Optical coherence tomography (OCT) is an imaging modality that enables assessment of tissue structural characteristics. Studies have indicated that OCT is a useful method to assess both blood vessel morphology and the response of a vessel to a deployed stent. We evaluated the ability of OCT to visualize the cellular lining of a tissue-engineered blood vessel mimic (BVM) and the response of this lining to a bare metal stent. We develop a side-firing endoscope that obtains intraluminal, longitudinal scans within the sterile bioreactor environment, enabling time-serial assessment. Seventeen BVMs are imaged with the endoscopic OCT system. The BVMs are then evaluated via fluorescence microscopy and/or standard histologic techniques. We determine that (1) the OCT endoscope can be repeatedly inserted without visible damage to the BVM cellular lining, (2) OCT provides a precise measure of cellular lining thickness with good correlation to measurements obtained from histological sections, and (3) OCT is capable of monitoring the accumulation of cellular material in response to a metallic stent. Our studies indicate that OCT is a useful technique for monitoring the BVM cellular lining, and that OCT may facilitate the use of BVMs for early stage device assessment.
Purpose: Optical coherence tomography (OCT) is a minimally invasive, depth-resolved imaging tool that can be
commissioned for small diameter endoscopic applications for imaging mouse models of colorectal cancer. In this study,
we utilized ultrahigh resolution OCT (UHR OCT) to serially image the lower colon of azoxymethane (AOM) treated A/J
mouse models of CRC, monitor the progression of neoplastic transformations, and determine if OCT is capable of
identifying early disease.
Experimental Design: Thirteen AOM treated A/J and two control A/J mice were surveyed at four timepoints (8, 14, 22,
and 26 weeks post AOM treatment) using a prototype 2.0 mm diameter UHR OCT endoscope-based system that
achieved resolutions of 3.2 um axial and 4.4 um lateral. Histological samples were obtained at the final imaging
timepoint serving as the gold standard.
Results: Gross and histological assessment of the excised colonic tissue revealed at least one tumor in all 13 AOM
treated mice, with most mice developing multiple tumors. In the corresponding OCT images, a progression from healthy
thin mucosa to adenoma appearing as large, structurally disorganized masses was visualized over the imaging time
points correlating to the locations of the grossly visualized tumors.
Conclusions: This study indicates that UHR OCT enables accurate identification of disease and non-destructive
visualization of CRC progression in the lower colon of mice.
Endoscopic ultrahigh-resolution optical coherence tomography (OCT) enables collection of minimally invasive cross-sectional images in vivo, which may be used to facilitate rapid development of reliable mouse models of colon disease as well as assess chemopreventive and therapeutic agents. The small physical scale of mouse colon makes light penetration less problematic than in other tissues and high resolution acutely necessary. In our 2-mm diameter endoscopic time domain OCT system, isotropic ultrahigh-resolution is supported by a center wavelength of 800 nm and full-width-at-half-maximum bandwidth of 150 nm (mode-locked titanium:sapphire laser) combined with 1:1 conjugate imaging of a small core fiber. A pair of KZFSN5/SFPL53 doublets provides excellent color correction to support wide bandwidth throughout the imaging depth. A slight deviation from normal beam exit angle suppresses collection of the strong back reflection at the exit window surface. Our system achieves axial resolution of 3.2 µm in air and 4.4-µm lateral spot diameter with 101-dB sensitivity. Microscopic features too small to see in mouse tissue with conventional resolution systems, including colonic crypts, are clearly resolved. Resolution near the cellular level is potentially capable of identifying abnormal crypt formation and dysplastic cellular organization.
Mouse models are increasingly important for studying human GI pathology. OCT provides minimally
invasive, cross-sectional images that indicate the thickness and scattering density of underlying tissue. We have
developed endoscopic ultrahigh resolution OCT (UHR-OCT) to imaging mouse colon in vivo. The reduced scale of the
mouse colon makes tissue light penetration much less problematic, and high resolution acutely necessary. Higher lateral
resolution requires a departure from the traditional cemented GRIN lens design. We support the need for better
chromatic aberration than can be achieved by a GRIN lens using commercial raytracing software. We have designed and
built a 2mm diameter endoscopic UHR-OCT system achromatized for 770-1020nm for use with a Titanium:sapphire
laser with 260 nm bandwidth at full-width-half-maximum centered at 800 nm while achieving a 4.4um lateral spot
dimension at focus. A pair of KZFSN5/SFPL53 doublets provides excellent primary and secondary color correction to
maintain wide bandwidth through the imaging depth. A slight deviation from normal beam exit angle suppresses
collection of the strong back reflection at the exit window surface. The novel design endoscope was built and
characterized for through focus bandwidth, axial resolution, signal to noise, and lateral spot dimension. Performance is
demonstrated on in vivo mouse colon. Ultrahigh-resolution images of mouse tissue enable the visualization of
microscopic features, including crypts that have previously been observed with standard resolution OCT in humans but
were too small to see in mouse tissue. Resolution near the cellular level is potentially capable of identifying abnormal
crypt formation and dysplastic cellular organization.
Mouse models are increasingly important for studying human GI pathology. OCT provides minimally invasive, cross-sectional images that indicate the thickness and scattering density of underlying tissue. We have developed endoscopic ultrahigh resolution OCT (UHR-OCT) for the purpose of in vivo imaging in mouse colon. The reduced scale of the mouse colon makes tissue light penetration much less problematic, and high resolution acutely necessary. Higher lateral resolution requires a departure from the traditional cemented GRIN lens design. We support the need for better chromatic aberration than can be achieved by a GRIN lens using commercial raytracing software. We have designed and built a 2mm diameter endoscopic UHR-OCT system achromatized for 770-1020nm for use with a Titanium:sapphire laser with 260 nm bandwidth at full-width-half-maximum centered at 800 nm while achieving a 4.4um lateral spot dimension at focus. A pair of KZFSN5/SFPL53 doublets provides excellent primary and secondary color correction to maintain wide bandwidth through the imaging depth. A slight deviation from normal beam exit angle suppresses collection of the strong back reflection at the exit window surface. The novel design endoscope was built and characterized for through focus bandwidth, axial resolution, signal to noise, and lateral spot dimension. Performance is demonstrated on a variety of ex vivo tissues and in situ mouse colon. Ultrahigh-resolution images of mouse tissue enable the visualization of microscopic features, including crypts that have previously been observed with standard resolution OCT in humans but were too small to see in mouse tissue. Resolution near the cellular level is potentially capable of identifying abnormal crypt formation and dysplastic cellular organization.
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