Nanoparticles, such as quantum dots (QDs), composed of biologically toxic materials degrade in highly oxidative environments. Varying the QD surface coating significantly affects the intracellular uptake of QDs. Although the addition of PEG does not alter the inherent QD cytotoxicity, we demonstrate that the improved biocompatibility due to PEG‐substitution arises from decreased intracellular uptake, which allows for biological applications of QDs with minimal toxicity. The image shows the live/dead reagent stain used to quantitate cytotoxicity. PEG: poly(ethylene glycol).

PrefaceCervical cancer is the leading cause of cancer death for women in developing countries 1 . Optical technologies can improve the accuracy and availability of cervical cancer screening. For example, battery-powered digital cameras can obtain multi-spectral images of the entire cervix highlighting suspicious areas, and high-resolution optical technologies can further interrogate suspicious areas, providing in vivo diagnosis with high sensitivity and specificity. In addition, targeted contrast agents can highlight changes in biomarkers of cervical neoplasia. Such advances should provide a much needed global approach to cervical cancer prevention. Cervical Cancer: A Global ChallengeCervical cancer is the second most common cancer in women worldwide 1 ; more than 80% of cervical cancers occur in the developing world where the least resources exist for management 1 . Most cases of cervical cancer can be prevented through screening programs, such as the Papanicolaou (Pap) smear aimed at detecting precancerous lesions for treatment. In countries in which organized programs have been established, the incidence and mortality of cervical cancer have dramatically reduced 2 . Yet, the necessary resources and infrastructure for screening are not available in many countries; as a result, 274,000 women die each year as a result of this preventable disease 1 .Cervical cancer is caused by chronic infection with high risk types of the human papilloma virus (HPV) 3 . The recent development of vaccines to prevent HPV infection promises to further reduce the incidence of cervical cancer in countries where vaccines are available 4 . However, the significant cost of vaccines and, in some cases, political or logistical barriers, could delay implementation of universal mass vaccination in many developing countries 5 . Furthermore, current vaccines are effective only against high-risk HPV types 16 and 18, which together account for approximately 70% of cervical cancers worldwide 5 . Because the vaccine does not cover all high-risk HPV subtypes, routine cervical cancer screening is still necessary, even for women who have been vaccinated, so cervical cancer screening remains necessary for the foreseeable future. Clinical Approaches to Cervical Cancer ScreeningCurrent screening and diagnosis of cervical precancer is based on optical techniques developed in the early 1900s 2 . As shown in the top row of Fig. 1, an abnormal Pap smear is followed by examination of the cervix using a low-power light microscope (colposcope) to visualize changes in tissue reflectance, which might indicate precancer. For decades, clinical investigators have searched for ways to improve the optical contrast between normal cervix and precancerous lesions. The use of simple agents such as acetic acid and Lugol's iodine, together with the use of a green illumination filter, can highlight suspicious regions. However, because the specificity of visual examination is low, colposcopically abnormal areas are routinely biopsied to confirm the presence of disease 6 . I...

Abstract. Early detection of neoplasia in patients with Barrett's esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barrett's esophagus. Nine patients with pathologically confirmed Barrett's esophagus underwent endoscopic examination with biopsies or endoscopic mucosal resection. Resected fresh tissue was imaged with fiber bundle microendoscopy; images were analyzed by visual interpretation or by quantitative image analysis to predict whether the imaged sites were non-neoplastic or neoplastic. The best performing pair of quantitative features were chosen based on their ability to correctly classify the data into the two groups. Predictions were compared to the gold standard of histopathology. Subjective analysis of the images by expert clinicians achieved average sensitivity and specificity of 87% and 61%, respectively. The best performing quantitative classification algorithm relied on two image textural features and achieved a sensitivity and specificity of 87% and 85%, respectively. This ex vivo pilot trial demonstrates that quantitative analysis of images obtained with a simple microendoscope system can distinguish neoplasia in Barrett's esophagus with good sensitivity and specificity when compared to histopathology and to subjective image interpretation.

Recent advancements in the endoscopic imaging of Barrett's esophagus can be used to probe a wide range of optical properties that are altered with neoplastic progression. This review summarizes relevant changes in optical properties as well as imaging approaches that measures those changes. Wide-field imaging approaches include narrow-band imaging that measures changes in light scattering and absorption, and autofluorescence imaging that measure changes in endogenous fluorophores. High-resolution imaging approaches include optical coherence tomography, endocytoscopy, confocal microendoscopy, and high-resolution microendoscopy. These technologies, some coupled with an appropriate contrast agent, can measure differences in glandular morphology, nuclear morphology, or vascular alterations associated with neoplasia. Advances in targeted contrast agents are further discussed. Studies that have explored these technologies are highlighted; as are the advantages and limitations of each.

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.