Browsing by Author "Richards-Kortum, Rebecca R."
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Item A Lateral Flow Assay for Quantitative Detection of Amplified HIV-1 RNA(Public Library of Science, 2012) Rohrman, Brittany A.; Leautaud, Veronica; Molyneux, Elizabeth; Richards-Kortum, Rebecca R.Although the accessibility of HIV treatment in developing nations has increased dramatically over the past decade, viral load testing to monitor the response of patients receiving therapy is often unavailable. Existing viral load technologies are often too expensive or resource-intensive for poor settings, and there is no appropriate HIV viral load test currently available at the point-of-care in low resource settings. Here, we present a lateral flow assay that employs gold nanoparticle probes and gold enhancement solution to detect amplified HIV RNA quantitatively. Preliminary results show that, when coupled with nucleic acid sequence based amplification (NASBA), this assay can detect concentrations of HIV RNA that match the clinically relevant range of viral loads found in HIV patients. The lateral flow test is inexpensive, simple and rapid to perform, and requires few resources. Our results suggest that the lateral flow assay may be integrated with amplification and sample preparation technologies to serve as an HIV viral load test for low-resource settings.Item A low-cost, paper-based hybrid capture assay to detect high-risk HPV DNA for cervical cancer screening in low-resource settings(Royal Society of Chemisty, 2023) Smith, Chelsey A.; Chang, Megan M.; Kundrod, Kathryn A.; Novak, Emilie N.; Parra, Sonia G.; López, Leticia; Mavume, Celda; Lorenzoni, Cesaltina; Maza, Mauricio; Salcedo, Mila P.; Carns, Jennifer L.; Baker, Ellen; Montealegre, Jane; Scheurer, Michael; Castle, Philip E.; Schmeler, Kathleen M.; Richards-Kortum, Rebecca R.Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of <$3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay (“Xpert”), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.Item A paper and plastic device for performing recombinase polymerase amplification of HIV DNA(Royal Society of Chemistry, 2012) Rohrman, Brittany A.; Richards-Kortum, Rebecca R.Despite the importance of early diagnosis and treatment of HIV, only a small fraction of HIV-exposed infants in low- and middle-income countries are tested for the disease. The gold standard for early infant diagnosis, DNA PCR, requires resources that are unavailable in poor settings, and no point-of-care HIV DNA test is currently available. We have developed a device constructed of layers of paper, glass fiber, and plastic that is capable of performing isothermal, enzymatic amplification of HIV DNA. The device is inexpensive, small, light-weight, and easy to assemble. The device stores lyophilized enzymes, facilitates mixing of reaction components, and supports recombinase polymerase amplification in five steps of operation. Using commercially available lateral flow strips as a detection method, we demonstrate the ability of our device to amplify 10 copies of HIV DNA to detectable levels in 15 minutes. Our results suggest that our device, which is designed to be used after DNA extraction from dried-blood spots, may serve in conjunction with lateral flow strips as part of a point-of-care HIV DNA test to be used in low resource settings.Item A paper and plastic device for the combined isothermal amplification and lateral flow detection of Plasmodium DNA(BioMed Central, 2015) Cordray, Michael S.; Richards-Kortum, Rebecca R.Background: Isothermal amplification techniques are emerging as a promising method for malaria diagnosis since they are capable of detecting extremely low concentrations of parasite target while mitigating the need for infrastructure and training required by other nucleic acid based tests. Recombinase polymerase amplification (RPA) is promising for further development since it operates in a short time frame (<30 min) and produces a product that can be visually detected on a lateral flow dipstick. A self-sealing paper and plastic system that performs both the amplification and detection of a malaria DNA sequence is presented. Methods: Primers were designed using the NCBI nBLAST tools and screened using gel electrophoresis. Paper and plastic devices were prototyped using commercial design software and parts were cut using a laser cutter and assembled by hand. Synthetic copies of the Plasmodium 18S gene were spiked into solution and used as targets for the RPA reaction. To test the performance of the device the same samples spiked with synthetic target were run in parallel both in the paper and plastic devices and using conventional bench top methods. Results: Novel RPA primers were developed that bind to sequences present in the four species of Plasmodium which infect humans. The paper and plastic devices were found to be capable of detecting as few as 5 copies/µL of synthetic Plasmodium DNA (50 copies total), comparable to the same reaction run on the bench top. The devices produce visual results in an hour, cost approximately $1, and are self-contained once the device is sealed. Conclusions: The device was capable of carrying out the RPA reaction and detecting meaningful amounts of synthetic Plasmodium DNA in a self-sealing and self-contained device. This device may be a step towards making nucleic acid tests more accessible for malaria detection.Item Algorithm to quantify nuclear features and confidence intervals for classification of oral neoplasia from high-resolution optical images(SPIE, 2020) Yang, Eric C.; Brenes, David R.; Vohra, Imran S.; Schwarz, Richard A.; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Richards-Kortum, Rebecca R.Purpose:In vivo optical imaging technologies like high-resolution microendoscopy (HRME) can image nuclei of the oral epithelium. In principle, automated algorithms can then calculate nuclear features to distinguish neoplastic from benign tissue. However, images frequently contain regions without visible nuclei, due to biological and technical factors, decreasing the data available to and accuracy of image analysis algorithms. Approach: We developed the nuclear density-confidence interval (ND-CI) algorithm to determine if an HRME image contains sufficient nuclei for classification, or if a better image is required. The algorithm uses a convolutional neural network to exclude image regions without visible nuclei. Then the remaining regions are used to estimate a confidence interval (CI) for the number of abnormal nuclei per mm2, a feature used by a previously developed algorithm (called the ND algorithm), to classify images as benign or neoplastic. The range of the CI determines whether the ND-CI algorithm can classify an image with confidence, and if so, the predicted category. The ND and ND-CI algorithm were compared by calculating their positive predictive value (PPV) and negative predictive value (NPV) on 82 oral biopsies with histopathologically confirmed diagnoses. Results: After excluding the images that could not be classified with confidence, the ND-CI algorithm had higher PPV (65% versus 59%) and NPV (78% versus 75%) than the ND algorithm. Conclusions: The ND-CI algorithm could improve the real-time classification of HRME images of the oral epithelium by informing the user if an improved image is required for diagnosis.Item Allele-Specific Recombinase Polymerase Amplification to Detect Sickle Cell Disease in Low-Resource Settings(American Chemical Society, 2021) Natoli, Mary E.; Chang, Megan M.; Kundrod, Kathryn A.; Coole, Jackson B.; Airewele, Gladstone E.; Tubman, Venée N.; Richards-Kortum, Rebecca R.Sickle cell disease (SCD) is a group of common, life-threatening disorders caused by a point mutation in the β globin gene. Early diagnosis through newborn and early childhood screening, parental education, and preventive treatments are known to reduce mortality. However, the cost and complexity of conventional diagnostic methods limit the feasibility of early diagnosis for SCD in resource-limited areas worldwide. Although several point-of-care tests are commercially available, most are antibody-based tests, which cannot be used in patients who have recently received a blood transfusion. Here, we describe the development of a rapid, low-cost nucleic acid test that uses real-time fluorescence to detect the point mutation encoding hemoglobin S (HbS) in one round of isothermal recombinase polymerase amplification (RPA). When tested with a set of clinical samples from SCD patients and healthy volunteers, our assay demonstrated 100% sensitivity for both the βA globin and βS globin alleles and 94.7 and 97.1% specificities for the βA globin allele and βS globin allele, respectively (n = 91). Finally, we demonstrate proof-of-concept sample-to-answer genotyping of genomic DNA from capillary blood using an alkaline lysis procedure and direct input of diluted lysate into RPA. The workflow is performed in <30 min at a cost of <$5 USD on a commercially available benchtop fluorimeter and an open-source miniature fluorimeter. This study demonstrates the potential utility of a rapid, sample-to-answer nucleic acid test for SCD that may be implemented near the point of care and could be adapted to other disease-causing point mutations in genomic DNA.Item 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, AshokMicroscopic 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.Item 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, AshokHistopathology 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.Item Development of an integrated multimodal optical imaging system with real-time image analysis for the evaluation of oral premalignant lesions(SPIE, 2019) Yang, Eric C.; Vohra, Imran S.; Badaoui, Hawraa; Schwarz, Richard A.; Cherry, Katelin D.; Quang, Timothy; Jacob, Justin; Lang, Alex; Bass, Nancy; Rodriguez, Jessica; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Richards-Kortum, Rebecca R.Oral premalignant lesions (OPLs), such as leukoplakia, are at risk of malignant transformation to oral cancer. Clinicians can elect to biopsy OPLs and assess them for dysplasia, a marker of increased risk. However, it is challenging to decide which OPLs need a biopsy and to select a biopsy site. We developed a multimodal optical imaging system (MMIS) that fully integrates the acquisition, display, and analysis of macroscopic white-light (WL), autofluorescence (AF), and high-resolution microendoscopy (HRME) images to noninvasively evaluate OPLs. WL and AF images identify suspicious regions with high sensitivity, which are explored at higher resolution with the HRME to improve specificity. Key features include a heat map that delineates suspicious regions according to AF images, and real-time image analysis algorithms that predict pathologic diagnosis at imaged sites. Representative examples from ongoing studies of the MMIS demonstrate its ability to identify high-grade dysplasia in OPLs that are not clinically suspicious, and to avoid unnecessary biopsies of benign OPLs that are clinically suspicious. The MMIS successfully integrates optical imaging approaches (WL, AF, and HRME) at multiple scales for the noninvasive evaluation of OPLs.Item Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents(National Academy of Sciences, 2016) Keahey, Pelham; Ramalingam, Preetha; Schmeler, Kathleen; Richards-Kortum, Rebecca R.Fiber optic microendoscopy has shown promise for visualization of molecular contrast agents used to study disease in vivo. However, fiber optic microendoscopes have limited optical sectioning capability, and image contrast is limited by out-of-focus light generated in highly scattering tissue. Optical sectioning techniques have been used in microendoscopes to remove out-of-focus light but reduce imaging speed or rely on bulky optical elements that prevent in vivo imaging. Here, we present differential structured illumination microendoscopy (DSIMe), a fiber optic system that can perform structured illumination in real time for optical sectioning without any opto-mechanical components attached to the distal tip of the fiber bundle. We demonstrate the use of DSIMe during in vivo fluorescence imaging in patients undergoing surgery for cervical adenocarcinoma in situ. Images acquired using DSIMe show greater contrast than standard microendoscopy, improving the ability to detect cellular atypia associated with neoplasia.Item Efficacy of a Low-Cost Bubble CPAP System in Treatment of Respiratory Distress in a Neonatal Ward in Malawi(Public Library of Science, 2014) Kawaza, Kondwani; Machen, Heather E.; Brown, Jocelyn; Mwanza, Zondiwe; Iniguez, Suzanne; Al, Gest; Smith, E. O'Brian; Oden, Maria; Richards-Kortum, Rebecca R.; Molyneux, ElizabethRespiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP) is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care. We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre,Malawi. Neonates weighing .1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups. 87 neonates (62 bCPAP, 25 controls) were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62)compared with 44.0% (11/25) for controls. 65.5% (19/29) of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13) of controls. 64.6% (31/48) of neonates with respiratory distress syndrome (RDS)receiving bCPAP survived to discharge, compared to 23.5% (4/17) of controls. 61.5% (16/26) of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived. Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries.Item Gold Nanoparticle Aggregation for Quantification of Oligonucleotides: Optimization and Increased Dynamic Range(Elsevier, 2012) Cordray, Michael S.; Amdahl, Matthew; Richards-Kortum, Rebecca R.A variety of assays have been proposed to detect small quantities of nucleic acids at the point-of-care. One approach relies on target-induced aggregation of gold nanoparticles functionalized with oligonucleotide sequences complementary to adjacent regions on the targeted sequence. In the presence of the target sequence, the gold nanoparticles aggregate, producing an easily detectable shift in the optical scattering properties of the solution. The major limitations of this assay are that it requires heating, and that long incubation times are required to produce a result. This study aims to optimize the assay conditions and optical readout, with the goals of eliminating the need for heating and reducing the time to result without sacrificing sensitivity or dynamic range. By optimizing assay conditions and measuring the spectrum of scattered light at the endpoint of incubation, we find that the assay is capable of producing quantifiable results at room temperature in 30 minutes with a linear dynamic range spanning from 150 amoles to 15 fmoles of target. If changes in light scattering are measured dynamically during the incubation process, the linear range can be expanded 2-fold, spanning 50 amoles to 500 fmoles, while decreasing the time to result down to 10 minutes.Item High-resolution microendoscopy for esophageal cancer screening in China: A cost-effectiveness analysis(Baishideng Publishing Group Inc., 2015) Hur, Chin; Choi, Sung Eun; Kong, Chung Yin; Wang, Gui-Qi; Xu, Hong; Polydorides, Alexandros D.; Xue, Li-Yan; Perzan, Katherine E.; Tramontano, Angela C.; Richards-Kortum, Rebecca R.; Anandasabapathy, SharmilaAIM: To study the cost-effectiveness of high-resolution microendoscopy (HRME) in an esophageal squamous cell carcinoma (ESCC) screening program in China. METHODS: A decision analytic Markov model of ESCC was developed. Separate model analyses were conducted for cohorts consisting of an average-risk population or a high-risk population in China. Hypothetical 50-year-old individuals were followed until age 80 or death. We compared three different strategies for both cohorts: (1) no screening; (2) standard endoscopic screening with Lugol's iodine staining; and (3) endoscopic screening with Lugol's iodine staining and an HRME. Model parameters were estimated from the literature as well as from GLOBOCAN, the Cancer Incidence and Mortality Worldwide cancer database. Health states in the model included non-neoplasia, mild dysplasia, moderate dysplasia, high-grade dysplasia, intramucosal carcinoma, operable cancer, inoperable cancer, and death. Separate ESCC incidence transition rates were generated for the average-risk and high-risk populations. Costs in Chinese currency were converted to international dollars (I$) and were adjusted to 2012 dollars using the Consumer Price Index. RESULTS: The main outcome measurements for this study were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). For the average-risk population, the HRME screening strategy produced 0.043 more QALYs than the no screening strategy at an additional cost of I$646, resulting in an ICER of I$11808 per QALY gained. Standard endoscopic screening was weakly dominated. Among the high-risk population, when the HRME screening strategy was compared with the standard screening strategy, the ICER was I$8173 per QALY. For both the high-risk and average-risk screening populations, the HRME screening strategy appeared to be the most cost-effective strategy, producing ICERs below the willingness-to-pay threshold, I$23500 per QALY. One-way sensitivity analysis showed that, for the average-risk population, higher specificity of Lugol's iodine (> 40%) and lower specificity of HRME (< 70%) could make Lugol's iodine screening cost-effective. For the high-risk population, the results of the model were not substantially affected by varying the follow-up rate after Lugol's iodine screening, Lugol's iodine test characteristics (sensitivity and specificity), or HRME specificity. CONCLUSION: The incorporation of HRME into an ESCC screening program could be cost-effective in China. Larger studies of HRME performance are needed to confirm these findingsItem 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.Item In Vivo Multimodal Optical Imaging: Improved Detection of Oral Dysplasia in Low-Risk Oral Mucosal Lesions(AACR, 2018) Yang, Eric C.; Schwarz, Richard A.; Lang, Alexander K.; Bass, Nancy; Badaoui, Hawraa; Vohra, Imran S.; Cherry, Katelin D.; Williams, Michelle D.; Gillenwater, Ann M.; Vigneswaran, Nadarajah; Richards-Kortum, Rebecca R.Early detection of oral cancer and oral premalignant lesions (OPL) containing dysplasia could improve oral cancer outcomes. However, general dental practitioners have difficulty distinguishing dysplastic OPLs from confounder oral mucosal lesions in low-risk populations. We evaluated the ability of two optical imaging technologies, autofluorescence imaging (AFI) and high-resolution microendoscopy (HRME), to diagnose moderate dysplasia or worse (ModDys+) in 56 oral mucosal lesions in a low-risk patient population, using histopathology as the gold standard, and in 46 clinically normal sites. AFI correctly diagnosed 91% of ModDys+ lesions, 89% of clinically normal sites, and 33% of benign lesions. Benign lesions with severe inflammation were less likely to be correctly diagnosed by AFI (13%) than those without (42%). Multimodal imaging (AFI+HRME) had higher accuracy than either modality alone; 91% of ModDys+ lesions, 93% of clinically normal sites, and 64% of benign lesions were correctly diagnosed. Photos of the 56 lesions were evaluated by 28 dentists of varied training levels, including 26 dental residents. We compared the area under the receiver operator curve (AUC) of clinical impression alone to clinical impression plus AFI and clinical impression plus multimodal imaging using k-Nearest Neighbors models. The mean AUC of the dental residents was 0.71 (range: 0.45–0.86). The addition of AFI alone to clinical impression slightly lowered the mean AUC (0.68; range: 0.40–0.82), whereas the addition of multimodal imaging to clinical impression increased the mean AUC (0.79; range: 0.61–0.90). On the basis of these findings, multimodal imaging could improve the evaluation of oral mucosal lesions in community dental settings.Item Line-scanning confocal microendoscope for nuclear morphometry imaging(SPIE, 2017) Tang, Yubo; Carns, Jennifer; Richards-Kortum, Rebecca R.Fiber-optic endomicroscopy is a minimally invasive method to image cellular morphology in vivo. Using a coherent fiber bundle as an image relay, it allows additional imaging optics to be placed at the distal end of the fiber outside the body. In this research, we use this approach to demonstrate a compact, low-cost line-scanning confocal fluorescence microendoscope that can be constructed for <$5000 . Confocal imaging is enabled without the need for mechanical scanning by synchronizing a digital light projector with the rolling shutter of a CMOS camera. Its axial performance is characterized in comparison with a nonscanned high-resolution microendoscope. We validate the optical sectioning capability of the microendoscope by imaging a two-dimensional phantom and ex vivo mouse esophageal and colon tissues. Results show that optical sectioning using this approach improves visualization of nuclear morphometry and suggest that this low-cost line-scanning microendoscope can be used to evaluate various pathological conditions.Item Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial(Elsevier, 2015) Protano, Marion-Anna; Xu, Hong; Wang, Guiqi; Polydorides, Alexandros D.; Dawsey, Sanford M.; Cui, Junsheng; Xue, Liyan; Zhang, Fan; Quang, Timothy; Pierce, Mark C.; Shin, Dongsuk; Schwarz, Richard A.; Bhutani, Manoop S.; Lee, Michelle; Parikh, Neil; Hur, Chin; Xu, Weiran; Moshier, Erin; Godbold, James; Mitcham, Josephine; Hudson, Courtney; Richards-Kortum, Rebecca R.; Anandasabapathy, SharmilaBackground & Aims: Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol’s chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. Methods: In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. Results: By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%–66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%–57%) could have been spared any biopsy. Conclusions: In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708.Item Low-cost, high-resolution imaging for detecting cervical precancer in medically-underserved areas of Texas(Elsevier, 2019) Parra, Sonia G.; Rodriguez, Ana M.; Cherry, Katelin D.; Schwarz, Richard A.; Gowen, Rose M.; Guerra, Laura B.; Milbourne, Andrea M.; Toscano, Paul A.; Fisher-Hoch, Susan P.; Schmeler, Kathleen M.; Richards-Kortum, Rebecca R.Objective: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center. Methods: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated. Results: 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33). Conclusions: HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings.Item Method and apparatus for dose measurement(2013-09-17) Oden, Maria; Lukomnik, Julia Ellen Davidson; Dinh, Cindy M.; Guiterrez, Amanda Michelle; Amaro, Carlos; Richards-Kortum, Rebecca R.; Rice University; United States Patent and Trademark OfficeThe present disclosure relates to devices for use in conjunction with a syringe in measuring a dose using the syringe. In certain embodiments, a clip is provided that includes an elongated portion for insertion into a barrel of a syringe and a locking portion that locks onto a feature of the syringe. Once inserted, the clip physically prevents retraction of a plunger of the syringe past a certain point corresponding to a desired dose.Item 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.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.