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.
Optical coherence tomography (OCT) is a non-invasive, label-free imaging modality that generates high-resolution threedimensional images. Based on OCT imaging, optical coherence tomography angiography (OCTA) and optical coherence elastography (OCE) can visualize vascular networks and measure the elastic properties of biological tissues. In previous studies, OCTA and OCE were performed separately, providing either vascular network information or elasticity properties of the tissue. We have developed a simultaneous angiography and elastography method using a simplified sample arm structure. After mechanical pressure is loaded on the sample by a glass plate, the deformation is analyzed by the OCT phase changes, and the elasticity is assessed. Meanwhile, the vascular network is visualized by intensity-based Doppler variance analysis. A transparent flexible reference layer is placed between the glass plate and the tissue, which closely contacts the tissue. Better elasticity measurements can be achieved without affecting vascular imaging. The simultaneous elastography and angiography method was demonstrated by the phantom experiments and rat skin measurements. The results show that the information on the microvascular networks and mechanical properties can be obtained at the same imaging location. The method can provide more comprehensive information on biological tissue for disease diagnosis and treatment monitoring.
Optical coherence tomography angiography (OCTA) is a label-free, high-resolution imaging technique for detecting blood flow based on optical coherence tomography (OCT) and time-series signal analysis. In OCTA, the time-series signals at the same position are captured, and the changes in the signals are analyzed to detect the blood flow. In this study, we evaluated different scan protocols for the OCTA regarding image quality and sampling time, including the dense A-scan, dense B-scan, and multiple B-scan protocols. In the dense A-scan or the dense B-scan protocols, the beam continues scanning with a slight change between adjacent positions. Whereas, the scan beam will pause at each slow scan position to repeatedly capture the B-scans in the multiple B-scan protocol. After the time-series signals were captured using different scan protocols and analyzed using an OCTA algorithm, the vasculature of the rat tissue was visualized. The image quality was analyzed to assess the efficiency of the scan protocols. The quantitative evaluation of the scan protocols allows for optimizing the sampling schemes in the OCTA imaging of biological tissues.
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.
In this paper, the method using lensless microscopic imaging techniques, to reconstruct the three-dimensional morphology of tumor cells is given. We demonstrate lensless microscopic platform which only use a CMOS image sensor and a controllable color LED array. Based on the principle of lensless computational imaging, we use the phase recovery algorithm under multi-wavelength and the diffraction tomography algorithm under multi-angle illumination, to reconstruct the three-dimensional morphology of tumor cells. Experiments have verified that this method can achieve large field of view imaging without labeling and reconstruct the three-dimensional morphology of tumor cells, which provides reliable morphological parameters for clinical research and is of great significance to the development of portable medical care.
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 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.
The deformability of red blood cells is the main factor affecting blood flow and viscosity, and the study of red blood cells (RBCs) deformability is an important subject of hemorheology. At present, most of the measurement methods for red blood cell deformability are achieved by physical contact with cells or static measurement, and non-destructive high-throughput detection methods still need to be studied. A high throughput measurement method of human red blood cells deformability combined with optical tweezers technology and the microfluidic chip was proposed to accurately characterize the deformability of RBCs statistically. Firstly, the effective stretching deformation of RBCs was realized by the interaction of photo-trapping force and fluid viscous resistance. Secondly, the characteristic parameters before and after the deformation of the single cell were extracted through the image processing method to obtain the deformation index of area and circumference. Finally, statistical analysis was performed, and the average deformation index parameters were used to characterize the deformability of RBCs. A high-throughput detection system was built, and the optimal experimental conditions were obtained through a large number of experiments. Several groups of samples with different deformability were used for statistical verification. The results show that high-throughput detection and characterization methods can effectively distinguish different deformed RBCs statistically, which provides a solution for high-throughput deformation analysis of other types of samples.
Speckle noise in optical coherence tomography (OCT) images seriously degrades the image quality and impairs the subsequent diagnosis of various ocular diseases. Most of the existing deep learning-based denoising models pay little attention to edge preservation, and rely on the large number of reference clean images which are hard to acquire in clinical OCT practice. In this work, an unsupervised retinal OCT image denoising model, named as edge-enhanced generative adversarial network (EEGAN), is proposed to free the dependence on reference clean images and enhance the edge information. Specifically, considering the noisy OCT image can be roughly divided into noisy retinal foreground and noise-only background regions, the generator of EEGAN is designed to denoise the noisy foreground samples based on the residual dense blocks, while the discriminator of EEGAN is employed to distinguish the real background noise samples from the fake noise samples, i.e., the difference images between the noisy foreground samples and its generated counterparts. As retinal edge details are the most vital information for disease diagnosis, an edge enhancement layer based on Sobel operators is integrated into the generator of EEGAN to strengthen the edge preservation ability of the model. Experimental results on clinical retinal OCT datasets show that our model has a better performance than the compared models in suppressing noise and preserving details, demonstrating the effectiveness of the proposed EEGAN.
Because of the shortcomings of the main methods used to analysis single cell, the need of single living cell analysis with no damage, unmarked and in situ dynamic multi-parameter measurement is urgent in the life sciences and biomedical advanced research field. And the method of for living cells analysis is proposed. The spectral pretreatment technology of living cell is the key work of laser confocal Raman spectroscopy. To study the spectrum processing methods for Raman spectrum on single living cell and develop the pre-process techniques to enhance the signal-to-noise ratio, sensitivity, and decrease the influence of fluorescence, elimination the cosmic rays was used to improve the spectrum. The classification, average and filtration of spectrum were applied to enhance signal-to-noise ratio. The fluorescence was depressed for quantity analysis or utilized for analysis by comparing the background and the spectrum. The results show that the proposed technique for laser confocal Raman spectrum of single cell can perform the sensitive and weak intensity peaks and reflect the information of molecules structures very well.
Because of the global characteristic of the Fourier transform method for fringe pattern analysis, it has been extensively
developed and widely used in optical metrology. Many other works were published afterward; however, the spatial
spectrum characteristic of the Fourier transform method has not been fully and systematically investigated. The spatial spectrum characteristic and its relationship with factors such as the quantization of grey levels, random noise, and spatial carrier frequency are discussed. The results indicate that, the maximum bandwidth can be measured by the Fourier transform method is close to Nyquist sampling theorem. That provides a theoretical quantitative basis for the study of extending the measurement range of the Fourier transform method, also builds the relationship between the spatial frequency can be measured and the resolution of interferogram detector.
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