Glaucoma surgery experiments using digital microscope-integrated optical coherence tomography and OCT-compatible instruments

There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.

Unified deep learning model for predicting fundus fluorescein angiography image from fundus structure image

The prediction of fundus fluorescein angiography(FFA)images from fundus structural images is a cutting-edge research topic in ophthalmological image processing.Prediction comprises estimating FFA from fundus camera imaging,single-phase FFA from scanning laser ophthalmoscopy(SLO),and three-phase FFA also from SLO.Although many deep learning models are available,a single model can only perform one or two of these prediction tasks.To accomplish three prediction tasks using a unified method,we propose a unified deep learning model for predicting FFA images from fundus structure images using a supervised generative adversarial network.The three prediction tasks are processed as follows:data preparation,network training under FFA supervision,and FFA image prediction from fundus structure images on a test set.By comparing the FFA images predicted by our model,pix2pix,and CycleGAN,we demonstrate the remarkable progress achieved by our proposal.The high performance of our model is validated in terms of the peak signal-to-noise ratio,structural similarity index,and mean squared error.

Large-field objective lens for multi-wavelength microscopy at mesoscale and submicron resolution

Conventional microscopes designed for submicron resolution in biological research are hindered by a limited field of view,typically around 1 mm.This restriction poses a challenge when attempting to simultaneously analyze various parts of a sample,such as different brain areas.In addition,conventional objective lenses struggle to perform consistently across the required range of wavelengths for brain imaging in vivo.Here we present a novel mesoscopic objective lens with an impressive field of view of 8 mm,a numerical aperture of 0.5,and a working wavelength range from 400 to 1000 nm.We achieved a resolution of 0.74μm in fluorescent beads imaging.The versatility of this lens was further demonstrated through high-quality images of mouse brain and kidney sections in a wide-field imaging system,a confocal laser scanning system,and a two-photon imaging system.This mesoscopic objective lens holds immense promise for advancing multi-wavelength imaging of large fields of view at high resolution.

Imaging of human parafoveal area with large field of view in adaptive optics line scanning ophthalmoscope

The parafoveal area,with its high concentration of photoreceptors andfine retinal capillaries,is crucial for central vision and often exhibits early signs of pathological changes.The current adaptive optics scanning laser ophthalmoscope(AOSLO)provides an excellent tool to acquire accurate and detailed information about the parafoveal area with cellular resolution.However,limited by the scanning speed of two-dimensional scanning,thefield of view(FOV)in the AOSLO system was usually less than or equal to 2,and the stitching for the parafoveal area required dozens of images,which was time-consuming and laborious.Unfortunately,almost half of patients are unable to obtain stitched images because of their poorfixation.To solve this problem,we integrate AO technology with the line-scan imaging method to build an adaptive optics line scanning ophthalmoscope(AOLSO)system with a larger FOV.In the AOLSO,afocal spherical mirrors in pairs are nonplanar arranged and the distance and angle between optical elements are optimized to minimize the aberrations,two cylinder lenses are orthogonally placed before the imaging sensor to stretch the point spread function(PSF)for sufficiently digitizing light energy.Captured human retinal images show the whole parafoveal area with 55FOV,60 Hz frame rate and cellular resolutions.Take advantage of the 5FOV of the AOLSO,only 9 frames of the retina are captured with several minutes to stitch a montage image with an FOV of 99,in which photoreceptor counting is performed within approximately 5eccentricity.The AOLSO system not only provides cellular resolution but also has the capability to capture the parafoveal region in a single frame,which offers great potential for noninvasive studying of the parafoveal area.

1.3μm broadband swept sources with enhanced nonlinear effects

In this work,a new structure is used to enhance the nonlinear effect in the cavity,which improvesthe performance of the 1.3μm broadband swept source.The swept source adopts a semiconductoroptical amplifier(SOA),a circulator,a coupler,and a tunable filter.In the structure,the lightpasses through the nonlinear medium(SOA)twice in two opposite directions,which excites thenonlinear ffect and increases the performance of the swept source.The tunable filter is based on apolygon rotating mirror and gratings.Traditionally,multiple SOAs are adopted to improve thesweep range and the optical power,which increases the cost and complexity of the swept source.The method proposed in this paper can improve the spectral range and optical power of the sweptsources without additional accessories.For the short-cavity swept source,the power increasesfrom 6 mW to 7.7 mW,and the sweep range increases from 98 nm to 120 nm.The broadband swept sources could have wide applications in biomedical imaging,sensor system,measurementand so on.

Improved wavelet hierarchical threshold filter method for optical coherence tomography image de-noising

According to the speckle feature in Optical coherence tomography(OCT),images with speckleindicate not only noise but also signals,an improved wavelet hierarchical threshold filter(IWHTF)method is proposed.At first,a modified hierarchical threshold-selected algorithm isused to prevent signals from being removed by asssing suitable thresholds for different noiselevels,Then,an improved wavelet threshold function based on two traditional threshold fumnc.tions is proposed to trade-ff betwen speckle removing and sharpness degradation.The de-noising results of an OCT finger skin image shows that the IWHTF method obtains betterobjective evaluation metrics and visual image quality improvement,Whenαa=0.2,β=5.0 andK=1.2,the improved method can achieve 9.58 dB improvement in signal-to-noise ratio,withsharpnesdegraded by 3.81%.

TIME-DOMAIN INTERPOLATION ON GRAPHICS PROCESSING UNIT

The signal processing speed of spectral domain optical coherence tomography(SD-OCT)has become a bottleneck in a lot of medical applications.Recently,a time-domain interpolation method was proposed.This method can get better signal-to-noise ratio(SNR)but much-reduced signal processing time in SD-OCT data processing as compared with the commonly used zeropadding interpolation method.Additionally,the resampled data can be obtained by a few data and coefficients in the cutoff window.Thus,a lot of interpolations can be performed simultaneously.So,this interpolation method is suitable for parallel computing.By using graphics processing unit(GPU)and the compute unified device architecture(CUDA)program model,time-domain interpolation can be accelerated significantly.The computing capability can be achieved more than 250,000 A-lines,200,000 A-lines,and 160,000 A-lines in a second for 2,048 pixel OCT when the cutoff length is L=11,L=21,and L=31,respectively.A frame SD-OCT data(400A-lines×2,048 pixel per line)is acquired and processed on GPU in real time.The results show that signal processing time of SD-OCT can befinished in 6.223 ms when the cutoff length L=21,which is much faster than that on central processing unit(CPU).Real-time signal processing of acquired data can be realized.

Automated cone photoreceptor cell identication in confocal adaptive optics scanning laser ophthalmoscope images based on object detection

Cone photoreceptor cell identication is important for the early diagnosis of retinopathy.In this study,an object detection algorithm is used for cone cell identication in confocal adaptive optics scanning laser ophthalmoscope(AOSLO)images.An effectiveness evaluation of identication using the proposed method reveals precision,recall,and F_(1)-score of 95.8%,96.5%,and 96.1%,respectively,considering manual identication as the ground truth.Various object detection and identication results from images with different cone photoreceptor cell distributions further demonstrate the performance of the proposed method.Overall,the proposed method can accurately identify cone photoreceptor cells on confocal adaptive optics scanning laser ophthalmoscope images,being comparable to manual identication.

Observation of the early blood vessels of cutaneous malignant melanoma using Swept Source Optical Coherence Tomography A ngiography(SS-OCTA)

Melanoma,characterized by high mortality,rapid development and accompanied with angio-genesis is the most typical malignant tumor in skin cancer.Hence,the detection of blood vessels is of much significanoe.The early vascular network has small scale.If we remove the tumor early and biopsy it,it will increase the spread of the cancer cells and infection and bleeding.In this case,we presented a new angiography method.A high-resolution OCT system for noninvasive an-giographic imaging of early skin melanoma-Swept Source Optical Coberence Tomography Angiography(SS-OCTA)is proposed.With a high lateral resolution of 10pm in vrivo tomographic angiography,SS-OCTA is used to image and identify the morphology of the early tumor blood vessels.In addition,a control group experiment is conducted to observe the growth of melanoma in the process of rupture,malormation of micro-vessels.The results of the analysis and statistical test(P<0.05)are statistically signifcant.

HIGH-SPEED SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY SIGNAL PROCESSING WITH TIME-DOMAIN INTERPOLATION USING GRAPHICS PROCESSING UNIT

Sensitivity and data processing speed are important in spectral domain Optical Coherence Tomography(SD-OCT)system.To get a higher sensitivity,zero-padding interpolation together with linear interpolation is commonly used to re-sample the interference data in SD-OCT,which limits the data processing speed.Recently,a time-domain interpolation for SD-OCT was proposed.By eliminating the huge Fast Fourier Transform Algorithm(FFT)operations,the operation number of the time-domain interpolation is much less than that of the zero-padding interpolation.In this paper,a numerical simulation is performed to evaluate the computational complexity and the interpolation accuracy.More than six times acceleration is obtained.At the same time,the normalized mean square error(NMSE)results show that the time-domain interpolation method with cut-offlength L?21 and L?31 can improve about 1.7 dB and 2.1 dB when the distance mismatch is 2.4mm than that of zero-padding interpolation method with padding times M?4,respectively.Furthermore,this method can be applied the parallel arithmetic processing because only the data in the cut-offwindow is processed.By using Graphics Processing Unit(GPU)with compute unified device architecture(CUDA)program model,a frame(400 A-lines
2048 pixels
12 bits)data can be processed in 6 ms and the processing capability can be achieved 164,000 line/s for 1024-OCT and 71,000 line/s for 2048-OCT when the cut-offlength is 21.Thus,a high-sensitivity and ultra-high data processing SD-OCT is realized.

Acceleration of optical coherence tomography signal processing by multi-graphics processing units

A multi-GPU system designed for high-speed,real-time signal processing of optical coherencetomography(OCT)is described herein.For the OCT data sampled in linear wave numbers,themaximum procesing rates reached 2.95 MHz for 1024-OCT and 1.96 MHz for 2048-OCT.Data sampled using linear wavelengths were re-sampled using a time-domain interpolation method and zero-padding interpolation method to improve image quality.The maximum processing rates for1024-OCT reached 2.16 MHz for the time-domain method and 1.26 MHz for the zero-paddingmethod.The maximum processing rates for 2048-0CT reached_1.58 MHz,and 0.68 MHz,respectively.This method is capable of high-speed,real-time processing for O CT systems.

DEVELOPMENT OF HIGH-SPEED SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY SYSTEM AT 1320 nm

A swept-source optical coherence tomography(SSOCT)system based on a high-speed scanning laser source at center wavelength of 1320 nm and scanning rate of 20 kHz is developed.The axial resolution is enhanced to 8.3μm by reshaping the spectrum in frequency domain using a window function and a wave number calibration method based on a Mach-Zender Interferometer(MZI)integrated in the SSOCT system.The imaging speed and depth range are 0.04 s per frame and 3.9 mm,respectively.The peak sensitivity of the SSOCT system is calibrated to be 112 dB.With the developed SSOCT system,optical coherence tomography(OCT)images of human finger tissue are obtained which enable us to view the sweat duct(SD),stratum corneum(SC)and epidermis(ED),demonstrating the feasibility of the SSOCT system for in vivo biomedical imaging.

High-Resolution Multiscale Imaging Enabled by Hybrid Open-Top Light-Sheet Microscopy

1.Introduction Light-sheet fluorescence microscopy(LSFM),since it was first coined the term selective-plane-illumination microscopy(SPIM)by Huisken et al.[1],has been developed for nearly two decades,needless to mention a landmark development of digitally scanned light-sheet microscopy(DSLM)innovated by Keller et al.[2].

Cost Optimal Selection of Storage Tanks in LPG Vaporization Station

Liquefied petroleum gas (LPG) is an important urban gas source in China. Before supplied to customers by pipeline supply systems, LPG is stored in tanks in LPG vaporization stations. Designers usually decide the number and the size of storage tanks by their experience during constructions of vaporization stations. These decisions are usually not best and most economical. To solve the problem, a compact mixed integer nonlinear programming model has been developed in this paper. The objective is to minimize annual storage cost of the vaporization station. The model has been transformed into a general nonlinear programming model by transforming integer variables and 0-1 variables into continuous variables. One LPG vaporization station was taken as an example to illustrate the usage of the model. The results show that the optimal storage scheme can be determined accurately and quickly by the model and about 15% of storage cost can be saved every year after optimization.

Flash nanocomplexation (FNC): A new microvolume mixing method for nanomedicine formulation

The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostics. The advancement of engineering particle design and fabrication is largely supported by a better understanding of how their apparent characteristics(e.g., size and size distribution, surface morphology, colloidal stability, chemical composition) influence their in vivo biological performance, which raises an urgent need for practical nanoformulation methods. Based on turbulent flow mixing and the self-assembly of molecules in fluids, flash technologies emerged as effective bottom-up fabrication strategies for effective nanoformulation. Among the flash technology family, flash nanocomplexation(FNC) is considered a novel and promising candidate that can promote and optimize formulation processes in a precise spatiotemporal manner, thus obtaining excellent fabrication efficiency, reproducibility and expandability. This review presents an overview of recent advances in fabricating drug-delivery nanoparticles using FNC platforms. Firstly, brief introductions to the basic principles of FNC technology were carried out, followed by descriptions of turbulent microvolume mixers that have significantly promoted the efficiency of FNC-based fabrications. Applications of real formulation cases were then categorized according to the self-assembly-driven interactions(including electrostatic interaction, coordination interaction,hydrogen bonding and hydrophobic interaction) and discussed to reveal the progressiveness of fabricating nanoparticles and discuss how its flexibility will provide advances and replenish the philosophy of nanomedicine formulation. In the end, the commercial potential, current limitations, and prospects of FNC technology for nanoformulation will be summarized and discussed.

Accuracy characterization of Shack-Hartmann sensor with residual error removal in spherical wavefront calibration

The widely used Shack-Hartmann wavefront sensor(SHWFS)is a wavefront measurement system.Its measurement accuracy is limited by the reference wavefront used for calibration and also by various residual errors of the sensor itself.In this study,based on the principle of spherical wavefront calibration,a pinhole with a diameter of 1μm was used to generate spherical wavefronts with extremely small wavefront errors,with residual aberrations of 1.0×10^(−4)λRMS,providing a high-accuracy reference wavefront.In the first step of SHWFS calibration,we demonstrated a modified method to solve for three important parameters(f,the focal length of the microlens array(MLA),p,the sub-aperture size of the MLA,and s,the pixel size of the photodetector)to scale the measured SHWFS results.With only three iterations in the calculation,these parameters can be determined as exact values,with convergence to an acceptable accuracy.For a simple SHWFS with an MLA of 128×128 sub-apertures in a square configuration and a focal length of 2.8 mm,a measurement accuracy of 5.0×10^(−3)λRMS was achieved across the full pupil diameter of 13.8 mm with the proposed spherical wavefront calibration.The accuracy was dependent on the residual errors induced in manufacturing and assembly of the SHWFS.After removing these residual errors in the measured wavefront results,the accuracy of the SHWFS increased to 1.0×10^(−3)λRMS,with measured wavefronts in the range ofλ/4.Mid-term stability of wavefront measurements was confirmed,with residual deviations of 8.04×10^(−5)λPV and 7.94×10^(−5)λRMS.This study demonstrates that the modified calibration method for a high-accuracy spherical wavefront generated from a micrometer-scale pinhole can effectively improve the accuracy of an SHWFS.Further accuracy improvement was verified with correction of residual errors,making the method suitable for challenging wavefront measurements such as in lithography lenses,astronomical telescope systems,and adaptive optics.

Methods to improve the performance of the swept source at 1.0 μm based on a polygon scanner

In this work, we investigate the methods to improve the performance of the swept source at 1.0 μm based on a polygon scanner, including in-cavity parameters and booster structures out of the cavity. The three in-cavity parameters are the cavity length, the rotating speed of the polygon scanner, and the in-cavity energy. With the decrease of cavity length, the spectrum bandwidth becomes wider and the duty cycle becomes higher.With the increase of the rotating speed of the polygon, the spectrum bandwidth becomes narrower, and the duty cycle becomes lower but the repetition rate becomes higher. With more energy in-cavity, the spectrum bandwidth becomes wider and the duty cycle becomes higher. The booster structures include the buffered structure, secondary amplifier, and dual-semiconductor optical amplifier configuration, which are used to increase the sweep frequency to 86 kHz, the output power to 18 mW, and the tuning bandwidth to 131 nm, respectively.

Automated superpixels-based identification and mosaicking of cone photoreceptor cells for adaptive optics scanning laser ophthalmoscope

An automated superpixels identification/mosaicking method is presented for the analysis of cone photoreceptor cells with the use of adaptive optics scanning laser ophthalmoscope(AO-SLO) images. This is an image oversegmentation method used for the identification and mosaicking of cone photoreceptor cells in AO-SLO images.It includes image denoising, estimation of the cone photoreceptor cell number, superpixels segmentation, merging of superpixels, and final identification and mosaicking processing steps. The effectiveness of the presented method was confirmed based on its comparison with a manual method in terms of precision, recall, and F1-score of 77.3%, 95.2%, and 85.3%, respectively.