Optical coherence tomography-guided laser marking with tethered capsule endomicroscopy in unsedated patients

Abstract

Tethered capsule endomicroscopy (TCE) is an emerging screening technology that comprehensively obtains microstructural OCT images of the gastrointestinal (GI) tract in unsedated patients. To advance clinical adoption of this imaging technique, it will be important to validate TCE images with co-localized histology, the current diagnostic gold standard. One method for co-localizing OCT images with histology is image-targeted laser marking, which has previously been implemented using a driveshaft-based, balloon OCT catheter, deployed during endoscopy. In this paper, we present a TCE device that scans and targets the imaging beam using a low-cost stepper motor that is integrated inside the capsule. In combination with a 4-laser-diode, high power 1430/1450 nm marking laser system (800 mW on the sample and 1s pulse duration), this technology generated clearly visible marks, with a spatial targeting accuracy of better than 0.5 mm. A laser safety study was done on swine esophagus ex vivo, showing that these exposure parameters did not alter the submucosa, with a large, 4-5x safety margin. The technology was demonstrated in living human subjects and shown to be effective for co-localizing OCT TCE images to biopsies obtained during subsequent endoscopy.

Fig. 1

Endoscopic image of TCE laser marking using a tissue irradiation power of 400 mW over a duration of 2 seconds. Blue arrows indicate the marking sites that are irregular and distorted due to tissue motion during the exposure period.

Fig. 2

(A) Photograph of the clinical compact imaging system (CIS) with marking laser system and TCE capsule. (B) Schematic of the clinical system.

Fig. 3

Schematic of marking laser subcomponents.

Fig. 4

Schematic of TCE capsule with a distal motor. The outer diameter of the capsule is 11 mm.

Fig. 5

Synchronized micro-stepping control signal for the distal stepper motor. The orange arrow indicates the zoom-in view of OCT engine and divided clock signal traces. V on vertical axis represents the voltage unit, volts.

Fig. 6

Flow chart of the laser marking process used in the clinical study.

Fig. 7

(A) Photograph of marking sites on an excised swine esophagus lumen. Marks were generated with laser parameters of 1430/1450 nm, 800 mw, and 1-4 s exposure time. The illumination spot size was 37 μm. (B) A representative digitized NBTC-slide showing the mark obtained using 800 mw for 1s. The non-stained region delineates the extent of laser thermal injury. Blue dash lines indicate the injury width and depth. The red line indicates the distance between the deepest portion of the mark to the submucosa.

Fig. 8

Laser marking data from swine esophagus ex vivo using 800 mW of 1430/1450 nm light. The total number of data points for each exposure parameter is 9. Three data points (distal, middle and proximal esophagus) are collected from each of the three animals. (A) Bar chart of the lateral width of laser mark for different exposure times. (B) Bar chart of the depths of laser marks as a function for different exposure times. (C) Bar chart of distance between the deepest portion of the laser mark to the most superficial aspect of the submucosal layer for various exposure times. The error bars indicate standard error.

Fig. 9

An OCT image of human esophagus acquired by the TCE device with a distal stepper motor in vivo. The blue arrow demarcates the electrical wires that send the driving waveforms to the motor.

Fig. 10

Histogram of increments of the beam’s position along the outer surface of the capsule when it is scanned using the micro-stepping motor (40 steps).

Fig. 11

TCE laser marking of a study subject’s (a BE patient) normal esophagus. (A) Pre-marking OCT image of a region of the normal esophagus. The red lines indicate where the operator intends to place the laser marks. (B) OCT image of the study subject’s esophagus after laser marking. Orange arrows demarcate the hyper-reflective signal from the cauterized laser marks. (C) Enlarged image of the marking sites, showing the OCT appearance of the laser marks (orange arrows) in greater detail. (D) Endoscopy image of the laser marks (red arrows). (E) Histology from a biopsy taken between the two laser marks confirms that the tissue between the marks is squamous epithelium.

Fig. 12

TCE laser marking of Barrett’s esophagus in a study subject. A) Pre-marking OCT image of BE mucosa. The red line indicates where the operator intends to place the laser marks. (B) OCT image of the study subject’s esophagus after laser marking. The orange arrow points to hyper-reflective signal from the cauterized laser mark. (C) Enlarged image of the marking site, showing the OCT appearance of the laser mark (orange arrow) in greater detail. (D) Endoscopy image of the laser mark (red arrow). (E) Histology from the biopsy taken adjacent to the laser mark, confirming that the marked tissue was BE.