Browsing by Author "Pierce, Mark C."
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Item 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, RebeccaCervical 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 showedItem 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.Item High-Resolution Microendoscopy for the Detection of Cervical Neoplasia in Low-Resource Settings(Public Library of Science, 2012) Quinn, Mary K.; Bubi, Tefo C.; Pierce, Mark C.; Kayembe, Mukendi K.; Ramogola-Masire, Doreen; Richards-Kortum, RebeccaCervical cancer is the second leading cause of cancer death among women in developing countries. Developing countries often lack infrastructure, cytotechnologists, and pathologists necessary to implement current screening tools. Due to their low cost and ease of interpretation at the point-of-care, optical imaging technologies may serve as an appropriate solution for cervical cancer screening in low resource settings. We have developed a high-resolution optical imaging system, the High Resolution Microendoscope (HRME), which can be used to interrogate clinically suspicious areas with subcellular spatial resolution, revealing changes in nuclear to cytoplasmic area ratio. In this pilot study carried out at the women's clinic of Princess Marina Hospital in Botswana, 52 unique sites were imaged in 26 patients, and the results were compared to histopathology as a reference standard. Quantitative high resolution imaging achieved a sensitivity and specificity of 86% and 87%, respectively, in differentiating neoplastic (≥CIN 2) tissue from non-neoplastic tissue. These results suggest the potential promise of HRME to assist in the detection of cervical neoplasia in low-resource settings.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 Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett's-associated neoplasia(SPIE, 2013-02) Thekkek, Nadhi; Pierce, Mark C.; Lee, Michelle H.; Polydorides, Alexandros D.; Flores, Raja M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.A modular video endoscope is developed and tested to allow imaging in different modalities. This system incorporates white light imaging (WLI), cross-polarized imaging (CPI), and vital-dye fluorescence imaging (VFI), using interchangeable filter modules. CPI and VFI are novel endoscopic modalities that probe mucosal features associated with Barrett's neoplasia. CPI enhances vasculature, while VFI enhances glandular architecture. In this pilot study, we demonstrate the integration of these modalities by imaging areas of Barrett's metaplasia and neoplasia in an esophagectomy specimen. We verify that those key image features are also observed during an in vivo surveillance procedure. CPI images demonstrate improved visualization of branching blood vessels associated with neoplasia. VFI images show glandular architecture with increased glandular effacement associated with neoplasia. Results suggests that important pathologic features seen in CPI and VFI are not visible during standard endoscopic white light imaging, and thus the modalities may be useful in future in vivo studies for discriminating neoplasia from Barrett's metaplasia. We further demonstrate that the integrated WLI/CPI/VFI endoscope is compatible with complementary high-resolution endomicroscopy techniques such as the high-resolution microendoscope, potentially enabling two-step (“red-flag” widefield plus confirmatory high-resolution imaging) protocols to be enhanced.Item Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost(Springer, 2014) Pierce, Mark C.; Weigum, Shannon E.; Jaslove, Jacob M.; Richards-Kortum, Rebecca; Tkaczyk, Tomasz S.; Rice 360 Institute for Global Health TechnologiesOne of the key elements in point-of-care (POC) diagnostic test instrumentation is the optical system required for signal detection and / or imaging. Many tests which use fluorescence, absorbance, or colorimetric optical signals are under development for management of infectious diseases in resource limited settings, where the overall size and cost of the device is of critical importance. At present, high-performance lenses are expensive to fabricate and difficult to obtain commercially, presenting barriers for developers of in vitro POC tests or microscopic image-based diagnostics. We recently described a compact “hybrid” objective lens incorporating both glass and plastic optical elements, with a numerical aperture of 1.0 and field-of-view of 250 μm. This design concept may potentially enable mass-production of high-performance, low-cost optical systems which can be easily incorporated in the readout path of existing and emerging POC diagnostic assays. In this paper, we evaluate the biological imaging performance of these lens systems in three broad POC diagnostic application areas; (1) bright field microscopy of histopathology slides, (2) cytologic examination of blood smears, and (3) immunofluorescence imaging. We also break down the fabrication costs and draw comparisons with other miniature optical systems. The hybrid lenses provided images with quality comparable to conventional microscopy, enabling examination of neoplastic pathology and infectious parasites including malaria and cryptosporidium. We describe how these components can be produced at below $10 per unit in full-scale production quantities, making these systems well suited for use within POC diagnostic instrumentation.Item Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinomaᅠ(Elsevier, 2015) Shin, Dongsuk; Protano, Marion-Anna; Polydorides, Alexandros D.; Dawsey, Sanford M.; Pierce, Mark C.; Kim, Michelle Kang; Schwarz, Richard A.; Quang, Timothy; Parikh, Neil; Bhutani, Manoop S.; Zhang, Fan; Wang, Guiqi; Xue, Liyan; Wang, Xueshan; Xu, Hong; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.Background & Aims: High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can be interpreted readily by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study, we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods: We performed an image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and at 1 hospital in the United States from May 2010 to October 2012. Biopsy specimens were collected from imaged sites (n = 375), and a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results: Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using the mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions: High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies.Item Quantitative analysis of high-resolution microendoscopic images for diagnosis of neoplasia in patients with Barrett’s esophagus(Elsevier, 2016) Shin, Dongsuk; Lee, Michelle H.; Polydorides, Alexandros D.; Pierce, Mark C.; Vila, Peter M.; Parikh, Neil D.; Rosen, Daniel G.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.Background and Aims: Previous studies show that microendoscopic images can be interpreted visually to identify the presence of neoplasia in patients with Barrett’s esophagus (BE), but this approach is subjective and requires clinical expertise. This study describes an approach for quantitative image analysis of microendoscopic images to identify neoplastic lesions in patients with BE. Methods: Images were acquired from 230 sites from 58 patients by using a fiberoptic high-resolution microendoscope during standard endoscopic procedures. Images were analyzed by a fully automated image processing algorithm, which automatically selected a region of interest and calculated quantitative image features. Image features were used to develop an algorithm to identify the presence of neoplasia; results were compared with a histopathology diagnosis. Results: A sequential classification algorithm that used image features related to glandular and cellular morphology resulted in a sensitivity of 84% and a specificity of 85%. Applying the algorithm to an independent validation set resulted in a sensitivity of 88% and a specificity of 85%. Conclusions: This pilot study demonstrates that automated analysis of microendoscopic images can provide an objective, quantitative framework to assist clinicians in evaluating esophageal lesions from patients with BE. (Clinical trial registration number: NCT01384227 and NCT02018367.)Item Snapshot 3D optical coherence tomography system using image mapping spectrometry(Optical Society of America, 2013) Nguyen, Thuc-Uyen; Pierce, Mark C.; Higgins, Laura; Tkaczyk, Tomasz S.A snapshot 3-Dimensional Optical Coherence Tomography system was developed using Image Mapping Spectrometry. This system can give depth information (Z) at different spatial positions (XY) within one camera integration time to potentially reduce motion artifact and enhance throughput. The current (x,y,λ) datacube of (85×356×117) provides a 3D visualization of sample with 400 μm depth and 13.4 μm in transverse resolution. Axial resolution of 16.0 μm can also be achieved in this proof-of-concept system. We present an analysis of the theoretical constraints which will guide development of future systems with increased imaging depth and improved axial and lateral resolutions.