Pei-Lin Hsiung

Micromotor endoscope catheter for in vivo, ultrahigh-resolution optical coherence tomography

A distally actuated, rotational-scanning micromotor endoscope catheter probe is demonstrated for ultrahigh-resolution in vivo endoscopic optical coherence tomography (OCT) imaging. The probe permits focus adjustment for visualization of tissue morphology at varying depths with improved transverse resolution compared with standard OCT imaging probes. The distal actuation avoids nonuniform scanning motion artifacts that are present with other probe designs and can permit a wider range of imaging speeds. Ultrahigh-resolution endoscopic imaging is demonstrated in a rabbit with <4-microm axial resolution by use of a femtosecond Cr:forsterite laser light source. The micromotor endoscope catheter probe promises to improve OCT imaging performance in future endoscopic imaging applications.

High-resolution optical coherence microscopy for high-speed, in vivo cellular imaging

Optical coherence microscopy (OCM) is demonstrated with a high-speed, broadband, reflective-grating phase modulator and a femtosecond Ti:Al2O3 laser. The novel system design permits high-resolution OCM imaging in a new operating regime in which a short coherence gate is used to relax the requirement for high-numerical-aperture confocal axial sectioning. In vivo cellular imaging is demonstrated in the Xenopus laevis tadpole and in human skin with a 3-microm coherence gate and a 30-microm confocal gate. The ability to achieve cellular imaging with a lower numerical aperture should facilitate the development of miniaturized probes for in vivo imaging applications.

Real-time, ultrahigh-resolution, optical coherence tomography with an all-fiber, femtosecond fiber laser continuum at 1.5 μm

Real-time, ultrahigh-resolution optical coherence tomography (OCT) is demonstrated in the 1.4-1.7-microm wavelength region with a stretched-pulse, passively mode-locked, Er-doped fiber laser and highly nonlinear fiber. The fiber laser generates 100-mW, linearly chirped pulses at a 51-MHz repetition rate. The pulses are compressed and then coupled into a normally dispersive highly nonlinear fiber to generate a low-noise supercontinuum with a 180-nm FWHM bandwidth and 38 mW of output power. This light source is stable, compact, and broadband, permitting high-speed, real-time, high-resolution OCT imaging. In vivo high-speed OCT imaging of human skin with approximately 5.5-microm resolution and 99-dB sensitivity is demonstrated.

Ultrahigh resolution real time OCT imaging using a compact femtosecond Nd:Glass laser and nonlinear fiber.

Ultrahigh resolution, real time OCT imaging is demonstrated using a compact femtosecond Nd:Glass laser that is spectrally broadened in a high numerical aperture single mode fiber. A reflective grating phase delay scanner enables broad bandwidth, high-speed group delay scanning. We demonstrate in vivo, ultrahigh resolution, real time OCT imaging at 1 microm center wavelength with <5 microm axial resolution in free space (<4 microm in tissue). The light source is robust, portable, and well suited for in vivo imaging studies.

Optical coherence tomography using a continuous-wave, high-power, Raman continuum light source.

High performance, short coherence length light sources with broad bandwidths and high output powers are critical for high-speed, ultrahigh resolution OCT imaging. We demonstrate a new, high performance light source for ultrahigh resolution OCT. Bandwidths of 140 nm at 1300 nm center wavelength with high output powers of 330 mW are generated by an all-fiber Raman light source based on a continuous-wave Yb-fiber laser-pumped microstructure fiber. The light source is compact, robust, turnkey and requires no optical alignment. In vivo, ultrahigh resolution, high-speed, time domain OCT imaging with <5 microm axial resolution is demonstrated.

Effects of axial resolution improvement on optical coherence tomography (OCT) imaging of gastrointestinal tissues

Optical coherence tomography (OCT) is an emerging medical imaging technology which generates high resolution, cross-sectional images in situ, without the need for excisional biopsy. Previous clinical studies using endoscopic OCT with standard 10-15 microm axial resolution have demonstrated its capability in diagnosing Barretts esophagus (BE) and high-grade dysplasia (HGD). Quantitative OCT image analysis has shown promise for detecting HGD in Barretts esophagus patients. We recently developed an endoscopic OCT system with an improved axial resolution of approximately 5 microm. The goal in this manuscript is to compare standard resolution OCT and ultrahigh resolution OCT (UHR-OCT) for image quality and computer-aided detection using normal and Barretts esophagus. OCT images of gastrointestinal (GI) tissues were obtained using UHR-OCT (5.5 microm) and standard resolution OCT (13 microm). Image quality including the speckle size and sharpness was compared. Texture features of endoscopic OCT images from normal and Barretts esophagus were extracted using quantitative metrics including spatial frequency analysis and statistical texture analysis. These features were analyzed using principal component analysis (PCA) to reduce the vector dimension and increase the discriminative power, followed by linear discrimination analysis (LDA). UHR-OCT images of GI tissues improved visualization of fine architectural features compared to standard resolution OCT. In addition, the quantitative image feature analysis showed enhanced discrimination of normal and Barretts esophagus with UHR-OCT. The ability of UHR-OCT to resolve tissue morphology at improved resolution enables visualization of subtle features in OCT images, which may be useful in disease diagnosis. Enhanced classification of image features using UHR-OCT promises to help in the computer-aided diagnosis of GI diseases.

Effect of tissue preservation on imaging using ultrahigh resolution optical coherence tomography.

Ultrahigh resolution optical coherence tomography (OCT) is an emerging imaging modality that enables noninvasive imaging of tissue with 1- to 3-microm resolutions. Initial OCT studies have typically been performed using harvested tissue specimens (ex vivo). No reports have investigated postexcision tissue degradation on OCT image quality. We investigate the effects of formalin fixation and commonly used cell culture media on tissue optical scattering characteristics in OCT images at different times postexcision compared to in vivo conditions. OCT imaging at 800-nm wavelength with 1.5-mum axial resolution is used to image the hamster cheek pouch in vivo, followed by excision and imaging during preservation in phosphate-buffered saline (PBS), Dulbeccos Modified Eagles Media (DMEM), and 10% neutral-buffered formalin. Imaging is performed in vivo and at sequential time points postexcision from 15 min to 10 to 18 h. Formalin fixation results in increases in scattering intensity from the muscle layers, as well as shrinkage of the epithelium, muscle, and connective tissue of approximately 50%. PBS preservation shows loss of optical contrast within two hours, occurring predominantly in deep muscle and connective tissue. DMEM maintains tissue structure and optical scattering characteristics close to in vivo conditions up to 4 to 6 h after excision and best preserved tissue optical properties when compared to in vivo imaging.

High‐resolution imaging of the thyroid gland using optical coherence tomography

Current diagnostic imaging modalities of the thyroid gland cannot reliably distinguish benign from malignant lesions, primarily because of their inability to visualize microscopic structure. A high‐resolution imaging technique capable of examining thyroid tissue architectural morphology in real time is needed. Optical coherence tomography (OCT) has been shown to achieve high resolutions approaching the cellular range (1–15 μm). The feasibility of optical coherence tomography for imaging thyroid tissue was explored ex vivo on the human thyroid gland.

Ultrahigh-resolution endoscopic optical coherence tomography for gastrointestinal imaging

Optical coherence tomography (OCT) is an emerging medical imaging technology which can generate high resolution, cross-sectional images of tissue in situ and in real time, without the removal of tissue specimen. Although endoscopic OCT has been used successfully to identify certain pathologies in the gastrointestinal tract, the resolution of current endoscopic OCT systems has been limited to 10-15 um for clinical procedures. In this study, in vivo imaging of the gastrointestinal tract is demonstrated at a three-fold higher axial resolution (<5 um), using a portable, broadband, Cr4+:Forsterite laser as the optical light source. Images acquired from the esophagus and colon on animal model display tissue microstructures and architectural details at ultrahigh resolution, and the features observed in the OCT images are well-matched with histology. The clinical feasibility study is conducted through delivering OCT imaging catheter using the standard endoscope. OCT images of normal esophagus and Barretts esophagus are demonstrated with distinct features.

Transverse priority scanning and microscopy for high-resolution optical coherence tomography

We demonstrate methods for achieving high resolution imaging using alternate scanning techniques in optical coherence tomography and optical coherence microscopy. These techniques enable high transverse resolutions and overcome depth of field limitations. Cellular level resolutions in human tissue may be achieved.