Wenxuan Liang

Diffractive catheter for ultrahigh-resolution spectral-domain volumetric OCT imaging

We present a novel design for an endoscopic imaging catheter utilizing diffractive optics for ultrahigh-resolution optical coherence tomography (OCT) imaging at 800 nm. A diffractive microlens was developed to alleviate severe chromatic aberration when a broadband light source was employed at the 800 nm wavelength range. Combined with a home-built fiber rotary joint and a broadband Ti:sapphire laser, the imaging catheter achieved a lateral resolution of 6.2 μm and an axial resolution of 3.0 μm in air. The performance of the catheter was demonstrated by three-dimensional full-circumferential endoscopic OCT imaging of guinea pig esophagus in vivo.

Increased illumination uniformity and reduced photodamage offered by the Lissajous scanning in fiber-optic two-photon endomicroscopy

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.

Optimal operational conditions for supercontinuum-based ultrahigh-resolution endoscopic OCT imaging.

We investigated the optimal operational conditions for utilizing a broadband supercontinuum (SC) source in a portable 800 nm spectral-domain (SD) endoscopic OCT system to enable high resolution, high-sensitivity, and high-speed imaging in vivo. A SC source with a 3-dB bandwidth of ∼246  nm was employed to obtain an axial resolution of ∼2.7  μm (in air) and an optimal detection sensitivity of ∼-107  dB with an imaging speed up to 35 frames/s (at 70 k A-scans/s). The performance of the SC-based SD-OCT endoscopy system was demonstrated by imaging guinea pig esophagus in vivo, achieving image quality comparable to that acquired with a broadband home-built Ti:sapphire laser.

Gold Nanocages as Contrast Agents for Two-photon Luminescence Endomicroscopy Imaging

UNLABELLED We explored the possibility of using gold (Au) nanocages as a new class of exogenous contrast agents for endomicroscopic nonlinear imaging. The two-photon luminescence cross-section of nanocages was characterized. Two-photon luminescence endomicroscopy imaging of a phantom, cancer cells and biological tissues was performed, demonstrating that Au nanocages can potentially serve as an effective molecular contrast agent for nonlinear endomicroscopy imaging. FROM THE CLINICAL EDITOR In this study, the utility of Au nanocages is described in a variety of settings as effective molecular contrast agent for nonlinear endomicroscopy imaging.

Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection

Cancer is known to alter the local optical properties of tissues. The detection of OCT-based optical attenuation provides a quantitative method to efficiently differentiate cancer from non-cancer tissues. In particular, the intraoperative use of quantitative OCT is able to provide a direct visual guidance in real time for accurate identification of cancer tissues, especially these without any obvious structural layers, such as brain cancer. However, current methods are suboptimal in providing high-speed and accurate OCT attenuation mapping for intraoperative brain cancer detection. In this paper, we report a novel frequency-domain (FD) algorithm to enable robust and fast characterization of optical attenuation as derived from OCT intensity images. The performance of this FD algorithm was compared with traditional fitting methods by analyzing datasets containing images from freshly resected human brain cancer and from a silica phantom acquired by a 1310 nm swept-source OCT (SS-OCT) system. With graphics processing unit (GPU)-based CUDA C/C++ implementation, this new attenuation mapping algorithm can offer robust and accurate quantitative interpretation of OCT images in real time during brain surgery.

Nonlinear optical endomicroscopy for label-free functional histology in vivo

This manuscript reports on the first two-photon, label-free, metabolic imaging of biological tissues in vivo at histological resolution on an extremely compact, fiber-optic endomicroscopy platform. This system provides new opportunities for performing non-invasive and functional histological imaging of internal organs in vivo, in situ and in real time. As a routine clinical procedure, traditional histology has made significant impacts on medicine. However, the procedure is invasive and time consuming, suffers random sampling errors, and cannot provide in vivo functional information. The technology reported here features an extremely compact and flexible fiber-optic probe ~2 mm in diameter, enabling direct access to internal organs. Unprecedented two-photon imaging quality comparable to a large bench-top laser scanning microscope was achieved through technological innovations in double-clad fiber optics and miniature objective lenses (among many others). In addition to real-time label-free visualization of biological tissues in situ with subcellular histological detail, we demonstrated for the first time in vivo two-photon endomicroscopic metabolic imaging on a functioning mouse kidney model. Such breakthroughs in nonlinear endoscopic imaging capability present numerous promising opportunities for paradigm-shifting applications in both clinical diagnosis and basic research.

Generic pixel-wise speckle detection in Fourier-domain optical coherence tomography images

We present a generic phase-domain processing method for detecting speckles in Fourier-domain optical coherence tomography (OCT) images. The physics behind the interferometry is revisited and analytically along with simulation results it indicates that the speckle formation comes with phase distortion to the complex OCT signal. The first and the second derivatives of phase along the imaging depth are then calculated for speckle identification. The phase-domain processing method was applied to images acquired by both spectral-domain OCT and swept-source OCT systems, and the experimental results show that this method enables pixel-wise speckle identification.

Focus scanning with feedback-control for fiber-optic nonlinear endomicroscopy

Fiber-optic endomicroscopes open new avenues for the application of non-linear optics to novel in vivo applications. To achieve focus scanning in vivo, shape memory alloy (SMA) wires have been used to move optical elements in miniature endomicroscopes. However, this method has various limitations, making it difficult to achieve accurate and reliable depth scanning. Here we present a feedback-controlled SMA depth scanner. With a Hall effect sensor, contraction of the SMA wire can be tracked in real time, rendering accurate and robust control of motion. The SMA depth scanner can achieve up to 490 µm travel and with open-loop operation, it can move more than 350 µm within one second. With the feedback loop engaged, submicron positioning accuracy was achieved along with superior positioning stability. The high-precision positioning capability of the SMA depth scanner was verified by depth-resolved nonlinear endomicroscopic imaging of mouse brain samples.

Automatic and robust segmentation of endoscopic OCT images and optical staining

We report a generic method for automatic segmentation of endoscopic optical coherence tomography (OCT) images. In this method, OCT images are first processed with L1 -L0 norm minimization based de-noising and smoothing algorithms to increase the signal-to-noise ratio (SNR) and enhance the contrast between adjacent layers. The smoothed images are then formulated into cost graphs based on their vertical gradients. After that, tissue-layer segmentation is performed with the shortest path search algorithm. The efficacy and capability of this method are demonstrated by automatically and robustly identifying all five interested layers of guinea pig esophagus from in vivo endoscopic OCT images. Furthermore, thanks to the ultrahigh resolution, high SNR of endoscopic OCT images and the high segmentation accuracy, this method permits in vivo optical staining histology and facilitates quantitative analysis of tissue geometric properties, which can be very useful for studying tissue pathologies and potentially aiding clinical diagnosis in real time.

An electrothermal/electrostatic dual driven MEMS scanner with large in-plane and out-of-plane displacement

This paper reports the design, fabrication and characterization of an MEMS scanner with combined electrothermal and electrostatic actuation. The scanner can generate large out-of-plane and in-plane displacement. The out-of-plane displacement is achieved by a pair of electro-thermal bimorph actuators, which is as much as 370 μm at only 2.5 V. The in-plane displacement is obtained by employing electrostatic comb drives, which can achieve fast scan up to 10 kHz. A special process has been developed to fabricate microstructures with both thin-film bimorphs and single-crystal-silicon comb drives.