Dynamic micro-optical coherence tomography (DµOCT) is a technology that is capable of interrogating intracellular dynamics in intact, viable tissues. Towards our goal of advancing DµOCT for phenotyping cells, we imaged freshly excised human biopsies and performed correlative studies with histological results. To date, more than 30 biopsies from 17 patients with numerous types of gastrointestinal pathologies, including cancer, diverticulitis, and Crohn’s disease were imaged. In addition, using mouse models, we performed DµOCT imaging studies on tumors locally treated with chemotherapeutics delivered via custom implantable microdevices to observe the impact of those drugs on the tumor. Cyclical immunofluorescence staining was used to co-register ~20 markers on the same cross-sectional plane. We further demonstrate the utility of principal component analysis, K-means clustering, and convolutional long short-term memory (ConvLSTM) neural network for expanding the capabilities of DµOCT.
Since the recognition that entry factors of SARS-CoV-2 are highly expressed in the nasal epithelium, a custom personal protection booth was developed to enable intranasal µOCT studies to be safely performed on Covid-positive subjects. The booth was designed to preserve familiarity of the prior established intranasal imaging techniques used by clinicians. A group of Covid-positive subjects (n=13) were imaged, shortly after onset of symptoms (7.8 ± 3.7 days). Historical data from healthy controls (n=10) were included in the study. While the blinded analysis is underway, an interim analysis of the µOCT data revealed several notable abnormalities in the nasal epithelium including delayed mucociliary transport, epithelial injury, and high inflammatory cell count in a pilot cohort. We anticipate that the pathophysiologies captured by intranasal µOCT will provide invaluable insights to the mechanisms of Covid-19 related mucociliary dysfunction.
Tethered capsule endomicroscopy (TCE) is a recently developed form of in vivo microscopy based on optical coherence tomography (OCT). With TCE, a small tethered pill is swallowed, procuring high resolution microscopic images of the esophageal wall. TCE does not require sedation and is thus a more rapid and convenient procedure comparing to traditional endoscopic examination. Our group and others have successfully conducted OCT-TCE in pilot, single-center studies that demonstrated the potential of this technology for upper GI tract diagnosis. Here, we demonstrate and evaluate the feasibility and safety of a next generation OCT-TCE system and device in patients with Barrett’s esophagus (BE) and report the initial longitudinal analysis of the natural history of BE.
The Tearney Lab at the Massachusetts General Hospital (MGH) has conducted a study using Tethered Capsule Endomicroscopy (TCE), a technique that involves swallowing a tethered capsule device that circumferentially scans an optical coherence technology (OCT) beam inside the body as it traverses the gastrointestinal tract. Throughout the procedure, microscopic images of the esophagus are acquired in real time in an unsedated subject. OCT TCE was used to screen for Barrett’s Esophagus in a setting of 2 primary care practices at MGH.The OCT TCE show promising results identifying BE in a primary care population.
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.
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