Spectral off-axis phase shifting in transmission optical coherence tomography

It is well known that the quantitative phase information which is vital in the biomedical study is hard to be directly obtained with bright-field microscopy under incoherent illumination. In addition, it is impossible to maintain the living sample in focus over long-term observation. Therefore, both the autofocusing and quantitative phase imaging techniques have to be solved in microscopy simultaneously. Here, we propose a lightweight deep learning-based framework, which is constructed by residual structure and is constrained by a novel loss function model, to realize both autofocusing and quantitative phase imaging. It outputs the corresponding in-focus amplitude and phase information at high speed (10fps) from a single-shot out-of-focus bright-field image. The training data were captured with a designed system under a hybrid incoherent and coherent illumination system. The experimental results verify that the focused and quantitative phase images of non-biological samples and biological samples can be reconstructed by using the framework. It provides a versatile quantitative technique for continuous monitoring of living cells in long-term and label-free imaging by using a traditional incoherent illumination microscopy system.

Objective To observe the imaging features of cystoid macular edema (CME) in multicolor imaging (MC), and to evaluate the value of MC in the diagnosis of CME. Methods Descriptive case series study. From August 2017 to June 2018, 42 eyes of 37 patients with CME diagnosed in the people's Hospital of Wuhan University were included in the study. Among them, there were 24 males and 13 females, with an average age of 48.51±10.29 years. There were 14 eyes with diabetic retinopathy, 14 eyes with central retinal vein occlusion, 8 eyes with branch retinal vein occlusion, 4 eyes with uveitis, and 2 eyes with Eales disease. The macular color fundus photography (CFP) was performed with Visucam 200 non-mydriatic fundus camera of Zeiss company in Germany. MC, frequnce domainoptical OCT (SD-OCT) and FFA were examined by Spectralis HRA2 + OCT of Heidelberg company in Germany. According to the MC standard method, five images, including 488 nm blue reflection (BR), 515 nm green reflection (GR), 820 nm infrared reflection (IR) imaging and standard MC and blue-green enhancement (BG), were obtained at the same time. Compared with SD-OCT, CFP and MC images were scored. Friedman M test and Wilcoxon signed rank test were used for statistical analysis. Results The standard MC and BG images showed blue-green uplift area or petal-shaped appearance, surrounded by green reflection areas with clear boundaries. BR image can be seen in the low reflexes area. On the GR image, there were patches or cystic low reflection areas, surrounded by a slightly high reflection. On the IR image, patches or cystoid high reflexes can be seen, surrounded by low reflection dark areas with clear boundaries. The average scores of CFP, standard MC, GB, IR, GR and BR were 1.20±0.94, 3.05±0.99, 2.90±1.04, 2.55±1.27, 2.00±0.94, 0.51±0.85 respectively, and the differences were statistically significant (χ2= 151.61, P=0.000). The score of CFP were significantly lower than that of standard MC (Z=-5.421), BG (Z=-5.354), IR (Z=-4.714), GR (Z=-4.438) and higher than that of BR (Z=-3.435). The differences were statistically significant (P=0.000, 0.000, 0.000, 0.000, 0.001). Conclusions The quality of MC imaging is better than that of CFP. Combined with SD-OCT, it can be used as an assistant method to diagnose CME. Key words: Macular edema/diagnosis; Tomographyoptical coherence; Fluorescein angiography; Multicolor imaging

Differential phase contrast (DPC) is a non-interferometric quantitative phase imaging method achieved by using an asymmetric imaging procedure. We report a pupil modulation differential phase contrast (PMDPC) imaging method by filtering a sample's Fourier domain with half-circle pupils. A phase gradient image is captured with each half-circle pupil, and a quantitative high resolution phase image is obtained after a deconvolution process with a minimum of two phase gradient images. Here, we introduce PMDPC quantitative phase image reconstruction algorithm and realize it experimentally in a 4f system with an SLM placed at the pupil plane. In our current experimental setup with the numerical aperture of 0.36, we obtain a quantitative phase image with a resolution of 1.73μm after computationally removing system aberrations and refocusing. We also extend the depth of field digitally by 20 times to ±50μm with a resolution of 1.76μm.

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.

Glaucoma is a leading cause of irreversible blindness worldwide, yet early detection can prevent vision loss. This paper proposes a novel deep learning approach that combines two ophthalmic imaging modalities, fundus photographs and optical coherence tomography scans, as paired images from the same eye of each patient for automated glaucoma detection. We develop separate convolutional neural network models for fundus and optical coherence tomography images and a fusion model that integrates features from both modalities for each eye. The models are trained and evaluated on a private clinical dataset (Bangladesh Eye Hospital and Institute Ltd.) consisting of 216 healthy eye images (108 fundus, 108 optical coherence tomography) from 108 patients and 200 glaucomatous eye images (100 fundus, 100 optical coherence tomography) from 100 patients. Our methodology includes image preprocessing pipelines for each modality, custom convolutional neural network/ResNet-based architectures for single-modality analysis, and a two-branch fusion network combining fundus and optical coherence tomography feature representations. We report the performance (accuracy, sensitivity, specificity, and area under curve) of the fundus-only, optical coherence tomography-only, and fusion models. In addition to a fixed test set evaluation, we perform five-fold cross-validation, confirming the robustness and consistency of the fusion model across multiple data partitions. On our fixed test set, the fundus-only model achieves 86% accuracy (AUC 0.89) and the optical coherence tomography-only model, 84% accuracy (AUC 0.87). Our fused model reaches 92% accuracy (AUC 0.95), an absolute improvement of 6 percentage points and 8 percentage points over the fundus and OCT baselines, respectively. McNemar’s test on pooled five-fold validation predictions (b = 3, c = 18) yields (p = 0.001), and on optical coherence tomography-only vs. fused (b_o = 5, c_o = 20) (p = 0.003), confirming that the fusion gains are significant. Five-fold cross-validation further confirms these improvements (mean AUC . We also compare our results with the existing literature and discuss the clinical significance, limitations, and future work. To the best of our knowledge, this is the first time a novel deep learning model has been used on a fusion of paired fundus and optical coherence tomography images of the same patient for the detection of glaucoma.

Quantitative phase imaging (QPI) has advanced by accurately quantifying phase shifts caused by weakly absorbing biological and artificial structures. Despite extensive research, the diffraction limits of QPI have not been established and examined. Hence, it remains unclear whether diffraction-affected QPI provides reliable quantification or merely visualizes phase objects, similar to phase contrast methods. Here, we develop a general diffraction phase imaging theory and show that it is intrinsically connected with Rayleigh’s resolution theory. Our approach reveals the entanglement of phases under restoration, imposing diffraction bounds on spatial phase resolution and, unexpectedly, on phase accuracy. We prove that the phase accuracy depends on the size, shape, and absorption of objects forming the sample and significantly declines if the object size approaches the Rayleigh limit (a relative phase error of −16% for an Airy disk-sized object with low phase shift). We show that the phase accuracy limits can be enhanced at the cost of deteriorated phase resolution by attenuating the sample background light. The QPI diffraction limits are thoroughly examined in experiments with certified phase targets and biological cells. The study’s relevance is underscored by results showing that the phase accuracy of some structures is lost (a relative phase error of −40%) even though they are spatially resolved (a phase visibility of 0.5). A reliable procedure is used to estimate phase errors in given experimental conditions, opening the way to mitigate errors’ impact through data post-processing. Finally, the phase accuracy enhancement in super-resolution QPI is discovered, which has not been previously reported.

We present a full-range Fourier-domain optical coherence tomography (OCT) system that is capable of acquiring two-dimensional images of living tissue in a single shot. By using line illumination of the sample in combination with a two-dimensional imaging spectrometer, 1040 depth scans are performed simultaneously on a sub-millisecond timescale. Furthermore, we demonstrate an easy and flexible real-time single-shot technique for full-range (complex-conjugate cancelled) OCT imaging that is compatible with both two-dimensional as well as ultrahigh-resolution OCT. By implementing a dispersion imbalance between reference and sample arms of the interferometer, we eliminate the complex-conjugate signal through numerical dispersion compensation, effectively increasing the useful depth range by a factor of two. The system allows us to record 6.7 x 3.2 mm images at 5 microm depth resolution in 0.2 ms. Data postprocessing requires only 4 s. We demonstrate the capability of our system by imaging the anterior chamber of a mouse eye in vitro, as well as human skin in vivo.

Objective To investigate the imaging features of optical coherence tomography (OCT) in diabetic retinopathy (DR). Methods From January 2015 to December 2017, 104 cases (208 eyes) with DR in the Ophthalmology Department of Inner Mongolia Hospital of Traditional Chinese Medicine were collected, and 289 cases (578 eyes) with DR in Tongren Ophthalmology Center of Beijing Tongren Hospital affiliated to Capital Medical University were collected. A total of 393 cases (786 eyes) were included in the two sites. Among them, there were 181 cases (356 eyes) and 212 cases (430 eyes). The age was 22~88 years, with an average age of (47.30 + 5.42) years. Name, sex, age, address, diabetes history, clinical diagnosis, fundus color photography and OCT report were recorded. Summarize and extract features in each phase of OCT inspection. Results According to the clinical staging standard of DR in 2002, 393 cases (786 eyes) were divided into three groups: 51 cases (102 eyes), 83 cases (166 eyes), 124 cases (248 eyes), 46 cases (92 eyes), 57 cases (114 eyes) and 32 cases (64 eyes) of DR stage VI. Eye only. The OCT of DR stage I was characterized by microangioma, occasional or minor bleeding spots between the retinal neuroepithelial layers; the OCT of DR stage II was characterized by rigid exudation and bleeding spots between the retinal neuroepithelial layers; the OCT of DR stage III was characterized by cotton flocculent plaques in addition to hard exudation and bleeding spots; and the OCT of DR stage IV was characterized by cotton flocculent plaques. In addition to hard exudation, bleeding spots and cotton wadding spots, there are also edema or cystoid edema and/or vitreous hemorrhage; in DRV stage, the OCT features are not only hard exudation, bleeding spots, cotton wadding spots, edema and vitreous hemorrhage, but also organic film; in DRVI stage, the OCT features are hard exudation, bleeding spots and vitreous hemorrhage. There were also traction retinal detachment outside cotton spots, edema, vitreous hemorrhage and organic membrane. In addition, according to the different stages of DR, blood flow OCT imaging (OCTA) can clearly show the characteristics of microangioma, hard exudation, hemorrhage, cystic edema, no perfusion area and neovascularization. Conclusion In the examination results of OCT, DR can appear characteristic image according to different stages. Mastering and using OCT can determine the clinical stages of DR and guide the clinical diagnosis and treatment. Key words: Diabetic retinopathy; Clinical stages; Diagnose; Optical coherence tomography

Most studies evaluating the potential of optical coherence tomography (OCT) for the diagnosis of oral cancer are based on visual assessment of OCT B-scans by trained experts. Human interpretation of the large pool of data acquired by modern high-speed OCT systems, however, can be cumbersome and extremely time consuming. Development of image analysis methods for automated and quantitative OCT image analysis could therefore facilitate the evaluation of such a large volume of data. We report automated algorithms for quantifying structural features that are associated with the malignant transformation of the oral epithelium based on image processing of OCT data. The features extracted from the OCT images were used to design a statistical classification model to perform the automated tissue diagnosis. The sensitivity and specificity of distinguishing malignant lesions from benign lesions were found to be 90.2% and 76.3%, respectively. The results of the study demonstrate the feasibility of using quantitative image analysis algorithms for extracting morphological features from OCT images to perform the automated diagnosis of oral malignancies in a hamster cheek pouch model.

In this paper we present, for the first time to our knowledge, the experimental results for determining suspension viscosity in a capillary type viscometer from flow velocity profiles measured by Doppler Optical Coherence Tomography. The suspension of 0.3?m polystyrene microspheres in a glycerol-water solution was used as a model fluid. The viscosity of the suspension was controlled by glycerol concentration. The shear rate and the shear stress at the capillary wall were measured at six flow rates. The corresponding viscosities were calculated. The comparison of the measured shear rates with the values calculated according to the flow rate of the syringe precision pump was performed. Additionally, the viscosities of the studied suspensions were measured by a rotational viscometer. Full Text: PDFReferences K.A. Hayes, M.R. buckley, I. Cohen, L.A. Archer, "High Resolution Shear Profile Measurements in Entangled Polymers", Phys. Rev. Lett. 101, 218301 (2008)[CrossRef] N. Willenbacher, H. Hanciogullari, H.G. Wagner, "High shear rheology of paper coating colors ? more than just viscosity", Chem. Eng. Technol. 20, 557 (1997)[CrossRef] M. Iotti, O.W. Gregersen, S. Moe, M. Lenes, "Rheological Studies of Microfibrillar Cellulose Water Dispersions", J. Polym. Environ. 19, 137 (2011)[CrossRef] M.T. Roberts, A. Mohraz, K.T. Christensen, J.A. Lewis, "Direct Flow Visualization of Colloidal Gels in Microfluidic Channels", Langmuir 23, 8726 (2007)[CrossRef] M. Schmidt, E. Wassner, H. Münstedt, "Setup and Test of a Laser Doppler Velocimeter for Investigations of Flow Behaviour of Polymer Melts", Mech. Time-Depend. Mater. 3, 371, (1999)[CrossRef] S. Schuberth, H. Münstedt, "Simultaneous measurements of velocity and stress distributions in polyisobutylenes using laser-Doppler velocimetry and flow induced birefringence", Rheol. Acta 47, 111 (2008)[CrossRef] Th. Wunderlich, P.O. Brunn, "A wall layer correction for ultrasound measurement in tube flow: comparison between theory and experiment", Flow Meas. Instrum. 11, 63 (2000)[CrossRef] J. Wiklund, I. Shahram, M. Stading, "Methodology for in-line rheology by ultrasound Doppler velocity profiling and pressure difference techniques", Chem. Eng. Sci. 62, 4277 (2007)[CrossRef] S. Yazdanfar, M.D. Kulkarni, J.A. Izatt, "High resolution imaging of in vivo cardiac dynamics using color Doppler optical coherence tomography", Opt. Express 1(13), 424 (1997)[CrossRef] Y. Zhao et al., "Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity", Opt. Lett. 25(2), 114 (2000)[CrossRef] J. Moger, S.J. Matcher C.P. Winlove, A. Shore, "Measuring red blood cell flow dynamics in a glass capillary using Doppler optical coherence tomography and Doppler amplitude optical coherence tomography", J. Biomed. Opt. 9(5), 982 (2004)[CrossRef] S. Tamborski et al., "Simultaneous analysis of flow velocity and spectroscopic properties of scattering media with the use of joint Spectral and Time domain OCT", Phot. Lett. Poland 1(2), 49 (2009) B. Povazay et al., "Submicrometer axial resolution optical coherence tomography", Opt. Lett. 27(20), 1800 (2002)[CrossRef] M. Harvey, T.A. Waigh, "Optical coherence tomography velocimetry in controlled shear flow", Phys. Rev. E 83, 031502 (2011)[CrossRef] J. Lauri, M. Wang, M. Kinnunen, R. Myllylä, "Measurement of microfluidic flow velocity profile with two Doppler optical coherence tomography systems", Proc. SPIE 6863, 68630F (2008)[CrossRef]

To evaluate the feasibility of detecting macrophage content on atherosclerotic plaques by optical coherence tomography (OCT) technique. Thirty New Zealand white rabbits were equally divided into 3 groups at random: Control group (fed normal rabbit chow, n = 10); lipid diet group (fed regular chow supplemented with cholesterol, n = 10) and balloon injury+ lipid diet group (balloon catheter injury of the common carotid artery after 2 weeks lipid diet, n = 10). After 12 weeks, all rabbits underwent pharmacological triggering with Chinese Russell's viper venom (CRVV, 15 mg/kg, i.p.) and histamine (0.02 mg/kg, i.v.). Common carotid arteries were detected with OCT and the Movat pentachrome stain respectively. OCT and histological examination results were compared and the correlation was analyzed. The intra thickness measured by Movat pentachrome stain and by the OCT was (15.2 ± 0.9) µm and (20.2 ± 7.6) µm, the medial thickness was (434.2 ± 86.5) µm and (453.8 ± 87.2) µm, the plaque thickness was (330.2 ± 87.1) µm and (392.2 ± 134.5) µm, the fibrous cap thickness was (58.3 ± 5.6) µm and (61.2 ± 4.9) µm, respectively (all P > 0.05). The normalized standard deviation of the OCT signal (NSD) was compared with immunohistochemical detection. The OCT signal within the cap is relatively homogeneous for low macrophage density in high lipid diet group. For the raw OCT data, a correlation of r = 0.846 (P < 0.01) was found between OCT NSD and a CD68 area<10%, whereas for the base 10 logarithm OCT data, a correlation of r = 0.646 (P < 0.05) was found between OCT NSD and a CD68 area<10%. In balloon injury + high lipid diet group, the OCT signal within the cap was relatively heterogeneous for high macrophage content. For the raw OCT data, a correlation of r = 0.906 (P < 0.01) was found between OCT NSD and a CD68 area >10%, whereas for the base 10 logarithm OCT data, a correlation of r = 0.593 (P < 0.05) was found between OCT NSD and a CD68 area >10%. For the raw OCT signal NSD, a range of NSDs (7.12% to 7.35%) demonstrated 100% sensitivity and specificity (Kappa value 1.0) for differentiating caps containing >10% CD68 staining. For the base 10 logarithm OCT signal, NSD values ranging from 7.81% to 7.92% provided 70% sensitivity and 75% specificity (value 0.44) for identifying caps containing >10% CD68 staining. OCT is an effective tool to determine macrophage content in this model. OCT imaging can clearly visualize different types of atherosclerotic plaques and provide detailed information on plaque characteristics.

Glaucoma is an ocular disease which of chronic and progressive nature which leads to optic neuropathy caused due to certain group of optic conditions which can cause damage to the nerve and further lead to loss of vision. Increased intraocular pressure remains the most common cause of glaucoma. A gradual and sustained rise in the intraocular pressure can occur because of increased formation of aqueous humour, problem in the drainage of the aqueous humour or it can also happen due to increased episcleral venous pressure. OCT imaging technique enables noncontact, non -invasive imaging of the anterior eye along with features of human retina including fovea and optic disc. Though imaging up 2 to 3 mm deep can be achieved in most tissues. This is similar to conventional biopsy and histology. Imaging depth of OCT is more than 10 to 100 times finer than the standard clinical ultrasound. OCT has been applied in vitro to image arterial pathology and can differentiate plaque morphology. Aim: To study the anterior segment OCT and optic nerve head OCT findings in glaucoma. Material and methods: The study was conducted at KRISHNA INSTITIUE OF MEDICAL SCIENCES ON 45 patients who inclusive fulfill the criteria's were chosen as study subjects. Patients suspected with Glaucoma coming to the OPD at Krishna Hospital, Karad were included in the study. All the patients underwent AS -OCT and RNFL under various modalities and data were collected. The collected data was compiled in Microsoft Excel 2010. Data was analyzed using SPSS (Statistical Programme for Social Sciences) software 21 version, OpenEpi Software Version 2.3. Results: There were 45 patients in my study who were included in it. Out of this, 67% (30) of the participants were men, and 33% (15) were women. The most affected age group was determined to be 61-70 years old with 36% incidence. It was discovered that the AOD and TISA declined linearly with increasing pupil size in 78.2% of instances. On assessment of the laterality, 33% were involved with the right side and 67% with the left side. Three patients exhibited trabecular iris angles less than 25 degrees on AS -OCT, while the other patients all had angles greater than 25 degrees. we found that most of the patients had CCT 500 m It was also found that 6 patients age group 20 -40 years with IOP range from 22 -30 mmhg had CCT above 550 m and corrected was found to be effective. . Of these 6 patients, all had CDR values more than 0.6, but NRR was healthy. A P value of 0.001 was reported for the macular thickness, which was 276 26 (223 -346) Because there hasn't been much research on AS -OCT and RNFL in relation to glaucoma, this work will be highly helpful for future references. Conclusion: Combining both aspects of the anterior and posterior segment which helps in early diagnosis of glaucoma and patient can start on treatment, as well as keeping track on progress, OCT imaging technique allows noncontact, non -invasive imaging of the anterior eye along with features of the human retina including fovea and optic disc and gives quantitative analysis, requiring minimal skills and taking less time to operate.

Numerical analysis of one-shot full-range FD-OCT system based on orthogonally polarized light

Optical coherence tomography (OCT) is a noninvasive imaging technique which provides microscopic tomographic sectioning of biological samples. This contribution presents a new spectral OCT technique, which allows to detect the phase of detected signal and thereby to remove the useless low- frequency terms from the registered signal. The basic principle is shown and experimental measurement sin vitro and in vivo are presented.

Dielectric metasurfaces have recently attracted much attention due to their ability to efficiently control light propagation, that is, its amplitude, phase and polarization, on micro- and macro- levels. Such metasurfaces also naturally allow for integration in compact optical setups due to their small sizes. An important issue of energy losses is also addressed by employing all-dielectric platform. Advancements in nanofabrication have enabled realization of metasurface-based high-resolution wavefront engineering devices, which have been employed in different imaging applications, for example, as metalenses, polarization filters, metaholograms, etc. Quantitative phase imaging is a powerful tool for the optical inspection of transparent samples in connection with biological and technical applications. By measuring thickness and/or refractive index profiles, phase imaging facilitates, for example, the observation of dynamic events in unstained cells. As such, it has become indispensable in biological imaging, wavefront correction and metrology. However, conventional cameras and photodetectors are inherently not sensitive to the phase of an incident lightwave. As a consequence, direct phase detection is challenging. Only by multiple intensity measurements or application of specialized interferometric schemes, the phase profile of an object can be in principle reconstructed. In this paper, we report on the ability of metasurfaces to contribute to quantitative phase imaging by independent control of the phase profiles in two orthogonal polarization states of an incident beam.