The diagnosis of most upper GI tract conditions is currently accomplished by upper endoscopy with biopsy
(EGD). EGD is costly primarily because it requires conscious sedation, necessitating that procedures be
conducted by physicians in a specialized endoscopy suite, and that patients take time away from work and
family. Another limitation is sampling error - endoscopic biopsies are frequently random, resulting in many
instances of missed disease. Methods such as unsedated transnasal endoscopy (uTNE) have been proposed
to decrease the cost of EGD. While in principle uTNE techniques could be used in most cases, physician-
associated expense, poor patient acceptance, and an inability to obtain adequate biopsies have hampered its
adoption. As a result, there remains an unmet clinical need for an unsedated, less expensive, and more
accessible technique that could supersede diagnostic EGD.
In this grant, we will develop a replacement for diagnostic EGD that combines video endoscopy with cellular-
resolution in vivo microscopy in a swallowable, tethered capsule. Once swallowed, the tethered capsule
endoscopy-endomicroscopy (TEEM) device will acquire wide area white light and microscopic images of the
esophagus, stomach, and duodenum. Because patients will be unsedated, the procedure can be performed by
non-physician personnel in an outpatient setting, thereby improving patient tolerance, increasing efficiency, and
lowering costs, resulting in better screening and treatment of this important source of mortality/morbidity. In
Aim 1, we will develop the TEEM imaging system and capsule that will incorporate a new cross-sectional, 1-µm-
resolution imaging modality known as µOCT, a controllable-stiffness and articulating tether that will facilitate
navigation of the stomach, side-viewing white light image acquisition, forward-viewing video, and algorithms for
registering µOCT and endoscopy imaging data for offline review. In Aim 2, we will conduct a histopathologic
correlative biopsy study to determine the accuracy of µOCT for diagnosing the most common upper GI tract
diseases. TEEM tolerance, inter/intra-observer variability, and test-retest reproducibility will then be tested in 55
patients to verify that this technology meets the clinical requirements for upper GI tract screening (Aim 3).
