Wang-Yuhl Oh

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing

Polarization sensitive optical coherence tomography (PS-OCT) provides a cross-sectional image of birefringence in biological samples that is complementary in many applications to the standard reflectance-based image. Recent ex vivo studies have demonstrated that birefringence mapping enables the characterization of collagen and smooth muscle concentration and distribution in vascular tissues. Instruments capable of applying these measurements percutaneously in vivo may provide new insights into coronary atherosclerosis and acute myocardial infarction. We have developed a polarization sensitive optical frequency domain imaging (PS-OFDI) system that enables high-speed intravascular birefringence imaging through a fiber-optic catheter. The novel design of this system utilizes frequency multiplexing to simultaneously measure reflectance of two incident polarization states, overcoming concerns regarding temporal variations of the catheter fiber birefringence and spatial variations in the birefringence of the sample. We demonstrate circular cross-sectional birefringence imaging of a human coronary artery ex vivo through a flexible fiber-optic catheter with an A-line rate of 62 kHz and a ranging depth of 6.2 mm.

Wide tuning range wavelength-swept laser with two semiconductor optical amplifiers

We demonstrate a wide tuning range high-speed wavelength-swept semiconductor laser based on a polygon scanning filter that is common to two laser cavities. Linear wavelength tuning was achieved over 145 nm around 1310 nm at a tuning repetition rate of 20 kHz. The wavelength tuning filter is expandable to accommodate multiple semiconductor optical amplifiers for further widening of the laser wavelength tuning range.

Ultrahigh-speed optical frequency domain imaging and application to laser ablation monitoring

We demonstrate a linear laser resonator incorporating a semiconductor optical amplifier and scanning filter for high repetition rate, broad wavelength, unidirectional scanning. The laser operates at up to 115kHz repetition rates and demonstrates a tuning-speed-independent power of >30mW. We apply this laser to enable ultrahigh-speed optical frequency domain imaging of the dynamics of laser ablation of biological tissue. The imaging system acquires single longitudinal scans (A-lines) in 8.7μs and complete cross-sectional images comprising 575A-lines at a rate of 200 frames per second.

>400 kHz repetition rate wavelength-swept laser and application to high-speed optical frequency domain imaging

We demonstrate a high-speed wavelength-swept laser with a tuning range of 104 nm (1228-1332 nm) and a repetition rate of 403 kHz. The design of the laser utilizes a high-finesse polygon-based wavelength-scanning filter and a short-length unidirectional ring resonator. Optical frequency domain imaging of the human skin in vivo is presented using this laser, and the system shows sensitivity of higher than 98 dB with single-side ranging depth of 1.7 mm over 4 dB sensitivity roll-off.

Complex wavefront shaping for optimal depth-selective focusing in optical coherence tomography

We report on an approach to exploit multiple light scattering by shaping the incident wavefront in optical coherence tomography (OCT). Most of the reflected signal from biological tissue consists of multiply scattered light, which is regarded as noise in OCT. A digital mirror device (DMD) is utilized to shape the incident wavefront such that the maximal energy is focused at a specific depth in a highly scattering sample using a coherence-gated reflectance signal as feedback. The proof-of-concept experiment demonstrates that this approach enhances depth-selective focusing in the presence of optical inhomogeneity, and thus extends the penetration depth in spectral domain-OCT (SD-OCT).

Mode transformer for miniaturized optical circuits.

A novel mode transformer was fabricated that transforms a modal area by a factor of 100. Using the mode transformer improves the efficiency of mode transformation by an order of magnitude compared with that when no mode transformer is used. With this mode transformer, input-output coupling of miniaturized, on-chip integrated optical circuits to external optical fibers is achieved with low loss. The mode transformers design, fabricated in silicon, is scalable to virtually any waveguide size, facilitating continuous miniaturization in silicon optoelectronics.

Spectral binning for mitigation of polarization mode dispersion artifacts in catheter-based optical frequency domain imaging

Polarization mode dispersion (PMD) has been recognized as a significant barrier to sensitive and reproducible birefringence measurements with fiber-based, polarization-sensitive optical coherence tomography systems. Here, we present a signal processing strategy that reconstructs the local retardation robustly in the presence of system PMD. The algorithm uses a spectral binning approach to limit the detrimental impact of system PMD and benefits from the final averaging of the PMD-corrected retardation vectors of the spectral bins. The algorithm was validated with numerical simulations and experimental measurements of a rubber phantom. When applied to the imaging of human cadaveric coronary arteries, the algorithm was found to yield a substantial improvement in the reconstructed birefringence maps.

High frame-rate intravascular optical frequency-domain imaging in vivo.

Intravascular optical frequency-domain imaging (OFDI), a second-generation optical coherence tomography (OCT) technology, enables imaging of the three-dimensional (3D) microstructure of the vessel wall following a short and nonocclusive clear liquid flush. Although 3D vascular visualization provides a greater appreciation of the vessel wall and intraluminal structures, a longitudinal imaging pitch that is several times bigger than the optical imaging resolution of the system has limited true high-resolution 3D imaging, mainly due to the slow scanning speed of previous imaging catheters. Here, we demonstrate high frame-rate intravascular OFDI in vivo, acquiring images at a rate of 350 frames per second. A custom-built, high-speed, and high-precision fiber-optic rotary junction provided uniform and high-speed beam scanning through a custom-made imaging catheter with an outer diameter of 0.87 mm. A 47-mm-long rabbit aorta was imaged in 3.7 seconds after a short contrast agent flush. The longitudinal imaging pitch was 34 μm, comparable to the transverse imaging resolution of the system. Three-dimensional volume-rendering showed greatly enhanced visualization of tissue microstructure and stent struts relative to what is provided by conventional intravascular imaging speeds.

Artifacts in polarization-sensitive optical coherence tomography caused by polarization mode dispersion

Polarization mode dispersion (PMD) severely degrades images of biological tissue measured with polarization-sensitive optical coherence tomography. It adds a bias to the local retardation value that can be spatially confined, resulting in regions of seemingly high sample birefringence that are purely artificial. Here, we demonstrate and analyze this effect, both experimentally and with numerical simulations, and show that artifacts can be avoided by limiting the system PMD to less than the system axial resolution. Even then, spatial averaging over a dimension larger than that characteristic of speckle is required to remove a PMD-induced bias of the local retardation values.