In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope

Abstract

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 microm in air and 4.4-microm 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.

Serial endoscopy in azoxymethane treated mice using ultra-high-resolution optical coherence tomography

“…The novel achromatized endoscope design has been previously described in detail, 22 as has the UHR OCT system. 23 Briefly, ultrahigh-resolution is achieved axially using a mode-locked Titanium:sapphire laser with a full-width-halfmaximum bandwidth of 50 nm, centered at 800 nm, and transversally by utilizing : conjugate imaging of a small core diameter fiber.…”

“…2 We recently developed a custom UHR time domain OCT endoscope fabricated specifically for the small proportions of the murine colon and achieving the highest resolution in OCT endoscopy to date. 22 In this study, we utilized the UHR OCT endoscope to image the lower colon of AOM treated A/J mouse models of CRC over time, monitor the progression of neoplastic transformations, determine if OCT is capable of identifying the early stages of colorectal disease in mouse models, and evaluate whether pathological interpretation of OCT images parallels histopathological diagnosis.…”

Endoscopic optical coherence tomography: technologies and clinical applications [Invited]

“…Despite the excellent resolution and promising potential, translational applications and wide acceptance of ultrahigh-resolution OCT endoscopy in the 800 nm wavelength range faced a prohibitive cost issue, since each superachromatic microlens cost about US$10,000, and few vendors were willing to fabricate the micro compound lens (such as Bern Optics, Inc.). The cost is expected to be even higher if a super-achromatic microlens smaller than the reported ones (i.e., of 1 1.5-1.7 mm optics diameter) [84,85] is needed for further reducing the overall 2-mm endoscope diameter. Recently a novel approach has been developed by using diffractive optics [7,86] (see Fig.…”

“…Among the many technical challenges in developing 800 nm ultrahighresolution OCT endoscopes, a significant one is managing the chromatic aberration in the micro optics so that all the wavelengths within the broad source spectrum can be equally focused along the imaging depth. Several prototypes of ultrahigh-resolution OCT endoscopes have been reported, including a side-viewing probe in which cross-sectional imaging was performed through pullback along the probe axis [84], and a forward-viewing probe where cross-sectional imaging was achieved by using a resonant fiber-optic PZT scanner [85]. In both cases, chromatic aberration was managed by customized multi-element miniature microlenses of a 2.0 mm diameter including the housing tube.…”

Common path Fourier domain optical coherence tomography based on multiple reflections within the sample arm

“…In this case, an additional interferometer (often called an autocorrelator) is required to bring together the distant arms of the first interferometer [10][11][12][13][14][15][16][17]. The second case uses a partially reflecting surface close to the specimen as the reference arm [18][19][20][21][22][23] thus obviating the need for the second interferometer. The third case incorporates a miniature interferometer close to tip of the fibre [19,21].…”