R-3 Repository :: Browsing by Author "Richards-Kortum, Rebecca"

Browsing by Author "Richards-Kortum, Rebecca"

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A High-Value, Low-Cost Bubble Continuous Positive Airway Pressure System for Low-Resource Settings: Technical Assessment and Initial Case Reports
(Public Library of Science, 2013) Brown, Jocelyn; Machen, Heather; Kawaza, Kondwani; Mwanza, Zondiwe; Iniguez, Suzanne; Lang, Hans; Gest, Alfred; Kennedy, Neil; Miros, Robert; Richards-Kortum, Rebecca; Molyneux, Elizabeth; Oden, Maria
Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately $350. Moreover, because of its simple designﾗconsumergrade pumps, medical tubing, and regulators—it requires only the simple replacement of a ,$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device.
A mobile-phone based high-resolution microendoscope to image cervical precancer
(Public Library of Science, 2019) Grant, Benjamin D.; Quang, Timothy; Possati-Resende, Júlio César; Scapulatempo-Neto, Cristovam; Matsushita, Graziela de Macedo; Mauad, Edmundo Carvalho; Stoler, Mark H.; Castle, Philip E.; Fregnani, José Humberto Tavares Guerreiro; Schmeler, Kathleen M.; Richards-Kortum, Rebecca
Nearly 90% of cervical cancer cases and deaths occur in low- and middle-income countries that lack comprehensive national HPV immunization and cervical cancer screening programs. In these settings, it is difficult to implement screening programs due to a lack of infrastructure and shortage of trained personnel. Screening programs based on visual inspection with acetic acid (VIA) have been successfully implemented in some low-resource settings. However, VIA has poor specificity and up to 90% of patients receiving treatment based on a positive VIA exam are over-treated. A number of studies have suggested that high-resolution cervical imaging to visualize nuclear morphology in vivo can improve specificity by better distinguishing precancerous and benign lesions. To enable high-resolution imaging in low-resource settings, we developed a portable, low-cost, high-resolution microendoscope that uses a mobile phone to detect and display images of cervical epithelium in vivo with subcellular resolution. The device was fabricated for less than $2,000 using commercially available optical components including filters, an LED and triplet lenses assembled in a 3D-printed opto-mechanical mount. We show that the mobile high-resolution microendoscope achieves similar resolution and signal-to-background ratio as previously reported high-resolution microendoscope systems using traditional cameras and computers to detect and display images. Finally, we demonstrate the ability of the mobile high-resolution microendoscope to image normal and precancerous squamous epithelium of the cervix in vivo in a gynecological referral clinic in Barretos, Brazil.
A novel tailed primer nucleic acid test for detection of HPV 16, 18 and 45 DNA at the point of care
(Springer Nature, 2023) Chang, Megan M.; Ma, Ariel; Novak, Emilie Newsham; Barra, Maria; Kundrod, Kathryn A.; Montealegre, Jane Richards; Scheurer, Michael E.; Castle, Philip E.; Schmeler, Kathleen; Richards-Kortum, Rebecca
Cervical cancer is a leading cause of death for women in low-resource settings despite being preventable through human papillomavirus (HPV) vaccination, early detection, and treatment of precancerous lesions. The World Health Organization recommends high-risk HPV (hrHPV) as the preferred cervical cancer screening strategy, which is difficult to implement in low-resource settings due to high costs, reliance on centralized laboratory infrastructure, and long sample-to-answer times. To help meet the need for rapid, low-cost, and decentralized cervical cancer screening, we developed tailed primer isothermal amplification and lateral flow detection assays for HPV16, HPV18, and HPV45 DNA. We translated these assays into a self-contained cartridge to achieve multiplexed detection of three hrHPV genotypes in a disposable cartridge. The developed test achieves clinically relevant limits of detection of 50–500 copies per reaction with extracted genomic DNA from HPV-positive cells. Finally, we performed sample-to-answer testing with direct lysates of HPV-negative and HPV-positive cell lines and demonstrated consistent detection of HPV16, HPV18, and HPV45 with 5000–50,000 cells/mL in < 35 min. With additional optimization to improve cartridge reliability, incorporation of additional hrHPV types, and validation with clinical samples, the assay could serve as a point-of-care HPV DNA test that improves access to cervical cancer screening in low-resource settings.
A Nucleic Acid Test to Diagnose Cryptosporidiosis: Lab Assessment in Animal and Patient Specimens
(American Chemical Society, 2014) Crannell, Zachary Austin; Castellanos-Gonzalez, Alejandro; Irani, Ayesha; Rohrman, Brittany; White, Arthur Clinton; Richards-Kortum, Rebecca
Diarrheal diseases cause more morbidity and mortality around the world than HIV, malaria or tuberculosis. Given that effective treatment of persistent diarrheal illness requires knowledge of the causative organism, diagnostic tests are of paramount importance. The protozoan parasites of the genus Cryptosporidium are increasingly recognized to be responsible for a significant portion of diarrhea morbidity. We present a novel nucleic acid test to detect the presence of Cryptosporidium species in DNA extracted from stool samples. The assay uses the isothermal amplification technique Recombinase Polymerase Amplification (RPA) to amplify trace amounts of pathogen DNA extracted from stool to detectable levels in 30 minutes; products are then detected visually on simple lateral flow strips. The RPA-based Cryptosporidium assay (RPAC assay) was developed and optimized using DNA from human stool samples spiked with pathogen. It was then tested using DNA extracted from the stool of infected mice where it correctly identified the presence or absence of 27 out of 28 stool samples. It was finally tested using DNA extracted from the stool of infected patients where it correctly identified the presence or absence of 21 out of 21 stool samples. The assay was integrated into a foldable, paper and plastic device that enables DNA amplification with only the use of pipettes, pipette tips, and a heater. The performance of the integrated assay is comparable to or better than PCR, without requiring the use of thermal cycling equipment. This platform can easily be adapted to detect DNA from multiple pathogens.
A paper-based immunoassay to determine HPV vaccination status at the point-of-care
(Elsevier, 2016) Grant, Benjamin D.; Smith, Chelsey A.; Castle, Philip E.; Scheurer, Michael E.; Richards-Kortum, Rebecca
Objective: To develop and evaluate a paper-based point-of-care HPV serology test to determine if an individual has received two or more HPV immunizations. Methods: The paper-based immunoassay was constructed using a nitrocellulose lateral flow strip with adsorbed HPV16 virus-like particles serving as the capturing moiety. Three capture zones containing virus-like particles were placed in series to allow for visual discrimination between high and low HPV16 plasma antibody concentrations. A plasma separation membrane was used to allow whole blood to be applied directly to the assay. All reagents were dried on glass fiber pads during device fabrication and were rehydrated with buffer at the time of use. A pilot study consisting of 35 subjects with a history of zero, one, two or three HPV vaccines was conducted to evaluate the immunoassay. The completed paper-based immunoassays were scanned for visual interpretation by three researchers who were blinded to the true results and separately evaluated quantitatively using MATLAB. Results: For the 28 tests valid for analysis, fifteen subjects reported receiving two or more HPV vaccines, three reported receiving one, and ten reported having no HPV vaccinations. The paper-based immunoassays for all fifteen subjects who reported having received two or more HPV vaccines were judged positive by all researchers. Twelve of the thirteen tests from individuals reporting one or zero vaccinations were deemed negative by all observers. One test from an unvaccinated individual was judged positive by two out of three reviewers. Quantitatively, all tests were correctly separated between the two groups. Conclusions: We successfully designed and tested a HPV serology test amenable to the point-of-care. The device showed promising results in a pilot study for discriminating between those who received two or more HPV vaccinations and those who did not. Furthermore, this device offers a platform for producing other semi-quantitative point-of-care serological tests.
A Pilot Study of Low-Cost, High-Resolution Microendoscopy as a Tool for Identifying Women with Cervical Precancer
(AACR, 2012) Pierce, Mark C.; Guan, YaoYao; Quinn, Mary Kate; Zhang, Xun; Zhang, Wen-Hua; Qiao, You-Lin; Castle, Philip; Richards-Kortum, Rebecca
Cervical cancer remains one of the leading causes of death among women in developing countries. Without resources to support Pap smear cytology and colposcopy, cost-effective approaches which enable single-visit "see-and-treat" protocols offer the potential to reduce morbidity and mortality due to this preventable disease. We carried out a pilot clinical study in Shanxi province, China, to evaluate a low-cost, high-resolution microendoscope (HRME) imaging system which enables evaluation of epithelial cell morphology in vivo. HRME images were obtained at discrete sites on the cervix in 174 women, in addition to visual inspection with acetic acid (VIA) and colposcopic examination. Of 69 sites appearing abnormal on colposcopy, only 12 showed high-grade disease (CIN2+) on pathology. Quantification of the nuclear-to-cytoplasm ratio by HRME enabled an ad hoc threshold to be defined, which correctly classified all 12 sites as abnormal, whilst classifying 38 of the remaining 57 pathology normal sites as normal. All patients with biopsy confirmed high-grade disease also tested positive for high-risk human papilloma virus (HPV) DNA and were classified as abnormal by HRME. Among the remaining patients who tested positive for HPV but were either normal by colposcopy or showed
Accuracy of In Vivo Multimodal Optical Imaging for Detection of Oral Neoplasia
(AACR, 2012) Pierce, Mark C.; Schwarz, Richard A.; Bhattar, Vijayashree S.; Mondrik, Sharon; Williams, Michelle D.; Lee, J. Jack; Richards-Kortum, Rebecca; Gillenwater, Ann M.
If detected early, oral cancer is eminently curable. However, survival rates for oral cancer patients remain low, largely due to late-stage diagnosis and subsequent difficulty of treatment. To improve cliniciansﾒ ability to detect early disease and to treat advanced cancers, we developed a multimodal optical imaging system (MMIS) to evaluate tissue in situ, at macroscopic and microscopic scales. The MMIS was used to measure 100 anatomic sites in 30 patients, correctly classifying 98% of pathologically confirmed normal tissue sites, and 95% of sites graded as moderate dysplasia, severe dysplasia, or cancer. When used alone, MMIS classification accuracy was 35% for sites determined by pathology as mild dysplasia. However, MMIS measurements correlated with expression of candidate molecular markers in 87% of sites with mild dysplasia. These findings support the ability of noninvasive multimodal optical imaging to accurately identify neoplastic tissue and premalignant lesions. This in turn may have considerable impact on detection and treatment of patients with oral cancer and other epithelial malignancies.
All-plastic, miniature, digital fluorescence microscope for three part white blood cell differential measurements at the point of care
(The Optical Society, 2015) Forcucci, Alessandra; Pawlowski, Michal E.; Majors, Catherine; Richards-Kortum, Rebecca; Tkaczyk, Tomasz S.
Three-part differential white blood cell counts are used for disease diagnosis and monitoring at the point-of-care. A low-cost, miniature achromatic microscope was fabricated for identification of lymphocytes, monocytes, and granulocytes in samples of whole blood stained with acridine orange. The microscope was manufactured using rapid prototyping techniques of diamond turning and 3D printing and is intended for use at the point-of-care in low-resource settings. The custom-designed microscope requires no manual adjustment between samples and was successfully able to classify three white blood cell types (lymphocytes, granulocytes, and monocytes) using samples of peripheral whole blood stained with acridine orange.
American Society of Clinical Oncology (ASCO) Cervical Cancer Prevention Program: A Hands-On Training Course in Nepal
(ASCO, 2021) Phoolcharoen, Natacha; Kremzier, Megan; Eaton, Vanessa; Sarchet, Vanessa; Acharya, Sandhya Chapagain; Shrestha, Eliza; Carns, Jennifer; Baker, Ellen; Varon, Melissa Lopez; Karmacharya, Saujanya; Aryal, Binod; Richards-Kortum, Rebecca; Salcedo, Mila Pontremoli; Schmeler, Kathleen M.; Pariyar, Jitendra
Cervical cancer is the leading cause of death among women in Nepal. The American Society of Clinical Oncology (ASCO) and The University of Texas MD Anderson Cancer Center collaborated with international and local experts to hold a cervical cancer prevention course in Nepal in November 2019. The course included didactic lectures and a hands-on workshop. The didactic lectures included the epidemiology of cervical cancer globally and locally, cervical cancer screening guidelines, human papillomavirus vaccination, colposcopy and visual inspection with acetic acid (VIA), cervical dysplasia, and cervical cancer treatment. The hands-on workshop consisted of four stations: (1) VIA; (2) colposcopy, cervical biopsy, and endocervical curettage; (3) thermal ablation; and (4) loop electrosurgical excision procedure (LEEP). A train-the-trainer model short course was held by the international faculty to assist six local faculty to become familiar with the instruments, procedures, and models used in the hands-on training stations. Forty-two people (84% gynecologist, 8% radiation oncologist, and 8% other) attended the course. Following the course, the international faculty visited the regional hospitals for additional educational activities. Increased knowledge in cervical cancer screening guidelines and ability in performing VIA, colposcopy and cervical biopsy, thermal ablation, and LEEP were reported by 89%, 84%, 84%, 87%, and 84% of participants, respectively, from the postcourse on-site evaluations. From the 6-month follow-up survey, all respondents reported that they had made practice changes based on what they learned in the course and had implemented or tried to implement the cervical cancer screening guidelines presented at the course. In conclusion, the course evaluations suggested an improvement in participants' ability to perform cervical cancer screening and diagnostic procedures and reported the changes in practices after training.
An optimized procedure to allow 3D optical imaging of biomarkers associated with neoplasia in the oral mucosa
(2016-11-22) Tran, Emily; Richards-Kortum, Rebecca
Implementation of an optical clearing technique, called the Passive Clarity Technique (PACT), in mouse tongues enables three-dimensional (3D) fluorescence imaging of intact oral epithelial tissue. Using 3D imaging to improve our understanding of the spatial and temporal patterns of biomarker expression and phenotypic features in oral pre-cancer can improve accuracy of early diagnostic tools. Current methods for 3D fluorescence imaging require thin sectioning and accurate image reconstruction or are limited in imaging depth by tissue scattering. Using a polymer-tissue hydrogel technique previously developed for brain tissue, light scattering molecules were removed from mouse tongues to improve tissue transparency and antibody permeability for imaging and immunolabeling. In this study, PACT-Cleared tongues resulted in resolution of tissue features up to 500 μm in depth, while preserving tissue architecture and molecular information in normal and precancerous tissue. These findings can facilitate further exploration of biomarkers of oral cancer progression in a mouse model.
Aptamer-Targeted Gold Nanoparticles As Molecular-Specific Contrast Agents for Reflectance Imaging
(American Chemical Society, 2008) Javier, David J.; Nitin, Nitin; Levy, Matthew; Ellington, Andrew; Richards-Kortum, Rebecca
Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This design strategy can easily be modified to incorporate multifunctional agents as part of a multimodal platform for reflectance imaging applications.
Automated frame selection process for high-resolution microendoscopy
(SPIE, 2015) Ishijima, Ayumu; Schwarz, Richard A.; Shin, Dongsuk; Mondrik, Sharon; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca
We developed an automated frame selection algorithm for high-resolution microendoscopy video sequences. The algorithm rapidly selects a representative frame with minimal motion artifact from a short video sequence, enabling fully automated image analysis at the point-of-care. The algorithm was evaluated by quantitative comparison of diagnostically relevant image features and diagnostic classification results obtained using automated frame selection versus manual frame selection. A data set consisting of video sequences collected in vivo from 100 oral sites and 167 esophageal sites was used in the analysis. The area under the receiver operating characteristic curve was 0.78 (automated selection) versus 0.82 (manual selection) for oral sites, and 0.93 (automated selection) versus 0.92 (manual selection) for esophageal sites. The implementation of fully automated high-resolution microendoscopy at the point-of-care has the potential to reduce the number of biopsies needed for accurate diagnosis of precancer and cancer in low-resource settings where there may be limited infrastructure and personnel for standard histologic analysis.
Automated In Vivo High-Resolution Imaging to Detect Human Papillomavirus–Associated Anal Precancer in Persons Living With HIV
(Wolters Kluwer, 2023) Brenes, David; Kortum, Alex; Carns, Jennifer; Mutetwa, Tinaye; Schwarz, Richard; Liu, Yuxin; Sigel, Keith; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila; Gaisa, Michael; Chiao, Elizabeth
INTRODUCTION: In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer. METHODS: The HRME, a fiber-optic fluorescence microscope, was used to capture real-time images of anal squamous epithelial nuclei. Nuclear staining is achieved using 0.01% wt/vol proflavine, a topical contrast agent. HRME images were analyzed by a multitask deep learning network (MTN) that computed the probability of AIN 2+ for each HRME image. RESULTS: The study accrued data from 77 people living with HIV. The MTN achieved an area under the receiver operating curve of 0.84 for detection of AIN 2+. At the AIN 2+ probability cutoff of 0.212, the MTN achieved comparable performance to expert HRA impression with a sensitivity of 0.92 (P = 0.68) and specificity of 0.60 (P = 0.48) when using histopathology as the gold standard. DISCUSSION: When used in combination with HRA, this system could facilitate more selective biopsies and promote same-day AIN2+ treatment options by enabling real-time diagnosis.
AutoSyP: A Low-Cost, Low-Power Syringe Pump for Use in Low-Resource Settings
(The American Society of Tropical Medicine and Hygiene, 2016) Juarez, Alexa; Maynard, Kelley; Skerrett, Erica; Molyneux, Elizabeth; Richards-Kortum, Rebecca; Dube, Queen; Oden, Z. Maria; Rice 360: Institute for Global Health Technologies
This article describes the design and evaluation of AutoSyP, a low-cost, low-power syringe pump intended to deliver intravenous (IV) infusions in low-resource hospitals. A constant-force spring within the device provides mechanical energy to depress the syringe plunger. As a result, the device can run on rechargeable battery power for 66 hours, a critical feature for low-resource settings where the power grid may be unreliable. The device is designed to be used with 5- to 60-mL syringes and can deliver fluids at flow rates ranging from 3 to 60 mL/hour. The cost of goods to build one AutoSyP device is approximately $500. AutoSyP was tested in a laboratory setting and in a pilot clinical study. Laboratory accuracy was within 4% of the programmed flow rate. The device was used to deliver fluid to 10 healthy adult volunteers and 30 infants requiring IV fluid therapy at Queen Elizabeth Central Hospital in Blantyre, Malawi. The device delivered fluid with an average mean flow rate error of −2.3% ± 1.9% for flow rates ranging from 3 to 60 mL/hour. AutoSyP has the potential to improve the accuracy and safety of IV fluid delivery in low-resource settings.
Avoid equipment graveyards: rigorous process to improve identification and procurement of effective, affordable, and usable newborn devices in low-resource hospital settings
(Springer Nature, 2023) Asma, Elizabeth; Heenan, Megan; Banda, George; Kirby, Rebecca P.; Mangwiro, Lucky; Acemyan, Claudia Ziegler; Palamountain, Kara M.; Kortum, Philip; Kawaza, Kondwani; Oden, Z. Maria; Richards-Kortum, Rebecca; Brandt, Alexsandra; Kumara, Danica; Jin, Li; Khalid, Ali; Osoo, Cliff; Bisceglia, Nicki; Gate, Vince; Valle, Maureen; Mjumira, Rowland; Chapin, Abby; Shapiro, Alyssa; Samuel, Christina; Kimmey, David; Belton, M. Grant; Wang, Yifan Jack; Johnston, Jake; Anderson, Jessica; Bailey, Joseph; Coyle, Josh; Gordon, Kaede; Weld, Madeleine Tadros; Bond, Meaghan; Mitchell, Natalie; Mobarhan, Sara Liaghati; Salter, Sarah Elina; Matin, Shababa B.; Saenz, Sonia E. Sosa; Kalikoff, Sylvie; Boles, Taylor; Technical Collaborative Authorship Group; Rice360 Institute for Global Health Technologies
Millions of newborns die annually from preventable causes, with the highest rates occurring in Africa. Reducing neonatal mortality requires investment to scale hospital care, which includes providing hospitals with appropriate technology to care for small and sick newborns. Expensive medical devices designed for high-resource settings often fail to withstand conditions in low-resource hospitals, including humidity, dust, frequent user turnover, complex maintenance, lack of stable power, or difficulty sourcing expensive consumables. Rigorous evaluation protocols are needed to identify effective, affordable, rugged, and easy-to-use medical devices appropriate for quality hospital-based newborn care in low-resource hospitals.
Bubble continuous positive airway pressure
(2019-06-11) Richards-Kortum, Rebecca; Oden, Maria Z.; Brown, Jocelyn Kaye; Miros, Robert H.J.; Molyneux, Elizabeth; Rice University; United States Patent and Trademark Office
A bubble continuous positive airway pressure system may include an adjustable flow generator configured to control a flow rate of air to be delivered to a patient. A pressure-regulated delivery system is configured to control a pressure delivered to the patient interface. The delivery system is operatively connected to a pressure control tube. One end of the pressure control tube is submerged in a liquid. A patient interface is configured to transfer pressure from the pressure control tube to the patient's airway.
Cervical cancer prevention program in Nepal: a ‘training of trainers’ approach
(International Society of Global Health, 2023) Batman, Samantha; Piya, Madan; Chapagain, Sandhya; Lama, Poonam; Maharjan, Pabitra; Aryal, Binod; Neupane, Maya; Pariyar, Shashwat; Phoolcharoen, Natacha; Eaton, Vanessa; Sarchet, Vanessa; Kremzier, Megan; Carns, Jenny; Richards-Kortum, Rebecca; Baker, Ellen; Varon, Melissa Lopez; Salcedo, Mila Pontremoli; Milan, Jessica; Schmeler, Kathleen; Pariyar, Jitendra
Background: Cervical cancer remains the leading cause of cancer-related death among Nepalese women. To this effect, Cancer Care Nepal established an international collaboration to implement a 'training of trainers' (TOT) program to expand the reach of cervical cancer prevention techniques. Methods: The Nepal cervical cancer prevention program began with an in-person TOT session in Kathmandu in November 2019. Due to the COVID-19 pandemic, two additional TOT courses were held in October and November 2021 with virtual support, didactic lectures from international faculty, and a hands-on component by Nepalese faculty. The Nepalese providers underwent training in these courses and then held further training in five collaborating centers across Nepal. Participants completed pre- and post-course knowledge assessments. The trainings were supplemented by the creation of a new Project ECHO® (Extension for Community Healthcare Outcomes) telementoring hub at Cancer Care Nepal. A capstone refresher course was held in November 2022. Results: 42 participants attended the initial TOT course in 2019. The two follow-up TOT courses held in October/November 2021 were two days long and included providers from five participating regions in Nepal. The courses included virtual didactic sessions followed by hands-on stations led by the Nepalese faculty who had participated in the 2019 TOT course. The stations included: visual inspection with acetic acid (VIA), colposcopy, thermal ablation, and loop electrosurgical excision procedure (LEEP). There were 41 participants in the October/November TOT courses. The trainers who received the TOT education then conducted local courses of similar content in each of the five regions for 152 local providers. Participants had improved mean knowledge scores after the training (0.70, 95% CI=0.67-0.72) in comparison to prior to training (0.50, 95% CI=0.47-0.53), p\<0.001. The program concluded with a capstone course in November 2022 attended by 26 participants. To date, 11 Project ECHO sessions have been held, with an average of 20 participants per session. Conclusions: Nepal's cervical cancer prevention program has increased the number of providers trained in cervical cancer prevention techniques. By increasing provider capacity, individuals will have increased access to cervical cancer screening and treatment of pre-invasive disease, hopefully decreasing the burden of cervical cancer in Nepal.
Clinical training and validation of the LeukoScope: a low-cost, point-of-care device to perform white blood cell and neutrophil counts
(Royal Society of Chemistry, 2019) Majors, Catherine E.; Pawlowski, Michal E.; Burke, Daniel C.; Tkaczyk, Tomasz S.; Rieber, Alyssa; Richards-Kortum, Rebecca
A white blood cell (WBC) count with partial differential is an important clinical laboratory test. However, current methods to perform a WBC count and differential are difficult to use at the point of care or too expensive for use in low-resource settings. To meet this need, we developed the LeukoScope: a low-cost system to measure a WBC and neutrophil count from a single drop of blood at the point of care. The LeukoScope is battery powered and has a sample-to-answer time of <5 minutes. A drop of blood from a finger stick is added to a LeukoScope sample cartridge where pre-dried acridine orange fluorescently stains WBCs. The cartridge is then inserted into the LeukoScope reader where a portable fluorescence microscope captures a color image of the sample, which is analyzed to report results to the user. The LeukoScope system was tested at the point of care using fingerprick samples collected from 105 general oncology patients in Houston, TX. Performance of the LeukoScope was compared to that of a HemoCue WBC DIFF performed using the same fingerprick sample; clinical laboratory analysis of a venous blood draw was used as the gold standard in all cases. Bland–Altman analysis showed that the LeukoScope and HemoCue WBC DIFF had similar accuracy for measurement of WBC and neutrophil counts as compared to the gold standard. Seven out of eight patients with abnormal WBC count values were correctly identified using the LeukoScope, while six out of eight were correctly identified using the HemoCue WBC DIFF. Five out of six patients with abnormal neutrophil counts were correctly identified using the LeukoScope, while six of six were correctly identified using the HemoCue WBC DIFF.
Confocal fluorescence microscopy for rapid evaluation of invasive tumor cellularity of inflammatory breast carcinoma core needle biopsies
(Springer, 2014) Dobbs, Jessica; Krishnamurthy, Savitri; Kyrish, Matthew; Benveniste, Ana Paula; Yang, Wei; Richards-Kortum, Rebecca
Tissue sampling is a problematic issue for inflammatory breast carcinoma, and immediate evaluation following core needle biopsy is needed to evaluate specimen adequacy. We sought to determine if confocal fluorescence microscopy provides sufficient resolution to evaluate specimen adequacy by comparing invasive tumor cellularity estimated from standard histologic images to invasive tumor cellularity estimated from confocal images of breast core needle biopsy specimens. Grayscale confocal fluorescence images of breast core needle biopsy specimens were acquired following proflavine application. A breast-dedicated pathologist evaluated invasive tumor cellularity in histologic images with hematoxylin and eosin staining and in grayscale and false-colored confocal images of cores. Agreement between cellularity estimates was quantified using a kappa coefficient. 23 cores from 23 patients with suspected inflammatory breast carcinoma were imaged. Confocal images were acquired in an average of less than 2 min per core. Invasive tumor cellularity estimated from histologic and grayscale confocal images showed moderate agreement by kappa coefficient: κ = 0.48 ± 0.09 (p < 0.001). Grayscale confocal images require less than 2 min for acquisition and allow for evaluation of invasive tumor cellularity in breast core needle biopsy specimens with moderate agreement to histologic images. We show that confocal fluorescence microscopy can be performed immediately following specimen acquisition and could indicate the need for additional biopsies at the initial visit.
Confocal foveated endomicroscope for the detection of esophageal carcinoma
(The Optical Society, 2015) Shadfan, Adam; Hellebust, Anne; Richards-Kortum, Rebecca; Tkaczyk, Tomasz
By mimicking the variable resolution of the human eye, a newly designed foveated endomicroscopic objective shows the potential to improve current endoscopic based techniques of identifying abnormal tissue in the esophagus and colon. The prototype miniature foveated objective is imaged with a confocal microscope to provide large field of view images combined with a high resolution central region to rapidly observe morphological structures associated with cancer development in a mouse model.

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