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80 D. Schmolze & V. J. A. Konda
algorithm was even able to automatically classify a majority of the
lesions.
Subsequent studies have imaged early gastric carcinoma and high-
grade dysplasia, a direct precursor lesion. For example, Li et al.
31
imaged a
large number of patients with suspected early gastric carcinoma. In a twophase study, diagnostic criteria were first established with concurrent CLE
and histopathology images. These criteria were then validated on 1786
patients. During the validation phase, the CLE-base criteria achieved an
overall accuracy of 98.8% for the distinction of cancer or high-grade dysplasia from non-neoplasticareas. By contrast, standard endoscopy achieved
an overall accuracy of 94.1%.
Disclosures
Vani Konda has received past honoraria from Mauna Kea Technologies.
References
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https://doi.org/10.1142/9789813206984_0006
Lower Gastrointestinal Tract Chapter
6
Sameera Sherwani∗, Martin Goetz†,
‡
Hany Osman
, and Andrew Quinn
Introduction
§
The lower gastrointestinal (GI) tract extends from the beginning of the
duodenum to the anus. With the exception of the anus, the small and large
intestines represent areas of significant investigational and clinical interest for in vivo microscopy (IVM) with applications involving neoplastic,
inflammatory, and environmental c onditions as well as surveillance, all with
an emphasis on image acquisition and interpretation during the endoscopic
procedure. The majority of work to date has been done with confocal laser
endomicroscopy (CLE). Where applicable, examples of optical coherence
tomography (OCT) and endocytoscopy (EC) will be supplied. This chapter
will thus focus primarily on CLE of the traditional tubal gut.
∗
Texas Women’s University, Dallas, TX, USA.
†
Medical Clinic IV — Gastroenterology/Oncology, Sindelfingen-Böblingen Clinic,
Böblingen Clinics, Böblingen, Germany.
‡
Dermatopathology, Fort Wayne Dermatology Consultants, Fort Wayne, Indiana, USA.
§
Pathology Informatics, Parkland Health, University of Texas Southwestern Medical Center
Dallas, TX, USA.
85
86 S. Sherwani
et al.
Normal Microanatomy
The lower GI tract generally consists of four layers (Figures 1–3):
• Mucosa: Columnar epithelium, lamina propria, and muscularis mucosa
(muscularis interna).
• Submucosa: Loose connective tissue and submucosal (Meissner) plexus.
• Muscularis propria: Inner circular and outer longitudinal layers and
myenteric (Auerbach) plexus.
• Adventitia/serosa: Loose connective tissue and largest blood vessels.
A more detailed description of the normal microanatomy of the superficial aspects of the small and large intestines follows as these are almost
exclusively visualized by CLE techniques.
The superficial aspects of the duodenum, jejunum, and ileum are similar. Villi are regular in shape and size, appearing as cylindrical extensions from the surface and c ircles with external cells in cross-section. Villi
are very evenly spaced — usually back-to-back — with no dropout. The
epithelium consists of a single layer of bland, thin enterocytes with luminal
Figure 1. Duodenum, mucosa, histology. Image courtesy of Dr. James Mitchell.
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Figure 2. Terminal ileum, histology. Image courtesy of Dr. James Mitchell.
microvilli and interspersed goblet cells with luminal mucin. In either cell,
nuclei are uniform, small, round, dark, and basally located. The lamina
propria is relatively acellular, containing the scattered small, regular, dark
nuclei of white blood cells. Vessels appear in a subepithelial distribution.
The superficial aspects of the colon include crypts of even size and
shape. Crypts appear as cylindrical involutions relative to the surface and
circles withinternal cells in cross-section.In a healthy state, crypts are backto-back with no dropout. The colonic epithelium consists of a single layer
of goblet cells with uniform, small, round, dark, and basally located nuclei.
Deeper features are as described for the duodenum, jejunum, and ileum.
Pathology reports typically characterize the above findings as being
“within normal limits” or as having “no specific pathologic change.”
Endoscopy
To screen, diagnose, treat, and manage neoplastic and non-neoplastic
diseases of the gastrointestinal tract, endoscopic surveillance is the
88 S. Sherwani
(a)
(b)
et al.
Figure 3. Colon, histology. Normal colon, full thickness. (a) 200×. (b) 400×. Images courtesy of
Dr. James Mitchell.
Lower Gastrointestinal Tract 89
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conventional tool
standard for diagnosis.
1,2
complemented by histologic examination as the gold
3, 4
The duodenum is typically visualized along with
the esophagus and stomach by esophagogastroduodenoscopy. The terminal
ileum and colon by colonoscopy. The jejunum and majority of the ileum
are seldom examined via traditional methods, though newer methods, such
as capsules, are in regular use. Disadvantages of current methods include
missed dysplastic lesions, especially flat ones, and visualization of only the
surface of the gastrointestinalmucosa by the human eye. Likewise, biopsies
come with a risk of absent findings, bleeding, infection, and perforation as
well as the time needed for their interpretation.
3,4
Lastly, endoscopes can
prove difficult to use in pediatric populations and require sedation (and its
associated costs and complications).
2
Confocal Laser Endomicroscopy
CLE of the GI tract was introduced in 20045and provides in vivo, real-time,
dynamic, and high-resolution imaging of microscopic structures of the gastrointestinal mucosa and lamina propria during endoscopy.
optical sections parallel to the tissue surface (histologic sections are usually
perpendicular). With traditional CLE, the epithelium is contrast-poor. However, as discussed in the following, intravenousor topicalcontrast agentsand
techniques are available for nuclear visualization. Microvilli are currently
beyond the resolution of most devices. The lamina propria is contrast-rich
in the middle and late phases of intravenous contrast administration. Ve ssels are contrast-rich, especially in the early phase of intravenous contrast
administration,and carry contrast-poorerythrocytes in single files. Standard
CLE techniques allow endoscopists to resolve erythrocytes as they move
through vessels. To reiterate, deeper structures are not typically visualized
unless pathologic.
CLE is based on the same principle as light microscopy with some
modifications.
6
Confocal refers to the positioning of both illumination and
light collection systems in the same focal plane from an objective lens. In
Figure 4, blue laser light travels from its source through a pinhole and then
through an objective lens to the tissue. Reflected light from the tissue is
then refocused by the same lens. Only the reflected light that re-traverses
3
CLE produces