Extension Of Optical Coherence Tomography Research Articles

Multiple instance learning based classification of diabetic retinopathy in weakly-labeled widefield OCTA en face images

Diabetic retinopathy (DR), a pathologic change of the human retinal vasculature, is the leading cause of blindness in working-age adults with diabetes mellitus. Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography, has shown potential as a tool for early diagnosis of DR through its ability to visualize the retinal vasculature in all spatial dimensions. Previously introduced deep learning-based classifiers were able to support the detection of DR in OCTA images, but require expert labeling at the pixel level, a labor-intensive and expensive process. We present a multiple instance learning-based network, MIL-ResNet,14 that is capable of detecting biomarkers in an OCTA dataset with high accuracy, without the need for annotations other than the information whether a scan is from a diabetic patient or not. The dataset we used for this study was acquired with a diagnostic ultra-widefield swept-source OCT device with a MHz A-scan rate. We were able to show that our proposed method outperforms previous state-of-the-art networks for this classification task, ResNet14 and VGG16. In addition, our network pays special attention to clinically relevant biomarkers and is robust against adversarial attacks. Therefore, we believe that it could serve as a powerful diagnostic decision support tool for clinical ophthalmic screening.

Intravascular optical coherence elastography.

Optical coherence elastography (OCE), a functional extension of optical coherence tomography (OCT), visualizes tissue strain to deduce the tissue's biomechanical properties. In this study, we demonstrate intravascular OCE using a 1.1 mm motorized catheter and a 1.6 MHz Fourier domain mode-locked OCT system. We induced an intraluminal pressure change by varying the infusion rate from the proximal end of the catheter. We analysed the pixel-matched phase change between two different frames to yield the radial strain. Imaging experiments were carried out in a phantom and in human coronary arteries in vitro. At an imaging speed of 3019 frames/s, we were able to capture the dynamic strain. Stiff inclusions in the phantom and calcification in atherosclerotic plaques are associated with low strain values and can be distinguished from the surrounding soft material, which exhibits elevated strain. For the first time, circumferential intravascular OCE images are provided side by side with conventional OCT images, simultaneously mapping both the tissue structure and stiffness.

Reconstitution of the Choriocapillaris in Acute Posterior Multifocal Placoid Pigment Epitheliopathy.

To describe findings derived from extensions of optical coherence tomography, including volume rendering and frame averaged OCT angiography (OCT-A), in a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Case report of a patient with APMPPE imaged during the acute and convalescent stages. A 20-year-old male presented with an acute change in vision. He had multiple yellow-white placoid lesions at the level of the retinal pigment epithelium (RPE) in the macula and nasal to the optic nerve in both eyes. Within 2 weeks, his visual acuity worsened to 20/80 and 20/400 in the right and left eyes, respectively. SD-OCT showed focal defects in the ellipsoid and RPE layers. Volume rendering OCT-A showed inflammatory cells in the outer nuclear layer (ONL) above the APMPPE lesion. Frame averaged OCT-A revealed significant loss of capillary flow signal within capillary segments of the choriocapillaris. Ten weeks after presentation, there was resolution of the placoid changes, discontinuance of the inflammatory infiltrate in the ONL, and significant reconstitution of flow in the choriocapillaris. The visual acuity was 20/20 in both eyes. Novel volume rendered and frame averaged OCT-A images in a patient with APMPPE allowed detection of inflammatory cell infiltrate in the ONL as well as reversible capillary segment non-perfusion of associated APMPPE lesions. The findings suggest short term insults to choriocapillaris function may be reversible and can be tracked with modern imaging techniques.

Diagnosing Diabetic Retinopathy in OCTA Images Based on Multilevel Information Fusion Using a Deep Learning Framework.

Objective As an extension of optical coherence tomography (OCT), optical coherence tomographic angiography (OCTA) provides information on the blood flow status at the microlevel and is sensitive to changes in the fundus vessels. However, due to the distinct imaging mechanism of OCTA, existing models, which are primarily used for analyzing fundus images, do not work well on OCTA images. Effectively extracting and analyzing the information in OCTA images remains challenging. To this end, a deep learning framework that fuses multilevel information in OCTA images is proposed in this study. The effectiveness of the proposed model was demonstrated in the task of diabetic retinopathy (DR) classification. Method First, a U-Net-based segmentation model was proposed to label the boundaries of large retinal vessels and the foveal avascular zone (FAZ) in OCTA images. Then, we designed an isolated concatenated block (ICB) structure to extract and fuse information from the original OCTA images and segmentation results at different fusion levels. Results The experiments were conducted on 301 OCTA images. Of these images, 244 were labeled by ophthalmologists as normal images, and 57 were labeled as DR images. An accuracy of 93.1% and a mean intersection over union (mIOU) of 77.1% were achieved using the proposed large vessel and FAZ segmentation model. In the ablation experiment with 6-fold validation, the proposed deep learning framework that combines the proposed isolated and concatenated convolution process significantly improved the DR diagnosis accuracy. Moreover, inputting the merged images of the original OCTA images and segmentation results further improved the model performance. Finally, a DR diagnosis accuracy of 88.1% (95%CI ± 3.6%) and an area under the curve (AUC) of 0.92 were achieved using our proposed classification model, which significantly outperforms the state-of-the-art classification models. As a comparison, an accuracy of 83.7 (95%CI ± 1.5%) and AUC of 0.76 were obtained using EfficientNet. Significance. The visualization results show that the FAZ and the vascular region close to the FAZ provide more information for the model than the farther surrounding area. Furthermore, this study demonstrates that a clinically sophisticated designed deep learning model is not only able to effectively assist in the diagnosis but also help to locate new indicators for certain illnesses.

Compressive-sensing swept-source optical coherence tomography angiography with reduced noise.

Optical coherence tomography angiography (OCTA), as a functional extension of optical coherence tomography (OCT), has exhibited a great potential to aid in clinical diagnostics. Currently, OCTA still suffers from motion artifact and noise. Therefore, in this article, we propose to implement compressive sensing (CS) on B-scans to reduce motion artifact by increasing B-scan rate. Meanwhile, a noise reduction filter is specially designed by combining CS, Gaussian filter and median filter. Specially, CS filtering is realized by averaging multiple CS repetitions on en-face OCTA images with varied sampling functions. The method is evaluated on in vivo OCTA images of human skin. The results show that vasculature structures can be reconstructed well through CS on B-scans with a sampling rate of 70%. Moreover, the noise can be significantly eliminated by the developed filter. This implies that our method has a good potential to expedite OCTA imaging and improve the image quality.

Development of a handheld compression optical coherence elastography probe with a disposable stress sensor.

Optical coherence elastography (OCE) is a functional extension of optical coherence tomography (OCT). OCE measures a sample's deformation under force stimuli. Compression is often used to generate the force stimuli in OCE. In this Letter, we report the development of a handheld quantitative compression OCE probe with a novel stress senor, dedicated to measuring the force. The stress sensor consists of a circular glass window and a metal ring which are connected with polyurethane spokes. This sensor is mounted on the tip of the OCT sample arm as an imaging window, so that the force applied to the sample through the window can be measured by detecting the window displacement from the OCT image. The force-displacement function was first developed through simulation on COMSOL Multiphysics and eventually calibrated experimentally. A phase-sensitive OCT technique was employed to measure both the window displacement and the sample deformation. The performance of an OCE probe with this stress sensor was evaluated on a two-layer phantom. The results show that it is extremely capable of measuring the sample Young's modulus. Finally, we successfully measured the elasticity of the human fingertip, indicating a good potential of this OCE probe for in vivo elastogram measurement on human skin.

Visualization of two-dimensional transverse blood flow direction using optical coherence tomography angiography.

.Significance: Evaluation of vessel patency and blood flow direction is important in various medical situations, including diagnosis and monitoring of ischemic diseases, and image-guided vascular surgeries. While optical coherence tomography angiography (OCTA) is the most widely used functional extension of optical coherence tomography that visualizes three-dimensional vasculature, inability to provide information of blood flow direction is one of its limitations.Aim: We demonstrate two-dimensional (2D) transverse blood flow direction imaging in en face OCTA.Approach: A series of triangular beam scans for the fast axis was implemented in the horizontal direction for the first volume scan and in the vertical direction for the following volume scan, and the inter A-line OCTA was performed for the blood flow direction imaging while the stepwise pattern was used for each slow axis scan. The decorrelation differences between the forward and the backward inter A-line OCTA were calculated for the horizontal and the vertical fast axis scans, and the ratio of the horizontal and the vertical decorrelation differences was utilized to show the 2D transverse flow direction information.Results: OCTA flow direction imaging was verified using flow phantoms with various flow orientations and speeds, and we identified the flow speed range relative to the scan speed for reliable flow direction measurement. We demonstrated the visualization of 2D transverse blood flow orientations in mouse brain vascular networks in vivo.Conclusions: The proposed OCTA imaging technique that provides information of 2D transverse flow direction can be utilized in various clinical applications and preclinical studies.

Optical microangiography reveals temporal and depth-resolved hemodynamic change in mouse barrel cortex during whisker stimulation.

.Significance: Cerebral blood flow (CBF) regulation at neurovascular coupling (NVC) plays an important role in normal brain functioning to support oxygen delivery to activating neurons. Therefore, studying the mechanisms of CBF adjustment is crucial for the improved understanding of brain activity.Aim: We investigated the temporal profile of hemodynamic signal change in mouse cortex caused by neural activation and its variation over cortical depth.Approach: Following the cranial window surgery, intrinsic optical signal imaging (IOSI) was used to spatially locate the activated region in mouse cortex during whisker stimulation. Optical microangiography (OMAG), the functional extension of optical coherence tomography, was applied to image the activated and control regions identified by IOSI. Temporal profiles of hemodynamic response signals obtained by IOSI and OMAG were compared, and OMAG signal was analyzed over cortical layers.Results: Our results showed that the hemodynamic response to neural activity revealed by blood flow change signal signal through IOSI is slower than that observed by OMAG signal. OMAG also indicated the laminar variation of the response over cortical depth, showing the largest response in cortical layer IV.Conclusions: Overall, we demonstrated the development and application of dual-modality imaging system composed of IOSI and OMAG, which may have potential to enable the future investigations of depth-resolved CBF and to provide the insights of hemodynamic events associated with the NVC.

Imaging depth extension of optical coherence tomography in rabbit eyes using optical clearing agents.

Optical coherence tomography has become an indispensable diagnostic tool in ophthalmology for imaging the retina and the anterior segment of the eye. However, the imaging depth of optical coherence tomography is limited by light attenuation in tissues due to optical scattering and absorption. In this study of rabbit eye both ex vivo and in vivo, optical coherence tomography imaging depth of the anterior and posterior segments of the eye was extended by using optical clearing agents to reduce multiple scattering. The sclera, the iris, and the ciliary body were clearly visualized by direct application of glycerol at an incision on the conjunctiva, and the posterior boundary of sclera and even the deeper tissues were detected by submerging the posterior segment of eye in glycerol solution ex vivo or by retro-bulbar injection of glycerol in vivo. The ex vivo rabbit eyes recovered to their original state in 60 s after saline-wash treatment, and normal optical coherence tomography images of the posterior segment of the sample eyes proved the self-recovery of in vivo performance. Signal intensities of optical coherence tomography images obtained before and after glycerol treatment were compared to analysis of the effect of optical clearing. To the best of our knowledge, this is the first study for imaging depth extension of optical coherence tomography in both the anterior and posterior segments of eye by using optical clearing agents.

Temporally and spatially adaptive Doppler analysis for robust handheld optical coherence elastography.

Optical coherence elastography (OCE), a functional extension of optical coherence tomography (OCT), can be used to characterize the mechanical properties of biological tissue. A handheld fiber-optic OCE instrument will allow the clinician to conveniently interrogate the localized mechanical properties of in vivo tissue, leading to better informed clinical decision making. During handheld OCE characterization, the handheld probe is used to compress the sample and the displacement of the sample is quantified by analyzing the OCT signals acquired. However, the motion within the sample inevitably varies in time due to varying hand motion. Moreover, the motion speed depends on spatial location due to the sample deformation. Hence, there is a need for a robust motion tracking method for manual OCE measurement. In this study, we investigate a temporally and spatially adaptive Doppler analysis method. The method described here strategically chooses the time interval (δt) between signals involved in Doppler analysis to track the motion speed v(z,t) that varies temporally and spatially in a deformed sample volume under manual compression. Enabled by temporally and spatially adaptive Doppler analysis, we report the first demonstration of real-time manual OCE characterization of in vivo tissue to the best of our knowledge.

Optical coherence tomography reveals complex motion between the basilar membrane and organ of corti in the gerbil cochlea

The mechanical basis of auditory transduction within the mammalian cochlea is not fully understood but relies on complex mechanical interactions between different structures within the Organ of Corti (OoC). We used spectral domain phase microscopy, a functional extension of optical coherence tomography (OCT), to measure the sound-evoked motion in response to “Zwuis” frequency complexes, in vivo, in the basal region of the gerbil cochlea. Because OCT allows for measurements from multiple axial positions along the optical path, we are able to simultaneously record vibration at different points within the OoC between the basilar membrane (BM) and tectorial membrane. Imaging through the round window membrane, we could record from several longitudinal locations along the cochlea and at each location, we measured from several radial positions. Both the BM and intra-OoC vibrations are tuned and show nonlinear amplification, or compressive growth, with the applied sound pressure level. Similar to recent reports (Ren et al, PNAS 2016; Ren and He, MoH 2017), we find that the motions of surfaces within the OoC can exhibit a greater degree of compressive nonlinearity (amplification) and physiological vulnerability than the motion of the BM. Additionally, some responses show sharp notches near the onset of the nonlinear regime.

Multifunctional OCT for preclincial imaging

SummaryFunctional extensions of optical coherence tomography (OCT) expand image contrast and enable quantitative measurements of optical tissue properties, improved segmentation of tissue morphology and the assessment of physiological parameters. In this presentation, we will discuss applications of multifunctional OCT including high‐resolution polarization‐sensitive OCT and OCT angiography for preclinical studies of ocular disease models.

OCT elastography

AbstractFunctional extensions of optical coherence tomography (OCT) are today extensively studied as they have the potential to further enhance the diagnostic capabilities of OCT. Modern Doppler OCT, as the most prominent functional extension, yields outstanding contrast for the vascular plexus down to even smallest capillaries. Optical or OCT elastography is a very young functional OCT approach that gained from the developments of high speed OCT technology. It is capable to sense smallest structural tissue deformation during mechanical stress. The achieved deformation sensitivity is on the nanometer scale even in living retinal tissue. Due to the high sensitivity, OCT elastography is capable to observe tissue derformation caused by the natural pulse of the perfusion bed. This avoids external mechanical stress applied to the eye bulb and allows studying the biomechanical properties of tissue in its natural environment. Of particular interest is the motion of the fundus and of the lamina cribrosa (LC). First results indicate differential motion within the retina and LC of a few micrometer/second. This might be the basis for using the biomechanical status of the LC as new diagnostic biomarker of disease for example for glaucoma.

In vivo, label-free, three-dimensional quantitative imaging of kidney microcirculation using Doppler optical coherence tomography

Doppler optical coherence tomography (DOCT) is a functional extension of optical coherence tomography (OCT) and is currently being employed in several clinical arenas to quantify blood flow in vivo. In this study, the objective was to investigate the feasibility of DOCT to image kidney microcirculation, specifically, glomerular blood flow. DOCT is able to capture three-dimensional (3D) data sets consisting of a series of cross-sectional images in real time, which enables label-free and non-destructive quantification of glomerular blood flow. The kidneys of adult, male Munich–Wistar rats were exposed through laparotomy procedure after being anesthetized. Following exposure of the kidney beneath the DOCT microscope, glomerular blood flow was observed. The effects of acute mannitol and angiotensin II infusion were also observed. Glomerular blood flow was quantified for the induced physiological states and compared with baseline measurements. Glomerular volume, cumulative Doppler volume, and Doppler flow range parameters were computed from 3D OCT/DOCT data sets. Glomerular size was determined from OCT, and DOCT readily revealed glomerular blood flow. After infusion of mannitol, a significant increase in blood flow was observed and quantified, and following infusion of angiontensin II, a significant decrease in blood flow was observed and quantified. Also, blood flow histograms were produced to illustrate differences in blood flow rate and blood volume among the induced physiological states. We demonstrated 3D DOCT imaging of rat kidney microcirculation in the glomerulus in vivo. Dynamic changes in blood flow were detected under altered physiological conditions demonstrating the real-time imaging capability of DOCT. This method holds promise to allow non-invasive imaging of kidney blood flow for transplant graft evaluation or monitoring of altered-renal hemodynamics related to disease progression.

Doppler optical coherence tomography in cardiovascular applications

The study of flow dynamics in complex geometry vessels is highly important in various biomedical applications where the knowledge of the mechanic interactions between the moving fluid and the housing media plays a key role for the determination of the parameters of interest, including the effect of blood flow on the possible rupture of atherosclerotic plaques. Doppler Optical Coherence Tomography (DOCT), as a functional extension of Optical Coherence Tomography (OCT), is an optic, non-contact, noninvasive technique able to achieve detailed analysis of the flow/vessel interactions. It allows simultaneous high resolution imaging (∼10 µm typical) of the morphology and composition of the vessel and determination of the flow velocity distribution along the measured cross-section. We applied DOCT system to image high-resolution one-dimensional and multi-dimensional velocity distribution profiles of Newtonian and non-Newtonian fluids flowing in vessels with complex geometry, including Y-shaped and T-shaped vessels, vessels with aneurism, bifurcated vessels with deployed stent and scaffolds. The phantoms were built to mimic typical shapes of human blood vessels, enabling preliminary analysis of the interaction between flow dynamics and the (complex) geometry of the vessels and also to map the related velocity profiles at several inlet volume flow rates. Feasibility studies for quantitative observation of the turbulence of flows arising within the complex geometry vessels are discussed. In addition, DOCT technique was also applied for monitoring cerebral mouse blood flow in vivo. Two-dimensional DOCT images of complex flow velocity profiles in blood vessel phantoms and in vivo sub-cranial mouse blood flow velocities distributions are presented.

Real-time in vivo color Doppler optical coherence tomography.

Color Doppler optical coherence tomography (CDOCT) is a functional extension of optical coherence tomography (OCT) that can image flow in turbid media. We have developed a CDOCT system capable of imaging flow in real time. Doppler processing of the analog signal is accomplished in hardware in the time domain using a novel autocorrelation technique. This Doppler processing method is compatible with a high speed OCT system capable of imaging in real time. Using this system, we demonstrate cross-sectional imaging of bidirectional flow with CDOCT at four frames per second in a tissue-simulating phantom consisting of intralipid solution flowing in glass capillaries. As a demonstration of real-time imaging of blood flow in vivo we imaged pulsatible blood flow in a rat femoral artery at eight frames per second. Issues of velocity sensitivity, imaging speed, and range of velocity measurement are discussed, as well as potential applications of real-time CDOCT.

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-microm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.