Multi-channel delay sampling to extend imaging depth in high-speed swept-source OCT systems.

We present a multi-channel delay sampling method to extend imaging depth in high-speed swept-source optical coherence tomography (SS-OCT). A balanced detector captures interference signals, converting them into electrical signals, which are then split into N channels, each with fixed time delays determined by the length of electrical cables. Then, they are digitized by an N-channel acquisition card. A calibration procedure is utilized to compensate for non-uniform phase shifts resulting from fixed time delays. The N-channel signals are merged in k-space and resampled to obtain a linearized spectrum, which increases the sampling rate by a factor of N, thereby extending the ranging distance by N times, all without altering k-clock triggering or sacrificing other imaging performance. The signal-to-noise ratio and sensitivity within the original depth range also have been enhanced. This advancement contributes to the improvement of the overall performance of SS-OCT systems.

Midwave resonant cavity infrared detectors (RCIDs) with suppressed background noise.

We report a resonant cavity infrared detector (RCID) with an InAsSb/InAs superlattice absorber with a thickness of only ≈ 100 nm, a 33-period GaAs/Al0.92Ga0.08As distributed Bragg reflector bottom mirror, and a Ge/SiO2/Ge top mirror. At a low bias voltage of 150 mV, the external quantum efficiency (EQE) reaches 58% at the resonance wavelength λres ≈ 4.6 µm, with linewidth δλ = 19-27 nm. The thermal background current for a realistic system scenario with f/4 optic that views a 300 K scene is estimated by integrating the photocurrent generated by background spanning the entire mid-IR spectral band (3-5 µm). The resulting specific detectivity is a factor of 3 lower than for a state-of-the-art broadband HgCdTe device at 300 K, where dark current dominates the noise. However, at 125 K where the suppression of background noise becomes critical, the estimated specific detectivity D* of 5.5 × 1012 cm Hz½/W is more than 3× higher. This occurs despite a non-optimal absorber cut-off that causes the EQE to decrease rapidly with decreasing temperature, e.g., to 33% at 125 K. The present RCID's advantage over the broadband device depends critically on its low EQE at non-resonance wavelengths: ≤ 1% in the range 3.9-5.5 µm. Simulations using NRL MULTIBANDS indicate that impact ionization in the bottom contact and absorber layers dominates the dark current at near ambient temperatures. We expect future design modifications to substantially enhance D* throughout the investigated temperature range of 100-300 K.

Low-power swept-source Raman spectroscopy.

'Molecular fingerprinting' with Raman spectroscopy can address important problems-from ensuring our food safety, detecting dangerous substances, to supporting disease diagnosis and management. However, the broad adoption of Raman spectroscopy demands low-cost, portable instruments that are sensitive and use lasers that are safe for human eye and skin. This is currently not possible with existing Raman spectroscopy approaches. Portability has been achieved with dispersive Raman spectrometers, however, fundamental entropic limits to light collection both limits sensitivity and demands high-power lasers and cooled expensive detectors. Here, we demonstrate a swept-source Raman spectrometer that improves light collection efficiency by up to 1000× compared to portable dispersive spectrometers. We demonstrate high detection sensitivity with only 1.5 mW average excitation power and an uncooled amplified silicon photodiode. The low optical power requirement allowed us to utilize miniature chip-scale MEMS-tunable lasers with close to eye-safe optical powers for excitation. We characterize the dynamic range and spectral characteristics of this Raman spectrometer in detail, and use it for fingerprinting of different molecular species consumed everyday including analgesic tablets, nutrients in vegetables, and contaminated alcohol. By moving the complexity of Raman spectroscopy from bulky spectrometers to chip-scale light sources, and by replacing expensive cooled detectors with low-cost uncooled alternatives, this swept-source Raman spectroscopy technique could make molecular fingerprinting more accessible.

Assessment of Barrett's esophagus and dysplasia with ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography.

BACKGROUND: This study aimed to evaluate the use of ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography (OCT) with micromotor catheters for the in vivo assessment of Barrett's esophagus and dysplasia. METHODS: 74 OCT datasets with correlated biopsy/endoscopic mucosal resection histology (49 nondysplastic Barrett's esophagus [NDBE], 25 neoplasia) were obtained from 14 patients with Barrett's esophagus and a history of dysplasia and 30 with NDBE. The associations between irregular mucosal patterns on en face OCT, absence of mucosal layering, surface signal > subsurface, and > 5 atypical glands on cross-sectional OCT vs. histology and treatment history were assessed by three blinded readers. RESULTS: Atypical glands under irregular mucosal patterns occurred in 75 % of neoplasia (96 % of treatment-naïve neoplasia) vs. 30 % of NDBE datasets (43 % of short- and 18 % of long-segment NDBE). Mucosal layering was absent in 35 % of neoplasia and 50 % of NDBE datasets, and surface signal > subsurface occurred in 29 % of neoplasia and 30 % of NDBE datasets. CONCLUSIONS: Atypical glands under irregular mucosal patterns are strongly associated with neoplasia, suggesting potential markers for dysplasia and a role in pathogenesis.

Endoscopic forward-viewing optical coherence tomography and angiography with MHz swept source.

Endoscopic optical coherence tomography (OCT) instruments are mostly side viewing and rely on at least one proximal scan, thus limiting accuracy of volumetric imaging and en face visualization. Previous forward-viewing OCT devices had limited axial scan speeds. We report a forward-viewing fiber scanning 3D-OCT probe with 900 µm field of view and 5 µm transverse resolution, imaging at 1 MHz axial scan rate in the human gastrointestinal tract. The probe is 3.3 mm diameter and 20 mm rigid length, thus enabling passage through the endoscopic channel. The scanner has 1.8 kHz resonant frequency, and each volumetric acquisition takes 0.17 s with 2 volumes/s display. 3D-OCT and angiography imaging of the colon was performed during surveillance colonoscopy.

ULTRAHIGH SPEED SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL AND CHORIOCAPILLARIS ALTERATIONS IN DIABETIC PATIENTS WITH AND WITHOUT RETINOPATHY.

PURPOSE: To investigate the utility of ultrahigh speed, swept source optical coherence tomography angiography in visualizing retinal microvascular and choriocapillaris (CC) changes in diabetic patients. METHODS: The study was prospective and cross-sectional. A 1,050 nm wavelength, 400 kHz A-scan rate swept source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography of the retinal and CC vasculatures in diabetic patients and normal subjects. Sixty-three eyes from 32 normal subjects, 9 eyes from 7 patients with proliferative diabetic retinopathy, 29 eyes from 16 patients with nonproliferative diabetic retinopathy, and 51 eyes from 28 diabetic patients without retinopathy were imaged. RESULTS: Retinal and CC microvascular abnormalities were observed in all stages of diabetic retinopathy. In nonproliferative diabetic retinopathy and proliferative diabetic retinopathy, optical coherence tomography angiography visualized a variety of vascular abnormalities, including clustered capillaries, dilated capillary segments, tortuous capillaries, regions of capillary dropout, reduced capillary density, abnormal capillary loops, and foveal avascular zone enlargement. In proliferative diabetic retinopathy, retinal neovascularization above the inner limiting membrane was visualized. Regions of CC flow impairment in patients with proliferative diabetic retinopathy and nonproliferative diabetic retinopathy were also observed. In 18 of the 51 of eyes from diabetic patients without retinopathy, retinal mircrovascular abnormalities were observed and CC flow impairment was found in 24 of the 51 diabetic eyes without retinopathy. CONCLUSION: The ability of optical coherence tomography angiography to visualize retinal and CC microvascular abnormalities suggests it may be a useful tool for understanding pathogenesis, evaluating treatment response, and earlier detection of vascular abnormalities in patients with diabetes.

Ultrahigh-Speed, Swept-Source Optical Coherence Tomography Angiography in Nonexudative Age-Related Macular Degeneration with Geographic Atrophy.

PURPOSE: To investigate ultrahigh-speed, swept-source optical coherence tomography (SSOCT) angiography for visualizing vascular changes in eyes with nonexudative age-related macular degeneration (AMD) with geographic atrophy (GA). DESIGN: Observational, prospective, cross-sectional study. PARTICIPANTS: A total of 63 eyes from 32 normal subjects and 12 eyes from 7 patients with nonexudative AMD with GA. METHODS: A 1050-nm, 400-kHz A-scan rate SSOCT system was used to perform volumetric optical coherence tomography angiography (OCTA) of the retinal and choriocapillaris (CC) vasculatures in normal subjects and patients with nonexudative AMD with GA. Optical coherence tomography angiography using variable interscan time analysis (VISTA) was performed to assess CC alteration and differentiate varying degrees of CC flow impairment. MAIN OUTCOME MEASURES: Qualitative comparison of retinal and CC vasculatures in normal subjects versus those in patients with a clinical diagnosis of nonexudative AMD with GA. RESULTS: In all 12 eyes with GA, OCTA showed pronounced CC flow impairment within the region of GA. In 10 of the 12 eyes with GA, OCTA with VISTA showed milder CC flow impairment extending beyond the margin of GA. Of the 5 eyes exhibiting foveal-sparing GA, OCTA showed CC flow within the region of foveal sparing in 4 of the eyes. CONCLUSIONS: The ability of ultrahigh-speed, swept-source OCTA to noninvasively visualize alterations in the retinal and CC vasculatures makes it a promising tool for assessing nonexudative AMD with GA. Optical coherence tomography angiography using VISTA can distinguish varying degrees of CC alteration and flow impairment and may be useful for elucidating disease pathogenesis, progression, and response to therapy.

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

In this paper, we present a 1050 nm electrically-pumped micro-electro-mechanically-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 & 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 & 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 meters ± 51 meters, far greater than required for ophthalmic SS-OCT and suggestive of other distance ranging applications.

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.

Swept source optical coherence microscopy using a 1310 nm VCSEL light source.

We demonstrate high speed, swept source optical coherence microscopy (OCM) using a MEMS tunable vertical cavity surface-emitting laser (VCSEL) light source. The light source had a sweep rate of 280 kHz, providing a bidirectional axial scan rate of 560 kHz. The sweep bandwidth was 117 nm centered at 1310 nm, corresponding to an axial resolution of 13.1 µm in air, corresponding to 8.1 µm (9.6 µm spectrally shaped) in tissue. Dispersion mismatch from different objectives was compensated numerically, enabling magnification and field of view to be easily changed. OCM images were acquired with transverse resolutions between 0.86 µm - 3.42 µm using interchangeable 40X, 20X and 10X objectives with ~600 µm x 600 µm, ~1 mm x 1 mm and ~2 mm x 2 mm field-of-view (FOV), respectively. Parasitic variations in path length with beam scanning were corrected numerically. These features enable swept source OCM to be integrated with a wide range of existing scanning microscopes. Large FOV mosaics were generated by serially acquiring adjacent overlapping microscopic fields and combining them in post-processing. Fresh human colon, thyroid and kidney specimens were imaged ex vivo and compared to matching histology sections, demonstrating the ability of OCM to image tissue specimens.

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.

Phase-sensitive swept-source optical coherence tomography imaging of the human retina with a vertical cavity surface-emitting laser light source.

Despite the challenges in achieving high phase stability, Doppler swept-source/Fourier-domain optical coherence tomography (OCT) has advantages of less fringe washout and faster imaging speeds compared to spectral/Fourier-domain detection. This Letter demonstrates swept-source OCT with a vertical cavity surface-emitting laser light source at 400 kHz sweep rate for phase-sensitive Doppler imaging, measuring pulsatile total retinal blood flow with high sensitivity and phase stability. A robust, simple, and computationally efficient phase stabilization approach for phase-sensitive swept-source imaging is also presented.

Multi-MHz MEMS-VCSEL swept-source optical coherence tomography for endoscopic structural and angiographic imaging with miniaturized brushless motor probes.

Swept source optical coherence tomography (SS-OCT) enables volumetric imaging of subsurface structure. However, applications requiring wide fields of view (FOV), rapid imaging, and higher resolutions have been challenging because multi-MHz axial scan (A-scan) rates are needed. We describe a microelectromechanical systems vertical cavity surface-emitting laser (MEMS-VCSEL) SS-OCT technology for A-scan rates of 2.4 and 3.0 MHz. Sweep to sweep calibration and resampling are performed using dual channel acquisition of the OCT signal and a Mach Zehnder interferometer signal, overcoming inherent optical clock limitations and enabling higher performance. We demonstrate ultrahigh speed structural SS-OCT and OCT angiography (OCTA) imaging of the swine gastrointestinal tract using a suite of miniaturized brushless motor probes, including a 3.2 mm diameter micromotor OCT catheter, a 12 mm diameter tethered OCT capsule, and a 12 mm diameter widefield OCTA probe. MEMS-VCSELs promise to enable ultrahigh speed SS-OCT with a scalable, low cost, and manufacturable technology, suitable for a diverse range of imaging applications.

Microscope-Integrated Intraoperative Ultrahigh-Speed Swept-Source Optical Coherence Tomography for Widefield Retinal and Anterior Segment Imaging.

BACKGROUND AND OBJECTIVE: To demonstrate the feasibility of retinal and anterior segment intraoperative widefield imaging using an ultrahigh-speed, swept-source optical coherence tomography (SS-OCT) surgical microscope attachment. PATIENTS AND METHODS: A prototype post-objective SS-OCT using a 1,050-nm wavelength, 400 kHz A-scan rate, vertical cavity surface-emitting laser (VCSEL) light source was integrated to a commercial ophthalmic surgical microscope after the objective. Each widefield OCT data set was acquired in 3 seconds (1,000 × 1,000 A-scans, 12 × 12 mm2 for retina and 10 × 10 mm2 for anterior segment). RESULTS: Intraoperative SS-OCT was performed in 20 eyes of 20 patients. In six of seven membrane peels and five of seven rhegmatogenous retinal detachment repair surgeries, widefield retinal imaging enabled evaluation pre- and postoperatively. In all seven cataract cases, anterior imaging evaluated the integrity of the posterior lens capsule. CONCLUSIONS: Ultrahigh-speed SS-OCT enables widefield intraoperative viewing in the posterior and anterior eye. Widefield imaging visualizes ocular structures and pathology without requiring OCT realignment. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:94-102.].

Cycloid scanning for wide field optical coherence tomography endomicroscopy and angiography in vivo.

Devices that perform wide field-of-view (FOV) precision optical scanning are important for endoscopic assessment and diagnosis of luminal organ disease such as in gastroenterology. Optical scanning for in vivo endoscopic imaging has traditionally relied on one or more proximal mechanical actuators, limiting scan accuracy and imaging speed. There is a need for rapid and precise two-dimensional (2D) microscanning technologies to enable the translation of benchtop scanning microscopies to in vivo endoscopic imaging. We demonstrate a new cycloid scanner in a tethered capsule for ultrahigh speed, side-viewing optical coherence tomography (OCT) endomicroscopy in vivo. The cycloid capsule incorporates two scanners: a piezoelectrically actuated resonant fiber scanner to perform a precision, small FOV, fast scan and a micromotor scanner to perform a wide FOV, slow scan. Together these scanners distally scan the beam circumferentially in a 2D cycloid pattern, generating an unwrapped 1 mm × 38 mm strip FOV. Sequential strip volumes can be acquired with proximal pullback to image centimeter-long regions. Using ultrahigh speed 1.3 µm wavelength swept-source OCT at a 1.17 MHz axial scan rate, we imaged the human rectum at 3 volumes/s. Each OCT strip volume had 166 × 2322 axial scans with 8.5 µm axial and 30 µm transverse resolution. We further demonstrate OCT angiography at 0.5 volumes/s, producing volumetric images of vasculature. In addition to OCT applications, cycloid scanning promises to enable precision 2D optical scanning for other imaging modalities, including fluorescence confocal and nonlinear microscopy.

Cubic meter volume optical coherence tomography.

Optical coherence tomography (OCT) is a powerful three-dimensional (3D) imaging modality with micrometer-scale axial resolution and up to multi-GigaVoxel/s imaging speed. However, the imaging range of high-speed OCT has been limited. Here, we report 3D OCT over cubic meter volumes using a long coherence length, 1310 nm vertical-cavity surface-emitting laser and silicon photonic integrated circuit dual-quadrature receiver technology combined with enhanced signal processing. We achieved 15 µm depth resolution for tomographic imaging at a 100 kHz axial scan rate over a 1.5 m range. We show 3D macroscopic imaging examples of a human mannequin, bicycle, machine shop gauge blocks, and a human skull/brain model. High-bandwidth, meter-range OCT demonstrates new capabilities that promise to enable a wide range of biomedical, scientific, industrial, and research applications.

Circumferential optical coherence tomography angiography imaging of the swine esophagus using a micromotor balloon catheter.

We demonstrate a micromotor balloon imaging catheter for ultrahigh speed endoscopic optical coherence tomography (OCT) which provides wide area, circumferential structural and angiographic imaging of the esophagus without contrast agents. Using a 1310 nm MEMS tunable wavelength swept VCSEL light source, the system has a 1.2 MHz A-scan rate and ~8.5 µm axial resolution in tissue. The micromotor balloon catheter enables circumferential imaging of the esophagus at 240 frames per second (fps) with a ~30 µm (FWHM) spot size. Volumetric imaging is achieved by proximal pullback of the micromotor assembly within the balloon at 1.5 mm/sec. Volumetric data consisting of 4200 circumferential images of 5,000 A-scans each over a 2.6 cm length, covering a ~13 cm(2) area is acquired in <18 seconds. A non-rigid image registration algorithm is used to suppress motion artifacts from non-uniform rotational distortion (NURD), cardiac motion or respiration. En face OCT images at various depths can be generated. OCT angiography (OCTA) is computed using intensity decorrelation between sequential pairs of circumferential scans and enables three-dimensional visualization of vasculature. Wide area volumetric OCT and OCTA imaging of the swine esophagus in vivo is demonstrated.

Choroidal Neovascularization Analyzed on Ultrahigh-Speed Swept-Source Optical Coherence Tomography Angiography Compared to Spectral-Domain Optical Coherence Tomography Angiography.

PURPOSE: To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device. DESIGN: Comparative analysis of diagnostic instruments. METHODS: Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of <.05 were considered statistically significant. RESULTS: Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type 1, 2 eyes (14.3%) as type 2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS OCT and SD OCT 3 mm × 3 mm OCTA were 0.949 ± 1.168 mm(2) and 0.340 ± 0.301 mm(2), respectively (P = .001). For the 6 mm × 6 mm OCTA the total CNV area using SS OCT and SD OCT were 1.218 ± 1.284 mm(2) and 0.604 ± 0.597 mm(2), respectively (P = .0019). The field of view did not significantly affect the measured CNV area (P = .19 and P = .18 for SS OCT and SD OCT, respectively). CONCLUSION: SS OCTA yielded significantly larger CNV areas than SD OCTA. It is possible that SS OCTA is better able to demarcate the full extent of CNV vasculature.