radiocontrast in positron emission tomography (PET) scans or for targeted radiotherapy. CLI is adaptable to endoscopy for selected applications and could be useful
for optical detection of radiotracers via an endoscope. A prototype CLI endoscope
has been demonstrated in animal studies using conventional endoscopic equipment
coupled with the PET radiotracer
18 F-fluorodeoxyglucose [22]. Further medical
applications of CLI are discussed at length in the latter section of this review.
Incident light that is reflected by tissues is modified in numerous ways by the
physical and biochemical properties of that tissue, which manifests in changes to
absorbance via intensities of specific wavelengths, variation in angular trajectories,
alteration of light polarity, etc. Reflectance spectroscopy takes advantage of these
resultant differences, using advanced analysis to construct quantitative “scattering
signatures” of reflected light to reveal morphological and biochemical information
about probed tissues without labeling. For endoscopy, reflectance spectroscopy
has several promising applications, most notably to detect the oxygenation level of
blood. The ratio of oxyhemoglobin to deoxyhemoglobin can be extrapolated by
the differential absorbance and reflectance profiles of each compound, providing an
endoscopic tool for detection of poorly perfused regions in mucosal tissue. A white
light reflectance spectroscopy method has been used to measure via colonoscopy to
analyze the success of induced colon polyp ischemia procedures in real time, as well
as identification of sites of mesenteric ischemia [23, 24].
Two-photon endomicroscopy (TPEM) is yet another emerging technology with
potential to be translated into clinical endoscopy. Two-photon imaging utilizes two
excitation photons using a femtosecond pulsed beam to produce fluorescent emission by excitation of individual atoms by two simultaneous photons. This method
can utilize near-infrared excitation sources for deep tissue penetration. Furthermore,
simultaneous absorbance of two photons is an extremely low-probability event
outside of the focal point due to insufficient photon density; therefore, emission
from outside the focal point is negligible. This permits exclusion of background light
outside of the focal plane, but without the pinhole aperture required in confocal
microscopy. TPEM is therefore a potentially advantageous alternative to CLEM,
with acquisition of deeper images possible. Like CLEM, however, TPEM would
require administration of fluorescent contrast agents. Prototype TPEM units have
been demonstrated in animal models but thus far have not yet been evaluated in
human patients [25, 26]. Clinical TPEM also requires further development and
approval of fluorescent contrast agents which are optimized for two-photon
excitation.
Summary Diagnostic endoscopic procedures are arguably the most commonly
used and most diverse application of optical imaging in medicine today. Nearly
every modality of optical imaging in current clinical use is represented in the array of
endoscopic imaging technologies currently available to physicians. Furthermore,
endoscopic procedures also have the largest frontier of technological advancement,
with a number of novel advanced optical technologies at or near the clinical
translation threshold.
210
E. P. Stater et al.
for optical detection of radiotracers via an endoscope. A prototype CLI endoscope
has been demonstrated in animal studies using conventional endoscopic equipment
coupled with the PET radiotracer
18 F-fluorodeoxyglucose [22]. Further medical
applications of CLI are discussed at length in the latter section of this review.
Incident light that is reflected by tissues is modified in numerous ways by the
physical and biochemical properties of that tissue, which manifests in changes to
absorbance via intensities of specific wavelengths, variation in angular trajectories,
alteration of light polarity, etc. Reflectance spectroscopy takes advantage of these
resultant differences, using advanced analysis to construct quantitative “scattering
signatures” of reflected light to reveal morphological and biochemical information
about probed tissues without labeling. For endoscopy, reflectance spectroscopy
has several promising applications, most notably to detect the oxygenation level of
blood. The ratio of oxyhemoglobin to deoxyhemoglobin can be extrapolated by
the differential absorbance and reflectance profiles of each compound, providing an
endoscopic tool for detection of poorly perfused regions in mucosal tissue. A white
light reflectance spectroscopy method has been used to measure via colonoscopy to
analyze the success of induced colon polyp ischemia procedures in real time, as well
as identification of sites of mesenteric ischemia [23, 24].
Two-photon endomicroscopy (TPEM) is yet another emerging technology with
potential to be translated into clinical endoscopy. Two-photon imaging utilizes two
excitation photons using a femtosecond pulsed beam to produce fluorescent emission by excitation of individual atoms by two simultaneous photons. This method
can utilize near-infrared excitation sources for deep tissue penetration. Furthermore,
simultaneous absorbance of two photons is an extremely low-probability event
outside of the focal point due to insufficient photon density; therefore, emission
from outside the focal point is negligible. This permits exclusion of background light
outside of the focal plane, but without the pinhole aperture required in confocal
microscopy. TPEM is therefore a potentially advantageous alternative to CLEM,
with acquisition of deeper images possible. Like CLEM, however, TPEM would
require administration of fluorescent contrast agents. Prototype TPEM units have
been demonstrated in animal models but thus far have not yet been evaluated in
human patients [25, 26]. Clinical TPEM also requires further development and
approval of fluorescent contrast agents which are optimized for two-photon
excitation.
Summary Diagnostic endoscopic procedures are arguably the most commonly
used and most diverse application of optical imaging in medicine today. Nearly
every modality of optical imaging in current clinical use is represented in the array of
endoscopic imaging technologies currently available to physicians. Furthermore,
endoscopic procedures also have the largest frontier of technological advancement,
with a number of novel advanced optical technologies at or near the clinical
translation threshold.
210
E. P. Stater et al.