Enhancing sensitivity of high resolution optical coherence tomography using an optional spectrally encoded extended source (Conference Presentation)

The conventional optical coherence tomography (OCT) images based on enhanced scattering and the photothermal (PT) images based on enhanced absorption of the localized surface plasmon (LSP) resonance of Au nanorings (NRIs) in a bio-tissue sample are demonstrated with the scans of an OCT system (1310-nm system), in which the spectral range covers the LSP resonance peak wavelength, and another OCT system (1060-nm system), in which the spectral range is away from the LSP resonance peak wavelength. A PT image is formed by evaluating the modulation frequency (400 Hz) response of an excitation laser with its wavelength (1308 nm) close to the LSP resonance peak at 1305 nm of the Au NRI solution. With the scan of the 1310-nm OCT system, the Au NRI distribution in the bio-tissue sample can be observed in both conventional OCT and PT images. However, with the scan of the 1060-nm OCT system, the Au NRI distribution can be clearly observed only in the PT image. The diffusion process of Au NRIs in the bio-tissue sample can be traced with the scan of either OCT system. Based on phantom experiments, it is shown that the PT image can help in resolving the ambiguity of a conventional OCT image between the enhanced scattering of Au NRIs and the strong scattering of a tissue structure in the 1310-nm OCT scanning. Also, under the condition of weak intrinsic sample scattering, particularly in the scan of the 1060-nm system, the PT signal can be lower than a saturating level, which is determined by the excitation power. By increasing OCT system signal-to-noise ratio or M-mode scan time, the PT signal level can be enhanced.

Conventional optical coherence tomography (OCT) systems generally have a limited imaging range within a depth of only 1-2 mm and suffers from unwanted noise such as speckle, ghost or mirror noise. To overcome these limitations, we developed a motorized-stage-based OCT system with an extended imaging range, using a common-path Fourier-domain optical coherence tomography (CP-FD-OCT) configuration. Using this OCT systems, OCT image was obtained from an onion, and their subsurface structure were observed. The result showed that the OCT images obtained using our motorized-stage-based system had a significantly extended imaging range due to its real-time accurate depth tracking. Consequently, the devised CP-FD-OCT systems and algorithms have good potential for the further development of endoscopic OCT for microsurgery.

Recent developments in Optical Coherence Tomography (OCT) allow measurements of cochlear motions through the bony cochlear wall without holes at spatial resolutions approaching about 10 µm. Measurements to date have been made with custom OCT systems with long development times. We present measurements made with a commercial OCT system driven by custom software (VibOCT) that facilitates near real-time frequency response measurements. The 905-nm wavelength laser and high-speed (100 kHz) camera provide higher axial resolution (3 µm in air) and temporal resolution than previous studies and a sub-nanometer noise floor in air. We gathered anatomical images of the gerbil cochlear apex in vivo at higher resolution than available previously, sufficient to resolve individual outer hair cells, pillar cells, tunnel of Corti and inner sulcus regions. Images from the 3rd apical turn show a bulging of Reissners membrane in vivo that flattened post-mortem with a concomitant reduction in the distance between the Henson cell border and the stria vascularis wall. Vibrometry of the organ of Corti shows a low-pass characteristic in-vivo and post-mortem with a traveling wave-like phase delay similar to a recent study rather than the sharp tuning seen more basally. This system can provide valuable information on cochlear function, which is also useful for the development of detailed cochlear models of the passive and active gerbil apex.

IMPACT: Despite its importance in systemic diseases such as diabetes, the eye is notably difficult to examine for non-specialists; this study introduces a fully automated approach for eye disease screening, coupling a deep learning algorithm with a robotically-aligned optical coherence tomography system to improve eye care in non-ophthalmology settings. OBJECTIVES/GOALS: This study aims to develop and test a deep learning (DL) method to classify images acquired from a robotically-aligned optical coherence tomography (OCT) system as normal vs. abnormal. The long-term goal of our study is to integrate artificial intelligence and robotic eye imaging to fully automate eye disease screening in diverse clinical settings. METHODS/STUDY POPULATION: Between August and October 2020, patients seen at the Duke Eye Center and healthy volunteers (age ≥18) were imaged with a custom, robotically-aligned OCT (RAOCT) system following routine eye exam. Using transfer learning, we adapted a preexisting convolutional neural network to train a DL algorithm to classify OCT images as normal vs. abnormal. The model was trained and validated on two publicly available OCT datasets and two of our own RAOCT volumes. For external testing, the top-performing model based on validation was applied to a representative averaged B-scan from each of the remaining RAOCT volumes. The model’s performance was evaluated against a reference standard of clinical diagnoses by retina specialists. Saliency maps were created to visualize the areas contributing most to the model predictions. RESULTS/ANTICIPATED RESULTS: The training and validation datasets included 87,697 OCT images, of which 59,743 were abnormal. The top-performing DL model had a training accuracy of 96% and a validation accuracy of 99%. For external testing, 43 eyes of 27 subjects were imaged with the robotically-aligned OCT system. Compared to clinical diagnoses, the model correctly labeled 18 out of 22 normal averaged B-scans and 18 out of 21 abnormal averaged B-scans. Overall, in the testing set, the model had an AUC for the detection of pathology of 0.92, an accuracy of 84%, a sensitivity of 86%, and a specificity of 82%. For the correctly predicted scans, saliency maps identified the areas contributing most to the DL algorithm’s predictions, which matched the regions of greatest clinical importance. DISCUSSION/SIGNIFICANCE OF FINDINGS: This is the first study to develop and apply a DL model to images acquired from a self-aligning OCT system, demonstrating the potential of integrating DL and robotic eye imaging to automate eye disease screening. We are working to translate this technology for use in emergency departments and primary care, where it will have the greatest impact.

We present a three-dimensional (3-D) endoscopic optical coherence tomography (OCT) system based on a dual axis microelectromechanical system (MEMS) mirror. The diameter of MEMS mirror was 1.2 mm and both axes were capable of scanning up to 20° (optical) at greater than 1 kHz with excellent linearity. The MEMS mirror was packaged in a machined acrylic endoscopic housing which provided mechanical protection and electrical interconnects as well as optical alignment of the MEMS device to a focusing GRIN lens. The endoscopic MEMS probe was integrated and tested with both a fiber-based time domain (TD) OCT system and Fourier domain (FD) OCT system. Combining the 2-axis lateral scanning of the MEMS device with an axial scan allowed 3-D volume images to be obtained at a rate of 3 frames/s for the TD system and 7 frames/s for the FD system. In the initial investigations, in vivo 3-D OCT images of a human finger as well as images of animal tissue such as healthy rabbit trachea, normal and cancerous regions of hamster cheek pouch tissue were obtained. These images allowed real-time diagnosis of diseased tissue and also clearly delineated important features and tissue structures.

Optical coherence tomography (OCT) is a noninvasive imaging modality generating cross sectional and volumetric images of translucent samples. In Fourier domain OCT (FD OCT), the depth profile is calculated by a fast Fourier transformation of the interference spectrum, providing speed and SNR advantage and thus making FD OCT well suitable in biomedical applications. The interference spectrum can be acquired spectrally resolved in spectral domain OCT or time-resolved in optical frequency domain imaging (OFDI). Since OCT images still suffer from motion artifacts, especially under in vivo conditions, increased depth scan rates are required. Therefor, the principle of Fourier domain mode locking has been presented by R. Huber et al. circumventing the speed limitations of conventional FD OCT systems. In FDML lasers, a long single mode fiber is inserted in the ring resonator of the laser resulting in an optical round trip time of a few microseconds. Sweeping the wavelength synchronously by a tunable Fabry-Perot filter can provide wavelength sweeps with repetition rates up to a few MHz used for OFDI. Imaging of subpleural lung tissue for investigation of lung dynamics and its elastic properties is a further biomedical application demanding high-speed OCT imaging techniques. For the first time, the visualization of subpleural alveolar structures of a rabbit lung is presented by the use of an FDML-based OCT system enabling repetition rates of 49.5 kHz and 122.6 kHz, respectively.

Optical coherence tomography (OCT) is a novel technique for noninvasive imaging based on low coherence interferometer. In order to get image with high resolution, the highly precise scanning and sample stages are essential. In this study, we develop a new optical fiber type of OCT with a commercial auto-focus device to simultaneously measure refractive index and thickness of a single-layer for demonstration. In order to diminish the measurement error resulting from the slight vibration of the sample or sample stage, we design an auto-focus device into the new OCT system. As compared to the conventional one, the new OCT setup is simpler and processes the data speedily. It is found that the conventional OCT with an auto-focus device would be extremely difficult in controlling stages.

In recent years, optical coherence tomography (OCT) became gained importance in medical disciplines like ophthalmology, due to its noninvasive optical imaging technique with micrometer resolution and short measurement time. It enables e. g. the measurement and visualization of the depth structure of the retina. In other medical disciplines like dermatology, histopathological analysis is still the gold standard for skin cancer diagnosis. The EU-funded project VIAMOS (Vertically Integrated Array-type Mirau-based OCT System) proposes a new type of OCT system combined with micro-technologies to provide a hand-held, low-cost and miniaturized OCT system. The concept is a combination of full-field and full-range swept-source OCT (SS-OCT) detection in a multi-channel sensor based on a micro-optical Mirau-interferometer array, which is fabricated by means of wafer fabrication. This paper presents the study of an experimental proof-of-concept OCT system as a one-channel sensor with bulk optics. This sensor is a Linnik-interferometer type with similar optical parameters as the Mirau-interferometer array. A commercial wavelength tunable light source with a center wavelength at 845nm and 50nm spectral bandwidth is used with a camera for parallel OCT A-Scan detection. In addition, the reference microscope objective lens of the Linnik-interferometer is mounted on a piezo-actuated phase-shifter. Phase-shifting interferometry (PSI) techniques are applied for resolving the conjugate complex artifact and consequently contribute to an increase of image quality and depth range. A suppression ratio of the complex conjugate term of 36 dB is shown and a system sensitivity greater than 96 dB could be measured.

The ability to detect glaucoma progression in a timely manner is crucial for adequate monitoring of the disease. Structural progression commonly precedes functional progression in glaucoma. Optical Coherence Tomography (OCT) is the current gold standard for detecting early structural progression in glaucoma. Spectral domain OCT systems can assess changes in the peripapillary retinal nerve fiber layer (RNFL), macular ganglion cells and their neural processes and optic nerve head simultaneously with high reliability. Commercially available OCT progression software of Cirrus HD-OCT is able to perform both event and trend analysis for all the above structural parameters. Spectralis OCT on the other hand mainly uses trend analysis. In order to fully benefit from these features of the OCT progression analysis, the clinician needs to be familiar with the basics of the analysis software and to understand the shortcomings of the current systems. This chapter presents examples of structural progression on OCT imaging in patients with early, moderate and advanced glaucoma. Progression analyses are provided for peripapillary RNFL, macular ganglion cells, and visual fields in order to familiarize the reader with the OCT progression analysis with a step-by-step approach. Although this chapter is based on Cirrus HD-OCT and Spectralis OCT progression analysis software, it can be helpful to the users of other OCT systems as all the OCT systems use at least one or more methods presented in these sample cases.

In the later years, a great effort has ben put into simulation of the geometry of an optical coherence tomography (OCT) system. Recently, a new analytical model of the OCT geometry has been developed based on the extended Huygens-Fresnel (EHF) principle. Although advanced, the result of the model are surprisingly simple and easy to handle for e.g. system optimization. To validate this model, new features have been added to the Monte Carlo (MC) simulation program MCML, which is widely used and recognized for its credibility. We have incorporated the true shape of a focused Gaussian beam including the finite size of the beam waist, which previously has been approximated by a point. This enables us to do high-resolution comparison of the intensity distribution in the focus plane and excellent agreement is found between the EHF model and the MC simulations. Results are also compared with previously published modeling result and it is shown that there are substantial differences. We emphasize the importance of the so-called shower curtain effect (SCE), which is an inherent - but often overlooked - effect in light propagation through random media. Finally, we calculate the OCT signal using MC simulation. This is done by keeping track of the path length traveled by each photon packet and restricting its access back into the OCT system from the sample using the antenna theorem. The degradation of the detected signal due to scattering is determined, and compared with the EHF model and experiments. The comparison of MC simulations with EHF allows us to show that the SCE is an inherent effect in MC simulation, and that for common tissue parameters, the EHF model yields the same results as the MC simulation but with faster computation time and with field and phase information available.

Optical coherence tomography (OCT) has become a novel approach to noninvasive imaging in the past three decades, bringing a significant potential to biological research and medical biopsy in situ, particularly in three-dimensional (3D) in vivo conditions. Specifically, OCT systems using broad bandwidth sources, mainly centered at near-infrared-II, allow significantly higher imaging depth, as well as maintain a high-resolution and better signal-to-noise ratio than the traditional microscope, which avoids the scattering blur and thus obtains more details from delicate biological structures not just limited to the surface. Furthermore, OCT systems combined the spectrometer with novel light sources, such as multiplexed superluminescent diodes or ultra-broadband supercontinuum laser sources, to obtain sub-micron resolution imaging with high-speed achieve widespread clinical applications. Besides improving OCT performance, the functional extensions of OCT with other designs and instrumentations, taking polarization state or birefringence into account, have further improved OCT properties and functions. We summarized the conventional principle of OCT systems, including time-domain OCT, Fourier-domain OCT, and several typical OCT extensions, compared their different components and properties, and analyzed factors that affect OCT performance. We also reviewed current applications of OCT in the biomedical field, especially in hearing science, discussed existing limitations and challenges, and looked forward to future development, which may provide a guideline for those with 3D in vivo imaging desires.

To determine whether optical coherence tomography (OCT) device-type influences clinical grading of OCT imaging in the context of exudative age-related macular degeneration (AMD). Ninety-six paired OCT scans from 49 patients with active exudative AMD were obtained on both the time-domain Stratus OCT system and the spectral-domain Cirrus OCT system at the same visit. Three independent graders judged each scan for the presence of intraretinal fluid (IRF) or subretinal fluid (SRF). The degree of grader consensus was evaluated and the ability of the systems to detect the presence of disease activity was analysed. Cirrus OCT generated a higher degree of inter-grader consensus than Stratus OCT with higher intraclass correlation coefficients for all parameters analysed. A pair-wise comparison of Cirrus OCT with Stratus OCT systems revealed that Cirrus-based gradings more frequently reported the presence of SRF and IRF and detected overall neovascular activity at a higher rate (P<0.05) compared with Stratus-based gradings. The choice of time-domain (Stratus) vs spectra-domain (Cirrus) OCT systems has a measurable impact on clinical decision making in exudative AMD. Spectral-domain OCT systems may be able to generate more consensus in clinical interpretation and, in particular cases, detect disease activity not detected by time-domain systems. Clinical trials using OCT-based clinical evaluations of exudative AMD may need to account for these inter-system differences in planning and analysis.

Comparative Study of Conventional and Ultrahigh-resolution Optical Coherence Tomography Imaging in Esophageal Neoplasia

We develop a high-speed tunable, quasi-continuous-wave laser source for frequency domain (FD) optical coherence tomography (OCT). The laser resonance is realized within a unidirectional all-fiber ring cavity consisting of a fiber coupler, two fiber isolators, a semiconductor optical amplifier (SOA), and a fiber Fabry-Perot tunable filter (FFP-TF) for frequency tuning. Light output from the coupler is further amplified and spectral shaped by a booster SOA terminated at both ends with two isolators. The developed laser source provides up to 8000 sweeps per second over a full-width wavelength tuning range of 120 nm at center wavelength of 1320 nm with an average power of 9 mW, yielding an axial resolution of 13.6 \mu m in air and a maximum sensitivity of about 112 dB for OCT imaging. The instantaneous linewidth is about 0.08 nm, enabling OCT imaging over an axial range of 3.4 mm in air. For optimization consideration based on this custom-built swept laser, experimental study on imaging quality relevant parameters of the swept laser with sine and ramp driving waveforms to the FFP-TF is conducted, and investigation of the swept laser on the cavity length is done. Implementing the laser source in our established swept source based OCT (SS-OCT) system, real-time structural imaging of biological tissue is demonstrated.

Fluorescence loss in enamel following demineralization has been correlated with the amount of mineral lost during the demineralization. The correlation between fluorescence loss measured by quantitative light-induced fluorescence (QLF) and the reflectivity loss measured by a versatile en face optical coherence tomography (OCT) system was investigated in a demineralization process to produce artificial dental caries. We used an OCT system that can collect A-scans (reflectivity versus depth), B-scans (longitudinal images), and C-scans (en face images). The power to the sample was 250 microW, the wavelength lambda = 850 nm, and the depth resolution in air 16 microm. A-scans, which show the profile of the reflectivity versus the depth of penetration into the tooth tissue, were used for quantitative analysis of the reflectivity loss. The results have shown that both the fluorescence radiance and reflectivity of the enamel decrease with increasing de- mineralization time. A linear correlation was observed between the percentage of fluorescence loss measured by QLF and the percentage of reflectivity loss measured by OCT. It was concluded that the decrease in reflectivity of the enamel during demineralization, measured by OCT, could be related to the amount of mineral lost during the de- mineralization process.