Three-dimensional wide-field optical coherence tomography using an ultrahigh-speed CMOS camera

We demonstrated wide-field optical coherence tomography (OCT) using an ultrahigh-speed CMOS (complementary metal oxide semiconductor) camera. We obtained en face OCT images (512 × 512 pixels) at 1500 frames per second by calculating two sequential images. Three-dimensional imaging was achieved by switching the illumination on and off at the same frequency as the beat signal generated by the axial scan in the reference arm to avoid decreasing the interference components in the camera output. A sample volume of 2.6 × 2.6 × 1.2 (x × y × z) mm³ (corresponding to 512 × 512 × 375 pixels) was imaged in 0.25 s in a single axial scan in the reference arm. We successfully imaged the human finger in vivo with a sensitivity of 73 dB, after 10 × 10 pixel averaging.     

In vivo ultrahigh-resolution optical coherence tomography

Ultrahigh-resolution optical coherence tomography (OCT) by use of state of the art broad-bandwidth femtosecond laser technology is demonstrated and applied to in vivo subcellular imaging. Imaging is performed with a Kerr-lens mode-locked Ti:sapphire laser with double-chirped mirrors that emits sub-two-cycle pulses with bandwidths of up to 350 nm, centered at 800 nm. Longitudinal resolutions of ~1mum and transverse resolution of 3mum, with a 110-dB dynamic range, are achieved in biological tissue. To overcome depth-of-field limitations we perform zone focusing and image fusion to construct a tomogram with high transverse resolution throughout the image depth. To our knowledge this is the highest longitudinal resolution demonstrated to date for in vivo OCT imaging.     

Nonmechanical grating-generated scanning coherence microscopy

A novel method of coherence microscopy with a grating-generated delay line is demonstrated to produce depth-lateral images without axial or lateral scanning. A new image-reconstruction approach based on random phase modulation of the reference beam is realized. The depth-lateral reflections of test objects are digitally reconstructed with a simple algorithm.     

Parallel optical coherence tomography using a CCD camera

Parallel optical coherence tomography is demonstrated using a 12-bit scientific-grade charge-coupled device array.A superluminescent diode in combination with a free-space Michelson interferometer was employed to achieve 10-μm axial resolution and 1.1-μm transverse resolution on a 902×575 μm2 field of view.We imaged a test mirror and bovine retinal tissue using a four-step phase shift method.     

Low-voltage polymer-based scanning cantilever for in vivo optical coherence tomography

Novel hand-held optical coherence tomography (OCT) probes with polymer cantilevers have been developed for clinical oral and skin imaging. An electroactive ionic polymer-metal composite cantilever was used to generate 3-mm transverse scanning movement of an optical fiber with applied 2-V linear alternating voltage at 1 Hz. Low driving voltage ensures safety. Two different optical designs achieve both forward and sidewise scanning and make it possible to image everywhere within the human oral cavity. In vivo OCT imaging of the human tongue is demonstrated.     

In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror

A biopsy is a well-known medical test used to evaluate tissue abnormality. Biopsy specimens are invasively taken from part of a lesion and visualized by microscope after chemical treatment. However, diagnosis by means of biopsy is not only variable due to depth and location of specimen but may also damage the specimen. In addition, only a limited number of specimens can be obtained, thus, the entire tissue morphology cannot be observed. We introduce a three-dimensional (3-D) endoscopic optical biopsy via optical coherence tomography employing a dual-axis microelectromechanical system scanning mirror. Since this technique provides high-resolution, noninvasive, direct, and multiple visualization of tissue, it could function as a clinical biopsy with advanced performance. The device was integrated with a conventional endoscope and utilized to generate in vivo 3-D clinical images in humans and animals.     

Paired-angle-rotation scanning optical coherence tomography forward-imaging probe

We report a novel forward-imaging optical coherence tomography (OCT), needle-probe paired-angle-rotation scanning OCT (PARS-OCT) probe. The probe uses two rotating angled gradient-index lenses to scan the output OCT probe beam over a wide angular arc (approximately 19 degrees half-angle) of the region forward of the probe. Among other advantages, this probe design is readily amenable to miniaturization and is capable of a variety of scan modes, including volumetric scans. To demonstrate the advantages of the probe design, we have constructed a prototype probe with an outer diameter of 1.65 mm and employed it to acquire four OCT images, with a 45 degrees angle between adjacent images, of the gill structure of a Xenopus laevis tadpole. The system sensitivity was measured to be 93 dB by using the prototype probe with an illumination power of 450 microW on the sample. Moreover, the axial and the lateral resolutions of the probe are 9.3 and 10.3-12.5 microm, respectively.     

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-microm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.     

Electrostatic micromachine scanning mirror for optical coherence tomography

Compact electrostatic micromirror structures for use in the scanning arm of an optical coherence tomography (OCT) system are described. These devices consist of millimeter-scale mirrors resting upon micrometer-scale polyimide hinges that are tilted by a linear micromachine actuator, the integrated force array (IFA). The IFA is a network of deformable capacitor cells that electrostatically contract with an applied voltage. The support structures, hinges, and actuators are fabricated by photolithography from polyimide-upon-silicon wafers. These devices were inserted into the scanning arm of an experimental OCT imaging system to produce in vitro and in vivo images at frame rates of 4 to 8 Hz.     

In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography

Noninvasive in vivo functional optical imaging of the intact retina is demonstrated by using high-speed, ultrahigh-resolution optical coherence tomography (OCT). Imaging was performed with 2.8 microm resolution at a rate of 24,000 axial scans per second. A white-light stimulus was applied to the dark-adapted rat retina, and the average reflectivities from different intraretinal layers were monitored as a function of time. A 10%-15% increase in the average amplitude reflectance of the photoreceptor outer segments was observed in response to the stimulus. The spatial distribution of the change in the OCT signal is consistent with an increase in backscatter from the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of OCT functional imaging in the intact retina.     

In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography

An ultrahigh-speed spectral domain optical coherence tomography (SD-OCT) system is presented that achieves acquisition rates of 29,300 depth profiles/s. The sensitivity of SD-OCT and time domain OCT (TD-OCT) are experimentally compared, demonstrating a 21.7-dB improvement of SD-OCT over TD-OCT. In vivo images of the human retina are presented, demonstrating the ability to acquire high-quality structural images with an axial resolution of 6 microm at ultrahigh speed and with an ocular exposure level of less than 600 microW.     

In vivo imaging of intrinsic optical signals in chicken retina with functional optical coherence tomography

Visually evoked intrinsic optical signals (IOSs) were measured in vivo for the first time to our knowledge from all retina layers of the chicken retina with a combined functional optical coherence tomography and electroretinography (ERG) system. IOS traces were recorded from a small volume in the retina with 3.5 μm axial resolution and 7 ms time resolution. Comparison of the IOS and ERG traces shows a correlation between the positive and negative IOS measured from different retinal layers and the timing of the a and b waves in the ERG recording.     

Rapid scanning all-reflective optical delay line for real-time optical coherence tomography

We describe a dispersion-free high-speed scanning optical delay line that is suitable for real-time optical coherence tomography, in particular, when an ultrabroadband light source is used. The delay line is based on all-reflective optics consisting of two flat and one curved mirrors. We achieve optical path-length scanning by oscillating one of the two flat mirrors with a resonant galvanometer. The delay line is compact and easy to implement. A total scanning depth of 1.50 mm with an 89% duty ratio, a maximal scanning speed of approximately 9.1 m/s, and a 4.1-kHz repetition rate has been demonstrated.     

Fast scanning transmissive delay line for optical coherence tomography

A novel Fourier domain fast scanning optical delay line is proposed in which the walk-off is eliminated by only two passes through a diffraction grating. Working in transmission, the novel delay line is ideal for balanced optical coherence tomography configurations with recirculation of the reference beam. We evaluate theoretically and experimentally its walk-off and dispersion compensation capabilities.     

Electrostatic forward-viewing scanning probe for Doppler optical coherence tomography using a dissipative polymer catheter

A novel flexible scanning optical probe is constructed with a finely etched optical fiber strung through a platinum coil in the lumen of a dissipative polymer. The packaged probe is 2.2 mm in diameter with a rigid length of 6mm when using a ball lens or 12 mm when scanning the fiber proximal to a gradient-index (GRIN) lens. Driven by constant high voltage (1-3 kV) at low current (< 5 microA), the probe oscillates to provide wide forward-viewing angle (13 degrees and 33 degrees with ball and GRIN lens designs, respectively) and high-frame-rate (10-140 fps) operation. Motion of the probe tip is observed with a high-speed camera and compared with theory. Optical coherence tomography (OCT) imaging with the probe is demonstrated with a wavelength-swept source laser. Images of an IR card as well as in vivo Doppler OCT images of a tadpole heart are presented. This optomechanical design offers a simple, inexpensive method to obtain a high-frame-rate forward-viewing scanning probe.     

Ultrahigh-resolution optical coherence tomography using continuum generation in an air-silica microstructure optical fiber

We demonstrate ultrahigh-resolution optical coherence tomography (OCT) using continuum generation in an air-silica microstructure fiber as a low-coherence light source. A broadband OCT system was developed and imaging was performed with a bandwidth of 370 nm at a 1.3-mu;m center wavelength. Longitudinal resolutions of 2.5 microm in air and ~2 microm in tissue were achieved. Ultrahigh-resolution imaging in biological tissue in vivo was demonstrated.     

Complex ambiguity-free Fourier domain optical coherence tomography through transverse scanning

We introduce a simple and cheap method for phase-shifting Fourier domain optical coherence tomography (FDOCT) that does not need additional devices and can easily be implemented. A small beam offset at the fast beam-scanning mirror introduces a causal phase shift, which can be used for B-scan-based complex image reconstruction. We derive the conditions for optimal conjugate suppression and demonstrate the method on human skin in vivo for spectrometer-based FDOCT operating at 1300 nm employing a handheld scanner.     

Retinal cone mosaic imaged with transverse scanning optical coherence tomography

We improved our recently reported retinal OCT system based on transverse priority scanning to achieve high resolution in both the transverse and the axial directions. The implementation of an additional SLO channel enables precise on-line focusing. The system enables imaging of the human retinal cone mosaic off the foveal center without adaptive optics. We demonstrate, for what is believed to be the first time, cone mosaic imaging simultaneously in the scanning laser ophthalmoscope and optical coherence tomography (OCT) channels. OCT B-scan images demonstrate that the cone mosaic is observable in two adjacent layers. Furthermore, we present what are believed to be the first C-scan OCT images of the cone mosaic and show that the major part of light backscattered from below the photoreceptor layer is not guided back toward the pupil by the photoreceptors.     

In vivo endoscopic optical coherence tomography by use of a rotational microelectromechanical system probe

A novel endoscopic optical coherence tomography probe was designed and constructed with a 1.9-mm microelectromechanical system (MEMS) motor. The new MEMS endoscopic probe design eliminates the need to couple the rotational energy from the proximal to the distal end of the probe. Furthermore, the endoscopic probe's sheath and fiber have the advantages of having a much smaller diameter and being more flexible than traditional endoscopes since no reinforcement is needed to couple the rotational torque. At the distal end, a prism mounted on a micromotor deflects the light rays to create a transverse circular-scanning pathway. Because our MEMS scanner does not require the coupling of a rotational single-mode fiber, a high scanning speed is possible while eliminating unstable optical signals caused by nonuniform coupling.     

In vivo sweat film layer thickness measured with Fourier-domain optical coherence tomography (FD-OCT)

While human sweat secretion is accepted as a mechanism by which the body cools off, excessive sweating (hyperhidrosis) is now appreciated as a medical condition and the primary site for diagnosis is the palm of the hand. We propose sweat film layer thickness as a potential clinical diagnostic parameter when screening for excessive sweating. In this preliminary study we demonstrate the usefulness of Fourier-domain optical coherence tomography (FD-OCT) for measurement of sweat film thickness in vivo with micron-scale resolution on the hand of a human volunteer. FD-OCT has a superior image acquisition time and identification of active sweat glands, ducts and pores is also possible.