Browsing by Author "Quang, Timothy"
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Item Development and Evaluation of a Multi-Modal Optical Imaging System for Early Identification of Oral Neoplasia(2016-10-27) Quang, Timothy; Richards-Kortum, RebeccaOver the last decade, the five-year survival rate for oral cancer has remained at only 64%. Despite easy access to the oral cavity, most patients with oral cancer are diagnosed at an advanced stage when treatment is more invasive and likely to be less successful. Imaging tools that can rapidly and accurately identify oral neoplasia could improve early detection of malignant oral lesions. This dissertation describes research to develop and evaluate a multi-modal optical imaging system with automated image processing to improve early detection of oral neoplasia. The multi-modal optical imaging system is comprised of two modalities, a high-resolution microendoscope (HRME) and a wide-field autofluorescence imager (AFI) to identify suspicious areas and to confirm whether suspicious areas contain neoplasia. A tablet-interfaced HRME with automated image analysis was developed and characterized to improve early detection of esophageal squamous cell carcinoma which has similar histologic patterns to oral neoplasia; results showed the tablet HRME can acquire comparable images to the first generation HRME design at a fraction of the cost and size. Training and validation was performed using a previously published dataset from a study of 177 patients referred for screening or surveillance endoscopy in China. Results showed that the automated image processing could differentiate between neoplastic and non-neoplastic images with a sensitivity of 95% and 91% in an independent validation set compared with 84% and 95% achieved in the original study. Additionally, automated image processing tools were developed to analyze wide-field autofluorescence images. The diagnostic performance of this approach was compared to previous results from a pilot study of 30 patients scheduled for surgical resection of a clinically suspicious oral lesion. The automated analysis method achieved a comparable area under the receiver operating characteristic curve (AUC) to the previous results based on manual analysis (0.862 automated vs. 0.877 manual) while minimizing dependence on user input. The automated analysis algorithms for AFI and HRME were then evaluated together to analyze images acquired from a population of 100 patients scheduled for surgical resection of a clinically suspicious oral lesion. A classification algorithm based on image metrics derived from AFI and HRME was able to correctly classify 100% of sites taken from biopsies pathologically diagnosed as normal and 85% of sites taken from biopsies diagnosed as moderate/severe dysplasia or cancer. These results provide evidence that multi-modal optical imaging with automated image analysis could be a valuable diagnostic adjunct for early detection of oral neoplasia.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.; BioengineeringOral 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 Feasibility of transoral robotic-assisted high-resolution microendoscopic imaging of oropharyngeal squamous cell carcinoma(Wiley, 2015) Patsias, Alexis; Giraldez-Rodriguez, Laureano A.; Polydorides, Alexandros D.; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila; Quang, Timothy; Sikora, Andrew G.; Miles, Brett A.; BioengineeringBackground: Transoral robotic-assisted oncologic surgery of the head and neck offers promising functional results. Nonetheless, the efficacy of oncologic surgery remains critically dependent on obtaining negative margins. We aimed to integrate a miniaturized high-resolution fiber-optic microendoscope (HRME), which provides real-time histological assessment, with the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA). Methods: Three patients undergoing transoral robotic surgery (TORS) were prospectively enrolled in this study. Optical imaging of the oropharynx was performed intraoperatively with the robotic-assisted HRME. Results: All patients underwent the procedure successfully with no complications. The HRME was successfully integrated with the da Vinci robotic system. Several sites of the oropharynx and associated malignancy were imaged, which correlated with the standard histopathological analysis. Conclusion: Transoral robotic-assisted HRME imaging of the oropharynx is a safe and technically feasible approach, providing a real-time histological assessment and may serve as a valuable aid in oncologic surgery.Item Fluorescence-based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer(Wiley, 2015) Sakuma, Shinji; Yu, James Y.H.; Quang, Timothy; Hiwatari, Ken-Ichiro; Kumagai, Hironori; Kao, Stephanie; Holt, Alex; Erskind, Jalysa; McClure, Richard; Siuta, Michael; Kitamura, Tokio; Tobita, Etsuo; Koike, Seiji; Wilson, Kevin; Richards-Kortum, Rebecca; Liu, Eric; Washington, Kay; Omary, Reed; Gore, John C.; Pham, Wellington; BioengineeringThomsen–Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.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, Sharmila; BioengineeringBackground & 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 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; BioengineeringNearly 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.Item Optical Molecular Imaging in the Gastrointestinal Tract(Elsevier, 2013-05) Carns, Jennifer; Keahey, Pelham; Quang, Timothy; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca; BioengineeringRecent developments in optical molecular imaging allow for real-time identification of morphological and biochemical changes in tissue associated with gastrointestinal neoplasia. This review summarizes widefield and high resolution imaging modalities currently in pre-clinical and clinical evaluation for the detection of colorectal cancer and esophageal cancer. Widefield techniques discussed include high definition white light endoscopy, narrow band imaging, autofluoresence imaging, and chromoendoscopy; high resolution techniques discussed include probe-based confocal laser endomicroscopy, high-resolution microendoscopy, and optical coherence tomography. Finally, new approaches to enhance image contrast using vital dyes and molecular-specific targeted contrast agents are evaluated.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.; BioengineeringBackground & 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 Real-time video mosaicing with a high-resolution microendoscope(Optical Society of America, 2012) Bedard, Noah; Quang, Timothy; Schmeler, Kathleen; Richards-Kortum, Rebecca; Tkaczyk, Tomasz S.; Bioengineering; Electrical and Computer EngineeringMicroendoscopes allow clinicians to view subcellular features in vivo and in real-time, but their field-of-view is inherently limited by the small size of the probe's distal end. Video mosaicing has emerged as an effective technique to increase the acquired image size. Current implementations are performed post-procedure, which removes the benefits of live imaging. In this manuscript we present an algorithm for real-time video mosaicing using a low-cost high-resolution microendoscope. We present algorithm execution times and show image results obtained from in vivo tissue.