Rollerball microendoscope for mosaicking in high-resolution oral imaging

Only 40% of oral cancers are diagnosed at an early, localized stage, when treatment is most effective [1]. Thus, implementing diagnostic imaging tools for early detection of highgrade dysplasia and cancer may help improve the survival rate of oral cancer patients [2]. The highresolution microendoscope (HRME) is a compact, portable, fiberbased imaging device that can image cell nuclei in tissue labeled with the fluorescent contrast agent proflavine [3]. The HRME allows clinicians to noninvasively image the size, shape and distribution of epithelial cell nuclei in vivo, enabling realtime evaluation of potentially neoplastic lesions [3]. The primary limitation of the HRME is the small field of view of its fiber probe (720 μm), which makes it timeconsuming to examine large areas of tissue. Mosaicking algorithms have previously been implemented to allow realtime generation of image mosaics during HRME imaging, thus interrogating a larger field of view than the fiber probe’s diameter [4]. However, this approach has had limited success in vivo due to the practical difficulty of translating the fiber probe across the tissue in a smooth, controlled manner in order for the mosaicking software to function properly. Here we report the construction and initial testing of a rollerball HRME probe that permits smooth, rolling translation across the tissue surface while maintaining image quality with subcellular resolution. The rollerball HRME consists of a standard HRME probe interfaced with a rollerball mechanism. The mechanism is composed of two 5mm sapphire ball lenses enclosed within a 3D printed penlike casing. The ball lenses serve as an optical relay, while the distal ball lens also serves as a rolling contact point with the tissue surface. Figure 1 shows the use of the rollerball HRME to generate a realtime mosaic of a calibration target (field finder slide) as it rolls across the surface of the target. Figure 2 shows the use of the rollerball HRME to generate a realtime mosaic showing cell nuclei on the lateral tongue of a healthy volunteer as it rolls across the tissue surface. The rollerball HRME will allow clinicians to more rapidly examine large areas of tissue with subcellular resolution, potentially aiding in the early detection of highgrade oral dysplasia and cance. Please click Additional Files below to see the full abstract

Accuracy of In Vivo Multimodal Optical Imaging for Detection of Oral Neoplasia

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

Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinomaﾠ

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

Internet of Nano-Things, Things and Everything: Future Growth Trends

The current statuses and future promises of the Internet of Things (IoT), Internet of Everything (IoE) and Internet of Nano-Things (IoNT) are extensively reviewed and a summarized survey is presented. The analysis clearly distinguishes between IoT and IoE, which are wrongly considered to be the same by many commentators. After evaluating the current trends of advancement in the fields of IoT, IoE and IoNT, this paper identifies the 21 most significant current and future challenges as well as scenarios for the possible future expansion of their applications. Despite possible negative aspects of these developments, there are grounds for general optimism about the coming technologies. Certainly, many tedious tasks can be taken over by IoT devices. However, the dangers of criminal and other nefarious activities, plus those of hardware and software errors, pose major challenges that are a priority for further research. Major specific priority issues for research are identified

Fluorescence-based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer

Thomsen–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

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

Background & 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

Early Pastoral Economies and Herding Transitions in Eastern Eurasia

While classic models for the emergence of pastoral groups in Inner Asia describe mounted, horse-borne herders sweeping across the Eurasian Steppes during the Early or Middle Bronze Age (ca. 3000–1500 BCE), the actual economic basis of many early pastoral societies in the region is poorly characterized. In this paper, we use collagen mass fingerprinting and ancient DNA analysis of some of the first stratified and directly dated archaeofaunal assemblages from Mongolia’s early pastoral cultures to undertake species identifications of this rare and highly fragmented material. Our results provide evidence for livestock-based, herding subsistence in Mongolia during the late 3rd and early 2nd millennia BCE. We observe no evidence for dietary exploitation of horses prior to the late Bronze Age, ca. 1200 BCE – at which point horses come to dominate ritual assemblages, play a key role in pastoral diets, and greatly influence pastoral mobility. In combination with the broader archaeofaunal record of Inner Asia, our analysis supports models for widespread changes in herding ecology linked to the innovation of horseback riding in Central Asia in the final 2nd millennium BCE. Such a framework can explain key broad-scale patterns in the movement of people, ideas, and material culture in Eurasian prehistory

Author Correction: Early Pastoral Economies and Herding Transitions in Eastern Eurasia (Scientific Reports, (2020), 10, 1, (1001), 10.1038/s41598-020-57735-y)

This Article contains a typographical error in the Introduction section under subheading ‘Understanding Early Horse Domestication and Transport’ where, “Historical records refer to horse-mounted warriors in western Asia by the 8th century BCE, while archaeological finds from localities like Arzhan 2 in southern Tuva show specialized horse equipment (bronze snaffle bits) and equine vertebral pathologies linked with mounted riding in Central Asia by the late 9th century BCE31.” should read: “Historical records refer to horse-mounted warriors in western Asia by the 8th century BCE, while archaeological finds from localities like Arzhan in southern Tuva show specialized horse equipment (bronze snaffle bits) and equine vertebral pathologies linked with mounted riding in Central Asia by the late 9th century BCE31.”