KEYWORDS: Optical coherence tomography, Image registration, 3D image processing, Visualization, Imaging systems, Algorithm development, Image quality, Eye, Detection and tracking algorithms, Signal to noise ratio
SignificanceOptical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol.AimWe aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol.ApproachWe developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM).ResultsThe results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume.ConclusionsThe multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies.
Optical Coherence Tomography (OCT) is a non-invasive imaging technique, essential in medical diagnostics due to its ability to produce high-resolution images of internal structures of biological tissues. One of the unique features of the FDML based MHz-OCT is the optical buffering that increases the A-scan rate by creating successive time-delayed copies of the original sweep. However, due to the optical buffering, numerous studies have reported that A-lines originates from different buffer can have different amplitude and phase. Another challenge associated with high A-scan laser source is to pair with the high-speed mechanical scanning protocol to avoid oversampling. Most of the FDML based OCT system is oversampled due to the mechanical limitation of the galvanometer. In this paper, an optimization method is applied to the backward scanning data to eliminate the distortions. Moreover, the phase and amplitude misalignment issues are also numerically corrected. The amplitude inconsistencies in the acquired interferogram are also addressed and solved.
Bidirectional scanning patterns in OCT allow for faster data acquisition with less mechanical strain on scanning components. However, the alternation in scanning direction could lead to phase drift between adjacent B-scans, due to hysteresis of the galvanometer or changes in the incident beam angle, causing errors for digital adaptive optics (DAO) methods. To overcome this limitation, we employed a phase bias estimation method, using bulk phase estimation (BPE) on de-interlaced bidirectional scans to calculate and compensate the systemic phase offset in alternating frames. The corrected scans are then re-interlaced, providing higher-quality DAO correction.
Our research investigates retinal pigmentary abnormalities in Retinitis Pigmentosa (RP) patients using ultra-wide-field high-speed Polarization Diversity Optical Coherence Tomography (PD-OCT) in a clinical setting. To account for the retinal curvature in the wide field of view, adaptive kernel-based spatial averaging is employed for Degree-of-Polarization-Uniformity (DOPU) contrast formation with two complex OCT signals from two orthogonal polarization channels. 20 patients diagnosed with RP were recruited for this study and imaged with PD-OCT. Then, the melanin distribution images from PD-OCT were compared to standard multimodal imaging techniques, including intensity-based OCT, fundus photography, and short-wavelength fundus autofluorescence images. Wide-field PD-OCT imaging technique presented in this study was capable of precisely assessing melanin-related changes in RP over a large field of view and monitoring the disease progression. As a next step, we are investigating the correlation of specific genetic mutations in RP patients with specific clinical presentations and disease progression rates as assessed by the quantitative measurements in PD-OCT. The clinical findings will be presented during the conference.
The proposed preclinical study investigates pathological characteristics of retinal diseases such as Age-related Macular Degeneration (AMD) with transgenic small animal models using a multi-modal functional small animal retinal imaging system. For characterizing the animal models, we visualize the melanin concentration, lipofuscin accumulation, and choriocapillaris using a single imaging system. The system implements Polarization-Sensitive Optical Coherence Tomography (PS-OCT), fluorescence Scanning Laser Ophthalmoscope (fSLO), and Sensorless Adaptive Optics (SAO) for the visualizations of pathological features. As preliminary data, we acquired three different mice models and visualized the outer retinal thickness and melanin concentration. The newly developing system is expected to provide multilateral perspectives for further studies in AMD, enabling vision scientists to investigate the correlations between melanin, lipofuscin, and choriocapillaris for the root cause of AMD.
Acute Respiratory Distress Syndrome (ARDS) is a heterogenic clinical condition that affects critically-ill patients and is associated with high mortality rates and treatment costs. It is characterized by severe acute hypoxemia and alveolar lung injuries. We previously designed an optical coherence tomography (OCT) system to evaluate the changes in mucosa thickness (MT) and proximal airway volume in a swine model after a smoke inhalation injury. However, the analysis relied on manual segmentation of OCT images. Since the manual segmentation of large amounts of OCT data is time-consuming, tedious, and prone to error, this study aims to assess proximal airway volume (PAV) using an automated method based on deep learning. We use convolutional neural networks (CNN) to calculate PAV in a swine model affected by ARDS. We compare the PAV of the swine affected by ARDS with non-ARDS swine. We evaluate OCT images obtained at baseline (BL), post-injury (PI), 24 hours, 48 hours, and 72 hours after smoke inhalation injury. The neural network is modeled utilizing the U-net architecture. The accuracy is evaluated by computing the Sørensen-Dice similarity coefficient. We also demonstrate the correlation between PAV and MT, PFR values obtained from our previous study.
Our research investigates retinal pigmentary abnormalities in retinitis pigmentosa (RP) patients using a wide-field high-speed polarization diversity optical coherence tomography (PD-OCT) in a clinical setting. To account for the retinal curvature in the wide field-of-view, adaptive kernel-based spatial averaging is employed for degree-of-polarization-uniformity (DOPU) contrast formation with two complex OCT signals from two orthogonal polarization channels. In 7 patients diagnosed with RP, retinal pigment epithelium (RPE) melanin loss centered at the macula is compared to standard multimodal imaging techniques, including intensity-based OCT, fundus photography, and short-wavelength fundus autofluorescence images.
For this study, we developed a multi-modal functional retinal imaging system for small animal models to investigate representative AMD mice models. The system can simultaneously acquire information on melanin concentration, lipofuscin accumulation, and choriocapillaris. The newly developed system is expected to provide multilateral perspectives for further studies in AMD, enabling vision scientists to investigate the correlations between melanin, lipofuscin, and choriocapillaris for the root cause of the disease.
A robust multi-volume three-dimensional (3D) registration algorithm is introduced to improve the contrast of optical coherence tomography (OCT) volumes. Our method involves registering multiple volumes to a selected reference volume to correct for the translational and rotational differences between each target and the reference volume and averaging the registered volumes. We tested our registration algorithm on the volumes obtained from three OCT systems with different field-of-views and resolutions. To demonstrate its accuracy, our developed method is evaluated using two different metrics, and its advantages over the other registration algorithms and its limitations are discussed.
Acute Respiratory Distress Syndrome (ARDS) is a severe form of lung injury characterized by hypoxemia. ARDS is estimated to affect at least 190,000 patients per year in the United States. The median time for ARDS onset is 48 hours after hospital admission. The early assessment of the ARDS due to smoke inhalation injury (SII) plays a vital role in facilitating appropriate treatment strategies and improved clinical outcomes. Optical coherence tomography (OCT) may be used as an effective diagnostic tool in quantifying the physiological changes in the airway after smoke inhalation injury. The objective of this study is to develop and evaluate a deep-learning technique to predict and early uncover (within 24 hours) ARDS in a pig model based on the information obtained from the OCT images. A convolutional neural network (CNN) is modeled to train and classify the pig airway images. The early prediction would help clinicians in the accurate diagnosis of ARDS which is of great clinical value.
One of the solutions for spectral-domain OCT (SD-OCT) system to improve its functionalities is to have multiple spectrometers to achieve high speed or sensitivity, but the multiple spectrometers require the performance of the spectrometers to be carefully matched. In this study, we introduce and demonstrate a numerical method to calibrate the performance of multiple spectrometers. The calibration was done by remapping the spectrum of the spectrometers and assessed by a merit function based on phase subtraction. This numerical method allowed us to match the performances of the two spectrometers by over 99%.
Fourier-domain mode-locked (FDML) laser sources allow OCT imaging systems with sweep rates reaching 1.6 MHz. However, physical limitations of conventional scanning systems require consideration. Resonant scanners fix imaging frequency, whereas galvanometer scanner (GS) systems require either raster scanning with large flyback that reduce usable data, or bi-directional scans that require many repeated scans. To overcome these limitations, we employed an effective 1.6 MHz stepped bi-directional scanning protocol, allowing 2 BM-scan OCT-angiography (OCTA) imaging using high-speed FDML. We present the ideal acquisition protocol and processing algorithm for optimum OCTA quality, with results demonstrating high vasculature contrast at 1.6 MHz scan rates.
Spectrally encoded interferometric microscopy (SEIM) is capable of detecting nanometer displacement at a frame rate in the kilohertz regime. By employing a wavelength-sweeping laser and a spectral disperser, SEIM can achieve en face imaging via one-axis scanning. In this study, we compared different processing algorithms for visualizing cilia-induced motion. Our Doppler-based method, combined with phase stabilization and bulk motion correction, provides the highest sensitivity for measuring ciliary beating frequency amongst the tested methods. Traveling waves induced by coordinated cilia motion were visualized. These results demonstrate the potential clinical utility of SEIM for monitoring respiratory function and therapeutic effects.
In this work, we demonstrate the ability to image and quantify airway changes, edema, and epithelial layer separation using OCT and automated tissue boundary identification in the rabbit large airways as early as 30-minutes post-chlorine gas exposure. We propose this novel approach will enable further investigations into using OCT for pre-hospital and point-of-care diagnostics of large airway injury due to airway toxic chemical exposure. With enhanced portability over conventional bronchoscopy, we believe our system is capable of field hospital deployment and investigating airway conditions in warfighters. Combining OCT with bronchoscopy would enhance the assessment and treatment of large airway chemical injury.
Due to the multiple scattering of light in biomedical tissue, the imaging depth of conventional optical coherence tomography is limited to 1-2 millimeters. In this research, a reflection-matrix-method-based optical coherence tomography has been developed to extend the imaging depth into scattering medium. After obtaining the matrix, singular value decomposition and imaging reconstruction are carried out in the post-process to recover the target image beneath turbid media. Specifically, in order to speed up the matrix measurement and reduce the phase noises during the acquisition process, wide-field heterodyne detection is adopted in our system by using a high-speed lock-in camera.
Unlike the classical electro-magnetic wave with uniform polarization distribution along the flat wave-front, the light pulses in either laboratory or industry usually have non-vanishing components in the direction of propagation. Therefore, the full description of a generally complex laser pulse should be implemented in multi-dimensional way, for the light in the free space is the combination of a three-dimensional(3D) electric field and a 3D magnetic field in the 3D Euclidean space which is the subspace of the four-dimensional space-time. Here we report on a novel technique for the full-vectorial characterization which includes the spatiotemporal amplitude and phase information as well as the vectorial features of the complex laser pulses. This new measurement capability opens the way to in-depth characterizations and optimizations of the complex laser pulses and ultimately to the study of new phenomena of the interactions between materials and structured ultra-short laser beams.
In recent years, the use of convolutional neural networks has been rapidly increasing in computer vision related tasks, thanks to its versatility and flexibility in its ability to be trained with large swaths of data. In the biomedical field, neural networks have great potential to streamline and perform tasks on the level of human ability without the drawbacks of human error potentially tainting the results. This study evaluates the efficiency and accuracy of a trained neural network in segmenting the trachea of rats before and after exposure to methyl isocyanate (MIC) and a drug candidate, nitro-oleic acid (NO2OA) . The images of the trachea were gathered using optical coherence tomography. The neural network was modeled after the U-net convolutional network model for biomedical image segmentation. Accuracy was evaluated by taking cross-sectional areas of the trachea and using the Sørensen-Dice similarity coefficient comparing the neural network’s prediction of segmentation to manual segmentation of the trachea. The trained neural network showed an accuracy similar, but not perfect, to human analysis of the trachea.
Despite the emerging market in energy-based devices to treat Genitourinary Syndrome of Menopause (GSM) in menopausal women, the exact effect of the laser on vaginal tissue remains poorly understood. We developed a point-of-care intravaginal endoscope that can obtain simultaneous information on structural and vascular information during the vaginal laser procedure. We evaluated the capability of assessing the treatment outcome by investigating patients receiving the CO2 fractional laser treatment. Our study supports the hypothesis that the treatment effect highly depends on the initial tissue parameters such as epithelium thickness and vascular density.
Laser pulses in either laboratory or industry are typically complex objects. Unlike the classical electro-magnetic wave with uniform polarization distribution along the flat wave-front or a general vector beam under the paraxial approximation, the real light pulses, such as the pulses from the high power multimode fiber laser and the dechirped femtosecond pulses with structured wave-front, spectrum and polarization distributions, usually have non-vanishing component in the propagation direction. Therefore, the description of a general vectorial laser pulse should be implemented in multi-dimensional way, for the light is the combination of a three-dimensional(3D) vector field (electric field E) and a 3D pseudovector field (magnetic field B) in the 3D Euclidean space (R3). Here we report on a novel technique for the multi-dimensional characterization which includes the spatiotemporal amplitude and phase information as well as the vectorial features in 3D Euclidean space of the complex laser pulses, such as the intrinsically controlled femtosecond pulses with higher-order Poincaré sphere beams and vectoral spherical beams. A two-steps-based polarization-sensitive Mach–Zehnder interferometer temporal scan technique was used, at the first time, to capture the complete information of the pulses. The corresponding measurement device, placed on the collimated and attenuated beam at the laser output is consists of a special Mach–Zehnder interferometer, a polarizing beam-splitter and charge-coupled device (CCD) cameras. The reference beam with vertical and horizontal polarization is exported from the cavity and attenuated to a suitable intensity by using a neutral-density filter. After 3D phase unwrapping, removal of the reference curvature, correction of achromatic wave-front distortions, spectral phase and amplitude reconstructions, as well as the measurement for the intrinsic phase of the reference pulse, the complete information of the pulse, include the phase information of the three electronic components, will be obtained. This new measurement capability opens the way to in-depth characterizations and optimizations of the complex laser pulses and ultimately to the study of new phenomena of multimode fiber laser generated laser pulse as well as the interactions between materials and structured ultra-short laser beams.
Light carries both spin and orbital angular momentum and the superpositions of these two dynamical properties have found many applications. Many techniques exist to create such light sources but none allow their creation at the femtosecond laser. Here we report on a novel mode-locked ytterbium-doped fiber laser that generates femtosecond pulses with higher-order Poincaré sphere beams. The controlled generation of such pulses such as azimuthally and radially polarized light with definite orbital angular momentum modes are demonstrated. A unidirectional ring cavity constructed with the Yb-doped fiber placed at the end of the fiber section to reduces unnecessary nonlinear effects is employed for self-starting operation. Two pairs of diffraction gratings are used for compensating the normal group velocity dispersion of the fiber and other elements. Mode-locked operation is achieved based on nonlinear polarization evolution, which is mainly implemented with the single mode fiber, the bulk wave plates and the variable spiral plates (q-plate with topological charge q=0.5). The conversion from spin angular momentum to the OAM and reverse inside the laser cavity are realized by means of a quarter-wave plate and a q-plate so that the polarization control was mapped to OAM mode control.
To demonstrate the total spatiotemporal and vectoral characterization of the new type femtosecond laser beams, here, a polarization-sensitive Mach–Zehnder interferometer temporal scan technique was used, at the first time, to capture the complete information of the pulse. The corresponding measurement device, placed on the collimated and attenuated beam at the laser output and simply consists of a special Mach–Zehnder interferometer, a polarizing beam-splitter and two charge-coupled device (CCD) cameras. The reference beam with vertical polarization is exported from the cavity and attenuated to a suitable intensity by using a neutral-density filter. After Fourier filtering, removal of the reference curvature, correction of achromatic wave-front distortions, spectral phase and amplitude reconstructions, as well as the measurement for the intrinsic phase of the reference pulse, the complete information of the pulse will be obtained. This new measurement capability opens the way to in-depth characterization and optimization of the vector vortex femtosecond laser pulse and ultimately to the detection of new phenomena of the interactions between materials and structured femtosecond laser beams in space–time and polarization.
Development of effective rescue countermeasures for toxic inhaled industrial chemicals such as methyl isocyanate (MIC) has been an emerging interest. The conducting airways are especially sensitive to such chemicals, and their inhalation can cause severe airway and lung damage. In an attempt to develop an effective therapeutic agent for MIC, animal models have been evaluated with molecular diagnostics, histological examination, and arterial blood gases. However, direct measurement of the airway structure has not been performed. Our group previously demonstrated anatomical OCT scanning of human proximal airways with endoscopic probes. However, a smaller probe with diameter of less than half a millimeter is required for scanning the MIC-exposed rat trachea. In this study, we acquired volumetric scanning of MIC-exposed rat trachea using a miniature endoscopic probe and performed automated segmentation to reconstruct a 3-D structure of the intraluminal surface. Our miniature probe is 0.4 mm in diameter and based on a fully fiberoptic design. In this design, three optical fibers with core sizes of 9, 12, and 20 um replace the lens, and the angle-polished fiber at the distal end reflects the beam at a perpendicular angle and replaces the mirror. Using automated segmentation, we reconstructed the three-dimensional structure of intraluminal space in MIC-exposed rat trachea. Compared to the non-exposed rat trachea, which had a hollow tubular structure with a relatively uniform cross-section area, the MIC-exposed rat trachea showed significant airway narrowing as a result of epithelial detachment and extravascular coagulation within the airway. This technique could potentially be applied to high-throughput drug screening of animal models.
KEYWORDS: Medical laser equipment, Optical testing, Elastography, Wave propagation, Near field optics, Tissue optics, Coherence (optics), Transducers, Tissues, 3D modeling
Shear wave measurement enables quantitative assessment of tissue viscoelasticity. In previous studies, a transverse shear wave was measured using optical coherence elastography (OCE), which gives poor resolution along the force direction because the shear wave propagates perpendicular to the applied force. In this study, for the first time to our knowledge, we introduce an OCE method to detect a longitudinally polarized shear wave that propagates along the force direction. The direction of vibration induced by a piezo transducer (PZT) is parallel to the direction of wave propagation, which is perpendicular to the OCT beam. A Doppler variance method is used to visualize the transverse displacement. Both homogeneous phantoms and a side-by-side two-layer phantom were measured. The elastic moduli from mechanical tests closely matched to the values measured by the OCE system. Furthermore, we developed 3D computational models using finite element analysis to confirm the shear wave propagation in the longitudinal direction. The simulation shows that a longitudinally polarized shear wave is present as a plane wave in the near field of planar source due to diffraction effects. This imaging technique provides a novel method for the assessment of elastic properties along the force direction, which can be especially useful to image a layered tissue.
Age-related macular degeneration (AMD) is an eye condition that is considered to be one of the leading causes of blindness among people over 50. Recent studies suggest that the mechanical properties in retina layers are affected during the early onset of disease. Therefore, it is necessary to identify such changes in the individual layers of the retina so as to provide useful information for disease diagnosis. In this study, we propose using an acoustic radiation force optical coherence elastography (ARF-OCE) system to dynamically excite the porcine retina and detect the vibrational displacement with phase resolved Doppler optical coherence tomography. Due to the vibrational mechanism of the tissue response, the image quality is compromised during elastogram acquisition. In order to properly analyze the images, all signals, including the trigger and control signals for excitation, as well as detection and scanning signals, are synchronized within the OCE software and are kept consistent between frames, making it possible for easy phase unwrapping and elasticity analysis. In addition, a combination of segmentation algorithms is used to accommodate the compromised image quality. An automatic 3D segmentation method has been developed to isolate and measure the relative elasticity of every individual retinal layer. Two different segmentation schemes based on random walker and dynamic programming are implemented. The algorithm has been validated using a 3D region of the porcine retina, where individual layers have been isolated and analyzed using statistical methods. The errors compared to manual segmentation will be calculated.
Age-related macular degeneration and keratoconus are two ocular diseases occurring in the posterior and anterior eye, respectively. In both conditions, the mechanical elasticity of the respective tissues changes during the early onset of disease. It is necessary to detect these differences and treat the diseases in their early stages to provide proper treatment. Acoustic radiation force optical coherence elastography is a method of elasticity mapping using confocal ultrasound waves for excitation and Doppler optical coherence tomography for detection. We report on an ARF-OCE system that uses modulated compression wave based excitation signals, and detects the spatial and frequency responses of the tissue. First, all components of the system is synchronized and triggered such that the signal is consistent between frames. Next, phantom studies are performed to validate and calibrate the relationship between the resonance frequency and the Young’s modulus. Then the frequency responses of the anterior and posterior eye are detected for porcine and rabbit eyes, and the results correlated to the elasticity. Finally, spatial elastograms are obtained for a porcine retina. Layer segmentation and analysis is performed and correlated to the histology of the retina, where five distinct layers are recognized. The elasticities of the tissue layers will be quantified according to the mean thickness and displacement response for the locations on the retina. This study is a stepping stone to future in-vivo animal studies, where the elastic modulus of the ocular tissue can be quantified and mapped out accordingly.
The rupture of atherosclerotic plaques is the leading cause of acute coronary events, so accurate assessment of plaque is critical. A large lipid pool, thin fibrous cap, and inflammatory reaction are the crucial characteristics for identifying vulnerable plaques. In our study, a tri-modality imaging system for intravascular imaging was designed and implemented. The tri-modality imaging system with a 1-mm probe diameter is able to simultaneously acquire optical coherence tomography (OCT), intravascular ultrasound (IVUS), and fluorescence imaging. Moreover, for fluorescence imaging, we used the FDA-approved indocyanine green (ICG) dye as the contrast agent to target lipid-loaded macrophages. Firstly, IVUS is used as the first step for identifying plaque since IVUS enables the visualization of the layered structures of the artery wall. Due to low soft-tissue contrast, IVUS only provides initial identification of the lipid plaque. Then OCT is used for differentiating fibrosis and lipid pool based on its relatively higher soft tissue contrast and high sensitivity/specificity. Last, fluorescence imaging is used for identifying inflammatory reaction to further confirm whether the plaque is vulnerable or not. Ex vivo experiment of a male New Zealand white rabbit aorta was performed to validate the performance of our tri-modality system. H and E histology results of the rabbit aorta were also presented to check assessment accuracy. The miniature tri-modality probe, together with the use of ICG dye suggest that the system is of great potential for providing a more accurate assessment of vulnerable plaques in clinical applications.
In this study, we have developed an acoustic radiation force orthogonal excitation optical coherence elastography
(ARFOE-OCE) method for the visualization of the shear wave and the calculation of the shear modulus based on the OCT
Doppler variance method. The vibration perpendicular to the OCT detection direction is induced by the remote acoustic
radiation force (ARF) and the shear wave propagating along the OCT beam is visualized by the OCT M-scan. The
homogeneous agar phantom and two-layer agar phantom are measured using the ARFOE-OCE system. The results show
that the ARFOE-OCE system has the ability to measure the shear modulus beyond the OCT imaging depth. The OCT
Doppler variance method, instead of the OCT Doppler phase method, is used for vibration detection without the need of
high phase stability and phase wrapping correction. An M-scan instead of the B-scan for the visualization of the shear
wave also simplifies the data processing.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.