Rapid-scanning forward-imaging miniature endoscope for real-time optical coherence tomography

We developed a miniature endoscope that is capable of rapid lateral scanning and is suitable for real-time forward-imaging optical coherence tomography (OCT). The endoscope has an outer diameter of 2.4 mm, consisting of a miniature tubular lead zirconate titanate (PZT) actuator, a single-mode fiber-optic cantilever, and a graded-index lens. Rapid lateral scanning at 2.8 kHz is achieved when the fiber-optic cantilever is resonated with the PZT actuator. This allows OCT imaging to be performed by fast lateral beam scanning followed by slow depth scanning, which is different from the conventional OCT imaging sequence. Real-time OCT imaging with the endoscope operated in the new image acquisition sequence at 6 frames/s is demonstrated.     

Fiber-optic scanning two-photon fluorescence endoscope

We report on the development of a miniature, flexible, fiber-optic scanning endoscope for two-photon fluorescence imaging. The endoscope uses a tubular piezoelectric actuator for achieving two-dimensional beam scanning and a double-clad fiber for delivery of the excitation light and collection of two-photon fluorescence. Real-time imaging of fluorescent beads and cancer cells has been performed.     

Compensation-free, all-fiber-optic, two-photon endomicroscopy at 1.55 μm

We present an all-fiber-optic scanning multiphoton endomicroscope with 1.55 μm excitation without the need for prechirping femtosecond pulses before the endomicroscope. The system consists of a 1.55 μm femtosecond fiber laser, a customized double-clad fiber for light delivery and fluorescence collection, and a piezoelectric scan head. We demonstrate two-photon imaging of cultured cells and mouse tissue, both labeled with indocyanine green. Free-space multiphoton imaging with near-IR emission has previously shown benefits in reduced background fluorescence and lower attenuation for the fluorescence emission. For fiber-optic multiphoton imaging there is the additional advantage of using the soliton effect at the telecommunication wavelengths (1.3-1.6 μm) in fibers, permitting dispersion-compensation-free, small-footprint systems. We expect these advantages will help transition multiphoton endomicroscopy to the clinic.     

Power-efficient nonreciprocal interferometer and linear-scanning fiber-optic catheter for optical coherence tomography

A nonreciprocal fiber-optic interferometer is demonstrated in an optical coherence tomography (OCT) system. The increased power efficiency of this system provides a 4.1-dB advantage over standard Michelson implementations. In addition, a new linear-scanning fiber-optic catheter is demonstrated that avoids the rotary optical junction that is required in circumferential scanning systems. These advancements have permitted the clinical implementation of OCT imaging in the human gastrointestinal tract.     

Intraluminal fiber-optic Doppler imaging catheter for structural and functional optical coherence tomography

We describe a miniature fiber-optic Doppler imaging catheter for integrated functional and structural optical coherence tomography (OCT) imaging. The Doppler catheter can map blood flow within a vessel as well as image vessel wall structures. A prototype Doppler catheter has been developed and demonstrated for measuring the intraluminal velocity profile in a vessel phantom (conduit). A simple mathematical model is demonstrated to estimate the total flow rate. This estimation technique also enables the spatial range of flow measurements to be extended by approximately two times the normal OCT image-penetration depth. The Doppler OCT catheter could be a powerful device for cardiovascular imaging.     

Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography

We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.     

Forward-imaging instruments for optical coherence tomography

We discuss the design and implementation of forward-imaging instruments for optical coherence tomography (OCT), which require the delivery, scanning, and collection of single-spatial-mode optical radiation. A hand-held surgical probe for use in open surgery can provide cross-sectional images of subsurface tissue before surgical incisions are made. A rigid laparoscope for minimally invasive surgical OCT imaging provides a simultaneous enface view of the area being imaged. OCT imaging is demonstrated on in vitro human specimens.     

Simultaneous multichannel nonlinear imaging: combined two-photon excited fluorescence and second-harmonic generation microscopy

Simultaneous two-photon excited fluorescence (TPF) and second-harmonic generation (SHG) imaging is demonstrated using a single femtosecond laser and a scanning microscope. This composite nonlinear microscopic technique was applied to imaging DNA and chromosomes, and it was shown that the two different interaction mechanisms provide complementary information on the structure and nonlinear properties of these biological materials, beyond that achievable using either TPF or SHG imaging alone. The use of separate modes of detection, in reflection and transmission respectively, and the simultaneous nature of the acquisition of the two images allows pure TPF and SHG images in precise registration to be obtained.     

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.     

Fourier domain optical coherence tomography using optical demultiplexers imaging at 60,000,000 lines/s

We describe high-speed Fourier domain optical coherence tomography (OCT) using optical demultiplexers (ODs) for spectral dispersion. The OD enables separation of a narrow spectral band of 14 GHz (0.11 nm) from a broadband incident light at 256 different frequencies in 25.0 GHz intervals centered at 192.2 THz (1559.8 nm). OCT imaging of 60,000,000 axial scans per second was achieved through parallel signal acquisition using 256 balanced photoreceivers to simultaneously detect all the output signals from the ODs in a Fourier domain OCT system. OCT imaging at a 16 kHz frame rate, 1100 A-lines per frame, 3 mm depth range, and 23 microm resolution was demonstrated using a resonant scanner for lateral scanning.     

Homodyne en face optical coherence tomography

We demonstrate, for what we believe to be the first time, the use of a 3 x 3 fiber-optic coupler to realize a homodyne optical coherence tomography (OCT) system for en face imaging of highly scattering tissues and turbid media. The homodyne OCT setup exploits the inherent phase shifts between different output ports of a 3 x 3 fiber-optic coupler to extract amplitude information of a sample. Our homodyne en face OCT system features a measured resolution of 14 microm axially and 9.4 microm laterally with a 90 dB signal-to-noise ratio at 10 micros integration time. En face OCT imaging of a stage 52 Xenopus laevis was successfully demonstrated at a depth of 600 microm within the sample.     

Full range complex ultrahigh sensitive optical microangiography

This Letter presents a useful method that combines the full range complex Fourier domain optical coherence tomography (OCT) with the ultrahigh sensitive optical microangiography (OMAG) to achieve full range complex imaging of blood flow within microcirculatory tissue beds in vivo. We propose to use the fast scanning axis to realize the full range complex imaging, while using the slow axis to achieve OMAG imaging of blood flow. We demonstrate the proposed method by using a high speed 1310?nm OCT/OMAG system running at 92?kHz line scan rate to image the flow phantoms in vitro, and the blood flows in tissue beds in vivo.     

Continuous focus tracking for real-time optical coherence tomography

We report an approach to achieving continuous focus tracking and a depth-independent transverse resolution for real-time optical coherence tomography (OCT) imaging. Continuous real-time focus tracking is permitted by use of a lateral-priority image acquisition sequence in which the depth-scanning rate is equivalent to the imaging frame rate. Real-time OCT imaging with continuous focus tracking is performed at 1 frame/s by reciprocal translation of a rapid lateral-scanning miniature imaging probe (e.g., an endoscope). The optical path length in the reference arm is scanned synchronously to ensure that the coherence gate coincides with the imaging beam focus. The image quality improvement is experimentally demonstrated by imaging a tissue phantom embedded with polystyrene microspheres and rabbit esophageal tissues.     

Increasing the imaging depth of coherent anti-Stokes Raman scattering microscopy with a miniature microscope objective

A miniature objective lens with a tip diameter of 1.3 mm was used for extending the penetration depth of coherent anti-Stokes Raman scattering (CARS) microscopy. Its axial and lateral focal widths were determined to be 11.4 and 0.86 microm, respectively, by two-photon excitation fluorescence imaging of 200 nm beads at a 735 nm excitation wavelength. By inserting the lens tip into a soft gel sample, CARS images of 2 microm polystyrene beads 5 mm deep from the surface were acquired. The miniature objective was applied to CARS imaging of rat spinal cord white matter with a minimal requirement for surgery.     

Simultaneous dual-wavelength-band common-path swept-source optical coherence tomography with single polygon mirror scanner

We report a novel (to the best of our knowledge) simultaneous 1310/1550 two-wavelength band swept laser source and dual-band common-path swept-source optical coherence tomography (SS-OCT). Synchronized dual-wavelength tuning is performed by using two laser cavities and narrowband wavelength filters with a single dual-window polygonal scanner. Measured average output powers of 60 and 27 mW have been achieved for the 1310 and 1550 nm bands, respectively, while the two wavelengths were swept simultaneously from 1227 to 1387 nm for the 1310 nm band and from 1519 to 1581 nm for the 1550 nm band at an A-scan rate of 65 kHz. Broadband wavelength-division multiplexing is used for coupling two wavelengths into a common-path single-mode GRIN-lensed fiber probe to form dual-band common-path SS-OCT. Simultaneous OCT imaging at 1310 and 1550 nm is achieved. This technique allows for in vivo high-speed OCT imaging with potential application in functional (spectroscopic) investigations.     

Dual-core ytterbium fiber amplifier for high-power 1060 nm swept source multichannel optical coherence tomography imaging

A novel (to our knowledge) dual-core ytterbium (Yb(3+)) doped fiber, as an optically pumped amplifier, boosts the output power from a 1060 nm swept source laser beyond 250 mW, while providing a wavelength tuning range of 93 nm, for optical coherence tomography (OCT) imaging. The design of the dual-core Yb-doped fiber amplifier and its multiple wavelength optical pumping scheme to optimize output bandwidth are discussed. Use of the dual-core fiber amplifier showed no appreciable degradation to the coherence length of the seed laser. The signal intensity improvement of this amplifier is demonstrated on a multichannel in vivo OCT imaging system at 1060 nm.     

Fiber-optic Fourier-domain common-path OCT

We experimentally and theoretically investigated the performance of a fiber-optic based Fourier-domain common-path optical coherence tomography （OCT）. The fiber-optic common-path OCT operated at the 840-nm center wavelength. The resolution of the system was 8.8 μm （in air） and the working depth using a bare fiber probe was approximately 1.5 mm. The signal-to-noise ratio （SNR） of the system was analyzed. OCT images obtained by the system were also presented.     

Imaging needle for optical coherence tomography

We describe a miniature optical coherence tomography (OCT) imaging needle that can be inserted into solid tissues and organs to permit interstitial imaging of their internal microstructures with micrometer scale resolution and minimal trauma. A novel rotational coupler with a glass capillary tube is also presented that couples light from a rotating single-mode fiber to a stationary one. A prototype needle with a 27-gauge (~410-mum) outer diameter has been developed and is demonstrated for in vivo imaging. The OCT needle can be integrated with standard excisional biopsy devices and used for OCT-guided biopsy.     

Optimal interferometer designs for optical coherence tomography

We introduce a family of power-conserving fiber-optic interferometer designs for low-coherence reflectometry that use optical circulators, unbalanced couplers, and (or) balanced heterodyne detection. Simple design equations for optimization of the signal-to-noise ratio of the interferometers are expressed in terms of relevant signal and noise sources and measurable system parameters. We use the equations to evaluate the expected performance of the new configurations compared with that of the standard Michelson interferometer that is commonly used in optical coherence tomography (OCT) systems. The analysis indicates that improved sensitivity is expected for all the new interferometer designs, compared with the sensitivity of the standard OCT interferometer, under high-speed imaging conditions.     

Subnanometer optical coherence tomographic vibrography

The ability to quantify and visualize submicrometer-scale oscillatory motions of objects in three dimensions has a wide range of application in acoustics, materials sciences, and medical imaging. Here we demonstrate that volumetric snapshots of rapid periodic motion can be captured using optical coherence tomography (OCT) with subnanometer-scale motion sensitivity and microsecond-scale temporal resolution. This technique, termed OCT vibrography, was applied to generate time-resolved volumetric vibrographs of a miniature drum driven acoustically at several kilohertz.