Optical coherence tomography (OCT) has wide applications in diagnosing diseases, benefitting from its non-invasive, high-resolution, and real-time visualization of tissue microstructures. Still, this technology faces the mutual constraint between transverse resolution and depth of focus. Metalens can modulate the light fields at subwavelength scales, effectively enhancing the depth of focus of an OCT system. In this paper, a metalens designed for the OCT system is proposed. The metalens with different structures can generate various phase modulation outcomes. Using the finite-difference time-domain (FDTD) simulation, the impacts of the nanopillar parameters (e.g. height, diameter, and spacing) and the materials (e.g. Si, SiO2, and TiO2) on phase modulation have been analyzed. Based on the simulation results, the phase modulation capability of nanopillars is compromised at reduced heights, while excessively tall structures can adversely decrease transmittance. With a constant height, the radius of the nanopillars can be manipulated to achieve a phase delay of 2π. Furthermore, the propagation efficiency and the typical depth of focus were calculated from the results of the beam intensity distribution, indicating an enhanced imaging performance of the OCT system. The results provide a basis for designing the metalens used in the OCT systems.
Optical coherence tomography (OCT) is widely used in ophthalmology and has been a standard method for diagnosing ocular diseases. Improving spatial resolution is crucial for the visualization of ocular microstructure. In conventional OCT systems, enhanced transverse resolution typically results in a reduction of depth of field (DOF). In our study, we designed four metalenses with different microstructures and then integrated them into the sample arm of an OCT imaging system. The metalens can modulate the amplitude and the phase of incident light in the sample. In this way, the depth of focus in the OCT system can be effectively enhanced while maintaining the transverse resolution. Also, the impact of different parameters, such as the size and the spacing of micro-units, has been discussed for OCT imaging. Finally, the experiment on the glass slides has been conducted to validate the performance of OCT imaging. The results demonstrate that the metalens with a specific microstructure could effectively enhance the DOF of OCT imaging. Furthermore, the enhanced depth of focus of the OCT system opens up new opportunities for investigating tissue morphology and function.
The viscoelasticity of the retina can reflect its function and state. Accurate assessment of retinal viscoelasticity can assist in early diagnosis of retinal diseases. With high-resolution and non-contact features, optical coherence elastography (OCE) has been used to evaluate the retinal elasticity based on the elastic wave velocity measurement. Nonetheless, the retinal viscosity cannot be assessed. In this study, a shear wave dispersion OCE method was proposed to measure the retinal viscosity and elasticity. After acoustic radiation force (ARF) induces a shear wave, optical coherence tomography (OCT) visualizes shear wave propagation in the retina. The wave velocities at different frequencies are analyzed, and the viscoelasticity is quantified based on the dispersion analysis. The accuracy of the method was verified on phantoms with different glycerol concentrations. The viscosity of the phantom is related to the concentration of glycerin, and its elasticity is adjusted by the agar concentration. The OCE results closely matched the elasticity measured by a mechanical testing system. Furthermore, the retinal shear wave velocity dispersion on the ex-vivo porcine eye was analyzed to determine its viscoelasticity. Our results demonstrate that ARF-OCE can quantitatively evaluate the viscoelasticity of the retina. The shear wave dispersion OCE method has great potential for diagnosing retinal diseases.
The biomechanical measurement of the crystalline lens can provide valuable information to assess the development of lens-related diseases, such as presbyopia and cataracts. Optical coherence elastography (OCE) has been used to measure the elasticity of the lens surface based on elastic wave imaging. However, measuring the elasticity of the lens interior poses a challenge because optical imaging cannot easily visualize elastic waves in the transparent lens. In this study, we develop an acoustic radiation force optical coherence elastography (ARF-OCE) method to detect the propagation of elastic waves on the surface of the lens and inside the lens for the elasticity measurement. The ultrasonic radiation force excites the lens from the side of the eye, subsequently inducing an elastic wave on the lens surface or inside the lens. Optical coherence tomography (OCT) images the crystalline lens from the front of the eye with the optical beam perpendicular to the acoustic beam. When the ARF is focused on the surface of the lens, the wave propagation on the lens surface is visualized by the OCT, and the elasticity of the lens surface can be quantified. When the ARF is focused inside the lens at different depths, the time the elastic wave reaches the lens surface will change. Therefore, the velocity of the elastic wave propagation inside the lens is calculated by the ratio of the depth change to the time difference, and the elasticity of the lens interior can be quantified. The elasticity of the surface and the interior of the ex-vivo porcine lens was measured using the ARF-OCE method. The elasticity measurement of the crystalline lens provides a quantitative assessment of its biomechanical properties and has the potential for the accurate diagnosis and treatment of lens-related diseases.
Optical coherence elastography (OCE) is an imaging technique for measuring elastic properties based on optical coherence tomography (OCT). Benefitting from the high-resolution imaging and sensitive motion detection of OCT, OCE has been used to assess the elasticity distribution of ocular tissue, skin tissue, etc. The biological tissues consist of multiple layers with various biomechanical properties and, thus, show directionally dependent elasticity. In previous OCE measurements, the tissues were regarded as isotropic materials, and the elasticity was measured in one direction, which may cause the bias of elasticity assessment. In this study, we developed the OCE method for directionally dependent elasticity assessment. Acoustic radiation force (ARF) generated by a ring ultrasonic transducer was applied to induce vibration in an axial direction and an elastic wave propagating in the lateral direction. The OCT beam, parallel to the ARF, scanned the sample through the central hole of the ring ultrasonic transducer. Then, phase-resolved OCT analysis was used to detect the vibration and visualize wave propagation. The vibration amplitude depends on the axial elasticity, and the lateral elasticity determines the elastic wave velocity. Therefore, the measurements of the vibration amplitude and the wave velocity using ARF-OCE can assess the elasticity of the sample in orthogonal directions. The results from the phantom measurements show that the OCE method can reliably evaluate the directionally dependent elasticity for the anisotropic samples.
Optical coherence tomography (OCT) enables high-resolution, label-free two-dimensional cross-sectional and three-dimensional volumetric imaging of biological tissues. Combining OCT imaging with external force excitation, optical coherence elastography (OCE) provides noninvasive elasticity quantification of samples for the pathological analysis of tissues and early diagnosis of diseases. However, the OCE system with a fixed OCT sample arm cannot be used for elasticity measurements of tissues located in a narrow space, such as an oral cavity and an ear canal, because the OCT beam and external force cannot easily reach the tissues. In this study, we developed a handheld OCE method for the elasticity measurements based on elastic wave imaging. The handheld probe integrated an air pulse excitation unit and a microelectromechanical system-based scan imaging unit. A short air pulse induced the elastic wave in a sample. Then the OCT data was captured by an M-B scan protocol, and the tissue vibration was analyzed by Doppler phase shifts. After elastic wave visualization, the elastic wave velocity was calculated for the elasticity quantification of the sample. The results show that the handheld OCE method can induce and image the elastic wave and, thus, quantify the elastic modulus with high flexibility for the tissue in a narrow, deep space.
Pathological changes in ocular tissues can cause differences in tissue elasticity. Therefore, tissue elasticity is a valuable indicator of early ocular diseases. To measure the elasticity of ocular tissues, we proposed a whole-eye optical coherence elastography (OCE) method. To image the whole eye, an electrically tunable lens (ETL) was integrated into the system to adjust the focal plane. For inducing elastic waves in an entire eye, the acoustic radiation force (ARF) from one transducer stimulated the anterior segment from the side of the eye, and another transducer excited the retina from the front of the eye. The elastic waves in the porcine cornea and retina were visualized by Doppler phase shift analysis. Then, we measured the elastic wave propagation velocities and calculated Young's moduli of the tissues. In the ex-vivo experiments of porcine eyes, the elastic moduli of the cornea and retina were quantified, respectively. The experimental results demonstrate the feasibility and potential clinical value of the proposed method for assessing tissue elasticity in ocular structures.
Optical coherence elastography (OCE) can quantify the tissue elasticity by measuring the velocities of elastic wave propagation in the tissue. Due to the high sensitivity and micron-level resolution, OCE is especially suitable for biomechanical property measurements of the ocular tissues. Usually, the external excited elastic wave is visualized by optical coherence tomography (OCT). However, the imaging depth of the OCE system is limited by the OCT system and the excitation depth of external force. In this study, we proposed a method extending the OCE imaging depth with an electrically tunable lens (ETL). The method was validated by detecting the propagation of elastic waves in the corneas and retinas of porcine eyes using an acoustic radiation force-based OCE system. Firstly, an acoustic simulation was taken for the ring ultrasound transducer. Secondly, a mathematical model of the ETL was established for dynamic control of the imaging depth. Thirdly, the optical simulation of the sample arm was performed to analyze the critical optical parameters and evaluating the imaging quality of the system. Also, the optimal working depth of the OCT system was discussed. Lastly, an OCE system with a ring ultrasound transducer and an ETL was built. The experimental results on ex vivo porcine eyes showed the imaging depth of the system was 22 mm. This method can extend the depth of elasticity detection and, thus, provides a powerful tool for non-invasive, high-resolution biomechanical analysis of the ocular tissues.
Optical coherence tomography (OCT) enables non-invasive imaging of biological tissue and has become one of the most effective tools for monitoring the retinal structures and detecting retinal diseases. However, the existence of speckle noise severely degrades the OCT image quality and makes it difficult to identify the retinal disorders accurately. In this work, a deep generative model, named as despeckling generative adversarial network (DSGAN), is proposed for retinal OCT image despeckling. The proposed DSGAN is composed of two components, i.e., a despeckling generator and a discriminator. The despeckling generator employs the residual-in-residual dense block-based U-shape network to learn how to map the noisy image to the clean image. The discriminator learns to accurately discriminate whether the real clean images are relatively more realistic than the image generated by the generator. To improve the structure preservation ability during speckle noise reduction, the structural similarity index measure (SSIM) loss is introduced into the objective function of DSGAN to achieve more structural constraints. The proposed DSGAN was evaluated and analyzed on two public OCT datasets. The qualitative and quantitative comparison results show that the proposed DSGAN can achieve higher image quality, and is more effective in both speckle noise reduction and structural information preservation than previous despeckling methods.
Optical coherence tomography-based angiography (OCTA) is a high-resolution imaging technology for mapping microvascular networks in vivo. Intensity variance OCTA methods have been developed for blood flow analysis. However, the complex statistical calculations of intensity variances result in high computational costs. In this study, we developed statistical algorithms for simplifying estimates of the intensity variances, including the range, the mean error, and the maximum error algorithms. A rat cerebral cortex was imaged by the simplified algorithms and the conventional algorithm. The number of repeated samplings was compared for the intensity variance analysis. Then the image quality and the calculation time were assessed. The results show that the simplified algorithms can shorten the calculation time and generate microvascular networks with similar image quality compared to the conventional intensity variance OCTA algorithm.
Coagulation tests are essential for diagnosis of blood disorders and treatment of cardiovascular diseases. Here, we developed a noncontact method for quantitative assessment of coagulation properties based on blood diffusion dynamics analysis using optical coherence tomography (OCT). After a blood sample was loaded into a centrifuge tube, an OCT Mscan was captured at a single lateral location. Then the amplitude components of the complex OCT sequences were extracted for autocorrelation analysis. The length of the OCT sequence was optimized for the autocorrelation calculation. The blood dynamics related to scattering particle diffusion were evaluated by the autocorrelation decay over the time delay. The results show that the OCT autocorrelation analysis can quantitatively assess the blood coagulation properties without contact. Therefore, it could be used for in situ monitoring and point-of-care testing of blood coagulation with high reliability.
The elastic properties can be an indicator of pathological changes of biological tissue. Acoustic radiation force optical coherence elastography (ARF-OCE) allows remote, non-invasive assessment of the elastic properties of tissue. In this study, we proposed an acousto-optic coupling ARF-OCE method for the elasticity measurements. The acousto-optic coupling unit employs a rectangular prism with a close refractive index but significantly different acoustic impedance compared to water. Therefore, the surface of the rectangular prism immersed in water can reflect the ultrasound beam while transmitting the optical coherence tomography (OCT) detection beam. We demonstrated the acousto-optic coupling ARFOCE method using agar phantoms. The results show that the ARF-OCE method can induce elastic vibrations in the direction parallel to the OCT beam, resulting in higher detection sensitivity and a larger scanning range.
Optical coherence tomography angiography (OCTA) has been widely used for neuroimaging with non-invasive and high-resolution advantages. However, the signals from the skull and the noise from the deep imaging areas reduce the microvascular clarity in the OCTA projections. Here we proposed a U-Net deep learning method to segment the superficial cortical area from the skull and other tissues for improving the quality of the OCTA projections. The peak signal-to-noise ratio (pSNR) and the average contrast-to-noise ratio (aCNR) were analyzed to evaluate the OCTA projection images. The results showed that the pSNR and aCNR values increased significantly and, thus, the image quality of the microvascular projections was improved after the cortical segmentation.
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