All-fiber ring-cavity based frequency swept laser source for frequency domain OCT

Optical coherence tomography (OCT) has become a useful and common diagnostic tool within the field of ophthalmology. Although presently a commercial technology, research continues in improving image quality and applying the imaging method to other tissue types. Swept-wavelength lasers based upon fiber ring cavities containing fiber Fabry-P´erot tunable filters (FFP-TF), as an intracavity element, provide swept-source optical coherence tomography (SS-OCT) systems with a robust and scalable platform. The FFP-TF can be fabricated within a large range of operating wavelengths, free spectral ranges (FSR), and finesses. To date, FFP-TFs have been fabricated at operating wavelengths from 400 nm to 2.2 µm, FSRs as large as 45 THz, and finesses as high as 30 000. The results in this paper focus on presenting the capability of the FFP-TF as an intracavity element in producing swept-wavelength lasers sources and quantifying the trade off between coherence length and sweep range. We present results within a range of feasible operating conditions. Particular focus is given to the discovery of laser configurations that result in maximization of sweep range and/or power. A novel approach to the electronic drive of the PZT-based FFP-TF is also presented, which eliminates the need for the existence of a mechanical resonance of the optical device. This approach substantially increases the range of drive frequencies with which the filter can be driven and has a positive impact for both the short all-fiber laser cavity (presented in this paper) and long cavity FDML designs as well.

Three-Dimensional Optical Coherence Tomography on Endoscopic Mucosal Resection Specimens Confirms Identification of Malignant From Metaplastic Lesions in Patients With Barrett's Esophagus

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.

The conventional approach for diagnosing dental caries is clinical examination and supplemented by radiographs. However, studies based on the clinical and radiographic examination methods often show low sensitivity and high specificity. Machine learning and deep learning techniques can be used to enhance optical coherence tomography (OCT) to more accurately identify diseased and damaged tissue. In this paper, we present a novel approach combining OCT imaging modality and deep convolutional neural network (CNN) for the detection of occlusal carious lesions. A total of 51 extracted human permanent teeth were collected and categorized into three groups: Non-carious teeth, caries extending into enamel, and caries extending into dentin. In data acquisition and ex-vivo OCT imaging, the samples were imaged using spectral-domain OCT system operating at 1300nm center wavelength with a scan rate of 5.5-76kHz, and axial resolution of 5.5μm in air. To acquire images with minimum inhomogeneity, imaging was performed multiple times at different points. For deep learning, OCT images of extracted human carious and non-carious teeth were input to a CNN classifier to determine variations in tissue densities resembling the demineralization process. The CNN model employs two convolutional and pooling layers to extract features and then classify each patch based on the probabilities from the SoftMax classification layer. The sensitivity and specificity of distinguishing between carious and non-carious lesions were found to be 98% and 100%, respectively. This proposed deep learning-based OCT method can reliably classify the oral tissues with various densities, and could be extremely valuable in early dental caries detection.

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.

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.

Previous studies have demonstrated that optical coherence tomography (OCT) could be used to delineate alterations in the microstructure of cartilage, and have suggested that changes in the polarization state of light as detected by OCT could provide information on the birefringence properties of articular cartilage as influenced by disease. In this study we have used both OCT and polarization sensitive optical coherence tomography (PS-OCT) technologies to evaluate normal and abnormal bovine articular cartilage according to established structural, organizational, and birefringent characteristics of degenerative joint disease (DJD) in order to determine if this technology can be used to differentiate various stages of DJD as a minimally invasive imaging tool. Fresh bovine femoral-tibial joints were obtained from an abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole ex vivo specimens of normal and degenerative articular cartilage were imaged by both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS-OCT images and corresponding histology sections of each specimen were scored according to a modified Mankin structural grading scale and compared. OCT and PS-OCT imaging allowed structural evaluation of intact articular cartilage along a 6 mm surface length to a depth of 2 mm with a transverse resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT images demonstrated characteristic alterations in the structure of articular cartilage with a high correlation to histological evaluation (kappa = 0.776). The OCT images were able to demonstrate early to advanced structural changes of articular cartilage while the optical phase retardation images obtained by PS-OCT imaging were able to discriminate areas where disorganization of the cartilage matrix was present, however, these characteristics are much different than those reported where OCT images alone were used to characterize tissue birefringence. No evidence of differences in OCT or PS-OCT images were detected between specimens of similar structural characteristics where proteoglycan was judged present or absent by safranin-O Fast Green staining. The combined use of OCT and PS-OCT technologies to obtain images from a single system is able to demonstrate and discriminate between characteristics of very early stages of surface irregularities not previously reported for OCT imaging, to deep clefts and collagen matrix disorganization for tissue at depths of up to 2 mm with good correlation to histology. PS-OCT and accumulated optical phase retardation images of articular cartilage as constructed from alterations in Stokes vector parameters appear to give a valuable but different assessment of alterations in tissue birefringence and organization than have been reported for OCT images obtained with the use of polarized or non-polarized light sources. This is the first time that alterations in the polarization state of light reflected from within the tissue have been demonstrated to be consistent with changes observed in the orientation and organization of the collagen matrix in advanced stages of DJD. The degree of phase transformation of light reflected from within the tissue as determined by PS-OCT imaging does not appear to be altered by the presence or absence of proteoglycan.

Objective To observe the features of frequency domain optical coherence tomography (FD-OCT) in acute central serous chorioretinopathy (CSC).Methods The data of FD-OCT and fundus fluorescein angiography (FFA) of 31 patients with unilateral acute CSC were retrospectively analyzed.The FD-OCT of retinal pigment epithelial (RPE) layer at leakage points, retinal detachment area and RPE layer in the fellow eyes was documented.Results Thirty-four leakage points were detected in 31 eyes on FFA.At the sites of fluorescein leakage, FD-OCT showed that serous pigment epithelial detachment (PED) in 18leakage points (52.9%) and 17 eyes (54.8%), a small RPE protrusion in 8 leakage points (23.5%) and 8eyes (25.8%), RPE irregularity in 6 leakage points (17.6%) and 4 eyes (12.9%) and no detectable RPE abnormality in 2 leakage points (5.9%) and 2 eyes (6.5%).An RPE defect at the edge of or within the fPED was found in 7 leakage points (20.6%) and 7 eyes (22.6%).Serous retinal detachment and interruption or complete disappearance of the hyper-reflective inner/outer segment junction (IS/OS) were detected in all diseased eyes.Uneven thickness of the outer segments (OS) was found in 24 eyes (77.4%),14 of which had sagging sign.Flaking of the OS was found in 10 eyes (32.3%), multiple hyper-reflective dots on the posterior surface of the detached neurosensory retina and on the surface of the RPE were found in 8 eyes (25.8%).Among 31 fellow eyes, FD-OCT also showed RPE abnormalities in 11 eyes (35.5%),in which PED, RPE protrusion and RPE irregularity were detected in 2 (6.5%), 1 (3.2%) and 8 eyes (25.8%), respectively.Conclusions In acute CSC the FD-OCT images at leakage points of are featured by PED, RPE protrusion, RPE irregularity and no detectable RPE abnormality; in retinal detachment area FD-OCT are featured by serous retinal detachment, interruption or disappearance of IS/OS, uneven thickness of OS, flaking of OS and hyper-reflective dots on the posterior surface of the detached neurosensory retina and on the surface of the RPE. Key words: Retinal diseases/ diagnosis; Choroid diseases/ diagnosis; Pigment epithelium of eye; Tomography, optical coherence; Diagnostic imaging

Complete characterization of a layered tissue requires probing both the biochemical and the morphological information from its different layers at various depths. We report the development of a combined Raman spectroscopy (RS) and optical coherence tomography (OCT) system that is capable of measuring depth-sensitive Raman signal from the tissue layers imaged by the OCT. The sample arm of a real-time time-domain OCT system was modified to allow for co-alignment of the OCT with the Raman probe beam. The depth sensitivity of Raman was obtained by incorporating confocal Raman configuration that minimized out-of-focus Raman scattered light. The system was first validated using a layered phantom prepared by depositing a thin layer of paraffin over acetaminophen. A good correlation was observed between the OCT images and the Raman signal. The system was also used to record OCT and Raman images of a resected mucosal tissue sample. While OCT image showed the presence of epithelial and stromal layers, Raman spectra measured from these layers confirmed the biochemical difference between the two.

The purpose of this single centre registry is to assess safety and feasibility of the frequency domain optical coherence tomography (FD-OCT) system during coronary interventions. Ninety patients with unstable or stable coronary artery disease were included in this study. OCT imaging was performed in a first group of 40 patients (group 1), to evaluate ambiguous/intermediate lesions (24 patients in group 1 had OCT also done post-PCI, for assessment of stent deployment); and in a second group of 50 patients (group 2), to address the adequacy of stent deployment. Therefore, 74 patients underwent FD-OCT after stent implantation. A complex-lesion population was studied (B2 type lesion=72.2% and C type lesion=20.3%). The mean time of a FD-OCT pull-back (from the set up to the completion of the pull back) was 2.1 min and in all but one (99.1%) the procedure was successful. No patients experienced major complications in terms of death, myocardial infarction, emergency revascularisation, embolisation, life-threatening arrhythmia, coronary dissection, prolonged and severe vessel spasm and contrast induced nephropathy. In the ambiguous lesion group, 60% of patients were treated with PCI, whilst in the others, PCI were deferred. In total, 113 deployed stents (33,6% chromium cobalt stent, 66,4% drug eluting stent) were imaged with OCT. OCT findings led to additional interventions in 24 out of 74 patients (32%): 15 had further balloon inflations, nine had additional stent deployment whilst two had both treatments. At clinical follow-up, (4.6 ± 3.,2 months), there were no death, acute myocardial infarctions and cases of stent thrombosis, whilst two patients underwent revascularisation for recurrence of angina. The present registry shows that FD-OCT is a feasible and safe technique for guidance of coronary interventions. Randomised studies will confirm whether the use of FD-OCT will improve the clinical outcome.

Microaneurysms (MAs) are pathognomonic signs that help clinicians to detect diabetic retinopathy (DR) in the early stages. Automatic detection of MA in retinal images is an active area of research due to its application in screening processes for DR which is one of the main reasons of blindness amongst the working-age population. The focus of these works is on the automatic detection of MAs in en face retinal images like fundus color and Fluorescein Angiography (FA). On the other hand, detection of MAs from Optical Coherence Tomography (OCT) images has 2 main advantages: first, OCT is a non-invasive imaging technique that does not require injection, therefore is safer. Secondly, because of the proven application of OCT in detection of Age-Related Macular Degeneration, Diabetic Macular Edema, and normal cases, thanks to detecting MAs in OCT, extensive information is obtained by using this imaging technique. In this research, the concentration is on the diagnosis of MAs using deep learning in the OCT images which represent in-depth structure of retinal layers. To this end, OCT B-scans should be divided into strips and MA patterns should be searched in the resulted strips. Since we need a dataset comprising OCT image strips with suitable labels and such large labelled datasets are not yet available, we have created it. For this purpose, an exact registration method is utilized to align OCT images with FA photographs. Then, with the help of corresponding FA images, OCT image strips are created from OCT B-scans in four labels, namely MA, normal, abnormal, and vessel. Once the dataset of image strips is prepared, a stacked generalization (stacking) ensemble of four fine-tuned, pre-trained convolutional neural networks is trained to classify the strips of OCT images into the mentioned classes. FA images are used once to create OCT strips for training process and they are no longer needed for subsequent steps. Once the stacking ensemble model is obtained, it will be used to classify the OCT strips in the test process. The results demonstrate that the proposed framework classifies overall OCT image strips and OCT strips containing MAs with accuracy scores of 0.982 and 0.987, respectively.

High-Definition and 3-dimensional Imaging of Macular Pathologies with High-speed Ultrahigh-Resolution Optical Coherence Tomography

To investigate morphological variations in the macular area with optical coherence tomography (OCT) after vitrectomy for diabetic fibrovascular proliferation. We reviewed 108 cases using OCT 7-15 months after vitrectomy. Of these, 32 received OCT within 3 months postoperatively. Morphological variations were categorized and correlated with visual outcome. Only 24 cases (21.4%) had no obvious abnormalities. The most frequent findings were epiretinal membrane (52.8%), macular thickening (37.0%) and macular cysts (28.7%). Multivariate regression showed that diffuse macular thickening, loss of foveal depression and diffuse retinal thinning were significantly associated with poor visual acuity. Sequential OCT (< 3 and >or= 7 months) revealed that epiretinal membrane and oedema outside of fovea changed significantly between two examinations. OCT may identify diverse morphological changes in the macular area after diabetic vitrectomy for fibrovascular proliferation. Macular appearance may change over time, and certain types of morphological changes may be associated with poor visual function.

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.

This study presents a time-stretched wavelength-swept laser source based on stretched-pulse mode-locking. A broadband semiconductor optical amplifier (SOA) technology is used as an optical gain element. The laser comprises a unidirectional ring cavity with matched positive and negative continuously chirped fiber Bragg gratings (FBG’s). One FBG generates a total positive dispersion of 454 ps/nm at 1275 nm and the other chirped FBG generates a total negative dispersion of -454 ps/nm at 1275 nm. A high-extension lithium-niobate intensity modulator (>30dB extinction at 1275 nm, 4.9 dB loss at maximum transmission) is driven with short pulses by a bit pattern generator providing approximately 0.235 ns full-width at half-maximum pulse profiles. These pulses are stretched, amplified, and compressed within the ring cavity, and the modulator pulsing is synchronized to a harmonic of the cavity round trip time. The laser output is provided from the cavity by a 25% coupler. The output light is amplified by another SOA. The laser source provides a sweeping range of approximately 90 nm centered at around 1275 nm at a repetition rate of ~5 MHz. This yields an estimated axial resolution of 8 μm in air.