Here, we introduce “tethered capsule endomicroscopy,” that involves swallowing an optomechanically-engineered pill that captures cross-sectional, 30 μm (lateral) × 7 μm (axial) resolution, microscopic images of the gut wall as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.

Background Biopsy surveillance protocols for the assessment of Barrett’s esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. Objective The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. Design A pilot feasibility study. Setting Massachusetts General Hospital. Patients A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett’s esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. Intervention Volumetric laser endomicroscopy. Main Outcome Measurements Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. Results There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%–83%), for VLE intent-to-biopsy images 93% (95% CI, 78%–99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. Limitations This is a single-center feasibility study with a limited number of patients. Conclusion Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. (Clinical trial registration number: NCT01439633.)

Background Optical frequency domain imaging (OFDI) is a second-generation form of optical coherence tomography (OCT) providing comprehensive cross-sectional views of the distal esophagus at a resolution of ∼7 μm. Aims Using validated OCT criteria for squamous mucosa, gastric cardia mucosa, and Barrett's Esophagus (BE), the objective of this study was to determine the inter- and intra-observer agreements by a large number of OFDI readers for differentiating these tissues. Methods OFDI images were obtained from 9 subjects undergoing screening and surveillance for BE. 64 OFDI image regions of interest were randomly selected for review. A training set of 19 images was compiled distinguishing squamous mucosa from gastric cardia and BE using previously validated OCT criteria. The 10 readers then interpreted images in a test set of 45 different images of squamous mucosa (n=15), gastric cardia (n=15), or BE (n=15). Interobserver agreement differentiating the three tissue types and BE vs. non-BE mucosa was determined using multi-rater Fleiss's κ value. The images were later randomized and four readers repeated the test three weeks later to assess intraobserver reliability. Results All 10 readers showed excellent agreement for the differentiation of BE vs. non-BE mucosa (κ= 0.811 p<0.0001) and for differentiating BE vs. gastric cardia vs. squamous mucosa (κ=0.866, p<0.0001). For the 4 readers who repeated the test, the median intraobserver agreement (BE vs. non-BE) was high (κ=0.975, IQR: 0.94, 1.0). Conclusions Trained readers have a high interobserver agreement for differentiating BE, squamous, and gastric cardia mucosa using OFDI.