Endomicroscopy - Biomedical Optical Imaging Technologies: Design and Applications - page 254

the contribution of these three channels to the overall image, an improvement in
contrast between abnormal and normal tissue can be achieved. In general, all of
these endoscopic imaging platforms and modes provide a macroscopic or “wide-
field” view of the tissue surface. This enables the endoscopist to evaluate an entire
organ for abnormalities and when necessary guide the selection of sites for biopsy
or endoscopic therapy.
To complement the traditional macroscopic scale view provided by endoscopy,
the concept of endomicroscopy emerged with the goal of providing images with
cellular level resolution, albeit over a small FOV. These approaches have been
variously described as “optical biopsy,” “ in vivo pathology,” and “endocytoscopy.”
Over the last 10 years, both the perception of endomicroscopy and methods for its
implementation have evolved significantly. Early enthusiasm led to the belief among
some communities that endomicroscopy might entirely replace traditional biopsies
and pathology evaluation. Today, a more realistic role for endomicroscopy appears
to lie in improving the diagnostic yield of pathology by allowing the endoscopist to
target biopsy collection to the most diagnostically informative sites. By first using
macroscopic methods of high-definition white light endoscopy or AFI/NBI as “red-
flag” methods to highlight suspicious areas, endomicroscopy can then be used to
evaluate those sites in greater detail and inform the endoscopist on whether a biopsy
should be taken or whether therapy should be applied.
Endomicroscopy encompasses several imaging modalities, each of which was
initially demonstrated on large-scale benchtop platforms, before undergoing the
miniaturization required for endoscopic deployment. These modalities include
full-field contact imaging (endocytoscopy or fiber bundle endomicroscopy),
scanning confocal microscopy (in reflectance and fluorescence), and nonlinear
microscopy (multiphoton, second-harmonic, and coherent scattering techniques).
These approaches all generate images with subcellular level resolution, most
commonly in the en face plane, to subsurface depths of a few hundred micrometers.
Optical coherence tomography (OCT) is an approach which is considered by some
to fall within the field of endomicroscopy, providing cross-sectional images of
tissue to depths of around 2 mm. While OCT can delineate tissue microstructure
and layered architectures, cellular level detail is generally not apparent. The related
method of optical coherence microscopy (OCM) however does offer en face
images with cellular level resolution, with similar operating parameters as confocal
microscopy.
These endomicroscopy techniques are at various stages of clinical implemen-
tation (see Sect. 8.3 for more details), with confocal fluorescence imaging having
been commercialized and under evaluation in several large-scale multicenter clinical
trials. Optical coherence tomography is also being evaluated in patients at several
large academic centers. Full-field contact imaging has been demonstrated in patients
with small- to medium-sized studies ongoing. Nonlinear imaging techniques remain
further behind in the translational pipeline largely due to the complexity of the
required light sources and fiber delivery methods. Nevertheless, these implemen-
tation challenges are being addressed in laboratory settings, with data from ex vivo