Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure

Abstract

Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution 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.

Figure 1. Tethered capsule endomicroscopy

(a) Photograph of the entire tethered capsule endomicroscopy device, showing the capsule portion adjacent to a penny for scale. (b) Close-up, time-integrated photograph of the tethered capsule endomicroscope, transmitting red light as the internal optics rotate. (c) The tether (arrow) is very flexible and a plastic ball, attached to the tether (arrowhead), facilitates manipulation of the device. (d) Tethered capsule endomicroscopy image of the normal esophagus, obtained from a normal volunteer in vivo. (e) 3x expanded view of (d) demonstrates the normal esophageal wall architectural morphology, including the squamous epithelium (E), muscularis mucosa (MM), lamina propria (L), submucosa (S), containing blood vessels (arrowheads), inner and outer muscularis (IM) and (OM), and myenteric plexus (MP). (f) Tethered capsule endomicroscopy cross-sectional image of the stomach, obtained from a normal volunteer in vivo, with a 3x expanded view in (g) displaying characteristic glandular “pits” (arrowheads). (h) Image obtained from a patient with histopathologically-confirmed Barrett’s esophagus in vivo. (i) The 3x-magnified view of (h) shows an irregular luminal surface, heterogeneous backscattering, and glands within the mucosa (arrowheads). Tick marks in (d, f, h) - 1 mm; scale bars in (e, g, i) denote 0.5 mm. * multiple reflection artifact.

Figure 2. Tethered capsule endomicroscopy data from a patient with a diagnosis of Barrett’s esophagus and high-grade dysplasia/intramucosal carcinoma

Portion of a cross-sectional tethered capsule microscopy image of stomach (a), Barrett’s with architectural atypia suggestive of high-grade dysplasia (b), and squamous mucosa (c) can be seen at the distal, mid, and proximal ends of the esophagus, respectively. (d) A three-dimensional representation of the tethered capsule endomicroscopy dataset shows a 4 cm segment of Barrett’s esophagus with multiple raised plaques/nodules, one of which corresponds to the features shown in (b). (e–g) Three-dimensional flythrough views of the stomach, Barrett’s segment, and squamous mucosa, respectively, demonstrating a clear difference between the superficial appearance of the rugal folds of the stomach, the crypt pattern of Barrett’s esophagus, and the smooth surface of the squamous mucosa. Tick marks and scale bars in (a–c) represent 1 mm. Scale bars in (d) represent 1 cm.