Laser spectroscopy imaging technique coupled withnanomaterials for cancer diagnosis: A review

Laser spectroscopic imaging techniques have received tremendous attention in the-eld of cancer diagnosis due to their high sensitivity,high temporal resolution,and short acquisition time.However,the limited tissue penetration of the laser is still a challenge for the in vivo diagnosis of deep-seated lesions.Nanomaterials have been universally integrated with spectroscopic imaging techniques for deeper cancer diagnosis in vivo.The components,morphology,and sizes of nanomaterials are delicately designed,which could realize cancer diagnosis in vivo or in situ.Considering the enhanced signal emitting from the nanomaterials,we emphasized their combination with spectroscopic imaging techniques for cancer diagnosis,like the surface-enhanced Raman scattering(SERS),photoacoustic,fluorescence,and laser-induced breakdown spectroscopy(LIBS).Applications ofthe above spectroscopic techniques offer new prospectsfor cancer diagnosis.

Imaging through scattering layers using a near-infrared low-spatial-coherence fiber random laser

Optical memory effect-based speckle-correlated technology has been developed for reconstructing hidden objectsfrom disordered speckle patterns,achieving imaging through scattering layers.However,the lighting efficiency and fieldof view of existing speckle-correlated imaging systems are limited.Here,a near-infrared low spatial coherence fiberrandom laser illumination method is proposed to address the above limitations.Through the utilization of random Rayleighscattering within dispersion-shifted fibers to provide feedback,coupled with stimulated Raman scattering for amplification,a near-infrared fiber random laser exhibiting a high spectral density and extremely low spatial coherence is generated.Based on the designed fiber random laser,speckle-correlated imaging through scattering layers is achieved,with highlighting efficiency and a large imaging field of view.This work improves the performance of speckle-correlated imagingand enriches the research on imaging through scattering medium.

Laser speckle contrast imaging to predict the effect of temporary spinal cord stimulation in postherpetic neuralgia patients: A prospective observational study

Temporary spinal cord stimulation(tSCS)can effectively reduce the pain and severity of postherpetic neuralgia(PHN).However,there are no effective and objective methods for predicting the effects of tSCS on PHN.Laser speckle contrast imaging(LSCI)is frequently used in neurology to evaluate the effectiveness of treatment.To assess the accuracy of LSCI in predicting the impact of tSCS on PHN,14 adult patients receiving tSCS treatments for spinal nerve-innervated(C6-T2)PHN participated in this observational study.Visual analog scale(VAS)assessments and LSCI bloodflow images of the-ngers were recorded after the tSCS procedure.The results showed that the VAS scores of all patients decreased signi-cantly.Moreover,the bloodflow index(BFI)values were signi-cantly higher than they were before the procedure.Increased bloodflow and pain alleviation were positively correlated.The-ndings indicated that spinal nerve PHN(C6-T2)was signi-cantly reduced by tSCS.Pain alleviation by tSCS was positively correlated with increased bloodflow in the hand.The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.

In vivo pilot study into superficial microcirculatory characteristics of colorectal adenomas using novel high-resolution magnifying endoscopy with blue laser imaging

BACKGROUND No studies have yet been conducted on changes in microcirculatory hemody-namics of colorectal adenomas in vivo under endoscopy.The microcirculation of the colorectal adenoma could be observed in vivo by a novel high-resolution magnification endoscopy with blue laser imaging(BLI),thus providing a new insight into the microcirculation of early colon tumors.AIM To observe the superficial microcirculation of colorectal adenomas using the novel magnifying colonoscope with BLI and quantitatively analyzed the changes in hemodynamic parameters.METHODS From October 2019 to January 2020,11 patients were screened for colon adenomas with the novel high-resolution magnification endoscope with BLI.Video images were recorded and processed with Adobe Premiere,Adobe Photoshop and Image-pro Plus software.Four microcirculation parameters:Microcirculation vessel density(MVD),mean vessel width(MVW)with width standard deviation(WSD),and blood flow velocity(BFV),were calculated for adenomas and the surrounding normal mucosa.RESULTS A total of 16 adenomas were identified.Compared with the normal surrounding mucosa,the superficial vessel density in the adenomas was decreased(MVD:0.95±0.18 vs 1.17±0.28μm/μm2,P<0.05).MVW(5.11±1.19 vs 4.16±0.76μm,P<0.05)and WSD(11.94±3.44 vs 9.04±3.74,P<0.05)were both increased.BFV slowed in the adenomas(709.74±213.28 vs 1256.51±383.31μm/s,P<0.05).CONCLUSION The novel high-resolution magnification endoscope with BLI can be used for in vivo study of adenoma superficial microcirculation.Superficial vessel density was decreased,more irregular,with slower blood flow.

Role of wide-field autofluorescence imaging and scanning laser ophthalmoscopy in differentiation of choroidal pigmented lesions

·AIM:Toevaluatethe diagnostic properties of wide-field fundus autofluorescence(FAF) scanning laser ophthalmoscope(SLO) imaging for differentiating choroidal pigmented lesions.·METHODS: A consecutive series of 139 patients were included, 101 had established choroidal melanoma with13 untreated lesions and 98 treated with radiotherapy.Thirty-eight had choroidal nevi. All patients underwent a full ophthalmological examination, undilated wide-field imaging, FAF and standardized US examination. FAF images and imaging characteristics from SLO were correlated with the structural findings in the two patient groups.·RESULTS: Mean FAF intensity of melanomas was significantly lower than the FAF of choroidal nevi. Only 1out of 38 included eyes with nevi touched the optic disc compared to 31 out of 101 eyes with melanomas. In 18 out of 101 melanomas subretinal fluid was seen at the pigmented lesion compared to none seen in eyes with confirmed choroidal nevi. In 'green laser separation', a trend towards more mixed FAF appearance of melanomas compared to nevi was observed. The mean maximal and minimal transverse and longitudinal diameters of melanomas were significantly higher than those of nevi.·CONCLUSION: Wide-field SLO and FAF imaging may be an appropriate non-invasive diagnostic screening tool to differentiate benign from malign pigmented choroidal lesions.

Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and confocal laser endomicroscopy

AIM:To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnifica-tion endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS:Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and tratment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stom-achs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with whitelight imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the "microvascular pattern and surface pattern" classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI:78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by MENBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI:73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar's test (P < 0.05). CONCLUSION:Higher diagnostic accuracy, sensitivityand specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.

Laser Ablation Atomic Beam Apparatus with Time-Sliced Velocity Map Imaging for Studying State-to-State Metal Reaction Dynamics

We report a newly constructed laser ablation crossed molecular beam apparatus, equipped with time-sliced velocity map imaging technique, to study state-to-state metal atom reaction dynamics. Supersonic metal atomic beam is generated by laser vaporization of metal rod, and free expansion design without gas flow channel has been employed to obtain a good quality of metal atomic beam. We have chosen the crossed-beam reaction Al＋O2 to test the performance of the new apparatus. Two-rotational-states selected AIO（X^2∑＋, v=0, N and N＋I4） products can be imaged via P（N） and R（N＋14） branches of the Av=l band at the same wavelength, during （1＋1） resonance-enhanced multi-photon ionization through the AIO（D2E＋） intermediate state. In our experiment at 244.145 nm for simultaneous transitions of P（15） and R（29） branch, two rings in slice image were clearly distinguishable, corresponding to the AiO（v=0, N=IS） and AIO（v=0, N=29） states respectively. The energy difference between the two rotational levels is 403 cm^-1. The success of two states resolved in our apparatus suggests a better collisional energy resolution compared with the recent research study [J. Chem. Phys. 140, 214304 （2014）].

A New Method for Evaluating Regional Cerebral Blood Flow Changes:Laser Speckle Contrast Imaging in a C57BL/6J Mouse Model of Photothrombotic Ischemia

The present study aimed to improve the processing of data acquired from laser speckle contrast imaging（LSCI） to provide a standardization method to explore changes in regional cerebral blood flow（r CBF） and to determine the correlations among r CBF, cerebral ischemic lesion volume and microvascular density over time in a focal ischemic region. C57BL/6J mice were subjected to focal photothrombotic（PT） ischemia. r CBF was measured using LSCI at different time points before and after PT ischemia through an intact skull. Standardized r CBF（Sr CBF）, defined as the ratio of r CBF measured in the ipsilateral region of interest（ROI） to that in the corresponding contralateral region, was calculated to evaluate potential changes. In addition, the volume of the ischemic lesion and the microvascular density were determined using Nissl staining and immunofluorescence, respectively. The relationships among the ischemic lesion volume, microvascular density and Sr CBF were analyzed over time. The results showed that the cortical r CBF measured using LSCI following PT ischemia in the C57BL/6J mice gradually increased. Changes in the cerebral ischemic lesion volume were negatively correlated with Sr CBF in the ischemic region. Changes in the microvascular density were similar to those observed in Sr CBF. Our findings indicate that LSCI is a practical technique for observing changes in murine cortical r CBF without skull opening and for analyzing the relationships among the ischemic lesion volume, microvascular density and Sr CBF following focal cerebral ischemia. Preliminary results also suggest that the use of LSCI to observe the formation of collateral circulation is feasible.

First commissioning results of the coherent scattering and imaging endstation at the Shanghai soft X-ray free-electron laser facility

The Shanghai soft X-ray free-electron laser(SXFEL)user facility project started in 2016 and is expected to be open to users by 2022.It aims to deliver ultra-intense coherent femtosecond X-ray pulses to five endstations covering a range of 100–620 eV for ultrafast X-ray science.Two undulator lines are designed and constructed,based on different lasing modes:self-amplified spontaneous emission and echo-enabled harmonic generation.The coherent scattering and imaging(CSI)endstation is the first of five endstations to be commissioned online.It focuses on high-resolution single-shot imaging and the study of ultrafast dynamic processes using coherent forward scattering techniques.Both the single-shot holograms and coherent diffraction patterns were recorded and reconstructed for nanoscale imaging,indicating the excellent coherence and high peak power of the SXFEL and the possibility of‘‘diffraction before destruction’’experiments at the CSI endstation.In this study,we report the first commissioning results of the CSI endstation.

Active hyperspectral imaging with a supercontinuum laser source in the dark

An active hyperspectral imaging(HSI) system was built with a supercontinuum(SC) laser illuminator and a visible/near-infrared hyperspectral camera, which was used for object spectrum detection in the dark. It was demonstrated that the Gaussian-like distribution of the SC illuminator can still be used for accurate reflectance spectrum measurement once the illuminator was characterized in advance. The validity of active HSI results was demonstrated by comparison with passive results. Then, the active HSI system was used to acquire reflectance spectra of different objects in just one pushbroom measurement successfully. With algorithms of principal component analysis clustering and unsupervised K-means spectral classification, this active HSI system with high spectral and spatial resolutions was demonstrated to be efficient and applicable for specific spectrum detections.

Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update

Adaptive optics scanning laser ophthalmoscopy（AOSLO） has been a promising technique in funds imaging with growing popularity. This review firstly gives a brief history of adaptive optics（AO） and AO-SLO. Then it compares AO-SLO with conventional imaging methods（fundus fluorescein angiography, fundus autofluorescence, indocyanine green angiography and optical coherence tomography） and other AO techniques（adaptive optics flood-illumination ophthalmoscopy and adaptive optics optical coherence tomography）. Furthermore, an update of current research situation in AO-SLO is made based on different fundus structures as photoreceptors（cones and rods）, fundus vessels, retinal pigment epithelium layer, retinal nerve fiber layer, ganglion cell layer and lamina cribrosa. Finally, this review indicates possible research directions of AO-SLO in future.

Improving sampling depth of laser speckle imaging by topical optical clearing:A theoretical and in vivo study

The effect of optical cleaning method combined with laser speckle imaging(LSI)was discussed to improve the detection depth of LSI due to high scattering characteristics of skin,which limit its clinical application.A double-layer skin tissue model embedded with a single blood vessel was established,and the Monte Carlo method was used to simulate photon propagation under the action of light-permeating agent.808 nm semiconductor and 632.8 nm He–Ne lasers were selected to study the e®ect of optical clearing agents(OCAs)on photon deposition in tissues.Results show that the photon energy deposition density in the epidermis increases with the amount of tissue°uid replaced by OCA.Compared with glucose solution,polyethylene glycol 400(PEG 400)and glycerol can considerably increase the average penetration depth of photons in the skin tissue,thereby raising the sampling depth of the LSI.After the action of glycerol,PEG 400,and glucose,the average photon penetration depth is increased by 51.78%,51.06%,and 21.51%for 808nm,68.93%,67.94%,and 26.67%for 632.8 nm lasers,respectively.In vivo experiment by dorsal skin chamber proves that glycerol can cause a substantial decrease in blood°ow rate,whereas PEG 400 can signicantly improve the capability of light penetration without a®ecting blood velocity,which exhibits considerable potential in the monitoring of blood°ow in skin tissues.

Laser speckle contrast imaging for monitoring of acutepancreatitis at ischemia-reperfusion injury of thepancreas in rats

The influence of ischemia-reperfusion(I/R)action on pancreatic blood flow(PBF)and the development of acute pancreatitis(AP)in laboratory rats is evaluated in vivo by using the laser speckle contrast imaging(LSCI).Additionally,the optical properties in norm and under condition of AP in rats were assessed using a modied integrating sphere spectrometer and inverse Monte Carlo(IMC)software.The results of the experimental study of microcirculation of the pancreas in 82 rats in the ischemic model are presented.The data obtained conrm the fact that local ischemia and changes in the blood°ow velocity of the main vessels cause and provoke acute pancreatitis.

Low-cost photoacoustic imaging systems based on laser diode and light-emitting diode excitation

Photoacoustic imaging,an emerging biomedical imaging modality,holds great promise for preclinical and clinical researches.It combines the high optical contrast and high ultrasound resolution by converting laser excitation into ultrasonic emission.In order to generate photoacoustic signal e±-ciently,bulky Q-switched solid-state laser systems are most commonly used as excitation sources and hence limit its commercialization.As an alternative,the miniaturized semiconductor laser system has the advantages of being inexpensive,compact,and robust,which makes a signi¯cant e®ect on production-forming design.It is also desirable to obtain a wavelength in a wide range from visible to nearinfrared spectrum for multispectral applications.Focussing on practical aspect,this paper reviews the state-of-the-art developments of low-cost photoacoustic system with laser diode and light-emitting diode excitation source and highlights a few representative installations in the past decade.

High-resolution x-ray monochromatic imaging for laser plasma diagnostics based on toroidal crystal

Monochromatic x-ray imaging is an essential method for plasma diagnostics related to density information.Large-field high-resolution monochromatic imaging of a He-like iron(Fe XXV)Kαcharacteristic line(6.701 keV)for laser plasma diagnostics was achieved using a developed toroidal crystal x-ray imager.A high-index crystal orientation Ge(531)wafer with a Bragg angle of 75.37°and the toroidal substrate were selected to obtain sufficient diffraction efficiency and compensate for astigmatism under oblique incidence.A precise offline assembly method of the toroidal crystal imager based on energy substitution was proposed,and a spatial resolution of 3-7μm was obtained by toroidal crystal imaging of a 600 line-pairs/inch Au grid within an object field of view larger than 1.0 mm.The toroidal crystal x-ray imager has been successfully tested via side-on backlight imaging experiments of the sinusoidal modulation target and a 1000 line-pairs/inch Au grid with a linewidth of 5μm using an online alignment method based on dual positioning balls to indicate the target and backlighter.This paper describes the optical design,adjustment method,and experimental results of a toroidal crystal system in a laboratory and laser facility.

ASSESSMENT OF OPTICAL CLEARING INDUCED IMPROVEMENT OF LASER SPECKLE CONTRAST IMAGING

Laser Speckle Contrast Imaging(LSCI)plays an important role in studying blood flow,but suffers from limited penetration depth of light in turbid tissue.The strong scattering of tissue obviously reduces the image contrast which decreases the sensitivity to flow velocity.Some image processing or optical clearing methods have been proposed to lessen the deficiency,but quantitative assessment of improvement is seldom given.In this study,LSCI was applied to monitor the blood flow through a capillary embedded within various tissue phantoms at depths of 0.25,0.45,0.65,0.85 and 1.05 mm,and the flow velocity in capillary was controllable from 0 to 4mm/s.Here,glycerol,a common optical clearing agent,was mixed with Intralipid at different volume ratio to make the reduced scattering coefficient of tissue phantom decrease from 13.00 to 0.50 cm−1.The quantitative analysis demonstrates that the optical clearing method can obviously enhance the image contrast,imaging depth,and sensitivity to blood flow velocity.Comparing the Laser Speckle Contrast Analysis methods and the optical clearing method,we find that for typical turbid tissue,the sensitivity to velocity estimated by the Laser Speckle Temporal Contrast Analysis(LSTCA)is twice of that by the Laser Speckle Spatial Contrast Analysis(LSSCA);while the sensitivity to velocity estimated by using the two analysis methods has a 10-fold increase,respectively,if addition of glycerol makes the reduced scattering coefficient of tissue phantom decrease by 30%.Combining the LSTCA and the optical clearing method,the sensitivity to flow velocity will be further enhanced.

Polarimetric Laser Range-Gated Underwater Imaging

For conventional laser range-gated underwater imaging （RG[） systems, the target image is obtained based oil the reflective character of the target. One of the main performance limiting factors of conventional RGI is that, when the underwater target has the same reflectivity as the background, it is difficult to distinguish the target from the background. An improvement is to use the polarization components of the reflected light. On the basis of conventional RGI, we propose a polarimetric RGI system that employs a polarization generator and a polarization analyzer to detect and recognize underwater objects. Experimental results demonstrate that, by combining polarization with intensity information, we are better able to enhance identification of the underwater target from other objects of the same reflectivity.

Digital Receiver for Laser Imaging Radar

With the extension of the application domains for laser imaging radar, it is necessary to find a new technical way to obtain high technical performance and adaptive ability. In this paper, A new concept of digital receiver of laser imaging radar system is presented. This digital receiver is defined as a time varying parameter receiver which possesses large dynamics region and time domain filter. The receiver’s mode, component structure as well as every function of its processing are described. The results and laboratorial data show the feasibility of digital reception. Also, it can exploit the inherent nature of laser imaging radar to obtain high probability of detection.

Real time detection of antibody-antigen interaction using a laser scanning confocal imaging-surface plasmon resonance system

A laser scanning confocal imaging-surface plasmon resonance （LSCI-SPR） instrument integrated with a wavelength-dependent surface plasmon resonance （SPR） sensor and a laser scanning confocal microscopy （LSCM） is built to detect the bonding process of human IgG and fluorescent-labeled affinity purified antibodies in real time. The shifts of resonant wavelength at different reaction time stages are obtained by SPR, corresponding well with the changes of the fluorescence intensity collected by using LSCM. The instrument shows the merits of the combination and complementation of the SPR and LSCM, with such advantages as quantificational analysis, high spatial resolution and real time monitor, which are of great importance for practical applications in biosensor and life science.

Three-dimensional coherent diffraction imaging of Mie-scattering spheres by laser single-orientation measurement

Three-dimensional imaging with single orientation is a potential and novel technique. We successfully demonstrate that three-dimensional（3D） structure can be determined by a single orientation diffraction measurement for a phase object of double-layer Mie-scattering silica spheres on a Si3N4 membrane. Coherent diffraction pattern at high numerical aperture was acquired with an optical laser, and the oversampled pattern was projected from a planar detector onto the Ewald sphere.The double-layered spheres are reconstructed from the spherical diffraction pattern and a 2D curvature-corrected pattern,which improve convergence speed and stability of reconstruction.