Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

While optical coherence tomography (OCT) provides a resolution down to 1 µm, it has difficulties in visualizing cellular structures due to a lack of scattering contrast. By evaluating signal fluctuations, a significant contrast enhancement was demonstrated using time-domain full-field OCT (FF-OCT), which makes cellular and subcellular structures visible. The putative cause of the dynamic OCT signal is the site-dependent active motion of cellular structures in a sub-micrometer range, which provides histology-like contrast. Here we demonstrate dynamic contrast with a scanning frequency-domain OCT (FD-OCT), which we believe has crucial advantages. Given the inherent sectional imaging geometry, scanning FD-OCT provides depth-resolved images across tissue layers, a perspective known from histopathology, much faster and more efficiently than FF-OCT. Both shorter acquisition times and tomographic depth-sectioning reduce the sensitivity of dynamic contrast for bulk tissue motion artifacts and simplify their correction in post-processing. Dynamic contrast makes microscopic FD-OCT a promising tool for the histological analysis of unstained tissues.

Dynamic contrast in scanning microscopic OCT.

A forward imaging endoscope for optical coherence tomography angiography (OCTA) featuring a piezoelectric fiber scanner is presented. Imaging is performed with an optical coherence tomography (OCT) system incorporating an akinetic light source with a center wavelength of 1300 nm, bandwidth of 90 nm and A-line rate of 173 kHz. The endoscope operates in contact mode to avoid motion artifacts, in particular, beneficial for OCTA measurements, and achieves a transversal resolution of 12 μm in air at a rigid probe size of 4 mm in diameter and 11.3 mm in length. A spiral scan pattern is generated at a scanning frequency of 360 Hz to sample a maximum field of view of 1.3 mm. OCT images of a human finger as well as visualization of microvasculature of the human palm are presented both in two and three dimensions. The combination of morphological tissue contrast with qualitative dynamic blood flow information within this endoscopic imaging approach potentially enables improved early diagnostic capabilities of internal organs for diseases such as bladder cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jbio.201800382

Endoscopic optical coherence tomography angiography using a forward imaging piezo scanner probe.

Volumetric imaging of dynamic processes with microscopic resolution holds a huge potential in biomedical research and clinical diagnosis. Using supercontinuum light sources and high numerical aperture (NA) objectives, optical coherence tomography (OCT) achieves microscopic resolution and is well suited for imaging cellular and subcellular structures of biological tissues. Currently, the imaging speed of microscopic OCT (mOCT) is limited by the line-scan rate of the spectrometer camera and ranges from 30 to 250 kHz. This is not fast enough for volumetric imaging of dynamic processes in vivo and limits endoscopic application. Using a novel CMOS camera, we demonstrate fast 3-dimensional OCT imaging with 600,000 A-scans/s at 1.8 µm axial and 1.1 µm lateral resolution. The improved speed is used for imaging of ciliary motion and particle transport in ex vivo mouse trachea. Furthermore, we demonstrate dynamic contrast OCT by evaluating the recorded volumes rather than en face planes or B-scans. High-speed volumetric mOCT will enable the correction of global tissue motion and is a prerequisite for applying dynamic contrast mOCT in vivo. With further increase in imaging speed and integration in flexible endoscopes, volumetric mOCT may be used to complement or partly replace biopsies.

Microscopic optical coherence tomography (mOCT) at 600 kHz for 4D volumetric imaging and dynamic contrast

We report an ultralow-voltage, electrothermal (ET) micro-electro-mechanical system (MEMS) based probe for forward-viewing endoscopic optical coherence tomography (OCT) imaging. The fully assembled probe has a diameter of 5.5 mm and a length of 55 mm, including the imaging optics and a 40 mm long fiber-optic cantilever attached on a micro-platform of the bimorph ET MEMS actuator. The ET MEMS actuator provides a sufficient mechanical actuation force as well as a large vertical displacement, achieving up to a 3 mm optical scanning range with only a 3 VACp-p drive voltage with a 1.5 VDC offset. The imaging probe was integrated with a swept-source OCT system of a 100 kHz A-scan rate, and its performance was successfully demonstrated with cross-sectional imaging of biological tissues ex vivo and in vivo at a speed up to 200 frames per second.

/pdf/ultralow-voltage-electrothermal-mems-based-fiber-optic-17uv6cu6vb.pdf

Ultralow-voltage electrothermal MEMS based fiber-optic scanning probe for forward-viewing endoscopic OCT

We present a forward-viewing fiber scanning endoscope (FSE) for high-speed volumetric optical coherence tomography (OCT). The reduction in size of the probe was achieved by substituting the focusing optics by an all-fiber-based imaging system which consists of a combination of scanning single-mode fibers, a glass spacer, made from a step-index multi-mode fiber, and a gradient-index fiber. A lateral resolution of 11 μm was achieved at a working distance of 1.2 mm. The newly designed piezo-based FSE has an outer diameter of 1.6 mm and a rigid length of 13.5 mm. By moving the whole imaging optic in spirals for scanning the sample, the beam quality remains constant over the entire field of view with a diameter of 0.8 mm. The scanning frequency was adjusted to 1.22 kHz for use with a 3.28 MHz Fourier domain mode locked OCT system. Densely sampled volumes have been imaged at a rate of 6 volumes per second.

Joshua Rehra

Papers

High-speed fiber scanning endoscope for volumetric multi-megahertz optical coherence tomography