MEMS tunable VCSEL light source for ultrahigh speed 60kHz - 1MHz axial scan rate and long range centimeter class OCT imaging

This paper demonstrates new wavelength swept light source technology, MEMS tunable VCSELs, for OCT imaging. The VCSEL achieves a combination of ultrahigh sweep speeds, wide spectral tuning range, flexibility in sweep trajectory, and extremely long coherence length, which cannot be simultaneously achieved with other technologies. A second generation prototype VCSEL is optically pumped at 980nm and a low mass electrostatically tunable mirror enables high speed wavelength tuning centered at ~1310nm with ~110nm of tunable bandwidth. Record coherence length >100mm enables extremely long imaging range. By changing the drive waveform, a single 1310nm VCSEL was driven to sweep at speeds from 100kHz to 1.2MHz axial scan rate with unidirectional and bidirectional high duty cycle sweeps. We demonstrate long range and high resolution 1310nm OCT imaging of the human anterior eye at 100kHz axial scan rate and imaging of biological samples at speeds of 60kHz - 1MHz. A first generation 1050nm device is shown to sweep over 100nm. The results of this study suggest that MEMS based VCSEL swept light source technology has unique performance characteristics and will be a critical technology for future ultrahigh speed and long depth range OCT imaging.National Institutes of Health (U.S.) (2R44CA10167-05)National Institutes of Health (U.S.) (R01-EY011289-25)National Institutes of Health (U.S.) (R01-EY01356-06)National Institutes of Health (U.S.) (R01-EY013178-11)National Institutes of Health (U.S.) (R01-CA075289-15)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)Thorlabs, Inc

Wideband Electrically Pumped 1050-nm MEMS-Tunable VCSEL for Ophthalmic Imaging

In this paper, we present a 1050-nm electrically pumped microelectromechanically tunable vertical cavity surface-emitting laser (MEMS-VCSEL) with a record dynamic tuning bandwidth of 63.8 nm, suitable for swept-source optical coherence tomography (SS-OCT) imaging. These devices provide reduced cost and complexity relative to previously demonstrated optically pumped devices by obviating the need for a pump laser and associated hardware. We demonstrate ophthalmic SS-OCT imaging with the electrically-pumped MEMS-VCSEL at a 400 kHz axial scan rate for wide-field imaging of the in vivo human retina over a 12 mm × 12 mm field and for OCT angiography of the macula over 6 mm × 6 mm and 3 mm × 3 mm fields to show retinal vasculature and capillary structure near the fovea. These results demonstrate the feasibility of electrically pumped MEMS-VCSELs in ophthalmic instrumentation, the largest clinical application of OCT. In addition, we estimate that the 3 dB coherence length in air is 225 ± 51 m, far greater than required for ophthalmic SS-OCT and suggestive of other distance ranging applications.National Eye InstituteNational Institutes of Health (U.S.) (Grant R01-EY011289-28)National Institutes of Health (U.S.) (Grant R44-EY022864-02)National Institutes of Health (U.S.) (Grant R44-EY022864-03)National Institutes of Health (U.S.) (Grant R01-CA075289-17)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-12-1-0499

Reproducibility of a Long-Range Swept-Source Optical Coherence Tomography Ocular Biometry System and Comparison with Clinical Biometers

Objective To demonstrate a novel swept source optical coherence tomography (SS-OCT) imaging device using a vertical cavity surface-emitting laser (VCSEL) capable of imaging the full eye length and to introduce a method using this device for noncontact ocular biometry. To compare the measurements of intraocular distances using this SS-OCT instrument with commercially available optical and ultrasound biometers. To evaluate the intersession reproducibility of measurements of intraocular distances using SS-OCT. Design Evaluation of technology. Participants Twenty eyes of 10 healthy subjects imaged at the New England Eye Center at Tufts Medical Center and Massachusetts Institute of Technology between May and September 2012. Methods Averaged central depth profiles were extracted from volumetric SS-OCT datasets. The intraocular distances, such as central corneal thickness (CCT), aqueous depth (AD), anterior chamber depth (ACD), crystalline lens thickness (LT), vitreous depth (VD), and axial length (AL), were measured and compared with a partial coherence interferometry device (IOLMaster; Carl Zeiss Meditec, Inc., Dublin, CA) and an immersion ultrasound (IUS) A-scan biometer (Axis-II PR; Quantel Medical, Inc., Cournon d'Auvergne Cedex, France). Main Outcome Measures Reproducibility of the measurements of intraocular distances, correlation coefficients, and intraclass correlation coefficients. Results The standard deviations of the repeated measurements of intraocular distances using SS-OCT were 6 μm (CCT), 16 μm (ACD), 14 μm (AD), 13 μm (LT), 14 μm (VD), and 16 μm (AL). Strong correlations among all 3 biometric instruments were found for AL (r > 0.98). The AL measurement using SS-OCT correlates better with the IOLMaster (r=0.998) than with IUS (r=0.984). The SS-OCT and IOLMaster measured higher AL values than ultrasound (175 and 139 μm, respectively). No statistically significant difference in ACD between the optical (SS-OCT or IOLMaster) and ultrasound methods was detected. High intersession reproducibility of SS-OCT measurements of all intraocular distances was observed with intraclass correlation coefficients >0.99. Conclusions The SS-OCT using VCSEL technology enables full eye length imaging and high-precision, noncontact ocular biometry. The measurements with the prototype SS-OCT instrument correlate well with commercial biometers. The SS-OCT biometry has the potential to provide clinically useful comprehensive biometric parameters for pre- and postoperative eye evaluation.National Institutes of Health (U.S.) (Grant R01-EY011289-27)National Institutes of Health (U.S.) (Grant R01-EY013178-12)National Institutes of Health (U.S.) (Grant R01-EY013516-09)National Institutes of Health (U.S.) (Grant R01-EY019029-04)National Institutes of Health (U.S.) (Grant R44EY022864-01)National Institutes of Health (U.S.) (Grant R01-CA075289-16)National Institutes of Health (U.S.) (Grant R01-NS057476-05)National Institutes of Health (U.S.) (Grant R44CA101067-05)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0551)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0063)Thorlabs, Inc

High-precision, high-accuracy ultralong-range swept-source optical coherence tomography using vertical cavity surface emitting laser light source

We demonstrate ultralong-range swept-source optical coherence tomography (OCT) imaging using vertical cavity surface emitting laser technology. The ability to adjust laser parameters and high-speed acquisition enables imaging ranges from a few centimeters up to meters using the same instrument. We discuss the challenges of long-range OCT imaging. In vivo human-eye imaging and optical component characterization are presented. The precision and accuracy of OCT-based measurements are assessed and are important for ocular biometry and reproducible intraocular distance measurement before cataract surgery. Additionally, meter-range measurement of fiber length and multicentimeter-range imaging are reported. 3D visualization supports a class of industrial imaging applications of OCT.National Institutes of Health (U.S.) (R01-EY011289-26)National Institutes of Health (U.S.) (R01 EY013178-12)National Institutes of Health (U.S.) (R01-EY013516-09)National Institutes of Health (U.S.) (R01-EY019029-03)National Institutes of Health (U.S.) (R01-CA075289-15)National Institutes of Health (U.S.) (R01-NS057476-05)National Institutes of Health (U.S.) (R44-CA101067-05)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-10-1-0063

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

Assessment of breast pathologies using nonlinear microscopy

Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen. Imaging was performed on fresh, intact specimens without the need for fixation, embedding, and sectioning required for conventional histopathology. A visualization method to aid pathological interpretation is presented that maps NLM contrast from two-photon fluorescence and second harmonic signals to features closely resembling histopathology using hematoxylin and eosin staining. Mosaicking is used to overcome trade-offs between resolution and field of view, enabling imaging of subcellular features over square-centimeter specimens. After NLM examination, specimens were processed for standard paraffin-embedded histology using a protocol that coregistered histological sections to NLM images for paired assessment. Blinded NLM reading by three pathologists achieved 95.4% sensitivity and 93.3% specificity, compared with paraffin-embedded histology, for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. Interobserver agreement was κ = 0.88 for NLM and κ = 0.89 for histology. These results show that NLM achieves high diagnostic accuracy, can be rapidly performed on unfixed specimens, and is a promising method for intraoperative margin assessment.National Institutes of Health (U.S.) (Grant R01-CA178636-01)National Institutes of Health (U.S.) (Grant R01-CA75289-16)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0551)United States. Air Force Office of Scientific Research (Grant FA9550-12-1-0499)National Institutes of Health (U.S.) (National Research Service Award Postdoctoral Fellowship F32-CA165484

Design of a portable wide field of view GPU-accelerated multiphoton imaging system for real-time imaging of breast surgical specimens

We present a portable multiphoton system designed for evaluating centimeter-scale surgical margins on surgical breast specimens in a clinical setting. The system is designed to produce large field of view images at a high frame rate, while using GPU processing to render low latency, video-rate virtual H&E images for real-time assessment. The imaging system and virtual H&E rendering algorithm are demonstrated by imaging unfixed human breast tissue in a clinical setting

Ultrahigh speed endoscopic swept source optical coherence tomography using a VCSEL light source and micromotor catheter

We developed an ultrahigh speed endoscopic swept source optical coherence tomography (OCT) system for clinical gastroenterology using a vertical-cavity surface-emitting laser (VCSEL) and micromotor based imaging catheter, which provided an imaging speed of 600 kHz axial scan rate and 8 μm axial resolution in tissue. The micromotor catheter was 3.2 mm in diameter and could be introduced through the 3.7 mm accessory port of an endoscope. Imaging was performed at 400 frames per second with an 8 μm spot size using a pullback to generate volumetric data over 16 mm with a pixel spacing of 5 μm in the longitudinal direction. Three-dimensional OCT (3D-OCT) imaging was performed in patients with a cross section of pathologies undergoing standard upper and lower endoscopy at the Veterans Affairs Boston Healthcare System (VABHS). Patients with Barrett’s esophagus, dysplasia, and inflammatory bowel disease were imaged. The use of distally actuated imaging catheters allowed OCT imaging with more flexibility such as volumetric imaging in the terminal ileum and the assessment of the hiatal hernia using retroflex imaging. The high rotational stability of the micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy for both en face and cross-sectional imaging. The ability to perform 3D OCT imaging in the GI tract with microscopic accuracy should enable a wide range of studies to investigate the ability of OCT to detect pathology as well as assess treatment response.National Institutes of Health (U.S.) (R44EY022864-01)National Institutes of Health (U.S.) (R01-CA75289-17)National Institutes of Health (U.S.) (R44-CA101067-06)National Institutes of Health (U.S.) ( R01-EY011289-27)National Institutes of Health (U.S.) (R01-HL095717-04)National Institutes of Health (U.S.) (R01-NS057476-05)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)United States. Air Force Office of Scientific Research. Medical Free Electron Laser Program (FA9550-10-1-0551)German Research Foundation (DFG-GSC80-SAOT)German Research Foundation (DFG-HO-1791/11-1)Center for Integration of Medicine and Innovative Technolog

Ultrahigh speed 1050nm swept source / Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second

We demonstrate ultrahigh speed swept source/Fourier domain ophthalmic OCT imaging using a short cavity swept laser at 100,000 – 400,000 axial scan rates. Several design configurations illustrate tradeoffs in imaging speed, sensitivity, axial resolution, and imaging depth. Variable rate A/D optical clocking is used to acquire linear-in-k OCT fringe data at 100kHz axial scan rate with 5.3um axial resolution in tissue. Fixed rate sampling at 1 GSPS achieves a 7.5mm imaging range in tissue with 6.0um axial resolution at 100kHz axial scan rate. A 200kHz axial scan rate with 5.3um axial resolution over 4mm imaging range is achieved by buffering the laser sweep. Dual spot OCT using two parallel interferometers achieves 400kHz axial scan rate, almost 2X faster than previous 1050nm ophthalmic results and 20X faster than current commercial instruments. Superior sensitivity roll-off performance is shown. Imaging is demonstrated in the human retina and anterior segment. Wide field 12×12mm data sets include the macula and optic nerve head. Small area, high density imaging shows individual cone photoreceptors. The 7.5mm imaging range configuration can show the cornea, iris, and anterior lens in a single image. These improvements in imaging speed and depth range provide important advantages for ophthalmic imaging. The ability to rapidly acquire 3D-OCT data over a wide field of view promises to simplify examination protocols. The ability to image fine structures can provide detailed information on focal pathologies. The large imaging range and improved image penetration at 1050nm wavelengths promises to improve performance for instrumentation which images both the retina and anterior eye. These advantages suggest that swept source OCT at 1050nm wavelengths will play an important role in future ophthalmic instrumentation.National Institutes of Health (U.S.) (5R01-EY011289-23)National Institutes of Health (U.S.) (5R01-EY013178-10)National Institutes of Health (U.S.) (2R01-EY013516-07)National Institutes of Health (U.S.) (1R01-EY019029-02)United States. Air Force Office of Scientific Research (Contract Number FA9550-07-1-0014)United States. Dept. of Defense. Medical Free Electron Laser Program (Contract Number FA9550-07-1-0101