Larynx cancer is one of the most common primary head and neck cancers. For early-stage laryngeal cancer, both
surgery and radiotherapy are effective treatment modalities, offering a high rate of local control and cure. Optical
coherence tomography (OCT) is an established non-invasive optical biopsy method, capable of imaging ranges of 2-
3 mm into tissue. By using the principles of low coherence light interferometry, OCT can be used to distinguish
normal from unhealthy laryngeal mucosa in patients. Two forward-looking endoscope OCT probes of different sizes
in a sweeping frequency OCT (SS-OCT) configuration were compared in terms of their performances for ex-vivo
laryngeal cancer imaging.
The setup configuration of the first OCT probe unit was designed and constructed at the Institute of Applied Physics
RAS, Russia (diameter of 1.9 mm and the rigid part at the distal end is 13 mm long). The second OCT endoscope
probe was constructed at the Department of Biomedical Engineering at Johns Hopkins University, USA, using a
tubular piezoelectric actuator with quartered electrodes in combination with a resonant fiber cantilever (diameter of
2.4 mm, and rigid part of 45 mm).
Cross-sectional images of laryngeal lesions using the two OCT configurations were aquired and compared with
OCT images obtained in a 1310 nm SS-OCT classical non-endoscopic system. The work presented here is an
intermediate step in our research towards in-vivo endoscopic laryngeal cancer imaging.
We compare the illumination uniformity and the associated effects of the spiral and Lissajous scanning patterns that are commonly used in an endomicroscope. Theoretical analyses and numerical simulations were first performed to quantitatively investigate the area illumination density in the spiral scanning pattern. The results revealed the potential problem of manifest photodamage due to the very high illumination density in the center of the spiral scan. Similar analyses of the Lissajous scanning pattern, which can be conveniently implemented on the same endomicroscope with no hardware modifications, showed a more uniform illumination density with about an 80-fold reduction in the peak illumination density. To underscore the benefit offered by the improved illumination uniformity, we conducted in vitro two-photon fluorescence imaging of cultured cells stained with a LIVE/DEAD viability assay using our home-built, fiber-optic, two-channel endomicroscopy system. Both the spiral and the Lissajous scans were implemented. Our experimental results showed that cells near the spiral scan center experienced obvious photodamage, whereas cells remained alive over the entire region under the Lissajous beam scanning, confirming the predicted advantage offered by the Lissajous scan over this spiral scan in an endomicroscopy setting.
A miniature endoscope probe for forward viewing in a 50 kHz swept source optical coherence tomography (SS-OCT)
configuration was developed. The work presented here is an intermediate step in our research towards in vivo
endoscopic laryngeal cancer screening. The endoscope probe consists of a miniature tubular lead zirconate titanate
(PZT) actuator, a single mode fiber (SMF) cantilever and a GRIN lens, with a diameter of 2.4 mm. The outer surface
of the PZT actuator is divided into four quadrants that form two pairs of orthogonal electrodes (X and Y). When
sinusoidal waves of opposite polarities are applied to one electrode pair, the PZT tube bends transversally with
respect to the two corresponding quadrants, and the fiber optic cantilever is displaced perpendicular to the PZT tube.
The cantilever's resonant frequency was found experimentally as 47.03 Hz. With the GRIN lens used, a lateral
resolution of ~ 13 μm is expected. 2D en face spiral scanning pattern is achieved by adjusting the phase between the
pairs of X and Y electrodes drive close to 90 degrees. Furthermore, we demonstrate the imaging capability of the
probe by obtaining B-scan images of diseased larynx tissue and compare them with those obtained in a 1310 nm SS-OCT
classical non-endoscopic system.
A miniature fiber optic endomicroscope with built-in dynamic focus scanning capability is developed for the first time for 3-D two-photon fluorescence (TPF) imaging of biological samples. Fast 2-D lateral beam scanning is realized by resonantly vibrating a double-clad fiber cantilever with a tubular piezoactuator. Slow axial scanning is achieved by moving the distal end of the imaging probe with an extremely compact electrically driven shape memory alloy (SMA). The 10-mm-long SMA allows 150-μm contractions with a driving voltage varying only from 50 to 100 mV. The response of the SMA contraction with the applied voltage is nonlinear, but repeatable and can be accurately calibrated. Depth-resolved imaging of acriflavine-stained biological tissues and unstained white paper with the endomicroscope is performed, and the results demonstrate the feasibility of 3-D nonlinear optical imaging with the SMA-based scanning fiber-optic endomicroscope.
This paper reviews our recent developments of ultrathin fiber-optic endomicroscopy technologies for transforming high-resolution
noninvasive optical imaging techniques to in vivo and clinical applications such as early disease detection and guidance of
interventions. Specifically we describe an all-fiber-optic scanning endomicroscopy technology, which miniaturizes a conventional
bench-top scanning laser microscope down to a flexible fiber-optic probe of a small footprint (i.e. ~2-2.5 mm in diameter), capable of
performing two-photon fluorescence and second harmonic generation microscopy in real time. This technology aims to enable realtime
visualization of histology in situ without the need for tissue removal. We will also present a balloon OCT endoscopy technology
which permits high-resolution 3D imaging of the entire esophagus for detection of neoplasia, guidance of biopsy and assessment of
therapeutic outcome. In addition we will discuss the development of functional polymeric fluorescent nanocapsules, which use only
FAD approved materials and potentially enable fast track clinical translation of optical molecular imaging and targeted therapy.
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