Diagnostic and prognostic utility of non-invasive imaging in diabetes management

Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed.

Can We Predict Abdominal Aortic Aneurysm (AAA) Progression and Rupture by Non-Invasive Imaging?—A Systematic Review

Introduction: The most commonly used predictor of aneurysm behavior in clinical decision-making is size. There are however small aneurysms that rupture and certain large aneurysms remain asymptomatic. There is growing evidence to suggest that other variables may provide better information on metabolic and physiological properties of aortic wall and therefore better predict aneurysm behavior. Methods: The literature was systematically reviewed from 1975-May 2011 to examine the evidence to support the use of non-invasive imaging modalities that might predict aneurysm behavior. Results: Ultrasound can be used to measure multiple dynamic aortic properties (i.e. distensibility and compliance) in addition to diameter. These parameters better predict aneurysm behavior. Computer tomography can utilize assessment of aortic calcification, presence of intra-luminal thrombus and distensibility. Finite element analysis model has been validated in-vivo to calculate peak wall stress, assess effects of intra-luminal thrombus and calcification. It however relies on assumptions related to aneurysm properties and therefore remains relatively inaccurate in the clinical setting. Small numbers of observational human studies have evaluated the role of 18F-FDG PET/CT in aneurysms. Larger studies are needed, as 18F-FDG uptake is patchy and heterogeneous even in small number of patients. It varies in the same patient with time, as aneurysms grow in intermittently. We discuss functional magnetic resonance imaging with novel tracers such as 99 mTc-annexin-V and nanoparticles. Conclusion: Multimodality imaging with complementary methods such as CT, functional MRI (fMRI), ultrasound and physiological measurements improve the definition of aneurysm pathobiology. Larger-scale clinical validation is beginning to promise a new paradigm in cardiovascular diagnostics.

Autoimmune pancreatitis:Multimodality non-invasive imaging diagnosis

Autoimmune pancreatitis(AIP)is characterized by obstructive jaundice,a dramatic clinical response to steroids and pathologically by a lymphoplasmacytic infiltrate,with or without a pancreatic mass.Type 1AIP is the pancreatic manifestation of an Ig G4-related systemic disease and is characterized by elevated Ig G4serum levels,infiltration of Ig G4-positive plasma cells and extrapancreatic lesions.Type 2 AIP usually has none or very few Ig G4-positive plasma cells,no serum Ig G4 elevation and appears to be a pancreas-specific disorder without extrapancreatic involvement.AIP is diagnosed in approximately 2%-6%of patients that undergo pancreatic resection for suspected pancreatic cancer.There are three patterns of autoimmune pancreatitis:diffuse disease is the most common type,with a diffuse,"sausage-like"pancreatic enlargement with sharp margins and loss of the lobular contours;focal disease is less common and manifests as a focal mass,often within the pancreatic head,mimicking a pancreatic malignancy.Multifocal involvement can also occur.In this paper we describe the features of AIP at ultrasonography,computed tomography,magnetic resonanceand positron emission tomography/computed tomography imaging,focusing on diagnosis and differential diagnosis with pancreatic ductal adenocarcinoma.It is of utmost importance to make an early correct differential diagnosis between these two diseases in order to identify the optimal therapeutic strategy and to avoid unnecessary laparotomy or pancreatic resection in AIP patients.Non-invasive imaging plays also an important role in therapy monitoring,in follow-up and in early identification of disease recurrence.

Non-invasive evaluation of liver steatosis with imaging modalities:New techniques and applications

In the world,nonalcoholic fatty liver disease(NAFLD)accounts for majority of diffuse hepatic diseases.Notably,substantial liver fat accumulation can trigger and accelerate hepatic fibrosis,thus contributing to disease progression.Moreover,the presence of NAFLD not only puts adverse influences for liver but is also associated with an increased risk of type 2 diabetes and cardiovascular diseases.Therefore,early detection and quantified measurement of hepatic fat content are of great importance.Liver biopsy is currently the most accurate method for the evaluation of hepatic steatosis.However,liver biopsy has several limitations,namely,its invasiveness,sampling error,high cost and moderate intraobserver and interobserver reproducibility.Recently,various quantitative imaging techniques have been developed for the diagnosis and quantified measurement of hepatic fat content,including ultrasound-or magnetic resonancebased methods.These quantitative imaging techniques can provide objective continuous metrics associated with liver fat content and be recorded for comparison when patients receive check-ups to evaluate changes in liver fat content,which is useful for longitudinal follow-up.In this review,we introduce several imaging techniques and describe their diagnostic performance for the diagnosis and quantified measurement of hepatic fat content.

Functional near-infrared spectroscopy in non-invasive neuromodulation

Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.

Magnetic resonance imaging of extraocular rectus muscles abnormalities in acute acquired concomitant esotropia

AIM:To investigate the difference of medial rectus(MR)and lateral rectus(LR)between acute acquired concomitant esotropia(AACE)and the healthy controls(HCs)detected by magnetic resonance imaging(MRI).METHODS:A case-control study.Eighteen subjects with AACE and eighteen HCs were enrolled.MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner.Extraocular muscles(EOMs)were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator.To form posterior partial volumes(PPVs),the LR and MR cross-sections in the image planes 8,10,12,and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness.The data were classified according to the right eye,left eye,dominant eye,and non-dominant eye,and the differences in mean cross-sectional area,maximum cross-sectional area,and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively.RESULTS:There were no significant differences between the two groups of demographic characteristics.The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes(P=0.028).The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was significantly greater than the HCs group(P=0.009,P=0.016).For the dominant eye,the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group(P=0.013),but not in the MR muscle(P=0.698).CONCLUSION:The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia.The LR muscle become larger to compensate for the enhanced convergence in the AACE.

In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

Intravascular photoacoustic and optical coherence tomography imaging dual-mode system for detecting spontaneous coronary artery dissection: A feasibility study

In this work,we present an intravascular dual-mode endoscopic system capable of both intravascular photoacoustic imaging(IVPAI)and intravascular optical coherence tomography(IVOCT)for recognizing spontaneous coronary artery dissection(SCAD)phantoms.IVPAI provides high-resolution and high-penetration images of intramural hematoma(IMH)at different depths,so it is especially useful for imaging deep blood clots associated with imaging phantoms.IVOCT can readily visualize the double-lumen morphology of blood vessel walls to identify intimal tears.We also demonstrate the capability of this dual-mode endoscopic system using mimicking phantoms and biological samples of blood clots in ex vivo porcine arteries.The results of the experiments indicate that the combined IVPAI and IVOCT technique has the potential to provide a more accurate SCAD assessment method for clinical applications.

A synthetic diagnostics platform for microwave imaging diagnostics in tokamaks

Interpreting experimental diagnostics data in tokamaks,while considering non-ideal effects,is challenging due to the complexity of plasmas.To address this challenge,a general synthetic diagnostics(GSD)platform has been established that facilitates microwave imaging reflectometry and electron cyclotron emission imaging.This platform utilizes plasma profiles as input and incorporates the finite-difference time domain,ray tracing and the radiative transfer equation to calculate the propagation of plasma spontaneous radiation and the external electromagnetic field in plasmas.Benchmark tests for classical cases have been conducted to verify the accuracy of every core module in the GSD platform.Finally,2D imaging of a typical electron temperature distribution is reproduced by this platform and the results are consistent with the given real experimental data.This platform also has the potential to be extended to 3D electromagnetic field simulations and other microwave diagnostics such as cross-polarization scattering.

Self-confocal NIR-II fluorescence microscopy for multifunctional in vivo imaging

Fluorescence imaging in the second near-infrared window(NIR-II,900–1880 nm)with less scattering background in biological tissues has been combined with the confocal microscopic system for achieving deep in vivo imaging with high spatial resolution.However,the traditional NIR-IIfluorescence confocal microscope with separate excitation focus and detection pinhole makes it possess low confocal e±ciency,as well as di±cultly to adjust.Two types of upgraded NIR-IIfluorescence confocal microscopes,sharing the same pinhole by excitation and emission focus,leading to higher confocal e±ciency,are built in this work.One type is-ber-pinhole-based confocal microscope applicable to CW laser excitation.It is constructed forfluorescence intensity imaging with large depth,high stabilization and low cost,which could replace multiphotonfluorescence microscopy in some applications(e.g.,cerebrovascular and hepatocellular imaging).The other type is air-pinhole-based confocal microscope applicable to femtosecond(fs)laser excitation.It can be employed not only for NIR-IIfluorescence intensity imaging,but also for multi-channelfluorescence lifetime imaging to recognize different structures with similarfluorescence spectrum.Moreover,it can be facilely combined with multiphotonfluorescence microscopy.A single fs pulsed laser is utilized to achieve up-conversion(visible multiphotonfluorescence)and down-conversion(NIR-II one-photonfluorescence)excitation simultaneously,extending imaging spectral channels,and thus facilitates multi-structure and multi-functional observation.

Performance optimization of the neutron-sensitive image intensifier used in neutron imaging

As a non-destructive testing technology,neutron imaging plays an important role in various fields,including material science,nuclear engineering,and fundamental science.An imaging detector with a neutron-sensitive image intensifier has been developed and demonstrated to achieve good spatial resolution and timing resolution.However,the influence of the working voltage on the performance of the neutron-sensitive imaging intensifier has not been studied.To optimize the performance of the neutron-sensitive image intensifier at different voltages,experiments have been performed at the China Spallation Neutron Source(CSNS)neutron beamline.The change in the light yield and imaging quality with different voltages has been acquired.It is shown that the image quality benefits from the high gain of the microchannel plate(MCP)and the high accelerating electric field between the MCP and the screen.Increasing the accelerating electric field is more effective than increasing the gain of MCPs for the improvement of the imaging quality.Increasing the total gain of the MCP stack can be realized more effectively by improving the gain of the standard MCP than that of the n MCP.These results offer a development direction for image intensifiers in the future.

Microwave-induced thermoacoustic elastic imaging:A simulation study

Microwave-induced thermoacoustic imaging(MTI)has the advantages of high resolution,high contrast,non-ionization,and non-invasive.Recently,MTI was used in the¯eld of breast cancer screening.In this paper,based on the¯nite element method(FEM)and COMSOL Multiphysics software,a three-dimensional breast cancer model suitable for exploring the MTI process is proposed to investigate the in°uence of Young's modulus(YM)of breast cancer tissue on MTI.It is found that the process of electromagnetic heating and initial pressure generation of the entire breast tissue is earlier in time than the thermal expansion process.Besides,compared with normal breast tissue,tumor tissue has a greater temperature rise,displacement,and pressure rise.In particular,YM of the tumor is related to the speed of thermal expansion.In particular,the larger the YM of the tumor is,the higher the heating and contraction frequency is,and the greater the maximum pressure is.Di®erent Young's moduli correspond to di®erent thermoacoustic signal spectra.In MTI,this study can be used to judge di®erent degrees of breast cancer based on elastic imaging.In addition,this study is helpful in exploring the possibility of microwave-induced thermoacoustic elastic imaging(MTAE).

Topic highlight on texture and color enhancement imaging in gastrointestinal diseases

Olympus Corporation developed texture and color enhancement imaging(TXI)as a novel image-enhancing endoscopic technique.This topic highlights a series of hot-topic articles that investigated the efficacy of TXI for gastrointestinal disease identification in the clinical setting.A randomized controlled trial demonstrated improvements in the colorectal adenoma detection rate(ADR)and the mean number of adenomas per procedure(MAP)of TXI compared with those of white-light imaging(WLI)observation(58.7%vs 42.7%,adjusted relative risk 1.35,95%CI:1.17-1.56;1.36 vs 0.89,adjusted incident risk ratio 1.48,95%CI:1.22-1.80,respectively).A cross-over study also showed that the colorectal MAP and ADR in TXI were higher than those in WLI(1.5 vs 1.0,adjusted odds ratio 1.4,95%CI:1.2-1.6;58.2%vs 46.8%,1.5,1.0-2.3,respectively).A randomized controlled trial demonstrated non-inferiority of TXI to narrow-band imaging in the colorectal mean number of adenomas and sessile serrated lesions per procedure(0.29 vs 0.30,difference for non-inferiority-0.01,95%CI:-0.10 to 0.08).A cohort study found that scoring for ulcerative colitis severity using TXI could predict relapse of ulcerative colitis.A cross-sectional study found that TXI improved the gastric cancer detection rate compared to WLI(0.71%vs 0.29%).A cross-sectional study revealed that the sensitivity and accuracy for active Helicobacter pylori gastritis in TXI were higher than those of WLI(69.2%vs 52.5%and 85.3%vs 78.7%,res-pectively).In conclusion,TXI can improve gastrointestinal lesion detection and qualitative diagnosis.Therefore,further studies on the efficacy of TXI in clinical practice are required.

Efficient single-pixel imaging encrypted transmission based on 3D Arnold transformation

Single-pixel imaging(SPI)can transform 2D or 3D image data into 1D light signals,which offers promising prospects for image compression and transmission.However,during data communication these light signals in public channels will easily draw the attention of eavesdroppers.Here,we introduce an efficient encryption method for SPI data transmission that uses the 3D Arnold transformation to directly disrupt 1D single-pixel light signals and utilizes the elliptic curve encryption algorithm for key transmission.This encryption scheme immediately employs Hadamard patterns to illuminate the scene and then utilizes the 3D Arnold transformation to permutate the 1D light signal of single-pixel detection.Then the transformation parameters serve as the secret key,while the security of key exchange is guaranteed by an elliptic curve-based key exchange mechanism.Compared with existing encryption schemes,both computer simulations and optical experiments have been conducted to demonstrate that the proposed technique not only enhances the security of encryption but also eliminates the need for complicated pattern scrambling rules.Additionally,this approach solves the problem of secure key transmission,thus ensuring the security of information and the quality of the decrypted images.

FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,its sensitivity,specificity,PPV,NPV,and AUROC were 44.2%,92.3%,82.1%,67.4%,and 0.82.The FIB-4 AUROC was 0.76.S index and GPR exhibited almost no diagnostic value for high-risk MASH.CONCLUSION FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI,Forns index,ARR,S index,and GPR;FAST is superior to FIB-4.

Five-view three-dimensional reconstructionfor ultrafast dynamic imaging of pulsedradiation sources

Multiaxial neutron/x-ray imaging and three-dimensional (3D) reconstruction techniques play a crucial role in gaining valuable insights intothe generation and evolution mechanisms of pulsed radiation sources. Owing to the short emission time (∼200 ns) and drastic changes of thepulsed radiation source, it is necessary to acquire projection data within a few nanoseconds in order to achieve clear computed tomography3D imaging. As a consequence, projection data that can be used for computed tomography image reconstruction at a certain moment are oftenavailable for only a few angles. Traditional algorithms employed in the process of reconstructing 3D images with extremely incomplete datamay introduce significant distortions and artifacts into the final image. In this paper, we propose an iterative image reconstruction methodusing cylindrical harmonic decomposition and a self-supervised denoising network algorithm based on the deep image prior method. Weaugment the prior information with a 2D total variation prior and a 3D deep image prior. Single-wire Z-pinch imaging experiments have beencarried out at Qin-1 facility in five views and four frames, with a time resolution of 3 ns for each frame and a time interval of 40 ns betweenadjacent frames. Both numerical simulations and experiments verify that our proposed algorithm can achieve high-quality reconstructionresults and obtain the 3D intensity distribution and evolution of extreme ultraviolet and soft x-ray emission from plasma.

An improved reverse time migration for subsurface imaging over complex geological structures:A numerical study

In seismic exploration,it is a critical task to image and interpret different seismic signatures over complex geology due to strong lateral velocity contrast,steep reflectors,overburden strata and dipping flanks.To understand the behavior of these seismic signatures,nowadays Reverse Time Migration(RTM)technique is used extensively by the oil&gas industries.During the extrapolation phase of RTM,the source wavefield needs to be saved,which needs high storage memory and large computing time.These two are the main obstacles of RTM for production use.In order to overcome these disadvantages,in this study,a second-generation improved RTM technique is proposed.In this improved form,a shift operator is introduced at the time of imaging condition of RTM algorithm which is performed automatically both in space and time domain.This effort is made to produce a better-quality image by minimizing the computational time as well as numerical artefacts.The proposed method is applied over various benchmark models and validated by implementing over one field data set from the Jaisalmer Basin,India.From the analysis,it is observed that the method consumes a minimum of 45%less storage space and reduce the execution time by 20%,as compared to conventional RTM.The proposed RTM is found to work efficiently in comparison to the conventional RTM both in terms of imaging quality and minimization of numerical artefacts for all the benchmark models as well as field data.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex

Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.