering a rapid and affordable slide-free histology platform for intraoperative tumor margin assessment and in low-resource settings.
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    Failures in COVID-19 Vaccine Administration Data Collection Complicated Efforts to Ensure Vaccine Equity in Texas
    (2022) Laroche, Robert A.S.; Llinas, Roxanna J.; Navara, Adam M.; Tan, Melody T.; Lakshmanan, Rekha; Matthews, Kirstin R.W.; James A. Baker III Institute for Public Policy
    The equitable distribution of the COVID-19 vaccines is a critical issue due to the stark differences in health care outcomes between individuals who have received a vaccine and those who have not.1,2 Several demographic groups have historically faced barriers to accessing health care services such as vaccinations, including the elderly, rural populations, lower income groups, and communities of color.3-6 Overcoming these disadvantages and ensuring easy and affordable access are critical components of health care. Moreover, as part of an effective government response to the COVID-19 pandemic, it is necessary for members of all demographic groups to reach high rates of vaccination in order to achieve herd immunity within a region.7 In this paper, we discuss the steps taken by the Texas Department of State Health Services (TX DSHS) to ensure equitable vaccine access and to assess how shortfalls in data collection led to vaccine inequities. We recommend changes to the Texas immunization registry that will improve data collection, allow for more effective monitoring of vaccine distribution, and better prepare Texas for future public health crises.
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    Identification and Risk Assessment of Oral Precancers and Cancers with Optical Markers and Molecular Biomarkers
    (2021-07-12) Tan, Melody T.; Richards-Kortum, Rebecca R.
    In the United States, approximately two-thirds of oral cancer patients are diagnosed after regional and distant metastasis, leading to poor survival rates. These outcomes result in part from difficulties in identifying oral precancers and cancers in the clinical setting and determining the likelihood of potentially precancerous oral lesions undergoing eventual malignant transformation. The research objective was to develop approaches to improve the identification and risk assessment of oral precancers and cancers, leveraging changes in optically detectable cellular and tissue features and altered molecular biomarker expression. First, an animal model of oral carcinogenesis that exhibited clinically relevant changes in histopathology, optical markers, and molecular biomarker expression was developed. Second, multimodal widefield autofluorescence and high-resolution microendoscopy images and cancer biomarker expression were analyzed to identify relationships between optically detectable changes and genetic alterations. Third, a process was developed to perform intraoperative oral surgical specimen assessment employing fluorescent vital staining, imaging with a novel artificial intelligence-enabled microscope with an extended depth-of-field, and the generation of virtual histology images for pathology evaluation. Finally, a policy analysis was conducted addressing barriers to oral cancer detection in rural and border regions of Texas. In all, this work is a step towards allowing clinicians to incorporate optical marker and molecular biomarker alterations into the clinical evaluation of potentially high-risk oral sites, better informing the risk assessment and subsequent management of oral precancers and early cancers.
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    Medical Freedom, Privacy, and Fear of Discrimination: The 2017 Texas Legislative Session Anti-vaccine Arguments
    (James A. Baker III Institute for Public Policy, 2018) Matthews, Kirstin R.W.; Tan, Melody T.; James A. Baker III Institute for Public Policy
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    Mildly dysplastic oral lesions with optically-detectable abnormalities share genetic similarities with severely dysplastic lesions
    (Elsevier, 2022) Brenes, David R.; Nipper, Allison J.; Tan, Melody T.; Gleber-Netto, Frederico O.; Schwarz, Richard A.; Pickering, Curtis R.; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Sikora, Andrew G.; Richards-Kortum, Rebecca R.; Bioengineering
    Objective Optical imaging studies of oral premalignant lesions have shown that optical markers, including loss of autofluorescence and altered morphology of epithelial cell nuclei, are predictive of high-grade pathology. While these optical markers are consistently positive in lesions with moderate/severe dysplasia or cancer, they are positive only in a subset of lesions with mild dysplasia. This study compared the gene expression profiles of lesions with mild dysplasia (stratified by optical marker status) to lesions with severe dysplasia and without dysplasia. Materials and methods Forty oral lesions imaged in patients undergoing oral surgery were analyzed: nine without dysplasia, nine with severe dysplasia, and 22 with mild dysplasia. Samples were submitted for high throughput gene expression analysis. Results The analysis revealed 116 genes differentially expressed among sites without dysplasia and sites with severe dysplasia; 50 were correlated with an optical marker quantifying altered nuclear morphology. Ten of 11 sites with mild dysplasia and positive optical markers (91%) had gene expression similar to sites with severe dysplasia. Nine of 11 sites with mild dysplasia and negative optical markers (82%) had similar gene expression as sites without dysplasia. Conclusion This study suggests that optical imaging may help identify patients with mild dysplasia who require more intensive clinical follow-up. If validated, this would represent a significant advance in patient care for patients with oral premalignant lesions.
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    Misconceptions and Limited Awareness of Chagas Disease in Texas Among Surveyed Houston Physicians
    (James A. Baker III Institute for Public Policy, 2018) Tan, Melody T.; Matthews, Kirstin R.W.; James A. Baker III Institute for Public Policy
    Chagas disease impacts approximately 6–7 million people worldwide. It is caused by the Trypanosoma cruzi (T. cruzi) parasite that is transmitted by the triatomine bug. In Texas, cases of T. cruzi infection have been documented as early as the 1930s. More recently, evidence of autochthonous transmission and infection in human and canine populations has led experts to believe that the disease is prevalent in the region. The disease progresses from an acute phase—which has symptoms that are difficult to diagnose or can be asymptomatic—to a chronic disease, with significant cardiac and esophageal complications that can result in death. Currently, Chagas is only treatable in the acute phase or early chronic phase, which makes prompt diagnosis important. In this exploratory study, 16 emergency room physicians, pediatricians, and general practitioners in the Texas Medical Center in Houston, Texas, were interviewed to gauge their awareness of Chagas disease in Texas and assess their knowledge of the symptoms, transmission, and prevention of the disease. Responses indicated that the physicians interviewed were unaware of the specifics and the local burden of Chagas disease. Those who were able to provide details about the vector (triatomine bug) or pathogen (T. cruzi) made associations with only a few aspects of the disease, such as the chronic symptom of cardiomyopathy or the fact that triatomine bugs hide in thatched roofs. The physicians did not recognize that Chagas can be found and locally transmitted in Texas. Based upon these preliminary findings, there may be a similar lack of awareness of the disease within the greater population of Houston-based physicians. These findings suggest a need for increased physicians’ education and awareness of Chagas—particularly in regions like Texas, where the triatomine bug and T. cruzi are present—in order to improve accurate diagnosis and timely treatment of patients.
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    Noninvasive diagnostic adjuncts for the evaluation of potentially premalignant oral epithelial lesions: current limitations and future directions
    (Elsevier, 2018) Yang, Eric C.; Tan, Melody T.; Schwarz, Richard A.; Richards-Kortum, Rebecca R.; Gillenwater, Ann M.; Vigneswaran, Nadarajah; Bioengineering
    Potentially premalignant oral epithelial lesions (PPOELs) are a group of clinically suspicious conditions, of which a small percentage will undergo malignant transformation. PPOELs are suboptimally diagnosed and managed under the current standard of care. Dysplasia is the most well-established marker to distinguish high-risk PPOELs from low-risk PPOELs, and performing a biopsy to establish dysplasia is the diagnostic gold standard. However, a biopsy is limited by morbidity, resource requirements, and the potential for underdiagnosis. Diagnostic adjuncts may help clinicians better evaluate PPOELs before definitive biopsy, but existing adjuncts, such as toluidine blue, acetowhitening, and autofluorescence imaging, have poor accuracy and are not generally recommended. Recently, in vivo microscopy technologies, such as high-resolution microendoscopy, optical coherence tomography, reflectance confocal microscopy, and multiphoton imaging, have shown promise for improving PPOEL patient care. These technologies allow clinicians to visualize many of the same microscopic features used for histopathologic assessment at the point of care.
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    Scientific Misconceptions and Myths Perpetuated in the 2017 Texas Legislative Session
    (James A. Baker III Institute for Public Policy, 2018) Tan, Melody T.; Matthews, Kirstin R.W.; James A. Baker III Institute for Public Policy
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