A PILOT CLINICAL STUDY OF SELF-PROPELLED RETROGRADE TETHERED CAPSULE ENDOMICROSCOPY (R-TCE) OF THE LOWER COLON IN UNSEDATED PATIENTS

Introduction: Although colonoscopy is considered an optimal method for detecting colorectal adenomas, it has limitations, such as frequent use of sedation and missed polyps. As an alternative method for adenoma screening, we have developed Retrograde Tethered Capsule Endomicroscopy (R-TCE) technology for sedation-free colon imaging at a microscopic level. Here, we describe initial clinical results using R-TCE to image a lower colon in unsedated patients.

Methods: Unsedated subjects with no known colonic pathologies were enrolled (MGB-IRB 2022P001154). Before a clinical procedure, patients completed reduced bowel preparation via two enemas. A gastroenterologist first performed a sigmoidoscopy. Then, a tethered capsule with external silicone threads (Fig.1) was introduced through an anus through an anoscope. After insertion, a drive cable rotated the capsule (v=15 rpm), propelling the capsule up a colon via a screw-like motion. While traversing, the R-TCE obtained circumferential Optical Coherence Tomography (OCT) images (1310nm, axial resolution 20µm, ranging depth 1.2cm). Once the capsule reached its target 30 cm in the lower colon, it was pulled back (v=2 mm/s) while acquiring a helical 3D microscopic OCT image (20 fps) of the entire lower colon. After removing the R-TCE device, a second sigmoidoscopy was conducted to evaluate whether the R-TCE produced any significant mucosal damage. Subjects completed a tolerability questionnaire after the procedures.

Results: We have conducted R-TCE in 5 unsedated subjects. The mean capsule insertion length in the colon was 21±6 cm, the maximum insertion length was 30 cm, and the mean insertion rate was 7.5±4.4 cm/min. Figure 2a shows a representative cross-sectional OCT image of the lower colon, showing mucosa with crypts over full colon circumference. R-TCE imaging enabled full circumferential OCT visualization of 95.4±0.2(95% CI) of the human colon wall. Although subjects were enema-prepped, residual fecal matter was evident in some images (20% of patients); OCT was able to visualize through fecal content to a depth of ~2 mm (Fig.2a). 3D-rendered flythroughs of OCT images (Fig.2b) demonstrate comprehensive visualization of colonic folds. A post-R-TCE sigmoidoscopy showed no significant mucosal damage attributable to R-TCE. The R-TCE procedure was well-tolerated, with a mean overall pain/discomfort score of 2.2/10(1-lowest, 10-highest).

Conclusion: In the first-in-human study with R-TCE, we found that this technology can reliably obtain 3D microscopic OCT images of the entire lower colon in unsedated subjects. The procedure is feasible, tolerable, and safe. Next steps involve advancing the capsule from splenic flexure to a cecum, followed by OCT imaging of an entire colon. R-TCE’s capacity to image the colon at a microscopic level without sedation makes it a promising technology for colorectal adenoma detection.