Beijing Key Laboratory of Molecular Imaging

Beijing, China

Beijing Key Laboratory of Molecular Imaging

Beijing, China
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Wang S.,CAS Institute of Automation | Wang S.,University of Chinese Academy of Sciences | Zhou M.,Stanford University | Liu Z.,Guangdong General Hospital | And 11 more authors.
Medical Image Analysis | Year: 2017

Accurate lung nodule segmentation from computed tomography (CT) images is of great importance for image-driven lung cancer analysis. However, the heterogeneity of lung nodules and the presence of similar visual characteristics between nodules and their surroundings make it difficult for robust nodule segmentation. In this study, we propose a data-driven model, termed the Central Focused Convolutional Neural Networks (CF-CNN), to segment lung nodules from heterogeneous CT images. Our approach combines two key insights: 1) the proposed model captures a diverse set of nodule-sensitive features from both 3-D and 2-D CT images simultaneously; 2) when classifying an image voxel, the effects of its neighbor voxels can vary according to their spatial locations. We describe this phenomenon by proposing a novel central pooling layer retaining much information on voxel patch center, followed by a multi-scale patch learning strategy. Moreover, we design a weighted sampling to facilitate the model training, where training samples are selected according to their degree of segmentation difficulty. The proposed method has been extensively evaluated on the public LIDC dataset including 893 nodules and an independent dataset with 74 nodules from Guangdong General Hospital (GDGH). We showed that CF-CNN achieved superior segmentation performance with average dice scores of 82.15% and 80.02% for the two datasets respectively. Moreover, we compared our results with the inter-radiologists consistency on LIDC dataset, showing a difference in average dice score of only 1.98%. © 2017


Meng H.,CAS Institute of Automation | Meng H.,Beijing Key Laboratory of Molecular Imaging | Hui H.,CAS Institute of Automation | Hui H.,Beijing Key Laboratory of Molecular Imaging | And 6 more authors.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2017

The ability of fast and single-neuron resolution imaging of neural activities enables light-sheet fluorescence microscopy (LSFM) as a powerful imaging technique in functional neural connection applications. The state-of-art LSFM imaging system can record the neuronal activities of entire brain for small animal, such as zebrafish or C. elegans at single-neuron resolution. However, the stimulated and spontaneous movements in animal brain result in inconsistent neuron positions during recording process. It is time consuming to register the acquired large-scale images with conventional method. In this work, we address the problem of fast registration of neural positions in stacks of LSFM images. This is necessary to register brain structures and activities. To achieve fast registration of neural activities, we present a rigid registration architecture by implementation of Graphics Processing Unit (GPU). In this approach, the image stacks were preprocessed on GPU by mean stretching to reduce the computation effort. The present image was registered to the previous image stack that considered as reference. A fast Fourier transform (FFT) algorithm was used for calculating the shift of the image stack. The calculations for image registration were performed in different threads while the preparation functionality was refactored and called only once by the master thread. We implemented our registration algorithm on NVIDIA Quadro K4200 GPU under Compute Unified Device Architecture (CUDA) programming environment. The experimental results showed that the registration computation can speed-up to 550ms for a full high-resolution brain image. Our approach also has potential to be used for other dynamic image registrations in biomedical applications. © 2017 SPIE.


Guan T.,Southern Medical University | Guan T.,CAS Institute of Automation | Guan T.,Beijing Key Laboratory of Molecular Imaging | Shang W.,CAS Institute of Automation | And 10 more authors.
Bioconjugate Chemistry | Year: 2017

Conventional imaging methods encounter challenges in diagnosing liver cancer that is less than 10 mm or without typical hypervascular features. With deep penetration and high spatial resolution imaging capability, the emerging photoacoustic tomography may offer better diagnostic efficacy for noninvasive liver cancer detection. Moreover, near-infrared fluorescence imaging-guided hepatectomy was proven to be able to identify nodules at the millimeter level. Thus, suitable photoacoustic and fluorescence dual-modality imaging probe may benefit patients in early diagnosis and complete resection. In this study, we fabricated indocyanine green loaded gold nanorod@liposome core-shell nanoparticles (Au@liposome-ICG) to integrate both imaging strategies. These nanoparticles exhibit superior biocompatibility, high stability, and enhanced dual-model imaging signals. Next, we explored their effectiveness of tumor detection and surgery guidance in orthotopic liver cancer mouse models. Histological analysis confirmed the accuracy of the probe in liver cancer detection and resection. This novel dual-modality nanoprobe holds promise for early diagnosis and better surgical outcome of liver cancer and has great potential for clinical translation. © 2017 American Chemical Society.


Guo H.,Northwest University, China | Guo H.,CAS Institute of Automation | He X.,Northwest University, China | Liu M.,Northwest University, China | And 9 more authors.
IEEE Transactions on Vehicular Technology | Year: 2017

Cerenkov luminescence tomography (CLT) provides a novel technique for 3-D noninvasive detection of radiopharmaceuticals in living subjects. However, because of the severe scattering of Cerenkov light, the reconstruction accuracy and stability of CLT is still unsatisfied. In this paper, a modified weight multispectral CLT (wmCLT) reconstruction strategy was developed which split the Cerenkov radiation spectrum into several sub-spectral bands and weighted the sub-spectral results to obtain the final result. To better evaluate the property of the wmCLT reconstruction strategy in terms of accuracy, stability and practicability, several numerical simulation experiments and in vivo experiments were conducted and the results obtained were compared with the traditional multispectral CLT (mCLT) and hybrid-spectral CLT (hCLT) reconstruction strategies. The numerical simulation results indicated that wmCLT strategy significantly improved the accuracy of Cerenkov source localization and intensity quantitation and exhibited good stability in suppressingnoise in numerical simulation experiments. And the comparison of the results achieved from different in vivo experiments further indicated significant improvement of the wmCLT strategy in terms of the shape recovery of the bladder and the spatial resolution of imaging xenograft tumors. Overall the strategy reported here will facilitate the development of nuclear and optical molecular tomography in theoretical study. © 2017 IEEE.


Chen Q.,Southern Medical University | Chen Q.,CAS Institute of Automation | Shang W.,CAS Institute of Automation | Shang W.,Beijing Key Laboratory of Molecular Imaging | And 13 more authors.
Oncotarget | Year: 2017

The accurate preoperative detection and intraoperative navigation afforded by imaging techniques have had significant impact on the success of liver cancer surgeries. However, it is difficult to achieve satisfactory performance in both diagnosis and surgical treatment processes using any single modality imaging method. Here, we report the synthesis and characteristics of a novel dual-modality magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) probe and verify its feasibility in nude mouse models with liver cancer. The probes are comprised of superparamagnetic iron oxide (SPIO) nanoparticles coated with liposomes to which a tumor-targeted agent, Arg-Gly-Asp peptides (RGD), and a NIRF dye (indocyanine green, ICG) have been conjugated. Specific targeting, biodistribution, and the imaging ability of the probes for MRI-NIRF were examined. Furthermore, we applied the dual-modality methodology toward the preoperative diagnosis and intraoperative guidance of radical resection in mouse models with both orthotopic liver tumors and intrahepatic tumor metastasis. The study demonstrated that both MRI and fluorescent images showed clear tumor delineation after probe injection (SPIO@Liposome-ICG-RGD). The contrast-to-noise ratio obtained from MRI was 31.9 ± 25.4 at post-injection for the preoperative diagnosis, which is helpful for detecting small tumors (0.9 ± 0.5 mm). The maximum tumor to background ratio of NIRF imaging was 2.5 ± 0.3 at 72 h post-injection for effectively capturing miniscule tumor lesions (0.6 ± 0.3 mm) intraoperatively. The novel MRI-NIRF dual modality probes are promising for the achievement of more accurate liver tumor detection and resection. © Chen et al.


Fang M.,CAS Institute of Automation | Fang M.,Beijing Key Laboratory of Molecular Imaging | Dong D.,CAS Institute of Automation | Dong D.,Beijing Key Laboratory of Molecular Imaging | And 11 more authors.
Scientific Reports | Year: 2016

Optical projection tomography (OPT) is a tool used for three-dimensional imaging of millimeter-scale biological samples, with the advantage of exhibiting isotropic resolution typically in the micron range. OPT can be divided into two types: transmission OPT (tOPT) and emission OPT (eOPT). Compared with eOPT, tOPT discriminates different tissues based on their absorption coefficient, either intrinsic or after specific staining. However, it fails to distinguish muscle fibers whose absorption coefficients are similar to surrounding tissues. To circumvent this problem, in this article we demonstrate a polarization sensitive OPT system which improves the detection and 3D imaging of muscle fibers by using polarized light. We also developed image acquisition and processing protocols that, together with the system, enable the clear visualization of muscles. Experimental results show that the muscle fibers of diaphragm and stomach, difficult to be distinguished in regular tOPT, were clearly displayed in our system, proving its potential use. Moreover, polarization sensitive OPT was fused with tOPT to investigate the stomach tissue comprehensively. Future applications of polarization sensitive OPT could be imaging other fiber-like structures such as myocardium or other tissues presenting high optical anisotropy.


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.


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.


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.

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