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    Article: Pre-clinical evaluation of fluorescent deoxyglucose as a topical contrast agent for the detection of Barrett's-associated neoplasia during confocal imaging.
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    ABSTRACT: The availability of confocal endomicroscopy motivates the development of optical contrast agents that can delineate the morphologic and metabolic features of gastrointestinal neoplasia. This study evaluates 2-NBDG, a fluorescent deoxyglucose, the uptake of which is associated with increased metabolic activity, in the identification of Barrett's-associated neoplasia. Surveillance biopsies from patients with varying pathologic grades of Barrett's esophagus were incubated ex vivo at 37°C with 2-NBDG and imaged with a fluorescence confocal microscope. Images were categorized as neoplastic (high grade dysplasia, esophageal adenocarcinoma) or metaplastic (intestinal metaplasia, low grade dysplasia) based on the degree of glandular 2-NBDG uptake. Classification accuracy was assessed using histopathology as the gold standard. Forty-four biopsies were obtained from twenty-six patients; 206 sites were imaged. The glandular mean fluorescence intensity of neoplastic sites was significantly higher than that of metaplastic sites (p<0.001). Chronic inflammation was associated with increased 2-NBDG uptake in the lamina propria but not in glandular epithelium. Sites could be classified as neoplastic or not with 96% sensitivity and 90% specificity based on glandular mean fluorescence intensity. Classification accuracy was not affected by the presence of inflammation. By delineating the metabolic and morphologic features of neoplasia, 2-NBDG shows promise as a topical contrast agent for confocal imaging. Further in vivo testing is needed to determine its performance in identifying neoplasia during confocal endomicroscopic imaging.
    Technology in cancer research & treatment 10/2011; 10(5):431-41. · 2.02 Impact Factor
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    Article: Emerging roles for multimodal optical imaging in early cancer detection: a global challenge.
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    ABSTRACT: Medical imaging technologies have become increasingly important in the clinical management of cancer, and now play key roles in cancer screening, diagnosis, staging, and monitoring response to treatment. Standard imaging modalities such as MRI, PET, and CT require significant financial resources and infrastructure, which limits access to these modalities to those patients in high-resource settings. In contrast, optical imaging strategies, with the potential for reduced cost and enhanced portability, are emerging as additional tools to facilitate the early detection and diagnosis of cancer. This article presents a vision for an expanding role for optical imaging in global cancer management, including screening, early detection at the point-of-care, biopsy guidance, and real-time histology. Multi-modal optical imaging - the combination of widefield and high resolution imaging - has the potential to aid in the detection and management of precancer and early cancer for traditionally underserved populations. Several recent widefield and high-resolution optical imaging technologies are described, along with requirements for implementing such devices into lower-resource - settings.
    Technology in cancer research & treatment 04/2010; 9(2):211-7. · 2.02 Impact Factor
  • Article: Vital-dye enhanced fluorescence imaging of GI mucosa: metaplasia, neoplasia, inflammation.
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    ABSTRACT: Confocal endomicroscopy has revolutionized endoscopy by offering subcellular images of the GI epithelium; however, the field of view is limited. Multiscale endoscopy platforms that use widefield imaging are needed to better direct the placement of high-resolution probes. Feasibility study. This study evaluated the feasibility of a single agent, proflavine hemisulfate, as a contrast medium during both widefield and high-resolution imaging to characterize the morphologic changes associated with a variety of GI conditions. The University of Texas MD Anderson Cancer Center, Houston, Texas, and Mount Sinai Medical Center, New York, New York. PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASUREMENTS: Resected specimens were obtained from 15 patients undergoing EMR, esophagectomy, or colectomy. Proflavine hemisulfate, a vital fluorescent dye, was applied topically. The specimens were imaged with a widefield multispectral microscope and a high-resolution microendoscope. The images were compared with histopathologic examination. Widefield fluorescence imaging enhanced visualization of morphology, including the presence and spatial distribution of glands, glandular distortion, atrophy, and crowding. High-resolution imaging of widefield abnormal areas revealed that neoplastic progression corresponded to glandular heterogeneity and nuclear crowding in dysplasia, with glandular effacement in carcinoma. These widefield and high-resolution image features correlated well with the histopathologic features. This imaging approach must be validated in vivo with a larger sample size. Multiscale proflavine-enhanced fluorescence imaging can delineate epithelial changes in a variety of GI conditions. Distorted glandular features seen with widefield imaging could serve as a critical bridge to high-resolution probe placement. An endoscopic platform combining the two modalities with a single vital dye may facilitate point-of-care decision making by providing real-time, in vivo diagnoses.
    Gastrointestinal endoscopy 01/2012; 75(4):877-87. · 6.71 Impact Factor
  • Article: Use of in vivo real-time optical imaging for esophageal neoplasia.
    Peter M Vila, Nadhi Thekkek, Rebecca Richards-Kortum, Sharmila Anandasabapathy
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    ABSTRACT: Esophageal adenocarcinoma carries a poor prognosis, as it typically presents at a late stage. Thus, a major research priority is the development of novel diagnostic-imaging strategies that can detect neoplastic lesions earlier and more accurately than current techniques. Advances in optical imaging allow clinicians to obtain real-time histopathologic information with instant visualization of cellular architecture and the potential to identify neoplastic tissue. The various endoscopic imaging modalities for esophageal neoplasia can be grouped into 2 major categories: (1) wide-field imaging, a comparatively lower-resolution view for imaging larger surface areas, and (2) high-resolution imaging, which allows individual cells to be visualized. This review will provide an overview of the various forms of real-time optical imaging in the diagnosis and management of Barrett's esophagus and esophageal adenocarcinoma.
    Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine 11/2011; 78(6):894-904. · 2.00 Impact Factor
  • Article: Endoscopic imaging: How far are we from real-time histology?
    Richa Shukla, Wasif M Abidi, Rebecca Richards-Kortum, Sharmila Anandasabapathy
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    ABSTRACT: Currently, in gastrointestinal endoscopy there is increasing interest in high resolution endoscopic technologies that can complement high-definition white light endoscopy by providing real-time subcellular imaging of the epithelial surface. These 'optical biopsy' technologies offer the potential to improve diagnostic accuracy and yield, while facilitating real-time decision-making. Although many endoscopic techniques have preliminarily shown high accuracy rates, these technologies are still evolving. This review will provide an overview of the most promising high-resolution imaging technologies, including high resolution microendoscopy, optical coherence tomography, endocytoscopy and confocal laser endoscopy. This review will also discuss the application and current limitations of these technologies for the early detection of neoplasia in Barrett's esophagus, ulcerative colitis and colorectal cancer.
    World journal of gastrointestinal endoscopy. 10/2011; 3(10):183-94.

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