Celiac disease (CD) is an autoimmune disease that damages the small intestine's villi upon gluten ingestion. Intestinal biopsy via esophagogastroduodenoscopy is the current diagnostic gold standard for CD, but this procedure requires sedation and suffers from sampling error. Here, we conducted a clinical study to test whether image biomarkers derived from duodenal OCT tethered capsule endomicroscopy (TCE) can be used to diagnose CD. Results showed a statistically significant difference in OCT image metrics (villus height & width, contrast, and homogeneity with p<0.0001) among active CD, inactive CD and healthy subjects, demonstrating the potential of TCE for the diagnosis of CD.
Environmental enteric dysfunction (EED) is a pathological condition of the small intestine that is endemic to low- and middle-income countries (LMICs). EED is thought to interfere with nutrient absorption and enteropathogen exclusion, resulting in altered immune response, increased infection, and limited neurological and physical development. Biopsy of the small intestine is the current diagnostic gold standard for diagnosis yet is untenable due to lack of availability in these countries. Endoscopic biopsy is further problematic since EED-related stunting can only be reversed if diagnosed in the first two years of life when endoscopy must be conducted under anesthesia in advanced medical care settings. Thus, there is an unmet need for a minimally invasive technology for obtaining small intestinal biopsies in unsedated infants in LMICs. To address this need, we have developed an OCT image-guided trans-nasal cryobiopsy device. The device comprises a dual-lumen 1.2 mm outer diameter (OD) probe, terminated by a metal tip, through which Freon is injected. The device is introduced through the lumen of a novel liquid-metal transnasal imaging tube that passively transits to the small intestine. M-mode OCT image guidance is used to determine when the metal tip is in contact with the mucosa so that cryobiopsies may be efficiently acquired. We have conducted feasibility experiments using this device in 10 swine in vivo, demonstrating residual bleeding that is comparable to conventional excisional biopsy, tissue sampling volumes that are greater than or equal to those of conventional biopsy, and high-quality histopathology. These results suggest that this transnasal cryobiopsy technique may be suitable for infants in low-resource settings where EED is prevalent, due to its simplicity and its ability to be used in unsedated subjects.
Upper endoscopy is a standard technique for imaging, sampling, and treating gastrointestinal tissue. Endoscopy is frequently requiring the subjects who undergo the procedure be consciously sedated. Sedation necessitates that the endoscopy procedure be conducted in a specialized setting to mitigate complications should they arise. Endoscopy is further problematic for infants and young children (aged 0-24 months) who sometimes need to be anesthetized. These issues motivate alternative methods for upper gastrointestinal tract visualization and biopsy that do not require conscious sedation/anesthesia. To address this need, we have developed a double lumen 6.5 Fr transnasal introduction catheter (TNIC). During transnasal insertion, real-time OCT imaging provides confirmation of the anatomical location of the device. Once in the stomach, a safe and high-density liquid metal fills a balloon at the distal tip of the TNIC, allowing it to passively transit through stomach into the small intestine. Once properly positioned, OCT-guided instruments for imaging and biopsy can be inserted through main lumen of the TNIC, performing many of the functions of conventional endoscopy and advanced endomicroscopy. To test the feasibility of the TNIC, we conducted a clinical study using the first version of the device in 4 unsedated normal volunteers. Results showed detailed OCT endomicroscopy images of the esophagi and duodena. These results suggest that TNIC may be an effective, less invasive method for the diagnosis of upper GI tract conditions.
KEYWORDS: Optical coherence tomography, Endomicroscopy, Intestine, Endoscopy, Inflammation, Biopsy, 3D image processing, Visualization, Control systems
Environmental Enteric Dysfunction (EED) is a poorly understood condition of the small intestine that is prevalent in regions of the world with inadequate sanitation and hygiene. EED affects 25% of all children globally and causes over a million deaths each year. The condition is associated with increased intestinal permeability, bacterial translocation, inflammation and villous blunting. The loss of absorptive area and intestinal function leads to nutrient malabsorption, with long term outcomes characterized by stunted growth and neurocognitive development. Currently, the only way to directly evaluate the morphology of the intestine is endoscopy with mucosal biopsy. Yet because EED is endemic in low and middle-income countries, endoscopy is untenable for studying EED. As a result, the diagnosis of EED and the assessment of the efficacy of EED interventions is hampered by an inability to evaluate the intestinal mucosa.
Our lab has previously developed a technology termed tethered capsule OCT endomicroscopy (TCE). The method involves swallowing an optomechanically-engineered pill that generates 3D images of the GI tract as it traverses the lumen of the organ via peristalsis, assisted by gravity. In order to study the potential of using TCE to investigate EED, we initiated and conducted a TCE study in adolescents at Aga Khan Medical Center in Pakistan. To make swallowing easier, the tethered capsule’s size was reduced from 11x25 mm to 8x22 mm. Villous morphologic visualization was enhanced by building a notch (x mm deep, y mm wide) in the capsule’s imaging window. To date, 26 Pakistani subjects with ages ranging from 14 to 18 y/o (16.4 +/- 1.0) have been enrolled and imaged. A total of 19 subjects were able to swallow the capsule. Of those, 9 successfully passed through the pylorus, allowing successful microscopic imaging of the entire duodenum. There were no adverse events in any of the cases. Maximum villous height and width were measured from 3 randomly chosen, representative frames from each Pakistan subject as well as a matching number from US controls. Preliminary results, comparing Pakistani vs US villous morphology, indicated that subjects from Pakistan have shorter (628.6 +/- 22.0 um and 492.3 +/- 13.2 um, respectively, p< 0.0001) and wider duodenal villi (244.9 +/- 8.8 um and 293.4 +/- 13.2 um, respectively, p< 0.0001). These findings suggest that OCT TCE of the duodenum may be a useful tool for evaluating villous morphology in EED.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.