High Resolution Optical Imaging of Barrett*s Esophagus Using N-Vision pVLE

In patients with Barrett oesophagus (BO) malignant degeneration may occur
through a series of phenotypic cellular changes detected and graded on
microscopy; beginning with non-dysplastic intestinal metaplasia (IM), then low-
(LGIN) and high-grade intraepithelial neoplasia (HGIN), and eventually early
cancer (EC) may arise1,2. Endoscopic surveillance of patients with BO is,
therefore, recommended to detect early neoplasia at a curable stage3. When
using standard endoscopy, however, it may be difficult to distinguish areas
with early neoplasia (i.e. HGIN a/o EC) within the normal Barrett mucosa4.
Thus, in the absence of visible abnormalities random four-quadrant biopsies are
obtained every 1-2 cm of the BO, to allow for histological evaluation for the
presence of neoplasia (Seattle protocol)4,5. However, random biopsies are
associated with a high rate of sampling error and may miss malignant lesions in
the BO6. Moreover, the extensive biopsy protocol poses significant burden on
the patient, the endoscopist and the health care system, due to prolonged
endoscopy time and high costs. To increase the detection rate of early
neoplasia during endoscopic surveillance of BO patients, different imaging
techniques have been developed. In this respect, roughly two imaging goals have
to be distinguished: first and foremost, suspicious lesions will have to be
identified in the BO, which requires a *red flag* imaging modality with the
ability to draw attention to a certain area of interest. Second, a
differentiating tool will have to be able to distinguish between truly
suspicious areas (i.e. HGIN/EC) or false positive areas.
The N-Vision pVLE system is a newly developed diagnostic tool that will allow
high resolution imaging of the oesophageal mucosa through Optical Frequency
Domain Imaging (OFDI), a second generation Optical Coherence Tomography (OCT)
technology. OFDI compares backscattered light from tissue to a reference
signal, which allows high resolution depth resolved imaging of the investigated
tissue. In essence, OFDI is a kind of optical ultrasound imaging. The N-Vision
probe based Volumetric Laser Endomicroscopy (pVLE) system incorporates OFDI in
a rotating endoscopic probe, that allows for real-time, 3D high resolution
imaging of the oesophageal mucosa. The N-Vision system can be used as an
additional tool during standard surveillance endoscopy for Barrett's oesophagus
or work-up of early neoplasia. The 3D mucosal map that is projected on the
screen of the n-Vision system may identify suspicious areas that would
otherwise have been overlooked by standard white light endoscopy.

In patients undergoing surveillance endoscopy for Barrett;s oesophagus or
work-up and treatment for early neoplasia in Barrett's oesophagus we will
evaluate the N-Vision pVLE system for the following items:
1) feasibility of the system
2) the capacity of the system to construct a high-resolution map of the mucosal
lining of the oesophagus
3) the capacity of detecting areas suspicious for neoplasia (by correlating the
suspicious areas identified by the N-Vision system to the histological
diagnosis of the biopsy specimen of that particular area).

In phase 1, 50 patients will be included in this study: 30 patients with a
Barrett's oesophagus without early neoplasia and 20 patients with early
neoplasia arising of Barrett's oesophagus.
During standard endoscopy for surveillance or work-up, the oesophagus will
first be examined with white light endoscopy, recording all marks, distances
and possible suspicious areas. Subsequently, the N-Vision probe will be
deployed through the working channel of the endoscope, the balloon inflated and
the inner lining of the oesophagus imaged. Areas suspicious for early neoplasia
identified on the N-Vision 3D image will be recorded.
Mapping with the N-Vision is followed by standard biopsies: all suspicious
areas and random four-quadrant biopsies, as required by the official guidelines.
All histological evaluation is done by both a junior and a senior pathologist.
All histology will be reviewed by a GI-expert pathologist. The histological
data will be correlated to the N-Vision data.

The N-Vision pVLE system is non-invasive in nature. The type of light delivered
by the optical fiber is equivalent in intensity to the standard light source
used and delivered by a standard endoscope; the excitation of tissue by the
light energy delivered by the optical biopsy system is non-damaging and does
not result in any thermal effects on tissue. The collection of physical tissue
biopsies in these subjects is standard part of the procedure for surveillance
or work-up endoscopies for Barrett oesophagus, with minimal potential risk to
the health, safety or welfare of the subject. All tissue biopsies taken as part
of this study will be part of the standard of care. Enrollment in the study
will not affect in any way the subject*s diagnosis, treatment or mitigation of
any identified disease. Due to the imaging with the N-Vision pVLE system prior
to the collection of physical biopsies, the endoscopy will take 15 minutes
longer than usual.