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.     

Submicrometer axial resolution optical coherence tomography

Optical coherence tomography (OCT) with unprecedented submicrometer axial resolution achieved by use of a photonic crystal fiber in combination with a compact sub-10-fs Ti:sapphire laser (Femtolasers Produktions) is demonstrated for what the authors believe is the first time. The emission spectrum ranges from 550 to 950 nm (lambda(c)=725 nm , P(out)=27 mW) , resulting in a free-space axial OCT resolution of ~0.75 mum , corresponding to ~0.5 mum in biological tissue. Submicrometer-resolution OCT is demonstrated in vitro on human colorectal adenocarcinoma cells HT-29. This novel light source has great potential for development of spectroscopic OCT because its spectrum covers the absorption bands of several biological chromophores.     

Adaptive-optics ultrahigh-resolution optical coherence tomography

Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and adaptive optics (AO), resulting in high axial (3 microm) and improved transverse resolution (5-10 microm) is demonstrated for the first time to our knowledge in in vivo retinal imaging. A compact (300 mm x 300 mm) closed-loop AO system, based on a real-time Hartmann-Shack wave-front sensor operating at 30 Hz and a 37-actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm bandwidth. Closed-loop correction of both ocular and system aberrations results in a residual uncorrected wave-front rms of 0.1 microm for a 3.68-mm pupil diameter. When this level of correction is achieved, OCT images are obtained under a static mirror configuration. By use of AO, an improvement of the transverse resolution of two to three times, compared with UHR OCT systems used so far, is obtained. A significant signal-to-noise ratio improvement of up to 9 dB in corrected compared with uncorrected OCT tomograms is also achieved.     

Compact,low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography

A compact, low-cost, prismless Ti:Al2O3 laser with 176-nm bandwidth (FWHM) and 20-mW output power was developed. Ultrahigh-resolution ophthalmic optical coherence tomography (OCT) ex vivo imaging in an animal model with approximately 1.2-microm axial resolution and in vivo imaging in patients with macular pathologies with approximately 3-microm axial resolution were demonstrated. Owing to the pump laser, this light source significantly reduces the cost of broadband OCT systems. Furthermore, the source has great potential for clinical application of spectroscopic and ultrahigh-resolution OCT because of its small footprint (500 mm x 180 mm including the pump laser), user friendliness, stability, and reproducibility.     

High-speed, high-resolution optical coherence tomography retinal imaging with a frequency-swept laser at 850 nm

High-speed, high-resolution optical coherence tomography (OCT) imaging of the human retina is demonstrated using a frequency-swept laser at 850 nm. A compact external cavity semiconductor laser design, optimized for swept-source ophthalmic OCT, is described. The laser enables an effective 16 kHz sweep rate with >10 mm coherence length and a tuning range of approximately 35 nm full width at half-maximum, yielding an axial resolution of <7 micro m in tissue.     

Holoscopy--holographic optical coherence tomography

Scanning optical coherence tomography (OCT) is limited in sensitivity and resolution by the restricted focal depth of the confocal detection scheme. Holoscopy, a combination of holography and Fourier-domain full-field OCT, is proposed as a way to detect photons from all depths of a sample volume simultaneously with uniform sensitivity and lateral resolution, even at high NAs. By using the scalar diffraction theory, as frequently applied in digital holographic imaging, we fully reconstruct the object field with depth-invariant imaging quality. In vivo imaging of human skin is demonstrated with an image quality comparable to conventionally scanned OCT.     

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

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.     

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.     

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.     

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.     

Endoscopic optical coherence tomography based on a microelectromechanical mirror

An endoscopic optical coherence tomography (OCT) system based on a microelectromechanical mirror to facilitate lateral light scanning is described. The front-view OCT scope, adapted to the instrument channel of a commercial endoscopic sheath, allows real-time cross-sectional imaging of living biological tissue via direct endoscopic visual guidance. The transverse and axial resolutions of the OCT scope are roughly 20 and 10.2mum, respectively. Cross-sectional images of 500x1000 pixels covering an area of 2.9 mmx2.8 mm can be acquired at ~5 frames/s and with nearly 100-dB dynamic range. Applications in thickness measurement and bladder tissue imaging are demonstrated.     

Interstitial Doppler optical coherence tomography

Doppler optical coherence tomography (OCT) can image tissue structure and blood flow at micrometer-scale resolution but has limited imaging depth. We report a novel, linear-scanning, needle-based Doppler OCT system using angle-polished gradient-index or ball-lensed fibers. A prototype system with a 19-guage (diameter of approximately 0.9 mm) echogenic needle is constructed and demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal cavity. To our knowledge, this is the first demonstration of Doppler OCT through a needle probe in interstitial applications to visualize deeply situated microcirculation.     

Spatially resolved spectral interferometry for determination of subsurface structure

We describe an instrument capable of obtaining two-dimensional images of subsurface structure in real time with no moving parts. The technique is based on spectral interferometry and uses an imaging spectrograph to obtain spatially resolved spectra. A test sample consisting of microscope coverslips and a Ronchi grating was measured, illustrating the system's depth resolution of 38 mum and transverse resolution of at least 12.7 mum . The technique is readily adaptable to endoscopic delivery as well as three-dimensional real-time image acquisition.     

光学相干层析术用于鲜红斑痣诊断

光学相干层析术(optical coherence tomography,简称OCT)具有非侵入性,高分辨及高速成像的优点,特别适合于生物医学领域。但由于大部分生物组织具高散射系数,通常仅能对表层组织下数毫米深度内进行成像。穿透深度不足限制了OCT在皮肤科等领域应用。作为常见多发病的鲜红斑痣具有病变组织浅,血管增生明显等特点,所以OCT非常适于鲜红斑痣的检测。通过选择皮肤穿透性好的中心波长为1310nm超辐射二极管,合理优化样品臂和参考臂光强比例及偏振控制,实现了对鲜红斑痣在体成像研究,采集了清晰的OCT图像,得到其关键特征参数,如表皮层厚度,血管直径等,对鲜红斑痣的诊断及制定合理治疗方案具有重要意义。     

Imaging of subcutaneous blood vessels and flow velocity profiles by optical coherence tomography

We have applied a compact low power rapid scanning Doppler Optical Coherence Tomography system to monitor multi-dimensional velocity profiles within the complex vessels and simultaneous real-time non-invasive imaging of skin tissues morphology in vivo, in the wavelength range of 1.3–1.5 nm. Optical clearing of skin tissues has been utilized to achieve depth of OCT images up to 1.7 mm. Current approach enables applying low-power (0.4–0.5 mW) and low-noise broadband near-infrared light sources and obtaining OCT images with down to 12 μm spatial resolution. Two-dimensional time-domain OCT images of complex flow velocity profiles in blood vessel phantom and in vivo subcutaneous human skin tissues are presented. The effect of optical clearing on in vivo images is demonstrated and discussed.     

In vivo imaging of dynamic biological specimen by real-time single-shot full-field optical coherence tomography

We demonstrate the feasibility of a compact single-shot full-field time domain optical coherence tomography (OCT) for imaging dynamic biological sample in real-time. The system is based on a Linnik type polarization Michelson interferometer and a four-quadrature phase-stepper optics, which can simultaneously capture four quadraturely phase-stepped interferograms on a single CCD. Using a superluminescent diode as light source with center wavelength of 842 nm and spectral width of 16.2 nm, the system yields an axial resolution of 19.8 μm, and covers a field of view of 280 × 320 μm² (220 × 250 pixels) with a transverse resolution of 4.4 μm by using a 10× microscope objective (0.3 NA). Three-dimensional OCT images of biological samples such as an onion slice and a diaptomus were obtained without any image averaging or pixel binning. In addition, in vivo depth resolved dynamic imaging was demonstrated to show the beating internal structure of a diaptomus with a fame rate of 5 fps.     

Adaptive optics optical coherence tomography for retina imaging

When optical coherence tomography (OCT) is used for human retina imaging, its transverse resolution is limited by the aberrations of human eyes. To overcome this disadvantage, a high resolution imaging system for living human retina, which consists of a time domain OCT system and a 37-elements adaptive optics (AO) system, has been developed. The AO closed loop rate is 20 frames per second, and the OCT has a 6.7-μm axial resolution. In this paper, this system is introduced and the high resolution imaging results for retina are presented.     

Compact,broad-bandwidth fiber laser for sub-2-microm axial resolution optical coherence tomography in the 1300-nm wavelength region

A novel, compact, user friendly fiber laser with a broad emission bandwidth (MenloSystems, lambdac = 1375 nm, deltalambda = 470 nm, Pout = 4 mW) was used to achieve unprecedented sub-2-microm axial resolution optical coherence tomography (OCT) in nontransparent biological tissue in the 1300-nm wavelength region. Fresh human skin and arterial biopsies were imaged ex vivo with approximately 1.4-microm axial and approximately 3-microm lateral resolution and 95-dB sensitivity, demonstrating the great potential for clinical OCT applications of this stable, low-cost, and turn-on-key fiber laser.     

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.     

基于旋转扫描探头的OCT内窥成像系统设计

为了同时获取样品的表面和深度信息,研究光学相干层析的成像原理,建立了基于光学相干层析技术的内窥系统,实现了旋转扫描成像,系统的工作波长为1 310 nm,工作带宽为80 nm.理论推导及计算机仿真得到了系统信噪比与干涉仪的分光比、反射率之间的关系并分析了理论分辨率和探测深度.提出外径为5 mm的内窥镜扫描探头,聚焦距离为12 mm,数值孔径NA为0.47,折射率分布常量A=0.218 7.利用微型电机驱动直角棱镜实现扫描,旋转速度为25 rpm,旋转一周得到640个采样点.采用多层盖玻片和洋葱表皮作为样品进行实验分析,得到了盖玻片和洋葱的图像,横向分辨率和纵向分辨率分别为10 μm和15 μm.结果表明,设计的光学相干层析内窥系统能够用于旋转扫描成像,获取更多的组织信息.