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210 D. Kwon
Figure 1. Superficial lateral oral tongue squamous cell carcinoma. Currently, the clinician uses visual
light to determine the appropriate margin for tumor resection.
et al.
(a) (b)
Figure 2. (a) High-resolution microendoscopy image of benign mucosal surface, lateral tongue. Note
the regularly shaped nuclei and uniform cellular architecture. (b) High-resolution microendoscopy
image of malignant lesion of the tongue. Note nuclear enlargement and disarray and the crowded,
irregular cellular architecture.
Head and Neck 211
Thus, the utility for surgical planning as well as real-time margin evaluation is promising. Similarly, other optical technologies such as confocal
microscopy and fluorescent visualization have been used in the oral cavity for guided surgical resection with studies demonstrating feasibility as
well as improved oncologic outcomes when compared with conventional
surgery.
33,34
Additional technologies which may offer significant translational promise in head and neck oncologic surgery include Raman spectroscopy, vibrational spectroscopy, lifetime widefield imaging to detect
protein–protein interactions in malignant tissues, and other advanced optical imaging technologies that allow the discrimination of benign and
35–38
malignant tissues.
In the era of minimally invasive surgery and the
de-escalation of treatment morbidity, in vivo, real-time, accurate optical
solutions will play an important role in the future controlling the extent of
surgery while providing clear oncologic margins.
Current Limitations
One of the primary intrinsic limitations of most in vivo optical modalities
is the limited depth of evaluation. Submucosal tumors, deep margins, and
tumors hidden in natural tissue folds or crypts cannot be easily evaluated.
Additionally, when being used for margin control, optics has no current
utility for aiding in deep tumor resection margins, which is typically the
most difficult margin to clear. As conventional biopsy and histopathologic
evaluation remain the gold standard for diagnosis in the foreseeable future,
optical evaluation can only serve as an adjunct at the present time.
In vivo optical evaluation offers real-time images with a resolution at
the cellular level. However, even at the highest resolutions, the evaluation
is purely phenotypic in the majority of currently available clinical systems.
There are no in vivo imaging modalities that can evaluate genetic alterations
or predict a propensity to malignancy prior to cellular expression, although
the technology does exist in the laboratory to explore these avenues. Given
the expanding genetic and molecular pathways leading to cancer, intracellular or genetic nanoprobes or optical technologies that detect molecular
signatures will likely be incorporated into optical techniques in the future.
212 D. Kwon
et al.
Finally, as with most experimental technologies, one of the primary
barriers to widespread clinical use is material development. Most probes
and equipment are not commercially available and are often not engineered
for use in the upper aerodigestive tract. While in vivo optical modalities
have shown promise in other fields, such as ophthalmology and gastroenterology, there has been some delay in c ross-over development in making
similar equipment appropriate for use in the upper aerodigestive tract. This
will also likely be driven by market forces, as the head and neck cancer
patient population, while traditionally small, may expand due to the current HPV-related oropharyngeal cancer epidemic. These new and exciting
technologies will nevertheless require continuedinvestigation, funding, and
development in order to overcome the aforementioned barriers.
Conclusion
In vivo optical technologies will continue to play an ever-expanding role in
the care of patients with head and neck cancer. Simpler technologies such
as narrow-band imaging have established an important usage and continue
to be adopted across clinical practices. Favorable experimental outcomes
in more advanced modalities show potential in the continued development
of optical systems that can improve head and neck cancer care. It is hoped
that advanced optical interrogation of genetic and molecular signatures as
well as protein interactions will aid in the discrimination of benign and
malignant lesions in the future.
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© 2024 World Scientific Publishing Company
https://doi.org/10.1142/9789813206984_0012
Genitourinary System Chapter
12
Maria M. S hevchuk∗, E ugene Shkolyar†,
and Joseph C. Liao
Introduction
†
In vivo microscopy (IVM) technologies are being actively studied for their
applications in urology and genitourinary pathology. The urinary tract, consisting of the renal pelvis, ureters, bladder, and urethra, are luminal organs
and amenable to endoscopic technologies validated in other organ systems,
particularly the gastrointestinal tract. Likewise, needle and probe-based
optical technologies are under investigation to image lesions of the kidney, prostate, and testes. The most common modalities under investigation
for clinical use are optical coherence tomography (OCT), confocal laser
endomicroscopy (CLE), multiphoton microscopy (MPM), as well as other
∗
Department of Pathology, Weill Cornell Medical College, New Y ork, NY, USA.
†
Department of Urology , Stanford University School of Medicine, Stanford, CA, USA.
217
218 M. M. Shevchuk
et al.
emerging technologies.The goal of these technologies is to provide an optical biopsy which can directly impact clinical management. OCT utilizes
near-infrared light to produce cross-sectional histological images with a
depth of up to 2.5 mm.
1, 2
CLE relies on endogenous reflected fluorescence
or on an exogenous fluorophore to provide subsurface tissue characterization with a spatial resolution of 1 µm and a depth of penetration of
120 µm.
1
MPM functions via endogenous tissue fluorescence to provide a
three-dimensionalhistologic image, with clinical probes currently in devel-
1
opment and allowing a depth of 500 µ m.
Most of the applications of IVM
in the genitourinary system are still in clinical feasibility studies. The following chapter summarizes the current status of IVM in the genitourinary
system and highlights its clinical significance as well as future promise in
the rapidly expanding fields of digital/virtual and AI assisted diagnoses and
treatments.
Bladder
Bladder cancer is the sixth most common cancer diagnosed in the United
3
States.
and, particularly for high-grade disease, holds the propensity to invade and
progress to muscle-invasive disease, which is typically managed with radical cystectomy.
of paramount importance. White light cystoscopy is the standard for diagnosis, resection, and surveillance of bladder cancer. Limitations of white
light cystoscopy are well known, including difficulties in identifying flat
lesions, identifying small satellite lesions, cancer grading, and determining the depth of invasion and margin assessment.
and narrow-band imaging provide additional enhancement for tumor localization, but they are unable to distinguish tumor grade and are suboptimal
for carcinoma in situ (CIS) diagnosis.
images of bladder mucosa with similar spatial resolution as histology, may
provide additional clinical intraprocedural information beyond that which
is available with current imaging modalities.
der cancer. OCT creates cross-sectional images (Figure 1) with spatial
Non-muscle invasive bladder cancer has a high recurrence rate
4
Accurate endoscopic grading and staging, therefore, are
1
Photodynamic diagnosis
1, 2
IVM technologies, which provide
OCT, which utilizes near-infrared light, has been investigated for blad-
Genitourinary System 219
(a)
(b)
Figure 1. OCT imaging of the bladder demonstrating (a) normal bladder with arrows indicating the
normal urothelium, lamina propria, and muscularis propria and (b) bladder with evidence of tumor
invasion of the lamina propria. Adapted from Ref. [7].
resolution similar to 4X H&E microscopic images (∼10 µm) and does
not require exogenous contrast agents.
1
The depth of penetration is 2 mm
along the Z-axis allowing the lamina propria and inner muscularis propria
to be imaged. OCT may be useful for intraoperative identification of tumor
invasion, guidance in targeting biopsies to improve staging accuracy, and
for evaluating resection margins. Another clinical advantage to the use of
OCT technology during diagnostic and treatment procedures for bladder
cancer is that OCT probes are compatible with standard cystoscopes. These
benefits are highlighted in a recent review.
5
Studies using OCT imaging in the bladder have demonstrated encour-
aging results. Lerner et al.
6
reported a 90% sensitivity and an 89% specificity for the OCT diagnosis of bladder tumors confined to the mucosa
as compared to the histology. Of muscle-invasive tumors, 100% were