A chorismate mutase from Radopholus similis plays an essential role in pathogenicity

In the process of infecting plants, plant parasitic nematodes release a series of proteins that play an essential role in the successful infection and pathogenesis of plant cells and tissues through stylets or body walls. In this study,based on transcriptome data, a chorismate mutase gene of Radopholus similis(RsCM) was identified and cloned,which is a single copy gene specifically expressed in the oesophageal gland and highly expressed in juveniles and females. Transient expression of RsCM in tobacco leaves showed that it was localised in the cytoplasm and nucleus of tobacco leaf cells, which inhibited the pattern-triggered immunity(PTI) induced by flg22, including callose deposition and defence gene expression, and cell death induced by immune elicitors BAX, but could not inhibit cell death induced by immune elicitors Gpa2/RBP-1. The RNA interference(RNAi) transgenic tomato of RsCM obviously inhibited the infection, pathogenicity, and reproduction of R. similis. However, the resistance of the overexpression transgenic tomato of RsCM to R. similis infection was significantly reduced, and the expression levels of two salicylic acid(SA) pathway genes(PR1 and PR5) in roots infected by the nematode were significantly down-regulated,which indicated that RsCM might be involved in the inhibition of SA pathway. The results of this study demonstrate that RsCM suppresses the host immune system and might be a new target for the control of R. similis, which also provides new data for the function and mechanism of CM genes of migratory parasitic plant nematodes.

PHOTOACOUSTIC VISCOELASTICITY IMAGING OF BIOLOGICAL TISSUES WITH INTENSITY-MODULATED CONTINUOUS-WAVE LASER

In this paper,a novel photoacoustic viscoelasticity imaging(PAVEI)technique that provides viscoelastic infornation of biological tissues is presented.We deduced the proocess of photoacoustic(PA)ffct on the basis of thermal viscoelasticity theory and est ablished the relationship between the PA phase delay and the vicoelasticity for soft solids.By detecting the phase delay of PA signal,the viscoelasticity distribution of absorbers can be mapped.Gelatin phantoms with diferent densities and different absorption cofficients were used to verify the dependence of PA VEI measurements.Moreover,tissue mimicking phantoms mixed with fat and collagen at different concentrations were used to testify the feasibility of this technique with reli able contrast.Finally,the PAVEI was sucossfully applied to discrimination between biological tissue constituents.Our experimental results demonstrate that this novel technique has the potential for visualizing the anatomical and biomechanical properties of biological tissues.

CONTRAST-ENHANCED PHOTOACOUSTIC IMAGING USING INDOCYANINE GREEN-CONTAINING NANOPARTICLES

Contrast agents are attracting a great deal of attention in photoacoustic inaging.Here weintroduce an exogenous contrast agent that provides high photoacoustic signal amplitude at thenear-infrared wavelength._Our_agents consist_of Indocyanine green(ICG)and phospholi-pid-polyethylene glycol(PL-PEG),entitled ICG-PL-PEG nanoparticles,These nanoparticleshave overcome numerous limitations of ICG,such as poor aqueous stability,concentration-dependent aggregation and lack of target specificity.ICG-PL-PEG nanoparticles are bio-compatible and relatively nontoxic.All the components of ICG-PL-PEG nanoparticles havebeen approved for human use.Upon pulsed laser irradiation,the nanoparticles are more eficient inproducing photoacoustic waves than ICG alone.The results showed that ICG-PL-PEG nano-particles act as good contrast agents for photoacoustic imaging.These unique ICG-PL-PEGnanoparticles have great potential in clinical applications.

Spatial weight matrix in dimensionality reduction reconstruction for microelectromechanical system-based photoacoustic microscopy

A micro-electromechanical system(MEMS)scanning mirror accelerates the raster scanning of optical-resolution photoacoustic microscopy(OR-PAM).However,the nonlinear tilt angular-voltage characteristic of a MEMS mirror introduces distortion into the maximum back-projection image.Moreover,the size of the airy disk,ultrasonic sensor properties,and thermal effects decrease the resolution.Thus,in this study,we proposed a spatial weight matrix(SWM)with a dimensionality reduction for image reconstruction.The three-layer SWM contains the invariable information of the system,which includes a spatial dependent distortion correction and 3D deconvolution.We employed an ordinal-valued Markov random field and the Harris Stephen algorithm,as well as a modified delay-and-sum method during a time reversal.The results from the experiments and a quantitative analysis demonstrate that images can be effectively reconstructed using an SWM;this is also true for severely distorted images.The index of the mutual information between the reference images and registered images was 70.33 times higher than the initial index,on average.Moreover,the peak signal-to-noise ratio was increased by 17.08%after 3D deconvolution.This accomplishment offers a practical approach to image reconstruction and a promising method to achieve a real-time distortion correction for MEMS-based OR-PAM.

MICROW AVE-INDUCED THERMOA COUSTIC IMAGING FOR EARLY BREAST CA NCER DETECTION

Microwave induced thermoacoustic tomography(TAT)is a noninvasive,nonionizing modality based on the inherent differences in microwave absorpt ion of malignant breast tissues and normal adipose dominated breast tissues.In this paper,a TAT system based on multielement acquisition system was built to receive signals.Slices from different layers in the sample were composed into a three-dimensional(3D)volume.Based on the 3D volume,inherent differences in microw ave absorption bet ween different biological tisues can be converted into structure information.Our experimental results of some minicked and human tumors indicate that TAT may potentially be used to detect early-stage breast cancers with high contrast.

Felicitous Labellings of Some Network Models

Building up graph models to simulate scale-free networks is an important method since graphs have been used in researching scale-free networks. One use labelled graphs for distinguishing objects of communication and information networks. In this paper some methods are given for constructing larger felicitous graphs from smaller graphs having special felicitous labellings, and some network models are shown to be felicitous.

Editorial—Introduction to the special issue on photoacoustic and microwave-thermoacoustic imaging

Photoacoustic imaging and microwave-thermoacoustic imaging are innovative hybrid imaging techniques that have experienced rapid development in recent years.Photoacoustic imaging is based on the photoacoustic e®ect.When the laser pulses(the width of the laser pulse is usually several nanoseconds to tens of nanoseconds)irradiate the biological tissue,the absorbers in the tissue absorb the optical energy and then induce the instantaneous rise in temperature,and radiate the thermal energy in the form of mechanical energy,i.e.ultrasound signals.We can detect the ultrasound signals with ultrasound transducer and recover the absorption information of the absorbers in the tissue with di®erent imaging algorithms.Photoacoustic imaging integrates the merit of high contrast of optical imaging and high imaging depth of ultrasound imaging.If the excitation source of the photoacoustic imaging is changed into the microwave(the width of the microwave pulse is usually from tens of nanoseconds to hundreds of nanoseconds),that is called thermoacoustic imaging,which can provide high-resolution imaging and imaging depth of more than ten centimeters.Meanwhile,photoacoustic imaging and thermoacoustic imaging have high molecular speci¯city and have already been widely used in the research of physics,chemistry,and biomedicine.

Correction to: Spatial weight matrix in dimensionality reduction reconstruction for micro-electromechanical system-based photoacoustic microscopy

Following publication of the original article[1],the keywords are missing in the article.Keywords:Photoacoustic microscopy,Spatial weight matrix,Dimensionality reduction,Distortion correction,Mutual information The original article has been updated.

Advancing insights into in vivo meningeal lymphatic vessels with stereoscopic wide-field photoacoustic microscopy

Meningeal lymphatic vessels(mLVs)play a pivotal role in regulating metabolic waste from cerebrospinal fluid(CSF).However,the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo.Here,we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system,including mLVs and glymphatic pathways.The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm,facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma.Subsequently,using this imaging technique,we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20–40 min after injection,along with determining the flow direction from CSF to lymph nodes.Inspiringly,in the Alzheimer’s disease(AD)mouse model,we observed that AD mice exhibit a~70%reduction in drainage volume of mLVs compared to wild-type mice.With the development of AD,there is be continued decline in mLVs drainage volume.This finding clearly demonstrates that the AD mouse model has impaired CSF drainage.Our study opens up a horizon for understanding the brain’s drainage mechanism and dissecting mLVs-associated neurological disorders.

Towards in vivo photoacoustic human imaging:Shining a new light on clinical diagnostics

Multiscale visualization of human anatomical structures is revolutionizing clinical diagnosis and treatment.As one of the most promising clinical diagnostic techniques,photoacoustic imaging(PAI),or optoacoustic imaging,bridges the spatial-resolution gap between pure optical and ultrasonic imaging techniques,by the modes of optical illumination and acoustic detection.PAI can non-invasively capture multiple optical contrasts from the endogenous agents such as oxygenated/deoxygenated hemoglobin,lipid and melanin or a variety of exogenous specific biomarkers to reveal anatomy,function,and molecular for biological tissues in vivo,showing significant potential in clinical diagnostics.In 2001,the worldwide first clinical prototype of the photoacoustic system was used to screen breast cancer in vivo,which opened the prelude to photoacoustic clinical diagnostics.Over the past two decades,PAI has achieved monumental discoveries and applications in human imaging.Progress towards preclinical/clinical applications includes breast,skin,lymphatics,bowel,thyroid,ovarian,prostate,and brain imaging,etc.,and there is no doubt that PAI is opening new avenues to realize early diagnosis and precise treatment of human diseases.In this review,the breakthrough researches and key applications of photoacoustic human imaging in vivo are emphatically summarized,which demonstrates the technical superiorities and emerging applications of photoacoustic human imaging in clinical diagnostics,providing clinical translational orientations for the photoacoustic community and clinicians.The perspectives on potential improvements of photoacoustic human imaging are finally highlighted.

Photoacoustic-enabled automatic vascular navigation:accurate and naked-eye real-time visualization of deep-seated vessels

Accurate localization of blood vessels with image navigation is a key element in vascular-related medical research and vascular surgery.However,current vascular navigation techniques cannot provide naked-eye visualization of deep vascular information noninvasively and with high resolution,resulting in inaccurate vascular anatomy and diminished surgical success rates.Here,we introduce a photoacousticenabled automatic vascular navigation method combining photoacoustic computed tomography with augmented and mixed reality,for the first time,to our knowledge,enabling accurate and noninvasive visualization of the deep microvascular network within the tissues in real time on a real surgical surface.This approach achieves precise vascular localization accuracy(<0.89 mm)and tiny vascular relocation latency(<1 s)through a zero-mean normalization idea-based visual tracking algorithm and a curved surfacefitting algorithm.Further,the subcutaneous vessels of minimum diameter(∼0.15 mm)in rabbit thigh and the maximum depth(∼7 mm)in human arm can be vividly projected on the skin surface with a computer visionbased projection tracking system to simulate preoperative and intraoperative vascular localization.Thereby,this strategy provides a way to visualize deep vessels without damage on the surgical surface and with precise image navigation,opening an avenue for the application of photoacoustic imaging in surgical operations.

Thermally confined shell coating amplifies the photoacoustic conversion efficiency of nanoprobes

Efficient probes/contrast agents are highly desirable for good-performance photoacoustic （PA） imaging, where the PA signal amplitude of a probe is dominated by both its optical absorption and the conversion efficiency from absorbed laser energy to acoustic waves. Nanoprobes have a unique micro- mechanism of PA energy conversion due to the size effect, which, however, has not been quantitatively demonstrated and effectively utilized. Here, we present quantitative simulations of the PA signal production process for plasmon- mediated nanoprobes based on the finite element analysis method, which were performed to provide a deep understanding of their PA conversion micromechanism. Moreover, we propose a method to amplify the PA conversion efficiency of nanoprobes through the use of thermally confined shell coating, which allows the active control of the conversion efficiency beyond that of conventional probes. Additionally, we deduced the dependence of the conversion efficiency on the shell properties. Gold-nanoparticles/polydimethylsiloxane nanocomposites were experimentally synthesized in the form of gel and microfilms to verify our idea and the simulation results agreed with the experiments. Our work paves the way for the rational design and optimization of nanoprobes with improved conversion efficiency.

In vivo volumetric monitoring of revascularization of traumatized skin using extended depth-of-field photoacoustic microscopy

Faster and better wound healing is a critical medical issue.Because the repair process of wounds is closely related to revascularization,accurate early assessment and postoperative monitoring are very important for establishing an optimal treatment plan.Herein,we present an extended depth-of-field photoacoustic microscopy system(E-DOF-PAM)that can achieve a constant spatial resolution and relatively uniform excitation efficiency over a long axial range.The superior performance of the system was verified by phantom and in vivo experiments.Furthermore,the system was applied to the imaging of normal and trauma sites of volunteers,and the experimental results accurately revealed the morphological differences between the normal and traumatized skin of the epidermis and dermis.These results demonstrated that the E-DOF-PAM is a powerful tool for observing and understanding the pathophysiology of cutaneous wound healing.

Imaging of human wrist joint by a flexible-transducer-based morphological-adaptive photoacoustic tomography: a feasibility study

In this study, the feasibility of visualization of human joints using photoacoustic tomography(PAT) is investigated. To verify this idea, the system of integrated optical fiber bundles and a custom-made flexible transducer is established, both of which give the advantage of morphological adaptation;therefore, the coupling section can be worn on human limbs. The imaging capacity of the flexible-transducer-based PAT system is validated by mapping the structures of the finger and the wrist joint. To the best of our knowledge, it is the first time to achieve photoacoustic imaging of such large human wrist joints. The cross-sectional photoacoustic images of a healthy joint clearly exhibit the main internal structures, including the phalanx, tendons, and blood vessels, which are comparable with the corresponding images by 3.0 T magnetic resonance imaging.The experimental results demonstrate that the proposed system holds promise for early diagnosis of joint disorders.

New insight into photoacoustic conversion efficiency by plasmon-mediated nanocavitation： Implications for precision theranostics

The probe-assisted integration of imaging and therapy into a single modality offers significant advantages in bio-applications. As a newly developed photoacoustic （PA） mechanism, plasmon-mediated nanocavitation, whereby photons are effectively converted into PA shockwaves, has excellent advantages for image-guided therapy. In this study, by simulating the laser absorption, temperature field, and nanobubble dynamics using both finite-element analysis and computational fluid dynamics, we quantified the cavitation-induced PA conversion efficiency of a water-immersed gold nanosphere, revealing new insights. Interestingly, sequential multi-bubble emission accompanied by high PA signal production occur under a single high-dose pulse of laser irradiation, enabling a cavitation-induced PA conversion efficiency up to 2%, which is -50 times higher than that due to thermal expansion. The cavitation-induced PA signal has unique frequency characteristics, which may be useful for a new approach for in vivo nanoparticle tracking. Our work offers theoretical guidance for accurate diagnosis and controllable therapy based on plasmon-mediated nanocavitation.

3D depth-coded photoacoustic microscopy with a large field of view for human skin imaging

Photoacoustic （PA） microscopy comes with high potential for human skin imaging, since it allows noninvasively high-resolution imaging of the natural hemoglobin at depths of several millimeters. Here, we developed a PA microscopy to achieve high-resolution, high-contrast, and large field of view imaging of skin. A three-dimensional （3D） depth-coding technology was used to encode the depth information in PA images, which is very intuitive for identifying the depth of blood vessels in a two-dimensional image, and the vascular structure can be analyzed at different depths. Imaging results demonstrate that the 3D depth-coded PA microscopy should be translated from the bench to the bedside.

Polarization microwave-induced thermoacoustic imaging for quantitative characterization of deep biological tissue microstructures

Polarization optical imaging can be used to characterize anisotropy in biological tissue microstructures and has been demonstrated to be a powerful tool for clinical diagnosis. However, the approach is limited by an inability to image targets deeper than ~1 mm due to strong optical scattering in biological tissues. As such, we propose a novel polarization microwave-induced thermoacoustic imaging(P-MTAI) technique to noninvasively detect variations in deep tissue by exploiting the thermoacoustic signals induced by four pulsed microwaves of varying polarization orientations. The proposed P-MTAI method overcomes the penetration limits of conventional polarization optical imaging and provides submillimeter resolution over depths of several centimeters. As part of the paper, the structural characteristics of tissues were quantified using a new parameter, the degree of microwave absorption anisotropy. P-MTAI was also applied to the noninvasive detection of morphological changes in cardiomyocytes as they transitioned from ordered to disordered states, providing a potential indication of myocardial infarction.

Collagen fiber anisotropy characterization by polarized photoacoustic imaging for just-in-time quantitative evaluation of burn severity

Just-in-time burn severity assessment plays a vital role in burn treatment and care.However,it is still difficult to quantitatively and promptly evaluate burn severity by existing medical imaging methods via initial burn depth measurement since burn wounds are usually dynamically developed.As an elastic skeleton of skin,the degree of conformational changes of collagen fibers caused by overheating can reflect the burn severity in a timelier manner.Herein,the polarized photoacoustic technique(PPAT)for just-in-time quantitative evaluation of burn severity via collagen fiber anisotropy assessment is proposed.First,phantom experiments demonstrate the ability of PPAT for deep imaging in a transport mean free path and accurately quantify changes in microstructural order by thermal damage.Then,the Pearson correlation coefficient of the PPAT in assessing burn severity is shown to be up to 0.95,validated by burn skin samples.The PPAT provides a just-in-time quantitative strategy for burn severity evaluation.

Tomography-assisted Doppler photoacoustic microscopy:proof of concept

The previous methods to measure flow speed by photoacoustic microscopy solely focused on either the transverse or the axial flow component, which did not reflect absolute flow speed. Here, we present absolute flow speed maps by combining Doppler bandwidth broadening with volumetric photoacoustic microscopy. Photoacoustic Doppler bandwidth broadening and photoacoustic tomographic images were applied to measure the transverse flow component and the Doppler angle, respectively. Phantom experiments quantitatively demonstrated that ranges of 55° to 90° Doppler angle and 0.5 to 10 mm/s flow speed can be measured. This tomography-assisted method provides the foundation for further measurement in vivo.

High-fluence relay-based disposable photoacoustic-ultrasonic endoscopy for in vivo anatomical imaging of gastrointestinal tract

Photoacoustic endomicroscopy combined with ultrasound(PAEM-US)has been a long-standing expectation for gastrointestinal tumor examination.Here,we introduce a prototype disposable PAEM-US catheter and corresponding power interface unit,featuring catheter switchability,self-internal three-dimensional scanning,and system repeatability for gastrointestinal endoscopy.By utilizing high-fluence relays,cascade insertion loss of the optical waveguide is minimized to 0.6 dB with a high performance of power resistance,and a focus-customizable acousto-optic coaxial probe is designed for high-sensitivity optical-resolution photoacoustic imaging.Imaging capability was demonstrated with in vivo anatomical imaging at 30 frames per second.Imaging results showed co-registered microscopic visualization of the microvascular and stratification of the rat colorectum with lateral resolution of 18μm and axial resolution of 63μm,holding great potential in the clinical detection of gastrointestinal diseases.