Xiaojie Yang

Ultrathin side-viewing needle probe for optical coherence tomography

We present the smallest reported side-viewing needle probe for optical coherence tomography (OCT). Design, fabrication, optical characterization, and initial application of a 30-gauge (outer diameter 0.31 mm) needle probe are demonstrated. Extreme miniaturization is achieved by using a simple all-fiber probe design incorporating an angle-polished and reflection-coated fiber-tip beam deflector. When inserted into biological tissue, aqueous interstitial fluids reduce the probes inherent astigmatism ratio to 1.8, resulting in a working distance of 300 μm and a depth-of-field of 550 μm with beam diameters below 30 μm. The needle probe was interfaced with an 840 nm spectral-domain OCT system and the measured sensitivity was shown to be only 7 dB lower than that of a comparable galvo-scanning sample arm configuration. 3D OCT images of lamb lungs were acquired over a depth range of ~600 μm, showing individual alveoli and bronchioles.

Static and dynamic imaging of alveoli using optical coherence tomography needle probes

Imaging of alveoli in situ has for the most part been infeasible due to the high resolution required to discern individual alveoli and limited access to alveoli beneath the lung surface. In this study, we present a novel technique to image alveoli using optical coherence tomography (OCT). We propose the use of OCT needle probes, where the distal imaging probe has been miniaturized and encased within a hypodermic needle (as small as 30-gauge, outer diameter 310 μm), allowing insertion deep within the lung tissue with minimal tissue distortion. Such probes enable imaging at a resolution of ∼12 μm within a three-dimensional cylindrical field of view with diameter ∼1.5 mm centered on the needle tip. The imaging technique is demonstrated on excised lungs from three different species: adult rats, fetal sheep, and adult pigs. OCT needle probes were used to image alveoli, small bronchioles, and blood vessels, and results were matched to histological sections. We also present the first dynamic OCT images acquired with an OCT needle probe, allowing tracking of individual alveoli during simulated cyclical lung inflation and deflation.

Imaging deep skeletal muscle structure using a high-sensitivity ultrathin side-viewing optical coherence tomography needle probe

We have developed an extremely miniaturized optical coherence tomography (OCT) needle probe (outer diameter 310 µm) with high sensitivity (108 dB) to enable minimally invasive imaging of cellular structure deep within skeletal muscle. Three-dimensional volumetric images were acquired from ex vivo mouse tissue, examining both healthy and pathological dystrophic muscle. Individual myofibers were visualized as striations in the images. Degradation of cellular structure in necrotic regions was seen as a loss of these striations. Tendon and connective tissue were also visualized. The observed structures were validated against co-registered hematoxylin and eosin (H&E) histology sections. These images of internal cellular structure of skeletal muscle acquired with an OCT needle probe demonstrate the potential of this technique to visualize structure at the microscopic level deep in biological tissue in situ.

Ultrathin fiber probes with extended depth of focus for optical coherence tomography.

We report on a novel scheme for extending the depth of focus (DOF) of ultrathin (125 μm diameter) fiber probes for optical coherence tomography (OCT) using a simple phase mask consisting of graded-index (GRIN) fiber. The technique is compatible with existing all-in-fiber probe fabrication techniques, and our simulations show that it can provide a DOF gain of ~2 at a modest ~5 dB reduction of peak sensitivity. In a prototype device using commercially available GRIN fiber, a DOF gain of 1.55 is obtained, validated by beam profiling and OCT imaging.

Quantitative assessment of muscle damage in the mdx mouse model of Duchenne muscular dystrophy using polarization-sensitive optical coherence tomography

Minimally invasive, high-resolution imaging of muscle necrosis has the potential to aid in the assessment of diseases such as Duchenne muscular dystrophy. Undamaged muscle tissue possesses high levels of optical birefringence due to its anisotropic ultrastructure, and this birefringence decreases when the tissue undergoes necrosis. In this study, we present a novel technique to image muscle necrosis using polarization-sensitive optical coherence tomography (PS-OCT). From PS-OCT scans, our technique is able to quantify the birefringence in muscle tissue, generating an image indicative of the tissue ultrastructure, with areas of abnormally low birefringence indicating necrosis. The technique is demonstrated on excised skeletal muscles from exercised dystrophic mdx mice and control C57BL/10ScSn mice with the resulting images validated against colocated histological sections. The technique additionally gives a measure of the proportion (volume fraction) of necrotic tissue within the three-dimensional imaging field of view. The percentage necrosis assessed by this technique is compared against the percentage necrosis obtained from manual assessment of histological sections, and the difference between the two methods is found to be comparable to the interobserver variability of the histological assessment. This is the first published demonstration of PS-OCT to provide automated assessment of muscle necrosis.

Accurate Modeling and Design of Graded-Index Fiber Probes for Optical Coherence Tomography Using the Beam Propagation Method

Fiber-optic probes for sensing and biomedical imaging applications such as optical coherence tomography (OCT) frequently employ sections of graded-index (GRIN) fiber to re-focus the diverging light from the delivery fiber. Such GRIN fiber microlenses often possess aberrations that cause significant distortions of the focused output beam. Current design methods based on ABCD matrix transformations of Gaussian beams cannot model such effects and are therefore inadequate for the analysis and design of high-performance probes that require diffraction-limited output beams. We demonstrate use of the beam propagation method (BPM) to analyze beam distortion in GRIN-lensed fibers resulting from index profiles that exhibit a deviation from the ideal parabolic shape or artifacts such as ripples or a central dip. Furthermore, we demonstrate the power of this method for exploring novel probe designs that incorporate GRIN phase masks to generate wavefront-shaped output beams with extended depth-of-focus (DOF). We present results using our method that are in good agreement with experimental data. The BPM enables accurate simulation of fiber probes using non-ideal or custom-engineered GRIN fibers with arbitrary refractive index profiles, which is important in the design of high-performance fiber-based micro-imaging systems for biomedical applications.

En face parametric imaging of tissue birefringence using polarization-sensitive optical coherence tomography

Abstract. A technique for generating en face parametric images of tissue birefringence from scans acquired using a fiber-based polarization-sensitive optical coherence tomography (PS-OCT) system utilizing only a single-incident polarization state is presented. The value of birefringence is calculated for each A-scan in the PS-OCT volume using a quadrature demodulation and phase unwrapping algorithm. The algorithm additionally uses weighted spatial averaging and weighted least squares regression to account for the variation in phase accuracies due to varying OCT signal-to-noise-ratio. The utility of this technique is demonstrated using a model of thermally induced damage in porcine tendon and validated against histology. The resulting en face images of tissue birefringence are more useful than conventional PS-OCT B-scans in assessing the severity of tissue damage and in localizing the spatial extent of damage.

Analysis of fiber-optic probes using graded-index fiber microlenses with non-ideal refractive index profiles

Fiber-optic probes for sensing and imaging applications often employ sections of graded-index (GRIN) fiber to re-focus the diverging light from the delivery fiber. Such GRIN fiber microlenses possess aberrations which can cause significant distortions of the focused output beam. Using a numerical beam propagation method, we analyze the output beams resulting from index profiles that exhibit a central dip or a deviation from the ideal parabolic shape. Our method is in good agreement with experimental data and it enables the accurate simulation of fiber probes for biomedical applications using non-ideal or custom-engineered GRIN fibers with arbitrary refractive index profiles.

Birefringence imaging for optical sensing of tissue damage

We present an automated technique to detect and quantify damage to biological tissue by sensing changes in the tissues optical birefringence. Birefringence is a property of many types of tissue, which decreases with damage. Using a polarisation-sensitive optical coherence tomography scanner, the method first acquires a 3D scan of the area of tissue under analysis. By calculating the birefringence at each location on the surface of the tissue, we build a 2D image indicative of the biological microstructure, with areas of abnormally low birefringence indicating tissue damage. The technique is demonstrated using a model of localised thermal damage on porcine tendon. The resulting birefringence images are validated against a histological gold standard, showing strong correspondence between areas of low and high birefringence, and areas of damaged and undamaged tissue respectively.

A Microscope in a Needle

A microscope small enough to fit into a needle creates many new possibilities for optics in medicine. We have developed a range of optical coherence tomography (OCT) needle probes. Connected to an OCT scanner via a single mode fiber, the probes are constructed by fusing exact lengths of no-core fiber and graded-index fiber to focus a broadband light beam. We terminated the optics with anglepolished, gold-coated no-core fiber to deflect the beam. Encased in a needle (outer diameter 310 ?m), these probes are capable of 3-D imaging. However, the important developments of 2012 have been where we have taken these needle probes.