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,i...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.展开更多
Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are ...Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,we identify the challenges and possible solutions for spinal cord neuron imaging.展开更多
A bimorph deformable mirror (DM) with a large stroke of more than 30 μm using 35 actuators is presented and characterized for an adaptive optics (AO) confocal scanning laser ophthalmoscope application. Facilitate...A bimorph deformable mirror (DM) with a large stroke of more than 30 μm using 35 actuators is presented and characterized for an adaptive optics (AO) confocal scanning laser ophthalmoscope application. Facilitated with a Shack-Hartmann wavefront sensor, the bimorph DM-based AO operates closed-loop AO corrections for hu- man eyes and reduces wavefront aberrations in most eyes to below 0.1 μm rms. Results from living eyes, including one exhibiting ~5D of myopia and ~2D of astigmatism along with notable high-order aberrations, reveal a prac- tical efficient aberration correction and demonstrate a great benefit for retina imaging, including improving resolution, increasing brightness, and enhancing the contrast of images.展开更多
AIM: To investigate the influence of hyperglycemia on the severity of choroidal neovascularization(CNV),especially the involvement of bone marrow-derived cells(BMCs) and underlying mechanisms.·METHODS: BMCs...AIM: To investigate the influence of hyperglycemia on the severity of choroidal neovascularization(CNV),especially the involvement of bone marrow-derived cells(BMCs) and underlying mechanisms.·METHODS: BMCs from firefly luciferase(Fluc)/green fluorescent protein(GFP) double transgenic mice were transplanted into C57BL/6J wide-type mice. The recipient mice were injected intraperitoneally with streptozotocin(STZ) daily for 5 consecutive days to induce diabetes mellitus(DM), followed by CNV laser photocoagulation.The BMCs recruitment in CNV exposed to hyperglycemia was firstly examined in Fluc/GFP chimeric mice by in vivo optical bioluminescence imaging(BLI) and in vitro Fluc assays. The CNV severity was evaluated by H&E staining and choroidal flatmount. The expression of vascular endothelial growth factor(VEGF) and stromal cell derived factor-1(SDF-1) was detected by Western blot.·RESULTS: BLI showed that the BMCs exerted dynamic effects in CNV model in Fluc/GFP chimeric mice exposed to hyperglycemia. The signal intensity of transplanted Fluc+GFP+BMCs in the DM chimeric mice was significantly higher than that in the control chimeric mice with CNV induction at days 5, 7, 14 and 21(121861.67 ±9948.81 vs 144998.33 ±13787.13 photons/second/cm2/sr for control and DM mice, P5d〈0.05; 178791.67±30350.8 vs240166.67 ±22605.3, P7d〈0.05; 124176.67 ±16253.52 vs196376.67 ±18556.79, P14d〈0.05; 97951.60 ±10343.09 vs119510.00 ±14383.76, P21d〈0.05), which was consistent with in vitro Fluc assay at day 7 [relative light units of Fluc(RLU1)], 215.00±52.05 vs 707.33±88.65, P 〈0.05; RLU1/relative light units of renilla luciferase(RLU2), 0.90 ±0.17 vs 1.83 ±0.17, P 〈0.05]. The CNVs in the DM mice were wider than those in the control group at days 5, 7, 14 and21(147.83±17.36 vs 220.33±20.17 μm, P5d〈0.05; 212.17 ±24.63 vs 326.83 ±19.49, P7d〈0.05; 163.17 ±18.24 vs265.17 ±20.55, P14d〈0.05; 132.00 ±10.88 vs 205.33 ±12.98,P21d〈0.05). The average area of CNV in the DM group was larger at 7d(20688.67±3644.96 vs 32218.00±4132.69 μm2,P 〈0.05). The expression of VEGF and SDF-1 was enhanced in the DM mice.·CONCLUSION: Hyperglycemia promots the vasculo-genesis of CNV, especially the contribution of BMCs,which might be triggered by VEGF and SDF-1 production.展开更多
Digital radiography (DR) and whole-body fluorescent optical imaging (WFOI) have been widely applied in the field of molecular imaging, with the advantages in tissues and functional imaging. The integration of them...Digital radiography (DR) and whole-body fluorescent optical imaging (WFOI) have been widely applied in the field of molecular imaging, with the advantages in tissues and functional imaging. The integration of them contributes to the development and discovery of medicine. We introduce an equipment, performance of which is better than that of another molecular imaging system manufactured by Kodak Corp. It can take real-time small animal imaging in vivo, with lower cost and shorter development cycle on the LabVIEW platform. At last, a paradigm experiment on a nude mouse with green fluorescent protein (GFP) transgenic tumor is given to present a real-time DR-WFOI fusion simultaneous image.展开更多
Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body.Cell therapies have become a strong therapeutic modal...Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body.Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes,understanding pathophysiological mechanisms of diseases,and evaluating the kinetics/dynamics of cell therapies.In particular,mesenchymal stem cells(MSCs)have shown promise in recent years as drug carriers for cancer treatment.They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells,and to optimize therapy.The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition,and the exact interactions between MSCs and specific cancer microenvironments are not clear.In this review,a multitude of labeling approaches,imaging modalities,and the merits/demerits of each strategy are outlined.In addition,specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided.Finally,present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.展开更多
Laser diodes(LDs)have been considered as cost-effective and compact excitation sources to overcome the requirement of costly and bulky pulsed laser sources that are commonly used in photoacoustic microscopy(PAM).Howev...Laser diodes(LDs)have been considered as cost-effective and compact excitation sources to overcome the requirement of costly and bulky pulsed laser sources that are commonly used in photoacoustic microscopy(PAM).However,the spatial resolution and/or imaging speed of previously reported LD-based PAM systems have not been optimized simultaneously.In this paper,we developed a high-speed and high-resolution LD-based PAM system using a continuous wave LD,operating at a pulsed mode,with a repetition rate of 30 kHz,as an excitation source.A hybrid scanning mechanism that synchronizes a one-dimensional galvanometer mirror and a two-dimensional motorized stage is applied to achieve a fast imaging capability without signal averaging due to the high signal-to-noise ratio.By optimizing the optical system,a high lateral resolution of 4.8μm has been achieved.In vivo microvasculature imaging of a mouse ear has been demonstrated to show the high performance of our LD-based PAM system.展开更多
In vivo imaging system (IVIS) is a new and rapidly expanding technology, which has a wide range of applications in life science such as cell tracing. By counting the number of photons emitted from a specimen, IVIS can...In vivo imaging system (IVIS) is a new and rapidly expanding technology, which has a wide range of applications in life science such as cell tracing. By counting the number of photons emitted from a specimen, IVIS can quantify biological events such as tumor growth. We used B16F10-luc-G5 tumor cells and 20 Babl/C mice injected subcutaneously with B16F10-luc-G5 tumor cells (1×106 in 100 μL) to develop a method to quantitatively analyze cells traced by IVIS in vitro and in vivo, respectively. The results showed a strong correlation between the number of tumor cells and the intensity of bioluminescence signal (R2=0.99) under different exposure conditions in in vitro assay. The results derived from the in vivo experiments showed that tumor luminescence was observed in all mice by IVIS at all days, and there was significant difference (P<0.01) between every two days from day 3 to day 14. Moreover, tumor dynamic morphology could be monitored by IVIS when it was in- visible. There was a strong correlation between tumor volume and bioluminescence signal (R2=0.97) by IVIS. In summary, we demonstrated a way to accurately carry out the quantitative analysis of cells using IVIS both in vitro and in vivo. The data indicate that IVIS can be used as an effective and quantitative method for cell tracing both in vitro and in vivo.展开更多
Regenerative medicine has become a new therapeutic approach in which stem cells or genetically reprogrammed cells are delivered to diseased areas in the body with the intention that such multipotent cells will differe...Regenerative medicine has become a new therapeutic approach in which stem cells or genetically reprogrammed cells are delivered to diseased areas in the body with the intention that such multipotent cells will differentiate into healthy tissue and exchange damaged tissue. The success of such cell-based therapeutic approaches depends on precise dosing and delivery of the cells to the desired site in the human body. To determine the accuracy and efficacy of the therapy, tracking of the engrafted cells in an intact living organism is crucial. There is a great need for sensitive, noninvasive imaging methods, which would allow clinicians to monitor viability, migration dynamics, differentiation towards specific cell type, regeneration potential and integration of transplanted cells with host tissues for an optimal time period. Various in vivo tracking methods are currently used including: MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), SPECT (Single Photon Emission Computer Tomography), optical imaging (OI), photoacoustic imaging (PAI) and ultrasound (US). In order to carry out the detection with each of the aforementioned techniques, the cells must be labeled either exogenously (ex vivo) or endogenously (in vivo). For tracking the administrated cells, scientists usually manipulate cells outside the living organism by incorporating imaging contrast agents (CAs) or reporter genes. Strategies for stem cell labeling using CAs will be reviewed in the light of various imaging techniques.展开更多
In recent years,persistent luminescence materials(PLMs)excited by X-rays and emitting in biological windows have received extensive attention in the field of high-sensitivity bioimaging.Transition metal Mn^(2+)is an i...In recent years,persistent luminescence materials(PLMs)excited by X-rays and emitting in biological windows have received extensive attention in the field of high-sensitivity bioimaging.Transition metal Mn^(2+)is an ideal emission center,but few studies focus on Mn^(2+)-doped PLMs with X-ray excitation and biological window emission.Here,we report a Mn^(2+)-doped PLM,LiYGeO_(4):Mn^(2+)(LYGM),with excellent biological window persistent luminescence emission.After excitation by UV,LYGM produces a durable biological window of persistent luminescence emission at 660 nm for up to 20 h.More importantly.LYGM can be repeatedly excited by X-rays,resulting in long-term biological window persistent luminescence emission.In addition,we obtain LYGM around 200 nm in diameter by ball milling and centrifugation and improve its biocompatibility by surface modification to apply it to in vivo imaging in mice.After LYGM are injected into mice through the tail vein,in situ excitation of X-rays can be achieved.After the persistent luminescence decays,LYGM can be re-excited for repeated imaging.Therefore,LYGM shows potential prospects for in vivo deep tissue and long-term bioimaging.展开更多
The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophag...The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophage therapy.In this work,the second near-infrared(NIR-II)fluorescence imaging in vivo tracking of M2 macrophages during a pro-healing therapy in the mice model of rotator cuff injury revealed that the behavior of administrated macrophages was influenced by the timing of their administration.The delayed cell therapy(DCT)group had a longer retention time of injected M2 macrophages in the repairing tissue than that in the immediate cell therapy(ICT)group.Both Keller-Segel model and histological analysis further demonstrated that DCT altered the chemotaxis of M2 macrophages and improved the healing outcome of the repaired structure in comparison with ICT.Our results offer a possible explanation of previous conflicting results on reparative cell therapy and provoke reconsideration of the timing of these therapies.展开更多
AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli(E. coli) using optical imaging.METHODS: We choose to evaluate the tumor m...AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli(E. coli) using optical imaging.METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume(mm^3). Inflammation measuring myeloperoxidase(MPO) activity and reactive oxygen species production was monitored by a bioluminescent(BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay(ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells(HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitisCEABAC10 DSS models, which mimicked Crohn's disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume(P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group(P < 0.005). ELISA confirmed that MPO levels were significantly higher(1556 ± 313.6 vs 234.6 ± 121.6 ng/m L P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model(CEABAC10/DSS).CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand hostpathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.展开更多
Acupuncture is a medical treatment that has been widely pra cticed in China for over 3000 years,yet the neural mechanisms of acupuncture are not fully understood.We hypothesized that neurons and astrocytes act indepen...Acupuncture is a medical treatment that has been widely pra cticed in China for over 3000 years,yet the neural mechanisms of acupuncture are not fully understood.We hypothesized that neurons and astrocytes act independently and synergistically under acupuncture stimulation.To investigate this,we used two-photon in vivo calcium reco rding to observe the effects of acupuncture stimulation at ST36(Zusanli)in mice.Acupuncture stimulation in peripheral acupoints potentiated calcium signals of pyramidal neurons and astrocytes in the somatosensory cortex and resulted in late-onset calcium transients in astrocytes.Chemogenetic inhibition of neurons augmented the astrocytic activity.These findings suggest that acupuncture activates neuronal and astrocytic activity in the somatosensory co rtex and provide evidence for the involvement of both neurons and astrocytes in acupuncture treatment.展开更多
AIM:To compare choroidal neovascularization(CNV)lesion measurements obtained by in vivo imaging modalities,with whole mount histological preparations stained with isolectin GS-IB4,using a murine laser-induced CNV mode...AIM:To compare choroidal neovascularization(CNV)lesion measurements obtained by in vivo imaging modalities,with whole mount histological preparations stained with isolectin GS-IB4,using a murine laser-induced CNV model.METHODS:B6 N.Cg-Tg(Csf1 r-EGFP)1 Hume/J heterozygous adult mice were subjected to laser-induced CNV and were monitored by fluorescein angiography(FA),multicolor(MC)fundus imaging and optical coherence tomography angiography(OCTA)at day 14 after CNV induction.Choroidalretinal pigment epithelium(RPE)whole mounts were prepared at the end of the experiment and were stained with isolectin GS-IB4.CNV areas were measured in all different imaging modalities at day 14 after CNV from three independent raters and were compared to choroidal-RPE whole mounts.Intraclass correlation coefficient(ICC)type 2(2-way random model)and its 95%confidence intervals(CI)were calculated to measure the correlation between different raters’measurements.Spearman’s rank correlation coefficient(Spearman’s r)was calculated for the comparison between FA,MC and OCTA data and histology data.RESULTS:FA(early and late)and MC correlates well with the CNV measurements ex vivo with FA having slightly better correlation than MC(FA early Spearman’s r=0.7642,FA late Spearman’s r=0.7097,and MC Spearman’s r=0.7418),while the interobser ver reliability was good for both techniques(FA early ICC=0.976,FA late ICC=0.964,and MC ICC=0.846).In contrast,OCTA showed a poor correlation with ex vivo measurements(Spearman’s r=0.05716)and high variability between different raters(ICC=0.603).CONCLUSION:This study suggests that FA and MC imaging could be used for the evaluation of CNV areas in vivo while caution must be taken and comparison studies should be performed when OCTA is employed as a CNV monitoring tool in small rodents.展开更多
AIM: To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin(LHT7) in a neovascularized mouse cornea using an in vivo optical ima...AIM: To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin(LHT7) in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS: A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization(CoNV) was induced in the inferior cornea(IC) of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7(LHT7-Cy5.5) in 0.02 mL solution was topically instilled onto the cornea in the experimental group(n=5). Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group(n=5). In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea(SC) and the IC. RESULTS: The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively(P=0.832). The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min(P=0.038), 2 h(P=0.041), and 4 h(P=0.041) after application. The IC intensity fell to less than half of its initial value(42.9%±8.6%) at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION: Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.展开更多
Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and dru...Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and drug release rates at different p H values to assess the biodistribution and drug delivery pathways in vivo. Here, we established a strategy to integrate Bi-doped carbon quantum dots(CQDs)with liposomes to produce fluorescence visualization and therapeutic effects, namely lipo/Bi-doped CQDs.Lipo/Bi-doped CQDs show good water solubility and physicochemical properties, which can be used for in vitro labeling of colon cancer(CT26) cells and in vivo imaging localization tracking tumors for monitoring. Simultaneously, thanks to the excellent p H sensitivity and ion doping characteristic of Bi-doped CQDs, lipo/Bi-doped CQDs can be used to reveal the drug release rate of liposomes at different p H values and exhibit potential effects in vivo antitumor therapy.展开更多
Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tun...Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tuning,and in vivo imaging of NIR-Ⅱluminescent AuNCs.In this review,we briefly introduce the synthesis of NIR-Ⅱluminescent AuNCs using various surface ligands.We discuss the origins and properties of NIR-ⅡPL in AuNCs,and summarize the strategies for improving and/or tuning NIR-ⅡPL emissions.We also provide an overview of the recent progress in the application of AuNCs in tumor-targeted imaging,molecular imaging,and other areas(such as the sensitive imaging of bones,vessels,lymph nodes,etc.).Finally,we present the prospects and challenges in the field of NIR-Ⅱluminescent AuNCs and related imaging applications,expecting to offer comprehensive understanding of this field,and thereby deepening and broadening the biological application of AuNCs.展开更多
Near-infrared fluorescence imaging has emerged as a noninvasive,inexpensive,and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy.In particular,ultrasound switchable fluorescenc...Near-infrared fluorescence imaging has emerged as a noninvasive,inexpensive,and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy.In particular,ultrasound switchable fluorescence(USF)imaging has been explored with improved imaging sensitivity and spatial resolution in centimeter-deep tissues.This study achieved the size control of polymer-based and indocyanine green(ICG)encapsulated USF contrast agents,capable of accumulating in the tumor after intravenous injections.These nanoprobes varied in size from 58 to 321 nm.The bioimaging profiles demonstrated that the proposed nanoparticles can efficiently eliminate the background light from normal tissue and show a tumor-specific fluorescence enhancement in the BxPC-3 tumor-bearing mice models possibly via the enhanced permeability and retention effect.In vivo tumor USF imaging further demonstrated that these nanoprobes can effectively be switched“ON”with enhanced fluorescence in response to a focused ultrasound stimulation in the tumor microenvironment,contributing to the high-resolution USF images.Therefore,our findings suggest that ICG-encapsulated nanoparticles are good candidates for USF imaging of tumors in live animals,indicating their great potential in optical tumor imaging in deep tissue.展开更多
Background: Hemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent de...Background: Hemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent degree of histopathological changes and the development of bone pathology in a mouse model of hemophilic arthropathy.Methods: FVIII knock-out(F8-KO) mice were dosed with a micro-CT blood pool agent prior to induction of hemarthrosis. Eight hours after induction, the bleed volume was quantified with micro computed tomography(micro-CT) and recombinant FVIII treatment initiated. On Day 8, inflammation in the knees was characterized by fluorescence molecular tomography. On Day 14, knee pathology was characterized by micro-CT and histopathology. In a second study, contrast agent was injected into the knee of wild-type(WT) mice, followed by histopathological evaluation on Day 14.Results: The average joint bleed volume before treatment was 3.9 mm3. The inflammation-related fluorescent intensities in the injured knees were significantly increased on Day 8. The injured knees had significantly increased synovitis scores, vessel counts, and areas of hemosiderin compared to un-injured knees. However, no cartilage-or bone pathology was observed. The bleed volume before initiation of treatment correlated with the degree of synovitis and was associated with high fluorescent intensity on Day 8. In F8-KO and WT mice, persistence of contrast agent in the joint elicited morphological changes.Conclusion: When applying a delayed on-demand treatment regimen to hemophilic mice subjected to an induced knee hemarthrosis, the degree of histopathological changes on Day 14 reflected the bleed volume prior to initiation of treatment.展开更多
Even though multispectral imaging is considered very significant in biological imaging,it is only commonly used in microscopy in a 2D approach.Here,we present a Fluorescence Molecular Tomography system capable of reco...Even though multispectral imaging is considered very significant in biological imaging,it is only commonly used in microscopy in a 2D approach.Here,we present a Fluorescence Molecular Tomography system capable of recording simultaneously tomographic data at several spectral windows,enabling multispectral tomography.3D reconstructed data from several spectral windows is used to construct a linear unmixing algorithm for multispectral deconvolution of overlapping fluorescence signals.The method is applied on tomographic 3D fluorescence concentration maps in tissue-mimicking phantoms,yielding absolute quantification of the concentration of each individual fluorophore.Results are compared to the case when unmixing is performed in the raw 2D data instead of the reconstructed 3D concentration map,showing greater accuracy when unmixing algorithms are applied in the reconstructed data.Both the reflection and transmission geometries are considered.展开更多
基金supported by the National Natural Science Foundation of China(81870841 and 82171192 to X.S.L.,82101349 to G.L.Q.)。
文摘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.
基金supported by the National Natural Science Foundation of China,No.82272478(to PT)。
文摘Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,we identify the challenges and possible solutions for spinal cord neuron imaging.
基金supported by the National Science Foundation of China(No.61605210)the National Instrumentation Program(NIP)(No.2012YQ120080)+4 种基金the National Key Research and Development Program of China(No.2016YFC0102500)the Jiangsu Province Science Fund for Distinguished Young Scholars(No.BK20060010)the Frontier Science Research Project of the Chinese Academy of Sciences(No.QYZDB-SSWJSC03)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB02060000)the Zhejiang Province Technology Program(No.2013C33170)
文摘A bimorph deformable mirror (DM) with a large stroke of more than 30 μm using 35 actuators is presented and characterized for an adaptive optics (AO) confocal scanning laser ophthalmoscope application. Facilitated with a Shack-Hartmann wavefront sensor, the bimorph DM-based AO operates closed-loop AO corrections for hu- man eyes and reduces wavefront aberrations in most eyes to below 0.1 μm rms. Results from living eyes, including one exhibiting ~5D of myopia and ~2D of astigmatism along with notable high-order aberrations, reveal a prac- tical efficient aberration correction and demonstrate a great benefit for retina imaging, including improving resolution, increasing brightness, and enhancing the contrast of images.
基金Supported by the National Natural Science Foundation of China(No.81070748,No.81200708)National Basic Research Program of China(973 Program)
文摘AIM: To investigate the influence of hyperglycemia on the severity of choroidal neovascularization(CNV),especially the involvement of bone marrow-derived cells(BMCs) and underlying mechanisms.·METHODS: BMCs from firefly luciferase(Fluc)/green fluorescent protein(GFP) double transgenic mice were transplanted into C57BL/6J wide-type mice. The recipient mice were injected intraperitoneally with streptozotocin(STZ) daily for 5 consecutive days to induce diabetes mellitus(DM), followed by CNV laser photocoagulation.The BMCs recruitment in CNV exposed to hyperglycemia was firstly examined in Fluc/GFP chimeric mice by in vivo optical bioluminescence imaging(BLI) and in vitro Fluc assays. The CNV severity was evaluated by H&E staining and choroidal flatmount. The expression of vascular endothelial growth factor(VEGF) and stromal cell derived factor-1(SDF-1) was detected by Western blot.·RESULTS: BLI showed that the BMCs exerted dynamic effects in CNV model in Fluc/GFP chimeric mice exposed to hyperglycemia. The signal intensity of transplanted Fluc+GFP+BMCs in the DM chimeric mice was significantly higher than that in the control chimeric mice with CNV induction at days 5, 7, 14 and 21(121861.67 ±9948.81 vs 144998.33 ±13787.13 photons/second/cm2/sr for control and DM mice, P5d〈0.05; 178791.67±30350.8 vs240166.67 ±22605.3, P7d〈0.05; 124176.67 ±16253.52 vs196376.67 ±18556.79, P14d〈0.05; 97951.60 ±10343.09 vs119510.00 ±14383.76, P21d〈0.05), which was consistent with in vitro Fluc assay at day 7 [relative light units of Fluc(RLU1)], 215.00±52.05 vs 707.33±88.65, P 〈0.05; RLU1/relative light units of renilla luciferase(RLU2), 0.90 ±0.17 vs 1.83 ±0.17, P 〈0.05]. The CNVs in the DM mice were wider than those in the control group at days 5, 7, 14 and21(147.83±17.36 vs 220.33±20.17 μm, P5d〈0.05; 212.17 ±24.63 vs 326.83 ±19.49, P7d〈0.05; 163.17 ±18.24 vs265.17 ±20.55, P14d〈0.05; 132.00 ±10.88 vs 205.33 ±12.98,P21d〈0.05). The average area of CNV in the DM group was larger at 7d(20688.67±3644.96 vs 32218.00±4132.69 μm2,P 〈0.05). The expression of VEGF and SDF-1 was enhanced in the DM mice.·CONCLUSION: Hyperglycemia promots the vasculo-genesis of CNV, especially the contribution of BMCs,which might be triggered by VEGF and SDF-1 production.
基金supported by the National HighTech Researchthe National"863"Project of China(No.2006AA020801)
文摘Digital radiography (DR) and whole-body fluorescent optical imaging (WFOI) have been widely applied in the field of molecular imaging, with the advantages in tissues and functional imaging. The integration of them contributes to the development and discovery of medicine. We introduce an equipment, performance of which is better than that of another molecular imaging system manufactured by Kodak Corp. It can take real-time small animal imaging in vivo, with lower cost and shorter development cycle on the LabVIEW platform. At last, a paradigm experiment on a nude mouse with green fluorescent protein (GFP) transgenic tumor is given to present a real-time DR-WFOI fusion simultaneous image.
基金Supported by Basic Science Research Program via the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Republic of South Korea,No.NRF-2019R1I1A1A01061296 and No.NRF-2019R1I1A3A01063308.
文摘Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body.Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes,understanding pathophysiological mechanisms of diseases,and evaluating the kinetics/dynamics of cell therapies.In particular,mesenchymal stem cells(MSCs)have shown promise in recent years as drug carriers for cancer treatment.They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells,and to optimize therapy.The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition,and the exact interactions between MSCs and specific cancer microenvironments are not clear.In this review,a multitude of labeling approaches,imaging modalities,and the merits/demerits of each strategy are outlined.In addition,specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided.Finally,present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.
基金Hong Kong Innovation and Technology Commission,No.ITS/036/19Research Grants Council of the Hong Kong Special Administrative Region,No.26203619.
文摘Laser diodes(LDs)have been considered as cost-effective and compact excitation sources to overcome the requirement of costly and bulky pulsed laser sources that are commonly used in photoacoustic microscopy(PAM).However,the spatial resolution and/or imaging speed of previously reported LD-based PAM systems have not been optimized simultaneously.In this paper,we developed a high-speed and high-resolution LD-based PAM system using a continuous wave LD,operating at a pulsed mode,with a repetition rate of 30 kHz,as an excitation source.A hybrid scanning mechanism that synchronizes a one-dimensional galvanometer mirror and a two-dimensional motorized stage is applied to achieve a fast imaging capability without signal averaging due to the high signal-to-noise ratio.By optimizing the optical system,a high lateral resolution of 4.8μm has been achieved.In vivo microvasculature imaging of a mouse ear has been demonstrated to show the high performance of our LD-based PAM system.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30901364)grants from the National Basic Research Program of China (No. 2003CB515505, 2009CB522407)
文摘In vivo imaging system (IVIS) is a new and rapidly expanding technology, which has a wide range of applications in life science such as cell tracing. By counting the number of photons emitted from a specimen, IVIS can quantify biological events such as tumor growth. We used B16F10-luc-G5 tumor cells and 20 Babl/C mice injected subcutaneously with B16F10-luc-G5 tumor cells (1×106 in 100 μL) to develop a method to quantitatively analyze cells traced by IVIS in vitro and in vivo, respectively. The results showed a strong correlation between the number of tumor cells and the intensity of bioluminescence signal (R2=0.99) under different exposure conditions in in vitro assay. The results derived from the in vivo experiments showed that tumor luminescence was observed in all mice by IVIS at all days, and there was significant difference (P<0.01) between every two days from day 3 to day 14. Moreover, tumor dynamic morphology could be monitored by IVIS when it was in- visible. There was a strong correlation between tumor volume and bioluminescence signal (R2=0.97) by IVIS. In summary, we demonstrated a way to accurately carry out the quantitative analysis of cells using IVIS both in vitro and in vivo. The data indicate that IVIS can be used as an effective and quantitative method for cell tracing both in vitro and in vivo.
基金funding from the European Union’s Seventh Framework Programme(FP7/2007-2013)under grant agreement no 242175 and from the Sonnenfeld Stiftung,Berlin,Germany.
文摘Regenerative medicine has become a new therapeutic approach in which stem cells or genetically reprogrammed cells are delivered to diseased areas in the body with the intention that such multipotent cells will differentiate into healthy tissue and exchange damaged tissue. The success of such cell-based therapeutic approaches depends on precise dosing and delivery of the cells to the desired site in the human body. To determine the accuracy and efficacy of the therapy, tracking of the engrafted cells in an intact living organism is crucial. There is a great need for sensitive, noninvasive imaging methods, which would allow clinicians to monitor viability, migration dynamics, differentiation towards specific cell type, regeneration potential and integration of transplanted cells with host tissues for an optimal time period. Various in vivo tracking methods are currently used including: MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), SPECT (Single Photon Emission Computer Tomography), optical imaging (OI), photoacoustic imaging (PAI) and ultrasound (US). In order to carry out the detection with each of the aforementioned techniques, the cells must be labeled either exogenously (ex vivo) or endogenously (in vivo). For tracking the administrated cells, scientists usually manipulate cells outside the living organism by incorporating imaging contrast agents (CAs) or reporter genes. Strategies for stem cell labeling using CAs will be reviewed in the light of various imaging techniques.
基金Project supported by the National Natural Science Foundation of China(62105333)the Key Research Program of the Chinese Academy of Sciences(ZDRW-CN-2021-3)+1 种基金Fujian Science&Technology Innovation Laboratory for Optoelectronic Information of China(2020ZZ114)the Xiamen Medical and Health Guidance Project,China(3502Z20209124)。
文摘In recent years,persistent luminescence materials(PLMs)excited by X-rays and emitting in biological windows have received extensive attention in the field of high-sensitivity bioimaging.Transition metal Mn^(2+)is an ideal emission center,but few studies focus on Mn^(2+)-doped PLMs with X-ray excitation and biological window emission.Here,we report a Mn^(2+)-doped PLM,LiYGeO_(4):Mn^(2+)(LYGM),with excellent biological window persistent luminescence emission.After excitation by UV,LYGM produces a durable biological window of persistent luminescence emission at 660 nm for up to 20 h.More importantly.LYGM can be repeatedly excited by X-rays,resulting in long-term biological window persistent luminescence emission.In addition,we obtain LYGM around 200 nm in diameter by ball milling and centrifugation and improve its biocompatibility by surface modification to apply it to in vivo imaging in mice.After LYGM are injected into mice through the tail vein,in situ excitation of X-rays can be achieved.After the persistent luminescence decays,LYGM can be re-excited for repeated imaging.Therefore,LYGM shows potential prospects for in vivo deep tissue and long-term bioimaging.
基金the approval of ethics by Ethics Committee of Fudan University(No.202208005Z)supported by the National Natural Science Foundation of China(Nos.81972129,82072521,82111530200)+1 种基金Shanghai Talent Development Funding Scheme(No.2020080)Shanghai Committee of Science and Technology(Nos.22DZ2204900,23ZR1445700)。
文摘The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophage therapy.In this work,the second near-infrared(NIR-II)fluorescence imaging in vivo tracking of M2 macrophages during a pro-healing therapy in the mice model of rotator cuff injury revealed that the behavior of administrated macrophages was influenced by the timing of their administration.The delayed cell therapy(DCT)group had a longer retention time of injected M2 macrophages in the repairing tissue than that in the immediate cell therapy(ICT)group.Both Keller-Segel model and histological analysis further demonstrated that DCT altered the chemotaxis of M2 macrophages and improved the healing outcome of the repaired structure in comparison with ICT.Our results offer a possible explanation of previous conflicting results on reparative cell therapy and provoke reconsideration of the timing of these therapies.
基金Supported by Veziant J was supported by«année-recherche»grants from the Ministère de la Santéand the Facultéde Médecine de Clermont-FerrandGagnière J was supported by a“Nuovo Soldati Foundation for Cancer Research”grant.
文摘AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli(E. coli) using optical imaging.METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume(mm^3). Inflammation measuring myeloperoxidase(MPO) activity and reactive oxygen species production was monitored by a bioluminescent(BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay(ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells(HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitisCEABAC10 DSS models, which mimicked Crohn's disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume(P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group(P < 0.005). ELISA confirmed that MPO levels were significantly higher(1556 ± 313.6 vs 234.6 ± 121.6 ng/m L P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model(CEABAC10/DSS).CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand hostpathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.
基金National Key Research and Development Program of China,No.2016YFC1306702(to KFS and LZ)the National Natural Science Foundation of China,No.81771455(to KFS)+1 种基金Science and Technology Program of Guangdong Province of China,No.2018B030334001(to KFS)the Natural Science Foundation of Guangdong of China,No.2019A1515011772(to LZ)。
文摘Acupuncture is a medical treatment that has been widely pra cticed in China for over 3000 years,yet the neural mechanisms of acupuncture are not fully understood.We hypothesized that neurons and astrocytes act independently and synergistically under acupuncture stimulation.To investigate this,we used two-photon in vivo calcium reco rding to observe the effects of acupuncture stimulation at ST36(Zusanli)in mice.Acupuncture stimulation in peripheral acupoints potentiated calcium signals of pyramidal neurons and astrocytes in the somatosensory cortex and resulted in late-onset calcium transients in astrocytes.Chemogenetic inhibition of neurons augmented the astrocytic activity.These findings suggest that acupuncture activates neuronal and astrocytic activity in the somatosensory co rtex and provide evidence for the involvement of both neurons and astrocytes in acupuncture treatment.
基金Supported by the Swiss RetinAward 2017 from the Swiss Vitreo Retinal Group(SVRG)Bayer AG+2 种基金CSC(Chinese Scholarship Council)EAKAS(Swiss Excellence Scholarship)Natural Science Basic Research Program of Shaanxi,China(No.2020JM-400)。
文摘AIM:To compare choroidal neovascularization(CNV)lesion measurements obtained by in vivo imaging modalities,with whole mount histological preparations stained with isolectin GS-IB4,using a murine laser-induced CNV model.METHODS:B6 N.Cg-Tg(Csf1 r-EGFP)1 Hume/J heterozygous adult mice were subjected to laser-induced CNV and were monitored by fluorescein angiography(FA),multicolor(MC)fundus imaging and optical coherence tomography angiography(OCTA)at day 14 after CNV induction.Choroidalretinal pigment epithelium(RPE)whole mounts were prepared at the end of the experiment and were stained with isolectin GS-IB4.CNV areas were measured in all different imaging modalities at day 14 after CNV from three independent raters and were compared to choroidal-RPE whole mounts.Intraclass correlation coefficient(ICC)type 2(2-way random model)and its 95%confidence intervals(CI)were calculated to measure the correlation between different raters’measurements.Spearman’s rank correlation coefficient(Spearman’s r)was calculated for the comparison between FA,MC and OCTA data and histology data.RESULTS:FA(early and late)and MC correlates well with the CNV measurements ex vivo with FA having slightly better correlation than MC(FA early Spearman’s r=0.7642,FA late Spearman’s r=0.7097,and MC Spearman’s r=0.7418),while the interobser ver reliability was good for both techniques(FA early ICC=0.976,FA late ICC=0.964,and MC ICC=0.846).In contrast,OCTA showed a poor correlation with ex vivo measurements(Spearman’s r=0.05716)and high variability between different raters(ICC=0.603).CONCLUSION:This study suggests that FA and MC imaging could be used for the evaluation of CNV areas in vivo while caution must be taken and comparison studies should be performed when OCTA is employed as a CNV monitoring tool in small rodents.
基金Supported by a grant(No.2016-7026)from the Asan Institute for Life Science,Seoul,Republic of Korea
文摘AIM: To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin(LHT7) in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS: A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization(CoNV) was induced in the inferior cornea(IC) of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7(LHT7-Cy5.5) in 0.02 mL solution was topically instilled onto the cornea in the experimental group(n=5). Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group(n=5). In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea(SC) and the IC. RESULTS: The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively(P=0.832). The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min(P=0.038), 2 h(P=0.041), and 4 h(P=0.041) after application. The IC intensity fell to less than half of its initial value(42.9%±8.6%) at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION: Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.
基金funded by Beijing Natural Science Foundation (Nos.L222109, 3222018)Military Health Care Project(No.22BJZ22)+6 种基金Science Foundation of China University of Petroleum (Nos.2462019QNXZ02, 2462019BJRC007)National Natural Science Foundation of China (Nos.52211530034, 82273236)Guangdong Provincial Basic and Applied Basic Research Foundation (Nos.2022A151522004, 2022A1515220042)Science and Technology Innovation Commission of Shenzhen (Nos.JSGG20210802153410031, JCYJ20220530141609021)Science and Technology Plan of Shenzhen Nanshan District (No.NS016)Discipline Leader Foundation of Huazhong University of Science and Technology Union Shenzhen Hospital (No.YN2021002)Crosswise Project of Daan Gene (No.HXKY2022002)。
文摘Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and drug release rates at different p H values to assess the biodistribution and drug delivery pathways in vivo. Here, we established a strategy to integrate Bi-doped carbon quantum dots(CQDs)with liposomes to produce fluorescence visualization and therapeutic effects, namely lipo/Bi-doped CQDs.Lipo/Bi-doped CQDs show good water solubility and physicochemical properties, which can be used for in vitro labeling of colon cancer(CT26) cells and in vivo imaging localization tracking tumors for monitoring. Simultaneously, thanks to the excellent p H sensitivity and ion doping characteristic of Bi-doped CQDs, lipo/Bi-doped CQDs can be used to reveal the drug release rate of liposomes at different p H values and exhibit potential effects in vivo antitumor therapy.
基金supported by the National Key Research&Development Program of China(2020YFA0709900)the National Natural Science Foundation of China(22027805,22274024)+2 种基金the Major Project of Science and Technology of Fujian Province(2020HZ06006)the Young Elite Scientist Sponsorship Program by CAST(YESS20200110)China Postdoctoral Science Foundation(2022M720737,2021T140117)
文摘Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tuning,and in vivo imaging of NIR-Ⅱluminescent AuNCs.In this review,we briefly introduce the synthesis of NIR-Ⅱluminescent AuNCs using various surface ligands.We discuss the origins and properties of NIR-ⅡPL in AuNCs,and summarize the strategies for improving and/or tuning NIR-ⅡPL emissions.We also provide an overview of the recent progress in the application of AuNCs in tumor-targeted imaging,molecular imaging,and other areas(such as the sensitive imaging of bones,vessels,lymph nodes,etc.).Finally,we present the prospects and challenges in the field of NIR-Ⅱluminescent AuNCs and related imaging applications,expecting to offer comprehensive understanding of this field,and thereby deepening and broadening the biological application of AuNCs.
基金This work was supported in part by funding from the National Institute of Biomedical Imaging and Bioengineering(No.1R15EB030809-01)the Research Enhancement Program(No.270089)the Cancer Prevention&Research Institute of Texas(Nos.RP170564 and RP210206).
文摘Near-infrared fluorescence imaging has emerged as a noninvasive,inexpensive,and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy.In particular,ultrasound switchable fluorescence(USF)imaging has been explored with improved imaging sensitivity and spatial resolution in centimeter-deep tissues.This study achieved the size control of polymer-based and indocyanine green(ICG)encapsulated USF contrast agents,capable of accumulating in the tumor after intravenous injections.These nanoprobes varied in size from 58 to 321 nm.The bioimaging profiles demonstrated that the proposed nanoparticles can efficiently eliminate the background light from normal tissue and show a tumor-specific fluorescence enhancement in the BxPC-3 tumor-bearing mice models possibly via the enhanced permeability and retention effect.In vivo tumor USF imaging further demonstrated that these nanoprobes can effectively be switched“ON”with enhanced fluorescence in response to a focused ultrasound stimulation in the tumor microenvironment,contributing to the high-resolution USF images.Therefore,our findings suggest that ICG-encapsulated nanoparticles are good candidates for USF imaging of tumors in live animals,indicating their great potential in optical tumor imaging in deep tissue.
文摘Background: Hemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent degree of histopathological changes and the development of bone pathology in a mouse model of hemophilic arthropathy.Methods: FVIII knock-out(F8-KO) mice were dosed with a micro-CT blood pool agent prior to induction of hemarthrosis. Eight hours after induction, the bleed volume was quantified with micro computed tomography(micro-CT) and recombinant FVIII treatment initiated. On Day 8, inflammation in the knees was characterized by fluorescence molecular tomography. On Day 14, knee pathology was characterized by micro-CT and histopathology. In a second study, contrast agent was injected into the knee of wild-type(WT) mice, followed by histopathological evaluation on Day 14.Results: The average joint bleed volume before treatment was 3.9 mm3. The inflammation-related fluorescent intensities in the injured knees were significantly increased on Day 8. The injured knees had significantly increased synovitis scores, vessel counts, and areas of hemosiderin compared to un-injured knees. However, no cartilage-or bone pathology was observed. The bleed volume before initiation of treatment correlated with the degree of synovitis and was associated with high fluorescent intensity on Day 8. In F8-KO and WT mice, persistence of contrast agent in the joint elicited morphological changes.Conclusion: When applying a delayed on-demand treatment regimen to hemophilic mice subjected to an induced knee hemarthrosis, the degree of histopathological changes on Day 14 reflected the bleed volume prior to initiation of treatment.
基金E.U.FP6 Integrated Project“Molecular Imaging”LSHG-CT-2003-503259E.U.FP7 Collaborative Project“FMT-XCT”.R.F.acknowledges support from the Marie Curie Program EST-MolecImag Early Stage Training MEST-CT-2004-007643.
文摘Even though multispectral imaging is considered very significant in biological imaging,it is only commonly used in microscopy in a 2D approach.Here,we present a Fluorescence Molecular Tomography system capable of recording simultaneously tomographic data at several spectral windows,enabling multispectral tomography.3D reconstructed data from several spectral windows is used to construct a linear unmixing algorithm for multispectral deconvolution of overlapping fluorescence signals.The method is applied on tomographic 3D fluorescence concentration maps in tissue-mimicking phantoms,yielding absolute quantification of the concentration of each individual fluorophore.Results are compared to the case when unmixing is performed in the raw 2D data instead of the reconstructed 3D concentration map,showing greater accuracy when unmixing algorithms are applied in the reconstructed data.Both the reflection and transmission geometries are considered.