Miniaturized magnetic-driven scanning probe for endoscopic optical coherence tomography

We designed and implemented a magnetic-driven scanning (MDS) probe for endoscopic optical coherence tomography (OCT). The probe uses an externally-driven tiny magnet in the distal end to achieve unobstructed 360-degree circumferential scanning at the side of the probe. The design simplifies the scanning part inside the probe and thus allows for easy miniaturization and cost reduction. We made a prototype probe with an outer diameter of 1.4 mm and demonstrated its capability by acquiring OCT images of ex vivo trachea and artery samples from a pigeon. We used a spectrometer-based Fourier-domain OCT system and the system sensitivity with our prototype probe was measured to be 91 dB with an illumination power of 850 μW and A-scan exposure time of 1 ms. The axial and lateral resolutions of the system are 6.5 μm and 8.1 μm, respectively.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.2150) Endoscopic imaging, (120.5800) Scanners     

Birefringence imaging of posterior eye by multi-functional Jones matrix optical coherence tomography

A clinical grade prototype of posterior multifunctional Jones matrix optical coherence tomography (JM-OCT) is presented. This JM-OCT visualized depth-localized birefringence in addition to conventional cumulative phase retardation imaging through local Jones matrix analysis. In addition, it simultaneously provides a sensitivity enhanced scattering OCT, a quantitative polarization uniformity contrast, and OCT-based angiography. The probe beam is at 1-μm wavelength band. The measurement speed and the depth-resolution were 100,000 A-lines/s, and 6.6 μm in tissue, respectively. Normal and pathologic eyes are examined and several clinical features are revealed, which includes high birefringence in the choroid and lamina cribrosa, and birefringent layered structure of the sclera. The theoretical details of the depth-localized birefringence imaging and conventional phase retardation imaging are formulated. This formulation indicates that the birefringence imaging correctly measures a depth-localized single-trip phase retardation of a tissue, while the conventional phase retardation can provide correct single-trip phase retardation only for some specific types of samples.OCIS codes: (170.4500) Optical coherence tomography, (170.4460) Ophthalmic optics and devices, (110.5405) Polarimetric imaging, (120.5410) Polarimetry, (170.4470) Ophthalmology, (110.4500) Optical coherence tomography     

In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo.OCIS codes: (170.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.1610) Clinical applications, (170.4580) Optical diagnostics for medicine     

Ultrahigh speed endoscopic optical coherence tomography using micromotor imaging catheter and VCSEL technology

We developed a micromotor based miniature catheter with an outer diameter of 3.2 mm for ultrahigh speed endoscopic swept source optical coherence tomography (OCT) using a vertical cavity surface-emitting laser (VCSEL) at a 1 MHz axial scan rate. The micromotor can rotate a micro-prism at several hundred frames per second with less than 5 V drive voltage to provide fast and stable scanning, which is not sensitive to the bending of the catheter. The side-viewing probe can be pulled back to acquire a three-dimensional (3D) data set covering a large area on the specimen. The VCSEL provides a high axial scan rate to support dense sampling under high frame rate operation. Using a high speed data acquisition system, in vivo 3D-OCT imaging in the rabbit GI tract and ex vivo imaging of a human colon specimen with 8 μm axial resolution, 8 μm lateral resolution and 1.2 mm depth range in tissue at a frame rate of 400 fps was demonstrated.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.2150) Endoscopic imaging, (170.2680) Gastrointestinal, (140.3600) Three-dimensional image acquisition, (110.2350) Fiber optics imaging, (120.5800) Scanners, (120.3890) Medical optics instrumentation     

Adaptive optics optical coherence tomography at 1 MHz

Image acquisition speed of optical coherence tomography (OCT) remains a fundamental barrier that limits its scientific and clinical utility. Here we demonstrate a novel multi-camera adaptive optics (AO-)OCT system for ophthalmologic use that operates at 1 million A-lines/s at a wavelength of 790 nm with 5.3 μm axial resolution in retinal tissue. Central to the spectral-domain design is a novel detection channel based on four high-speed spectrometers that receive light sequentially from a 1 × 4 optical switch assembly. Absence of moving parts enables ultra-fast (50ns) and precise switching with low insertion loss (−0.18 dB per channel). This manner of control makes use of all available light in the detection channel and avoids camera dead-time, both critical for imaging at high speeds. Additional benefit in signal-to-noise accrues from the larger numerical aperture afforded by the use of AO and yields retinal images of comparable dynamic range to that of clinical OCT. We validated system performance by a series of experiments that included imaging in both model and human eyes. We demonstrated the performance of our MHz AO-OCT system to capture detailed images of individual retinal nerve fiber bundles and cone photoreceptors. This is the fastest ophthalmic OCT system we know of in the 700 to 915 nm spectral band.OCIS codes: (110.1080) Active or adaptive optics, (170.4500) Optical coherence tomography, (120.3890) Medical optics instrumentation, (170.0110) Imaging systems, (170.4470) Ophthalmology, (330.5310) Vision - photoreceptors     

Miniature forward-viewing common-path OCT probe for imaging the renal pelvis

We demonstrate an ultrathin flexible cone-scanning forward-viewing OCT probe which can fit through the working channel of a flexible ureteroscope for renal pelvis imaging. The probe is fabricated by splicing a 200 µm section of core-less fiber and a 150 µm section of gradient-index (GRIN) fiber to the end of a single mode (SM) fiber. The probe is designed for common-path OCT imaging where the back-reflection of the GRIN fiber/air interface is used as the reference signal. Optimum sensitivity was achieved with a 2 degree polished probe tip. A correlation algorithm was used to correct image distortion caused by non-uniform rotation of the probe. The probe is demonstrated by imaging human skin in vivo and porcine renal pelvis ex vivo and is suitable for imaging the renal pelvis in vivo for cancer staging.OCIS codes: (110.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.3890) Medical optics instrumentation     

Maximum-likelihood estimation in Optical Coherence Tomography in the context of the tear film dynamics

Understanding tear film dynamics is a prerequisite for advancing the management of Dry Eye Disease (DED). In this paper, we discuss the use of optical coherence tomography (OCT) and statistical decision theory to analyze the tear film dynamics of a digital phantom. We implement a maximum-likelihood (ML) estimator to interpret OCT data based on mathematical models of Fourier-Domain OCT and the tear film. With the methodology of task-based assessment, we quantify the tradeoffs among key imaging system parameters. We find, on the assumption that the broadband light source is characterized by circular Gaussian statistics, ML estimates of 40 nm +/− 4 nm for an axial resolution of 1 μm and an integration time of 5 μs. Finally, the estimator is validated with a digital phantom of tear film dynamics, which reveals estimates of nanometer precision.OCIS codes: (030.0030) Coherence and statistical optics, (110.3000) Image quality assessment     

Multimodal instrument for high-sensitivity autofluorescence and spectral optical coherence tomography of the human eye fundus

In this paper we present a multimodal device for imaging fundus of human eye in vivo which combines functionality of autofluorescence by confocal SLO with Fourier domain OCT. Native fluorescence of human fundus was excited by modulated laser beam (λ = 473 nm, 20 MHz) and lock-in detection was applied resulting in improving sensitivity. The setup allows for acquisition of high resolution OCT and high contrast AF images using fluorescence excitation power of 50-65 μW without averaging consecutive images. Successful functioning of constructed device have been demonstrated for 8 healthy volunteers of different age ranging from 24 to 83 years old.OCIS codes: (110.0110) Imaging systems, (170.4460) Ophthalmic optics and devices, (170.4500) Optical coherence tomography, (170.5755) Retina scanning, (170.6280) Spectroscopy, fluorescence and luminescence     

Miniature real-time intraoperative forward-imaging optical coherence tomography probe

Optical coherence tomography (OCT) has a tremendous global impact upon the ability to diagnose, treat, and monitor eye diseases. A miniature 25-gauge forward-imaging OCT probe with a disposable tip was developed for real-time intraoperative ocular imaging of posterior pole and peripheral structures to improve vitreoretinal surgery. The scanning range was 2 mm when the probe tip was held 3-4 mm from the tissue surface. The axial resolution was 4-6 µm and the lateral resolution was 25-35 µm. The probe was used to image cellophane tape and multiple ocular structures.OCIS codes: (170.4500) Optical coherence tomography, (120.3890) Medical optics instrumentation     

A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography

We present a power-efficient fiber-based imaging system capable of co-registered autofluorescence imaging and optical coherence tomography (AF/OCT). The system employs a custom fiber optic rotary joint (FORJ) with an embedded dichroic mirror to efficiently combine the OCT and AF pathways. This three-port wavelength multiplexing FORJ setup has a throughput of more than 83% for collected AF emission, significantly more efficient compared to previously reported fiber-based methods. A custom 900 µm diameter catheter ‒ consisting of a rotating lens assembly, double-clad fiber (DCF), and torque cable in a stationary plastic tube ‒ was fabricated to allow AF/OCT imaging of small airways in vivo. We demonstrate the performance of this system ex vivo in resected porcine airway specimens and in vivo in human on fingers, in the oral cavity, and in peripheral airways.OCIS codes: (110.0110) Imaging systems, (110.2350) Fiber optics imaging, (110.4500) Optical coherence tomography, (170.2520) Fluorescence microscopy, (170.3890) Medical optics instrumentation     

Handheld,rapidly switchable,anterior/posterior segment swept source optical coherence tomography probe

We describe the first handheld, swept source optical coherence tomography (SSOCT) system capable of imaging both the anterior and posterior segments of the eye in rapid succession. A single 2D microelectromechanical systems (MEMS) scanner was utilized for both imaging modes, and the optical paths for each imaging mode were optimized for their respective application using a combination of commercial and custom optics. The system has a working distance of 26.1 mm and a measured axial resolution of 8 μm (in air). In posterior segment mode, the design has a lateral resolution of 9 μm, 7.4 mm imaging depth range (in air), 4.9 mm 6dB fall-off range (in air), and peak sensitivity of 103 dB over a 22° field of view (FOV). In anterior segment mode, the design has a lateral resolution of 24 μm, imaging depth range of 7.4 mm (in air), 6dB fall-off range of 4.5 mm (in air), depth-of-focus of 3.6 mm, and a peak sensitivity of 99 dB over a 17.5 mm FOV. In addition, the probe includes a wide-field iris imaging system to simplify alignment. A fold mirror assembly actuated by a bi-stable rotary solenoid was used to switch between anterior and posterior segment imaging modes, and a miniature motorized translation stage was used to adjust the objective lens position to correct for patient refraction between −12.6 and + 9.9 D. The entire probe weighs less than 630 g with a form factor of 20.3 x 9.5 x 8.8 cm. Healthy volunteers were imaged to illustrate imaging performance.OCIS codes: (110.4500) Optical coherence tomography, (170.4460) Ophthalmic optics and devices, (080.3620) Lens system design, (170.0110) Imaging systems, (170.5755) Retina scanning, (170.4470) Ophthalmology     

A 5-mm piezo-scanning fiber device for high speed ultrafast laser microsurgery

Towards developing precise microsurgery tools for the clinic, we previously developed image-guided miniaturized devices using low repetition rate amplified ultrafast lasers for surgery. To improve the speed of tissue removal while reducing device diameter, here we present a new 5-mm diameter device that delivers high-repetition rate laser pulses for high speed ultrafast laser microsurgery. The device consists of an air-core photonic bandgap fiber (PBF) for the delivery of high energy pulses, a piezoelectric tube actuator for fiber scanning, and two aspheric lenses for focusing the light. Its inline optical architecture provides easy alignment and substantial size reduction to 5 mm diameter as compared to our previous MEMS-scanning devices while realizing improved intensity squared (two-photon) lateral and axial resolutions of 1.16 μm and 11.46 μm, respectively. Our study also sheds light on the maximum pulse energies that can be delivered through the air-core PBF and identifies cladding damage at the input facet of the fiber as the limiting factor. We have achieved a maximum energy delivery larger than 700 nJ at 92% coupling efficiency. An in depth analysis reveals how this value is greatly affected by possible slight misalignments of the beam during coupling and the measured small beam pointing fluctuations. In the absence of these imperfections, self-phase modulation becomes the limiting factor for the maximum energy delivery, setting the theoretical upper bound to near 2 μJ for a 1-m long, 7-μm, air-core PBF. Finally, the use of a 300 kHz repetition rate fiber laser enabled rapid ablation of 150 µm x 150 µm area within only 50 ms. Such ablation speeds can now allow the surgeons to translate the surgery device as fast as ~4 mm/s to continuously remove a thin layer of a 150 µm wide tissue. Thanks to a high optical transmission efficiency of the in-line optical architecture of the device and improved resolution, we could successfully perform ablation of scarred cheek pouch tissue, drilling through a thin slice. With further development, this device can serve as a precise and high speed ultrafast laser scalpel in the clinic.OCIS codes: (170.1020) Ablation of tissue, (140.7090) Ultrafast lasers, (180.4315) Nonlinear microscopy, (170.3890) Medical optics instrumentation, (190.4370) Nonlinear optics, fibers     

Piezoelectric-transducer-based miniature catheter for ultrahigh-speed endoscopic optical coherence tomography

We developed a piezoelectric-transducer- (PZT) based miniature catheter with an outer diameter of 3.5 mm for ultrahigh-speed endoscopic optical coherence tomography (OCT). A miniaturized PZT bender actuates a fiber and the beam is scanned through a GRIN lens and micro-prism to provide high-speed, side-viewing capability. The probe optics can be pulled back over a long distance to acquire three-dimensional (3D) data sets covering a large area. Imaging is performed with 11 μm axial resolution in air (8 μm in tissue) and 20 μm transverse resolution, at 960 frames per second with a Fourier domain mode-locked laser operating at 480 kHz axial scan rate. Using a high-speed data acquisition system, endoscopic OCT imaging of the rabbit esophagus and colon in vivo and human colon specimens ex vivo is demonstrated.     

Ultrafast laser surgery probe with a calcium fluoride miniaturized objective for bone ablation

We present a miniaturized ultrafast laser surgery probe with improved miniaturized optics to deliver higher peak powers and enable higher surgical speeds than previously possible. A custom-built miniaturized CaF₂ objective showed no evidence of the strong multiphoton absorption observed in our previous ZnS-based probe, enabling higher laser power delivery to the tissue surface for ablation. A Kagome fiber delivered ultrashort pulses from a high repetition rate fiber laser to the objective, producing a focal beam radius of 1.96 μm and covering a 90×90 μm² scan area. The probe delivered the maximum available fiber laser power, providing fluences >6 J/cm² at the tissue surface at 53% transmission efficiency. We characterized the probe’s performance through a parametric ablation study on bovine cortical bone and defined optimal operating parameters for surgery using an experimental- and simulation-based approach. The entire opto-mechanical system, enclosed within a 5-mm diameter housing with a 2.6-mm diameter probe tip, achieved material removal rates >0.1 mm³/min, however removal rates were ultimately limited by the available laser power. Towards a next generation surgery probe, we simulated maximum material removal rates when using a higher power fiber laser and found that removal rates >2 mm³/min could be attained through appropriate selection of laser surgery parameters. With future development, the device presented here can serve as a precise surgical tool with clinically viable speeds for delicate applications such as spinal decompression surgeries.     

Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure

We present optical coherence micro-elastography, an improved form of compression optical coherence elastography. We demonstrate the capacity of this technique to produce en face images, closely corresponding with histology, that reveal micro-scale mechanical contrast in human breast and lymph node tissues. We use phase-sensitive, three-dimensional optical coherence tomography (OCT) to probe the nanometer-to-micrometer-scale axial displacements in tissues induced by compressive loading. Optical coherence micro-elastography incorporates common-path interferometry, weighted averaging of the complex OCT signal and weighted least-squares regression. Using three-dimensional phase unwrapping, we have increased the maximum detectable strain eleven-fold over no unwrapping and the minimum detectable strain is 2.6 με. We demonstrate the potential of mechanical over optical contrast for visualizing micro-scale tissue structures in human breast cancer pathology and lymph node morphology.OCIS codes: (110.4500) Optical coherence tomography, (110.1650) Coherence imaging, (100.5088) Phase unwrapping     

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.OCIS codes: (060.2370) Fiber optics sensors, (170.4500) Optical coherence tomography, (170.6935) Tissue characterization, (230.3990) Micro-optical devices     

Laser tissue coagulation and concurrent optical coherence tomography through a double-clad fiber coupler

Double-clad fiber (DCF) is herein used in conjunction with a double-clad fiber coupler (DCFC) to enable simultaneous and co-registered optical coherence tomography (OCT) and laser tissue coagulation. The DCF allows a single channel fiber-optic probe to be shared: i.e. the core propagating the OCT signal while the inner cladding delivers the coagulation laser light. We herein present a novel DCFC designed and built to combine both signals within a DCF (>90% of single-mode transmission; >65% multimode coupling). Potential OCT imaging degradation mechanisms are also investigated and solutions to mitigate them are presented. The combined DCFC-based system was used to induce coagulation of an ex vivo swine esophagus allowing a real-time assessment of thermal dynamic processes. We therefore demonstrate a DCFC-based system combining OCT imaging with laser coagulation through a single fiber, thus enabling both modalities to be performed simultaneously and in a co-registered manner. Such a system enables endoscopic image-guided laser marking of superficial epithelial tissues or laser thermal therapy of epithelial lesions in pathologies such as Barrett’s esophagus.OCIS codes: (060.2340) Fiber optics components, (170.2150) Endoscopic imaging, (170.3880) Medical and biological imaging, (170.3890) Medical optics instrumentation, (170.4500) Optical coherence tomography     

Motion analysis and removal in intensity variation based OCT angiography

In this work, we investigated how bulk motion degraded the quality of optical coherence tomography (OCT) angiography that was obtained through calculating interframe signal variation, i.e., interframe signal variation based optical coherence angiography (isvOCA). We demonstrated theoretically and experimentally that the spatial average of isvOCA signal had an explicit functional dependency on bulk motion. Our result suggested that the bulk motion could lead to an increased background in angiography image. Based on our motion analysis, we proposed to reduce image artifact induced by transient bulk motion in isvOCA through adaptive thresholding. The motion artifact reduced angiography was demonstrated in a 1.3μm spectral domain OCT system. We implemented signal processing using graphic processing unit for real-time imaging and conducted in vivo microvasculature imaging on human skin. Our results clearly showed that the adaptive thresholding method was highly effective in the motion artifact removal for OCT angiography.OCIS codes: (110.4500) Optical coherence tomography, (170.2655) Functional monitoring and imaging, (100.2000) Digital image processing     

Development of a graded index microlens based fiber optical trap and its characterization using principal component analysis

We demonstrate a miniaturized single beam fiber optical trapping probe based on a high numerical aperture graded index (GRIN) micro-objective lens. This enables optical trapping at a distance of 200μm from the probe tip. The fiber trapping probe is characterized experimentally using power spectral density analysis and an original approach based on principal component analysis for accurate particle tracking. Its use for biomedical microscopy is demonstrated through optically mediated immunological synapse formation.OCIS codes: (060.2310) Fiber optics, (110.2760) Gradient-index lenses, (170.0170) Medical optics and biotechnology, (170.3880) Medical and biological imaging, (170.4520) Optical confinement and manipulation, (180.0180) Microscopy, (180.2520) Fluorescence microscopy, (350.4855) Optical tweezers or optical manipulation     

Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue.OCIS codes: (170.0180) Microscopy, (170.4500) Optical coherence tomography, (170.2520) Fluorescence microscopy, (110.2350) Fiber optics imaging