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.
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.
We developed a prototype dual-modal ocular imaging system integrating optical-resolution photoacoustic microscopy and high-frequency ultrasound imaging modalities. This system can perform high-resolution ocular imaging from the anterior region down to the fundus area. The novel system successfully imaged the murine eyes in vivo, including iris, lens, retina, and retinal pigment epithelium. Our results demonstrated that this system has a great potential in the diagnosis of ophthalmic diseases.
Fluorescence molecular tomography (FMT) gains increasing interests in deep tissue imaging. Here we report a novel FMT system setup with full angel projections. In this system, a tungsten-halogen lamp is applied as illumination, while a scientific complementary metal oxide semiconductor (sCMOS) is used as a detecting device. With a unique line-pattern illumination and a high sensitivity sCMOS, our FMT system can complete data acquisition over 36 perspective angles along the animal within 10 minutes. We also employ a novel transparent animal bed, which is suitable to hold the animal for long time experiments. Both phantom and in vivo animal experiments have been studied, and our results demonstrate this FMT system has a great potential for small animal study. In addition, our design allows this FMT system to be easily applied in either stand-alone fluorescent systems or combined with other molecular imaging methods.
By allowing more photons to reach deeper tissue, the optical clearing agent (OCA) has gained increasing attention in various optical imaging modalities. However, commonly used OCAs have high fluidity, limiting their applications in in vivo studies with oblique, uneven, or moving surfaces. In this work, we reported an OCA with high viscosity. We measured the properties of this viscous OCA, and tested its successful performances in the imaging of a living animal’s skin with two optical imaging modalities: photoacoustic microscopy and optical coherence tomography. Our results demonstrated that the viscous OCA has a great potential in the study of different turbid tissues using various optical imaging modalities.
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.
Photoacoustic tomography (PAT) detects ultrasound signals generated by the objects after absorbing illuminating photons. However, the widely used piezoelectric ultrasound transducers are generally not optically transparent, which would cause conflicts between the light illumination and the ultrasonic detection in PAT. We report a different acoustically penetrable optical reflector (APOR) concept to provide a solution to this conflict. We measured the properties of an APOR and experimentally tested its performance in a PAT system. The results demonstrated that the APOR successfully allowed the transducer to detector photoacoustic signals without affecting the light illumination. Moreover, the APOR concept can be readily implemented in various PAT systems.
Ocular imaging plays a key role for the diagnosis of various ocular diseases. In this work, we have developed an ocular
imaging system based on the photoacoustic tomography. This system has successfully imaged the entire eye of a mouse,
from its iris to the retina region, and the imaging is label-free and non-invasively. The resolution of this system reaches
several micron meters, allowing the study of microstructures in various ocular tissues. Our system has the potential to be
a powerful non-invasive imaging method for the ophthalmology.
Fluorescent microscopy has become an essential tool to study biological molecules, pathways and events in living cells, tissues and animals. Meanwhile even the most advanced confocal microscopy can only yield optical resolution approaching Abbe diffraction limit of ~200 nm. This is still larger than many subcellular structures, which are too small to be resolved in detail. These limitations have driven the development of super-resolution optical imaging methodologies over the past decade.
In stimulated emission depletion (STED) microscopy, the excitation focus is overlapped by an intense doughnut-shaped spot to instantly de-excite markers from their fluorescent state to the ground state by stimulated emission. This effectively eliminates the periphery of the Point Spread Function (PSF), resulting in a narrower focal region, or super-resolution. Scanning a sharpened spot through the specimen renders images with sub-diffraction resolution. Multi-color STED imaging can present important structural and functional information for protein-protein interaction.
In this work, we presented a two-color, synchronization-free STED microscopy with a Ti:Sapphire oscillator. The excitation wavelengths were 532nm and 635nm, respectively. With pump power of 4.6 W and sample irradiance of 310 mW, we achieved super-resolution as high as 71 nm. Human respiratory syncytial virus (hRSV) proteins were imaged with our two-color CW STED for co-localization analysis.
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.
Small animal models, such as zebrafish, drosophila, C. elegan, is considered to be important models in comparative
biology and diseases researches. Traditional imaging methods primarily employ several optical microscopic imaging
modalities that rely on fluorescence labeling, which may have potential to affect the natural physiological progress. Thus
a label-free imaging method is desired. Photoacoustic (PA) microscopy (PAM) is an emerging biomedical imaging
method that combines optical contrast with ultrasonic detection, which is highly sensitive to the optical absorption
contrast of living tissues, such as pigments, the vasculature and other optically absorbing organs. In this work, we
reported the whole body label-free imaging of zebrafish larvae and drosophila pupa by PAM. Based on intrinsic optical
absorption contrast, high resolution images of pigments, microvasculature and several other major organs have been
obtained in vivo and non-invasively, and compared with their optical counterparts. We demonstrated that PAM has the
potential to be a powerful non-invasive imaging method for studying larvae and pupa of various animal models.
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.
Analysis and applications of vision correction via accommodating intraocular lens (AIOL) are presented. By Gaussian optics, analytic formulas for the accommodation rate function (M) for two-optics and three-optics systems are derived and compared with the exact numerical results. In a single-optics AIOL, typical value of M is (0.5-1.5) D/mm, for an IOL power of (10-20) diopter. For a given IOL power, higher M is achieved in positive-IOL than negative-IOL. In the dual-optics AIOL, maximum accommodation is predicted when the front positive-optics moves toward the corneal plan and the back negative-optics moves backward. Our analytic formulas predict that greater accommodative rate may be achieved by using a positive-powered front optics, a general feature when either front or back optics is mobile. The M function is used to find the piggy-back IOL power for customized design based on the individual ocular parameters. Many of the new features demonstrated in this study can be easily realized by our analytic formulas, but not by raytracing method.
A fiber-optic bundle-based submillimeter probe for endoscopic common-path optical coherence tomography with focusing system is presented. Three different focusing systems, bulk lenses, a gradient index (GRIN) lens, and a microlens array, are proposed and compared. The simulation results show that all the focusing systems can focus the beam with different degrees of effectiveness. The major differences between the different focusing systems exist in the beam size and the divergence angle between the inner and outer pixels of the fiber bundle. The microlens array shows the smallest change in beam size from the central fiber to the outermost fiber, while the GRIN lens exhibits the largest. Signal-to-noise ratio of the system, taking attenuation and cross talk between adjacent pixels of the fiber bundle into account, is also analyzed.
The signal intensity is derived firstly on the basis of point spread function. Then the effect of pinhole radius on
resolution is discussed for different central obstruction rate
ε. According to the simulated plots, the optimum
relationship of axial resolution to pinhole radius and central obstruction rate ε is proposed. Finally the confocal
imaging system is designed and established. The axial response is measured for different pinhole radius.
Experimental results agree well with theoretical analysis. The in-focus images of bar target is obtained by the
confocal imaging system which shows good performance
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.
A novel endoscopic confocal imaging system is presented by modifying the conventional laser confocal scanning
microscope. Based on point spread function and Fourier optics, the coherent transmission function of the system is
derived and the influence of fiber on axial resolution is investigated in detail. It is shown that the system acts as a
coherent imaging system and the axial resolution of the system decays with increasing fiber radius A. Finally, an
endoscopic confocal imaging system was built, and the in-focus and out-of-focus images of glass grating are obtained,
which show good lateral resolution.
The 1450-nm diode laser has been found to be effective for the treatment of inflammatory acne in USA, Europe and
Japan. However, there is no report on its efficacy in Chinese acne vulgaris patients. We conduct this pilot study to
evaluate the efficacy and safety of the 1450-nm diode laser in the treatment of inflammatory facial acne vulgaris in
Chinese patients. Nineteen patients with inflammatory facial acne were treated with the 1450-nm diode laser at 4- to
6-week intervals. Clinical photographs and lesion counts were obtained at baseline and after each treatment. Subjective
evaluation of response to treatment and pain was assessed using a questionnaire. In our study, clinical improvement was
seen in all patients and was generally dramatic. Lesion counts decreased 34% after one treatment (p<0.01), 56% after
two treatments (p<0.01), and 81% after three treatments (p<0.01). However, the treatment-related pain was
comparatively hard to be tolerated in Chinese patitents, and the other main adverse effect was the hyper-pigmentation
after treatments (36.84%, 7/19).
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.
Many lasers have claimed the clinical efficacy on skin rejuvenation. Systematic and comparative studies are needed to compare different laser effects and probe into the mechanism of laser skin rejuvenation. We performed this study to compare collagen remodeling with different laser effects on mice model in vivo. After depilation, the back skin of KM mice was used for the study. The 595nm pulsed dye laser (10ms), 1320nm Nd:YAG laser(350 ?s), 1064nm Q-switched
(5ns) and long-pulsed Nd:YAG(0.3ms) lasers were applied based on optimal tissue reaction fluence test to irradiate one side of the mice back and leave the other side as the control. Then the collagen remodelling was evaluated at 0, 1, 7, 21, 30 and 60 days, with biophysical parameters' measurements, histological and biochemical examination. All lasers applied showed a statistical improvement in skin elasticity, dermal thickness and synthesis of hydroxyproline compared with their own controls. The Q-switched 1064-nm laser resulted in greater improvement of skin elasticity, dermal
thickness, and higher synthesis of hydroxyproline than the other lasers after two months of treatments, while there was no significant difference among the 595nm, 1320nm and long-pulsed 1064nm lasers. Collagen type III increased markedly after the Q-switched 1064-nm laser treatment whereas more collagen type I was elicited by the 1320-nm laser.
A novel confocal endoscopic imaging system is designed for imaging thick sample. The lateral and axial detected image intensity is deduced and calculated based on point spread function (PSF). The analysis of influence of pinhole and fiber on resolution is given. Our researches show that the lateral resolution improvement is much more sensitive to pinhole size than the axial resolution. Confocal system has narrower half width at half maximum (HWHM) and higher lateral and axial resolution for smaller pinhole. At last a criterion for pinhole size is introduced first of all to ensure confocal imaging and maximize signal-to-noise ratio, which is very helpful in the practical design of confocal endoscopic imaging system.
The pulsed dye laser (PDL) has a history of producing safe and effective clearance of dermal vascular lesions; however, non-ablative treatments of rhytids with 595nm PDL are seldom studied. The purpose of our research is to evaluate the changes of skin elasticity, histology and the amount of hydroxyproline after 595nm PDL non-ablative rejuvenation and to offer references for effective clinical treatments. Forty KM mice were used for this experiment. Laser parameters were as follows: an energy fluence of 8 to 12J/cm2, a pulse duration of 10ms, and a spot size of 7mm with 10% overlap. Skin elasticity was measured using Reviscometer RVM 600. Specimens were sectioned for hematoxylin-eosin and Van-Gieson staining, and dermal thickness was recorded in an ocular micrometer. The amount of hydroxyproline in the dermis was quantified by the biochemical method. No marked side effects such as blister and purpura were noted during laser treatments. New collagen synthesized with an improvement in the organization of collagen fibrils. The 12 J/cm2 group improved skin elasticity by 31.7%, dermal thickness by 25.3% and the amount of hydroxyproline by 55.9%. There were the good correlations between dermal thickness and the amount of hydroxyproline. Therefore 595nm PDL non-ablative photo-rejuvenation is a safe and effective method for wrinkle reduction. And the energy level of 12 J/cm2 has the greatest effect in improving skin mechanical properties and accelerating new collagen formation.
Three optometry methods which include auto-refractor, wavefront aberrometer and subjective manual refraction were studied and compared in measuring low order aberrations of 60 people’s 117 normal eyes. Paired t-test and linear regression were used to study these three methods’ relationship when measuring myopia with astigmatism. In order to make the analysis more clear, we divided the 117 normal eyes into different groups according to their subjective manual refraction and redid the statistical analysis. Correlations among three methods show significant in sphere, cylinder and axis in all groups, with sphere’s correlation coefficients largest(R>0.98, P<0.01) and cylinder’s smallest (0.900.01). Auto-refractor had significant change from the other two methods when measuring cylinder (P<0.01). The results after grouping differed a little from the analysis among total people. Although three methods showed significant change from each other in certain parameters, the amplitude of these differences were not large, which indicated that the coherence of auto-refractor, wavefront aberrometer and subjective refraction is good. However, we suggested that wavefront aberration measurement could be a good starting point of optometry, subjective refraction is still necessary for refinement.
Purpose: To study how test results of wavefront aberrations are affected by displacement during wavefront measurement.
Methods: A Shack-Hartmann based wavefront sensor was used to measure an artificial eye at controlled positions along axial and lateral directions. We use deviation amplitude and relative deviation amplitude to study the changes of reconstructed wavefront aberrations during the displacement within 1.00 mm. The analysis was performed with a 4th-order Zernike polynomial expansion with the 0th-order (piston) and 1st-order (tip and tilt) removed. RMS of the whole and each order are studied.
Results: Effects caused by movement along axis within 1.00 mm are not apparent. A dramatic change was observed in relative deviation amplitude during the movement off the center, although the absolute value of changes are small. The changes are highly polynomials depended. RMS stays relatively stable during both procedures.
Conclusions: When wavefront aberration is introduced into customized refractive surgery, it is important for physicians to align the device during measurements, particularly in lateral direction.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.