Here, we analytically study the signal digitization procedure in FD-OCT and propose a novel mixed-signal framework to model its time-domain image formation. It turns out that FD-OCT is a shift-variant system, if the conventional IDFT-based technique is used to reconstruct the A-lines. Specifically, both amplitude and phase responses of the system are dependent on the axial location of the input sample. We believe this finding could provide us with new insights towards the image reconstruction of FD-OCT and guide researchers to develop better reconstruction algorithms in the future.
Transcorneal electrical stimulation (TES), which as a noninvasive approach of retinal electrical stimulation, can activate releasing of neurotrophic factors and regenerate injured retinal neurons, has become a potential therapeutic method for retinal diseases. However, the mechanism of TES on the regeneration of retinal neurons has not been completely determined. The purpose of this study was to explore how the depth-resolved intrinsic optical signals (IOSs) and blood flow in cat retina change with TES. In the experiments, the cat retinae were imaged by our custom-designed spectraldomain OCT with a central wavelength of 840nm. OCT scanning and TES were synchronized so as to record images of retina at pre-, during and post-stimulation period, respectively. In each period, the IOSs were then extracted in structure images by registration and segmentation algorithms. And the blood flow was extracted in phase contrast images derived by phase-resolved Doppler OCT method including bulk motion compensation and phase unwrapping. Based on our preliminary results on 5 eyes of 4 cats, we found a significant increase of both positive and negative IOSs in each layer during and after TES compared to those of pre-stimulation and sham stimulation, while the changes of average blood flow before, during and 6 seconds after TES were not obvious. The preliminary results provide experimental data of neurovascular alterations under TES, which will benefit the study of the therapeutic mechanism of TES. But complete understanding of neurovascular response to TES should be further investigated.
Determination of the precise location and degree of condition of the Choroidal neovascularization (CNV) lesion is essential for diagnosation Neovascular age-related macular degeneration (AMD) and evaluation the efficacy of treatment. Given the complimentary contrast mechanisms of Photoacoustic microscopy (PAM) and Optical coherence tomography (OCT), the combination of PAM and OCT imaging could potentially provide much sensitive and specific detection of CNV. In this paper, we validated the opportunity to evaluate the information of laser-induced CNV and presented the in vivo time-serial evaluation of the CNV by simultaneously using PAM and OCT techniques. In vivo PAM and OCT examination was performed after laser photocoagulation applied to the rat fundus at days 1, 3, 5, 7, 14. Time-serial results showed that CNV in rats increased to its maximum at day 7 and decreased at day 14. Evolution of CNV information was given in PAM images with a high contrast and details of high axial resolution OCT images were simultaneously given to show the hyperreflective reaction progress.
Heart pumps blood through the blood vessels to provide body with oxygen and nutrients. As the result, the blood flow, volume and oxygenation in arteries has a pulsatile nature. Measuring these pulsatile parameters enables more precise monitoring of oxygen metabolic rate and is thus valuable for researches and clinical applications. Photoacoustic microscopy (PAM) is a proven label-free method for in vivo measuring blood oxygenation at single blood vessel level. However, studies using PAM to observe the pulsatile nature of blood oxygenation in arteries were not reported. In this paper, we use optical-resolution PAM (OR-PAM) technology to study the blood oxygenation dynamics of pulsatile arteries. First, the ability of our OR-PAM system to accurately reflect the change of optical absorption in imaged objects is demonstrated in a phantom study. Then the system is used to image exposed cortical blood vessels of cat. The pulsatile nature of blood volume and oxygenation in arteries is clearly reflected in photoacoustic (PA) signals, whereas it’s not observable in veins. By using a multi-wavelength laser, the dynamics of the blood oxygenation of pulsatile arteries in cardiac cycles can be measured, based on the spectroscopic method.
KEYWORDS: Blood, Photoacoustic microscopy, Blood vessels, Oxygen, Monte Carlo methods, Absorption, Tissues, Photoacoustic spectroscopy, Sensors, In vivo imaging
Accuracy of photoacoustic signal is the crux on measurement of oxygen saturation in functional photoacoustic imaging, which is influenced by factors such as defocus of laser beam, curve shape of large vessels and nonlinear saturation effect of optical absorption in biological tissues. We apply Monte Carlo model to simulate energy deposition in tissues and obtain photoacoustic signals reaching a simulated focused surface detector to investigate corresponding influence of these factors. We also apply compensation on photoacoustic imaging of in vivo cat cerebral cortex blood vessels, in which signals from different lateral positions of vessels are corrected based on simulation results. And this process on photoacoustic images can improve the smoothness and accuracy of oxygen saturation results.
Laser-scanning optical-resolution photoacoustic microscopy (LSOR-PAM) has a high application potential in ophthalmology and other clinical fields because of its high resolution and imaging speed. The stationary unfocused ultrasonic transducer of this system decides the efficiency and field of view (FOV) of photoacoustic signal detection, but the refraction and attenuation of laser generated photoacoustic signal in different tissue mediums will cause signal strength and direction distribution uneven. In this study, we simulated the photoacoustic signal propagation and detection in compound medium models with different tissue parameters using k-space method based on LSOR-PAM imaging principle. The results show a distance related signal strength attenuation and FOV changes related to transducer angle. Our study provides a method for photoacoustic signal detection optimization for different complex tissue structure with LSOR-PAM.
KEYWORDS: Optical coherence tomography, Gold, Nanoparticles, Silver, Ovarian cancer, Signal to noise ratio, Scattering, Light scattering, In vivo imaging, Nanorods
For OCT imaging, enhancing contrast efficiency will lead to significant improvements in the detection limits in cancer. Recently, noble metal nanoparticles are considered to be better contrast agents than traditional ones, especially for gold and silver. Silver nanoparticles have more attractive optical properties than gold nanoparticles. But they are employed far less because of its poor chemical stability. In this paper, we introduced our recent progress on a new application of using gold/silver alloy nanoparticles as OCT contrast agents in the detection of ovarian cancer. The scattering properties and sensitivity of silver were investigated. By means of tuning LSPR wavelengths of the nanoparticles, they were able to match the central wavelength of light used in OCT. Before carrying out animal experiments, we evaluated the different performances of alloy nanoparticles and gold nanorods in vitro. It has been sufficiently demonstrated that the alloy nanoparticles revealed stronger OCT signals than gold nanorods because of the better scattering properties. Then in vivo study, we compared the contrast enhancement of gold/silver alloy nanoparticles and gold nanorods on the ovarian cancer model mice. This study contributes a new kind of contrast agent in OCT imaging, which has a profound effect on drug delivery and further therapeutic action.
In this work, we set up a denoising module to improve the imaging result for the photoacoustic microscopy (PAM) by improving the signal noise ratio. This module contains a series of data processing methods to reduce the noise from the tissues and the system. This module is adaptive to different imaging systems because of these methods’ intrinsic characteristics. Meanwhile, the parameters are decided based on the property of data being denoised. In this module, firstly data length is limited because each system has its own imaging depth capacity and data outside is mostly noise. Data is filtered in frequency domain in accordance with bandwidth of the imaging system and the image is filtered with the Wiener adaptive filter. Secondly data is presented in time-frequency domain with different time-frequency analysis methods. With the aid of this presentation in time-frequency domain, we can decide denoising parameters based on the characteristics of denoised data. Thirdly data is denoised using wavelet and empirical mode decomposition (EMD) methods. These methods demonstrate strong denoising capacity in the data processing field and are very suitable for processing data from biological tissues. With decided parameters, wavelet and EMD methods are set down and data is denoised automatically to get the best imaging effect instead of processing each data manually with different methods. This denoising module improves the imaging quality and has adaptive ability to reach promising result for different PAM imaging systems.
We presented an improved dual channel dual focus spectral domain optical coherence tomography (SD-OCT) with two illuminations at 840 nm and 1050 nm for whole eye segment imaging and biometry in vivo. The two light beams were coupled and optically optimized to scan the anterior and posterior segment of the eye simultaneously. This configuration with dichroic mirrors integrated in the sample arm enables us to acquire images from the anterior segment and retina effectively with minimum loss of sample signal. In addition, the full resolved complex (FRC) method was applied to double the imaging depth for the whole anterior segment imaging by eliminating the mirror image. The axial resolution for 1050 nm and 840 nm OCT was 14 μm and 8 μm in air, respectively. Finally, the system was successfully tested in imaging the unaccommodated and accommodated eyes. The preliminary results demonstrated the significant improvements comparing with our previous dual channel SD-OCT configuration in which the two probing beams had the same central wavelength of 840 nm.
To research retinal stretching or distortion with accommodation, accommodation-induced changes in retinal thickness (RT) in the macular area were investigated in a population of young adults (n=23) by using a dual-channel spectral domain optical coherence tomography (SD-OCT) system manufactured in-house for this study. This dual-channel SD-OCT is capable of imaging the cornea and retina simultaneously with an imaging speed of 24 kHz A-line scan rate, which can provide the anatomical dimensions of the eye, including the RT and axial length. Thus, the modification of the RT with accommodation can be calculated. A significant decrease in the RT (13.50±1.25 μm) was observed during maximum accommodation. In the 4 mm×4 mm macular area centered at the fovea, we did not find a significant quadrant-dependent difference in retinal volume change, which indicates that neither retinal stretching nor distortion was quadrant-dependent during accommodation. We speculate that the changes in RT with maximum accommodation resulted from accommodation-induced ciliary muscle contractions.
Quantitative analysis of optical clearing effects (OCE) induced by hyperosmotic agents is very important to optical tissue clearing applications in biomedical diagnostic imaging and therapeutics. This study aims at investigating the effect of glycerol concentration on the laser-scanning optical-resolution photoacoustic microscopy (LSOR-PAM) imaging contrast and light penetration depth. The photoacoustic (PA) signal amplitude changes are evaluated as a function of the concentration of glycerol. The results reveal that the PA signal amplitudes are enhanced with the glycerol concentration increasing, and also show that higher concentration of glycerol produces better light penetration and OCE on a phantom. The PA signal amplitude increases only 8.1% for 20% glycerol, but for higher concentrations, the increases are 76% and 165% for 40% and 60% glycerol, respectively. This preliminary study demonstrates that application of glycerol as an optical contrast agent reduces the tissue scattering and is beneficial to PAM imaging and optical diagnosis in clinical dermatology.
Recent reports have suggested that spectral domain optical coherence tomography (SD-OCT) is a useful tool for quantifying the permeability of hyperosmotic agents in various tissues. We report our preliminary results on quantification of glucose diffusion and assessment of the optical attenuation change due to the diffusion of glucose in normal and adenomatous human colon tissues in vitro by using a SD-OCT and then calculated the permeability coefficients (PC) and optical attenuation coefficients (AC). The PC of a 30% aqueous solution of glucose was 3.37±0.23×10 −6 cm/s in normal tissue and 5.65±0.16×10 −6 cm/s in cancerous colon tissue. Optical AC in a normal colon ranged from 3.48±0.37 to 2.68±0.82 mm −1 and was significantly lower than those seen in the cancerous tissue (8.48±0.95 to 3.16±0.69 mm −1 , p<0.05 ). The results suggest that quantitative measurements of using PC and AC from OCT images could be a potentially powerful method for colon cancer detection.
Anti-VEGF therapies have been widely explored for the management of posterior ocular disease, like neovascular
age-related macular degeneration (AMD). Loading anti-VEGF therapies in biodegradable microparticles may enable
sustained drug release and improved therapeutic outcome. However, existing microfabrication processes such as double
emulsification produce drug-loaded microparticles with low encapsulation rate and poor antibody bioactivity. To
overcome these limitations, we fabricate multifunctional microparticles by both single needle and coaxial needle
electrospray. The experimental setup for the process includes flat-end syringe needles (both single needle and coaxial
needle), high voltage power supplies, and syringe pumps. Microparticles are formed by an electrical field between the
needles and the ground electrode. Droplet size and morphology are controlled by multiple process parameters and
material properties, such as flow rate and applied voltage. The droplets are collected and freezing dried to obtain
multifunctional microparticles. Fluorescent beads encapsulated poly(DL-lactide-co-glycolide) acid (PLGA)
microparticles are injected into rabbits eyes through intravitreal injection to test the biodegradable time of microparticles.
It is necessary to apply the spectral-domain optical coherence tomography (SD-OCT) to image the whole eye segment
for practically iatrical application, but the imaging depth of SD-OCT is limited by the spectral resolution of the
spectrometer. By now, no result about this research has been reported. In our study, a new dual channel dual focus OCT
system is adopted to image the whole eye segment. The cornea and the crystalline lens are simultaneously imaged by
using full range complex spectral-domain OCT in one channel, the retina is detected by the other. The new system was
successfully tested in imaging of the volunteer' eye in vivo. The preliminary results presented in this paper
demonstrated the feasibility of this approach.
KEYWORDS: Ray tracing, Eye, Cornea, Monochromatic aberrations, Image quality, Eye models, Zemax, Optical design, Human vision and color perception, LASIK
Using raytracing method (ZEMAX program), the reduction of SA of the whole human eye may be reduced via the
combined effects of asphericity (Q) and the ratio of the front and back surface of an IOL. The overall SA for best image
quality may be defined by Q* when the image position off axis is reduced to that of the paraxial. Our calculations show
the following general features: (1) For a give Q value, the influence on the SA is proportional to the surface power; (2) for minimal whole eye SA, negative Q is needed in IOL; (3) for a given IOL power, the Q* is smaller when the front surface has a smaller power. All above features derived from numerical raytracing method are consistent with analytic formulas.
Purpose: To study correlation among corneal asphericity, higher-order aberrations and visual performance for eyes of
virgin myopia and postoperative laser in situ keratomileusis (LASIK).
Methods: There were 320 candidates 590 eyes for LASIK treatment included in this study. The mean preoperative
spherical equivalence was -4.35±1.51D (-1.25 to -9.75), with astigmatism less than 2.5 D. Corneal topography maps
and contrast sensitivity were measured and analyzed for every eye before and one year after LASIK for the analysis of
corneal asphericity and wavefront aberrations.
Results: Preoperatively, only 4th and 6th order aberration had significant correlation with corneal asphericity and apical
radius of curvature (p<0.001). Postoperatively, all 3th to 6th order aberrations had statistically significant correlation
with corneal asphericity (p<0.01), but only 4th and 6th order aberration had significant correlation with apical radius of
curvature (p<0.05). The asymmetrical aberration like coma had significant correlation with vertical offset of pupil center
(p<0.01). Preoperatively, corneal aberrations had no significant correlation with visual acuity and area under the log
contrast sensitivity (AULCSF) (P>0.05). Postoperatively, corneal aberrations still didn't have significant correlation
with visual acuity (P>0.05), but had significantly negative correlation with AULCSF (P<0.01). Corneal asphericity had
no significant correlation with AULCSF before and after the treatment (P>0.05).
Conclusions: Corneal aberrations had different correlation with corneal profile and visual performance for eyes of
virgin myopia and postoperative LASIK, which may be due to changed corneal profile and limitation of metrics of
corneal aberrations.
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