SELF-PROPELLED RETROGRADE TETHERED CAPSULE ENDOMICROSCOPY (R-TCE) IN THE COLON

Introduction
Gastric motility is coordinated, in part, by rhythmic bioelectrical events called slow waves. Dysrhythmic slow waves with abnormal propagation patterns have been associated with a number of motility disorders, including functional dyspepsia and gastroparesis, which affect approximately 10% of the global population.

High-resolution mapping of slow waves has emerged as a promising diagnostic tool for classifying gastric electrical dysrhythmias, however, current methods for generating detailed maps of gastric electrical activity to guide targeted therapy are surgically invasive. This study aimed to validate the clinical application of a novel, minimally-invasive, endoscopic device for high-resolution mapping in humans.

Methods
A novel endoscopic mapping device was constructed that primarily comprised of a Constellation cardiac mapping catheter (60 mm diameter, 8 splines, 64 electrodes; Boston Scientific, USA), and anorectal balloon (Mui Scientific, Canada) positioned inside the mapping catheter splines (Fig. 1A).

Ethical approval and informed consent (HDEC approval #17/STH/95) was gathered from patients undergoing elective gastroscopy to participate in the study. Patients were placed in the prone position prior to device deployment to minimize potential movement. The device was then advanced into the gastric antrum, alongside a gastroscope, using an endoscopic clip to hold the tip of the device. The balloon was inflated and the stomach suctioned to maintain contact between the mucosa and electrodes (Fig. 1C). Electrical recordings were obtained for approximately 7 min, following which the device was deflated and removed. Signals measured by the novel mapping device were digitally recorded by a Biosemi ActiveTwo system (Biosemi, Amsterdam, Netherlands) at a sampling frequency of 512 Hz, prior to local storage. Data were then analyzed in custom software to detect and quantify slow wave activation patterns.

Results
Device placement and data acquisition was successful in all patients (n=13). Slow waves were recorded with frequency 2.8±0.5 cycles/min, velocity 4.3±1.4 mm/s, and amplitude 2.6±1.9 mV. These values are within an established physiological range of antral slow wave propagation, demonstrating validity of our new endoscopic device. Slow wave detection was achieved with sufficient channel coverage (>33%), allowing spatiotemporal propagation map generation (Fig. 2B), in 5 of the patients.

Conclusions
This study demonstrates the first endoscopic, minimally-invasive, high-resolution slow wave mapping in humans, using a novel device design. This device could be used to localize gastric dysrhythmias in the future as a diagnostic tool, and to guide emerging treatments. Future studies will expand the patient cohort to compare gastric slow wave activity in healthy and diseased patients.

Introduction: While colonoscopy is the gold standard for diagnosing colorectal adenomas, it has limitations, including the use of conscious sedation and missed polyps frequently reside behind colonic folds. To overcome these limitations, we have developed a Retrograde Tethered Capsule Endomicroscopy (R-TCE) technology that is designed to image the entire colon at the microscopic level without requiring patient sedation. Here we describe our initial experience in living swine with this new technology.

Materials and Methods: The R-TCE device is a 11x25 mm capsule with silicone external threads attached to a 2-meter-long, ~ 4-mm-diameter, flexible tether. The tether contains a drive cable that rotates the capsule, an external 22-mm-diameter inflatable balloon at its distal tip, and a second channel for water delivery, as shown in Figure 1. After the capsule is inserted into the anus, rotation of the capsule at 15 rpm propels it up the large intestine via a screw-like motion. The capsule also implements optical coherence tomography (OCT) with integrated micromotor scanning (20 Hz) obtains 20 µm resolution cross-sectional images of the entire colonic wall.

R-TCE device prototypes were tested in n=5 Yorkshire swine (w=50 kg) in vivo. Bowel-prepped animals were anesthetized before the experimental procedure. The capsule was inserted in the anus, rotated, and progressed up the swine’s spiral colon approximately 1 m. Once the capsule reached its terminal location, the swine underwent multi-angle X-ray abdominal fluoroscopy to record the tether’s anatomical shape and position. Then, the balloon was inflated and the capsule pulled back at a rate of 1 mm/s, acquiring helical 3D microscopic OCT images of the entire large intestine. To evaluate whether R-TCE produced any mucosal damage, a gastroenterologist conducted a colonoscopy in the swine. After animals were sacrificed, histology was taken from regions of the colon with visible damage caused by either the R-TCE device or the colonoscope. A pathologist scored these slides using a histopathologic mucosal damage scoring system (R-TCE vs. colonoscopy)

Results: R-TCE enabled full circumferential visualization (95.94±0.13%) of the colon of ~1 m in vivo (n=5). As shown in Figure 2, 3D fly-throughs rendered from OCT images showed excellent visualization of the colon’s folds. The R-TCE histopathology mucosal damage score (8±2.6) was statistically equivalent to that of colonoscopy (9.5±4)(p =0.19, n=3).

Conclusion: We have successfully demonstrated a new tethered capsule device in living swine that obtains 3D microscopic OCT images of the entire colon. Preclinical safety is supported by statistically equivalent superficial mucosal damage caused by R-TCE and colonoscopy. Future work will involve first-in-human studies to evaluate the tolerability and imaging capabilities of this new technology in unsedated human subjects.