Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS)

Patients will undergo a VLE exam with and without IRIS per the standard of care. All patients
regardless of the study participation in this study would receive VLE with and without IRIS
clinically. They will be randomized into VLE without IRIS first vs VLE with IRIS first. The
BUDDY Randomization System, provided for use by the Northwell Health Biostatistics Unit, will
be used for this. Randomization will be stratified based on prior diagnosis of dysplasia. The
order in which the patient is randomized to will be recorded on the case report form. There
will be concealed allocation as the study coordinator performing the randomization will not
know the order of the next allocation.

Both VLE and IRIS imaging are being performed as standard of care. However, randomization of
the order allows for comparison of the two. Regions of interest (ROI) will be recorded using
a full scan and recorded on the case report form. The time to identification of ROIs will
also be recorded. Each group will then cross over such that the VLE without IRIS group will
then have IRIS turned on. ROI will then be recorded for each group based on full scans. A
consensus ROI will be recorded based on the two exams. Only one ROI per centimeter will be
allowed to avoid overlapping of laser marks. In addition, VLE without IRIS and IRIS marks
within 75 frames of each other or 2 hours (on a clock face orientation) will be considered
the same target.

Laser marking will then be performed. A double laser mark will be applied to all IRIS ROIs. A
single laser mark will be applied to VLE ROIs. Targeted biopsies will be taken of all laser
marks and placed in separate biopsy jars. Biopsies will be taken in between the laser marks
for double laser marked areas. For single laser marks, biopsies will be taken on either side
of the laser mark. Resection of visible lesions will then occur per standard of care (if
present) followed by random biopsies of the segment. Random biopsies are pinch biopsies every
1 cm the length of the Barrett's in a 4 quadrant fashion per gastrointestinal society
guidelines. There are no additional research biopsies being performed outside this study. The
targeted biopsies are based on the VLE features that are suspicious for dysplasia and thus
standard of care. The other biopsies being performed here are random biopsies which are also
being performed for standard of care. Biopsied samples will be stored per standard of care
procedures per the pathology department. They will not be stored for future research
purposes.

Following each procedure, the physician will be asked a series of Likert Scale questions to
assess the utility of IRIS in that procedure, including how it impacts their confidence in
image interpretation, their ability to assimilate data more easily and quickly, and their
overall perception of the technology.

Although, the VLE with IRIS and VLE without IRIS are being performed as standard of care, all
adverse events will be recorded and reported to the IRB.

All data will be entered into a central encrypted REDCap database.

Expert pathologists who specialize in gastrointestinal pathology will read the histology. A
second gastrointestinal pathologist will confirm any histologic diagnosis of dysplasia. This
is the standard of care at Northwell Health and academic medical centers per gastrointestinal
society guidelines.

All procedures (upper endoscopy, volumetric laser endomicroscopy, and IRIS enhanced VLE) will
be performed as standard of care. The prospective data collection and initial randomization
will be the research component. All data collected will be de-identified before being
transferred into a database. This will be kept in a safe place that is only accessible to the
research team.

Inclusion Criteria:

- 18 years of age or older at the time of informed consent

- Barrett's esophagus greater than 2 cm in length

- Undergoing a scheduled upper endoscopy with VLE exam for surveillance as standard of
care

Exclusion Criteria:

- Less than 18 years old at the time of informed consent

- Unable to provide written informed consent

- Esophageal stenosis/stricture preventing VLE

- Esophagitis

- Severe medical comorbidities preventing endoscopy

- Pregnancy

- Uncontrolled coagulopathy