Beijing Key Laboratory of Molecular Imaging

Beijing, China

Beijing Key Laboratory of Molecular Imaging

Beijing, China

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Peng D.,Xidian University | Peng D.,CAS Institute of Automation | Du Y.,CAS Institute of Automation | Du Y.,Beijing Key Laboratory of Molecular Imaging | And 11 more authors.
Nanoscale | Year: 2016

Photoacoustic imaging and fluorescence molecular imaging are emerging as important research tools for biomedical studies. Photoacoustic imaging offers both strong optical absorption contrast and high ultrasonic resolution, and fluorescence molecular imaging provides excellent superficial resolution, high sensitivity, high throughput, and the ability for real-time imaging. Therefore, combining the imaging information of both modalities can provide comprehensive in vivo physiological and pathological information. However, currently there are limited probes available that can realize both fluorescence and photoacoustic imaging, and advanced biomedical applications for applying this dual-modality imaging approach remain underexplored. In this study, we developed a dual-modality photoacoustic-fluorescence imaging nanoprobe, ICG-loaded Au@SiO2, which was uniquely designed, consisting of gold nanorod cores and indocyanine green with silica shell spacer layers to overcome fluorophore quenching. This nanoprobe was examined by both PAI and FMI for in vivo imaging on tumor and ischemia mouse models. Our results demonstrated that the nanoparticles can specifically accumulate at the tumor and ischemic areas and be detected by both imaging modalities. Moreover, this dual-modality imaging strategy exhibited superior advantages for a precise diagnosis in different scenarios. The new nanoprobe with the dual-modality imaging approach holds great potential for diagnosis and stage classification of tumor and ischemia related diseases. © 2016 The Royal Society of Chemistry.

Ma X.,CAS Institute of Automation | Ma X.,Stanford University | Ma X.,Beijing Key Laboratory of Molecular Imaging | Hui H.,CAS Institute of Automation | And 12 more authors.
Biomaterials | Year: 2016

SM5-1 is a humanized mouse monoclonal antibody, targeting an over-expressed membrane protein of approximately 230 kDa in hepatocellular carcinoma (HCC). SM5-1 can be used for target therapy in hepatocellular carinoma due to its ability of inhibiting cell growth and inducing apoptosis. However, the tumor inhibition efficacy of SM5-1 in HCC cancer treatment remains low. In this study, we synthesized SM5-1-conjugated gold nanoparticles (Au-SM5-1 NPs) and investigated their anticancer efficacy in HCC both in vitro and in vivo. The tumor inhibition rates of Au-SM5-1 NPs for subcutaneous tumor mice were 40.10% ± 4.34%, 31.37% ± 5.12%, and 30.63% ± 4.87% on day 12, 18, and 24 post-treatment as determined by bioluminescent intensity. In addition, we investigated the antitumor efficacy of Au-SM5-1 NPs in orthotopic HCC tumor models. The results showed that the inhibition rates of Au-SM5-1 NPs can reach up to 39.64% ± 4.87% on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, three-dimensional reconstruction results of the orthotopic tumor revealed that Au-SM5-1 NPs significantly inhibited tumor growth compared with SM5-1 alone. Our results suggested that the developed Au-SM5-1 NPs has great potential as an antibody-based nano-drug for HCC therapy. © 2016 The Authors.

Hu Z.,CAS Institute of Automation | Hu Z.,Beijing Key Laboratory of Molecular Imaging | Qu Y.,General Hospital of Chinese Peoples Armed Police Forces | Wang K.,CAS Institute of Automation | And 13 more authors.
Nature Communications | Year: 2015

Cerenkov luminescence imaging utilizes visible photons emitted from radiopharmaceuticals to achieve in vivo optical molecular-derived signals. Since Cerenkov radiation is weak, non-optimum for tissue penetration and continuous regardless of biological interactions, it is challenging to detect this signal with a diagnostic dose. Therefore, it is challenging to achieve useful activated optical imaging for the acquisition of direct molecular information. Here we introduce a novel imaging strategy, which converts γ and Cerenkov radiation from radioisotopes into fluorescence through europium oxide nanoparticles. After a series of imaging studies, we demonstrate that this approach provides strong optical signals with high signal-to-background ratios, an ideal tissue penetration spectrum and activatable imaging ability. In comparison with present imaging techniques, it detects tumour lesions with low radioactive tracer uptake or small tumour lesions more effectively. We believe it will facilitate the development of nuclear and optical molecular imaging for new, highly sensitive imaging applications. © 2015 Macmillan Publishers Limited. All rights reserved.

Jia X.-H.,CAS Institute of Automation | Du Y.,CAS Institute of Automation | Mao D.,Nankai University | Wang Z.-L.,Xidian University | And 7 more authors.
Oncotarget | Year: 2015

Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. However, the mechanism by which ZA exerts its antitumor activity is still unclear. The aim of this study is to investigate whether the prevention of tumor growth by ZA is through regulating the mesenchymal stem cells (MSC)-monocyte chemotactic protein 1 (MCP-1)-macrophages axis in the tumor microenvironment. To address this issue, MDA-MB-231-FLUC human breast cancer cells were cultured and injected either alone, or coupled with MSC into the mammary fat pads of nude mice. MSC were treated with either ZA or untreated. Tumor growth was determined by using an in vivo bioluminescence imaging (BLI) and the tumorassociated macrophages (TAMs) in tumor tissues were immunohistochemically analyzed by using CD206 antibody. The effects of ZA on the cytokine related gene expression of MSC were assessed by using real-time PCR. In this study, we found that ZA-treated mice showed a significant delay in tumor growth. In addition, our data revealed that ZA weakened the ability of MSC to promote tumor growth by impairing TAMs recruitment and tumor vascularization. Furthermore, it was found that ZA decreased MCP-1 expression of MSC, and therefore reduced the recruitment of TAMs to the tumor sites and hence inhibited the tumor growth. Altogether, our study demonstrated ZA can prevent the tumor-promoting effects of MSC. The antitumor effects of ZA were caused by decreasing the MCP-1 expression of MSC, which further decreased the infiltration of TAMs into tumor sites, and therefore inhibited the tumor growth.

Liu H.,CAS Institute of Automation | Liu H.,Beijing Key Laboratory of Molecular Imaging | Yang X.,CAS Institute of Automation | Yang X.,Beijing Key Laboratory of Molecular Imaging | And 10 more authors.
Journal of Biomedical Optics | Year: 2015

Cerenkov luminescence tomography (CLT) is a promising tool that enables three-dimensional noninvasive in vivo detection of radiopharmaceuticals. Conventionally, multispectral information and diffusion theory were introduced to achieve whole-body tomographic reconstruction. However, the diffusion theory inevitably causes systematic error in blue bands of the electromagnetic spectrum due to high-tissue absorption, and CL has a blue-weighted broad spectrum. Therefore, it is challenging to improve the accuracy of CLT. The performance of the n-order simplified spherical harmonics approximation (SPn) in different spectra is evaluated, and a multispectral hybrid CLT based on the combination of different SPn models is proposed to handle the Cerenkov photon transport problem in complex media. The in vivo xenograft experiment shows that this approach can effectively improve the quality and accuracy of the reconstructed light source. We believe that the new reconstruction method will advance the development of CLT for more in vivo imaging applications. © 2015 Society of Photo-Optical Instrumentation Engineers (SPIE).

Shen W.,CAS Institute of Automation | Shen W.,Beijing Key Laboratory of Molecular Imaging | Zhou M.,Stanford University | Yang F.,Beijing Jiaotong University | And 10 more authors.
Pattern Recognition | Year: 2016

We investigate the problem of lung nodule malignancy suspiciousness (the likelihood of nodule malignancy) classification using thoracic Computed Tomography (CT) images. Unlike traditional studies primarily relying on cautious nodule segmentation and time-consuming feature extraction, we tackle a more challenging task on directly modeling raw nodule patches and building an end-to-end machine-learning architecture for classifying lung nodule malignancy suspiciousness. We present a Multi-crop Convolutional Neural Network (MC-CNN) to automatically extract nodule salient information by employing a novel multi-crop pooling strategy which crops different regions from convolutional feature maps and then applies max-pooling different times. Extensive experimental results show that the proposed method not only achieves state-of-the-art nodule suspiciousness classification performance, but also effectively characterizes nodule semantic attributes (subtlety and margin) and nodule diameter which are potentially helpful in modeling nodule malignancy. © 2016 Elsevier Ltd.

Jia X.-H.,CAS Institute of Automation | Feng G.-W.,Tianjin Medical University | Feng G.-W.,Nankai University | Wang Z.-L.,Xidian University | And 9 more authors.
Oncotarget | Year: 2016

Cancer development and progression is linked to tumor-associated macrophages (TAMs). Distinct TAMs subsets perform either protective or pathogenic effects in cancer. A protective role in carcinogenesis has been described for M1 macrophages, which activate antitumor mechanisms. By comparison, TAMs isolated from solid and metastatic tumors have a suppressive M2-like phenotype, which could support multiple aspects of tumor progression. Currently, it has not been clearly understood how macrophages in tumor-associated stroma could be hijacked to support tumor growth. Mesenchymal stem cells (MSCs) actively interact with components of the innate immune system and display both anti-inflammatory and pro-inflammatory effects. Here, we tested whether MSCs could favor the tumor to escape from immunologic surveillance in the presence of M1 macrophages. We found that MSCs educated by M1 condition medium (cMSCs) possessed a greatly enhanced ability in promoting tumor growth in vivo. Examination of cytokines/chemokines showed that the cMSCs acquired a regulatory profile, which expressed high levels of iNOS and MCP1. Consistent with an elevated MCP1 expression in cMSCs, the tumor-promoting effect of the cMSCs depended on MCP1 mediated macrophage recruitment to tumor sites. Furthermore, IL-6 secreted by the cMSCs could polarize infiltrated TAMs into M2- like macrophages. Therefore, when macrophages changed into M1 pro-inflammation type in tumor microenvironment, the MSCs would act as poor sensors and switchers to accelerate tumor growth.

Liang X.,Southern Medical University | Liang X.,CAS Institute of Automation | Liang X.,Beijing Key Laboratory of Molecular Imaging | Shang W.,CAS Institute of Automation | And 12 more authors.
Cancer Letters | Year: 2016

Recently, photothermal therapy (PTT) has become viewed as an ideal auxiliary therapeutic treatment for cancers. However, the development of safe, convenient, and highly effective photothermal agents remains a great challenge. In this study, we prepared single-walled carbon nanotubes (SWNTs) for PTT against breast tumors under the guidance of infrared fluorescent cyanines. Tumors were accurately located using near-infrared imaging (NIR) and then exposed to laser irradiation. Both the in vivo and in vitro results showed that the SWNTs have high stability and low cytotoxicity. Introducing polyethylene glycol into our nanoparticles increased the blood-circulation time. Our in vivo results further showed that Cy5.5-conjugated SWNTs mediated PTT, resulting in efficient tumor suppression in mice under the guidance of near-infrared imaging. Due to the small amount of absorption at 808-nm, Cy5.5 increased the efficiency of PTT. Breast tumors significantly shrunk after irradiation under the 808-nm near-infrared laser. The treated mice developed scabs, but otherwise recovered after 15 days, and their physical conditions restored gradually. These data indicate that our unique photothermal-responsive SWNT-Cy5.5-based theranostic agent can serve as a promising candidate for PTT. © 2016 Elsevier Ireland Ltd

Mu W.,CAS Institute of Automation | Mu W.,Beijing Key Laboratory of Molecular Imaging | Chen Z.,CAS Institute of Automation | Chen Z.,Beijing Key Laboratory of Molecular Imaging | And 9 more authors.
Physics in Medicine and Biology | Year: 2015

The aim of the study is to assess the staging value of the tumor heterogeneity characterized by texture features and other commonly used semi-quantitative indices extracted from 18F-FDG PET images of cervical cancer (CC) patients. Forty-two patients suffering CC at different stages were enrolled in this study. Firstly, we proposed a new tumor segmentation method by combining the intensity and gradient field information in a level set framework. Secondly, fifty-four 3D texture features were studied besides of SUVs (SUVmax, SUVmean, SUVpeak) and metabolic tumor volume (MTV). Through correlation analysis, receiver-operating-characteristic (ROC) curves analysis, some independent indices showed statistically significant differences between the early stage (ES, stages I and II) and the advanced stage (AS, stages III and IV). Then the tumors represented by those independent indices could be automatically classified into ES and AS, and the most discriminative feature could be chosen. Finally, the robustness of the optimal index with respect to sampling schemes and the quality of the PET images were validated. Using the proposed segmentation method, the dice similarity coefficient and Hausdorff distance were 91.78 ± 1.66% and 7.94 ± 1.99 mm, respectively. According to the correlation analysis, all the fifty-eight indices could be divided into 20 groups. Six independent indices were selected for their highest areas under the ROC curves (AUROC), and showed significant differences between ES and AS (P < 0.05). Through automatic classification with the support vector machine (SVM) Classifier, run percentage (RP) was the most discriminative index with the higher accuracy (88.10%) and larger AUROC (0.88). The Pearson correlation of RP under different sampling schemes is 0.9991 ± 0.0011. RP is a highly stable feature and well correlated with tumor stage in CC, which suggests it could differentiate ES and AS with high accuracy. © 2015 Institute of Physics and Engineering in Medicine.

Zhang S.,Northeastern University China | Zhang S.,CAS Institute of Automation | Wang K.,CAS Institute of Automation | Wang K.,Beijing Key Laboratory of Molecular Imaging | And 8 more authors.
Molecular Imaging and Biology | Year: 2016

Purpose: Bioluminescence tomography (BLT) can provide in vivo three-dimensional (3D) images for quantitative analysis of biological processes in preclinical small animal studies, which is superior than the conventional planar bioluminescence imaging. However, to reconstruct light sources under the skin in 3D with desirable accuracy and efficiency, BLT has to face the ill-posed and ill-conditioned inverse problem. In this paper, we developed a new method for BLT reconstruction, which utilized the mathematical strategies of the split Bregman iterative and surrogate functions (SBISF) method. Procedures: The proposed method considered the sparsity characteristic of the reconstructed sources. Thus, the sparsity itself was regarded as a kind of a priori information, and the sparse regularization is incorporated, which can accurately locate the position of the sources. Numerical simulation experiments of multisource cases with comparative analyses were performed to evaluate the performance of the proposed method. Then, a bead-implanted mouse and a breast cancer xenograft mouse model were employed to validate the feasibility of this method in in vivo experiments. Results: The results of both simulation and in vivo experiments indicated that comparing with the L1-norm iteration shrinkage method and non-monotone spectral projected gradient pursuit method, the proposed SBISF method provided the smallest position error with the least amount of time consumption. Conclusions: The SBISF method is able to achieve high accuracy and high efficiency in BLT reconstruction and hold great potential for making BLT more practical in small animal studies. © 2016 World Molecular Imaging Society

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