# Screening for Barrett's Esophagus Progressors with Multimodality Tethered Capsule Image-Guided Biopsy

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $643,503

## Abstract

Esophageal adenocarcinoma (EAC) is a deadly cancer that is preceded by a metaplastic change called Barrett's
esophagus (BE). It has long been thought that endoscopic screening for BE followed by endoscopic surveillance
can significantly decrease the mortality of EAC. This unfortunately has not borne out as the cost and
inconvenience of conscious sedation prohibits endoscopy from being used as a population-based screening tool.
BE screening may become possible in the future, owing to innovative swallowable tethered capsule
endomicroscopes or cell sampling devices that can detect BE without requiring sedation. Yet, even if these
capsules were to identify the large number of people in the US who have BE (~15M), endoscopic surveillance
of this group would be prohibitively expensive. If we could use tissue biomarkers to identify the 5% of those with
BE who will develop EAC in their lifetimes, then endoscopic intervention could be given to those who really need
it, and those with low-risk BE would not require further follow up.
Recognition of this need has motivated the field to identify BE progression biomarkers derived from esophageal
tissue samples obtained by autofluorescence/reflectance-targeted endoscopy. This research has identified
biomarkers such as aneuploidy and aberrant p53/cyclin A expression as strong predictors of BE progression.
Unfortunately, the only way to target and obtain these tissues today is through sedated endoscopy. With the
modifications proposed here, a new BE screening technology that we have developed called optical coherence
tomography (OCT) tethered capsule endomicroscopy (TCE), could enable targeted biopsy without sedation.
OCT-TCE obtains 3D microscopic images of the entire esophagus in unsedated subjects, accurately identifies
BE, and has been successfully used by nurses and technicians in primary care settings. Here, we propose to
advance OCT-TCE for targeted biopsy by adding autofluorescence and reflectance spectral imaging technology
that can help identify tissue enriched in molecular alterations associated with BE progression risk. The new
capsule will also have a cryobiopsy mechanism for acquiring targeted tissue samples under real time image
guidance. In Aim 1 of this proposal, we will develop this multimodality TCE with biopsy (MM-TCEB) device and
show that it works as intended in a study of 20 BE patients. Then, we will conduct a clinical study in 100
unsedated BE patients to demonstrate that MM-TCEB collects tissue and identifies BE progression biomarkers
as well as sedated endoscopy. In Aim 3, we will develop image analysis and deep learning algorithms to mine
the Aim 2 data, uncovering new relationships between OCT, autofluorescence, and reflectance spectroscopy
and tissue-derived BE progression biomarkers. By acquiring targeted biopsies using a swallowable tethered
capsule in unsedated subjects, MM-TCEB can become a powerful technique for obtaining esophageal tissue
samples for BE progression biomarker dis...

## Key facts

- **NIH application ID:** 10591985
- **Project number:** 1R01EB034107-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Guillermo J Tearney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $643,503
- **Award type:** 1
- **Project period:** 2022-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10591985

## Citation

> US National Institutes of Health, RePORTER application 10591985, Screening for Barrett's Esophagus Progressors with Multimodality Tethered Capsule Image-Guided Biopsy (1R01EB034107-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10591985. Licensed CC0.

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