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  • Multichannel Double-Row Transmission Line Array for Human MR Imaging at Ultrahigh Fields

    Subjects: Biology >> Biophysics >> Imaging Medicine and Biomedical Engineering submitted time 2016-05-12

    Abstract: Objective: In microstrip transmission line (MTL) transmit/receive (transceive) arrays used for ultrahigh field MRI, the array length is often constrained by the required resonant frequency, limiting the image coverage. The purpose of this study is to increase the imaging coverage and also improve its parallel imaging capability by utilizing a double-row design. Methods: A 16-channel double-row MTL transceive array was designed, constructed, and tested for human head imaging at 7 T. Array elements between two rows were decoupled by using the induced current elimination or magnetic wall decoupling technique. In vivo human head images were acquired, and g-factor results were calculated to evaluate the performance of this double-row array. Results: Testing results showed that all coil elements were well decoupled with a better than -18 dB transmission coefficient between any two elements. The double-row array improves the imaging quality of the lower portion of the human head, and has low g-factors even at high acceleration rates. Conclusion: Compared with a regular single-row MTL array, the double-row array demonstrated a larger imaging coverage along the z-direction with improved parallel imaging capability. Significance: The proposed technique is particularly suitable for the design of large-sized transceive arrays with large channel counts, which ultimately benefits the imaging performance in human MRI.

  • Novel near-infrared BiFC systems from a bacterial phytochrome for imaging protein interactions and drug evaluation under physiological conditions

    Subjects: Biology >> Biophysics >> Imaging Medicine and Biomedical Engineering submitted time 2016-05-12

    Abstract: Monitoring protein protein interactions (PPIs) in live subjects is critical for understanding these fundamental biological processes. Bimolecular fluorescence complementation (BiFC) provides a good technique for imaging PPIs; however, a BiFC system with a long wavelength remains to be pursued for in vivo imaging. Here, we conducted systematic screening of split reporters from a bacterial phytochrome-based, near-infrared fluorescent protein (iRFP). Several new near-infrared phytochrome BiFC systems were built based on selected split sites including the amino acids residues 97/98, 99/100,122/123, and 123/124. These new near-infrared BiFC systems from a bacterial phytochrome were verified as powerful tools for imaging PPIs under physiological conditions in live cells and in live mice. The interaction between HIV-1 integrase (IN) and cellular cofactor protein Lens epithelium-derived growth factor (LEDGF/p75) was visualized in live cells using the newly constructed iRFP BiFC system because of its important roles in HIV-1 integration and replication. Because the HIV IN-LEDGF/p75 interaction is an attractive anti-HIV target, drug evaluation assays to inhibit the HIV IN-LEDGF/p75 interaction were also performed using the newly constructed BiFC system. The results showed that compound 6 and carbidopa inhibit the HIV IN-LEDGF/p75 interaction in a dose-dependent manner under physiological conditions in the BiFC assays. This study provides novel near-infrared BiFC systems for imaging protein interactions under physiological conditions and provides guidance for splitting other bacterial phytochrome-like proteins to construct BiFC systems. The study also provides a new method for drug evaluation in live cells based on iRFP BiFC systems and supplies some new information regarding candidate drugs for anti-HIV therapies. (C) 2015 Elsevier Ltd. All rights reserved.

  • A near-infrared phthalocyanine dye-labeled agent for integrin alpha v beta 6-targeted theranostics of pancreatic cancer

    Subjects: Biology >> Biophysics >> Imaging Medicine and Biomedical Engineering submitted time 2016-05-11

    Abstract: Integrin alpha v beta 6 is widely upregulated in variant malignant cancers but is undetectable in normal organs, making it a promising target for cancer diagnostic imaging and therapy. Using streptavidin-biotin chemistry, we synthesized an integrin alpha v beta 6-targeted near-infrared phthalocyanine dye-labeled agent, termed Dye-SA-B-HK, and investigated whether it could be used for cancer imaging, optical imaging-guided surgery, and phototherapy in pancreatic cancer mouse models. Dye-SA-B-HK specifically bound to integrin alpha v beta 6 in vitro and in vivo with high receptor binding affinity. Using small-animal optical imaging, we detected subcutaneous and orthotopic BxPC-3 human pancreatic cancer xenografts in vivo. Upon optical image-guidance, the orthotopically growing pancreatic cancer lesions could be successfully removed by surgery. Using light irradiation, Dye-SA-B-HK manifested remarkable antitumor effects both in vitro and in vivo. F-18-FDG positron emission tomography (PET) imaging and ex vivo fluorescence staining validated the observed decrease in proliferation of treated tumors by Dye-DA-B-HK phototherapy. Tissue microarray results revealed overexpression of integrin alpha v beta 6 in over 95% cases of human pancreatic cancer, indicating that theranostic application of Dye-DA-B-HK has clear translational potential. Overall, the results of this study demonstrated that integrin alpha v beta 6-specific Dye-SA-B-HK is a promising theranostic agent for the management of pancreatic cancer. (C) 2015 Elsevier Ltd. All rights reserved.

  • Inhibition of tumor growth and metastasis by photoimmunotherapy targeting tumor-associated macrophage in a sorafenib-resistant tumor model

    Subjects: Biology >> Biophysics >> Imaging Medicine and Biomedical Engineering submitted time 2016-05-05

    Abstract: Tumor-associated macrophages (TAMs) play essential roles in tumor invasion and metastasis, and contribute to drug resistance. Clinical evidence suggests that TAM levels are correlated with local tumor relapse, distant metastasis, and poor prognosis in patients. In this study, we synthesized a TAM-targeted probe (IRD-alpha CD206) by conjugating a monoclonal anti-CD206 antibody with a near-infrared phthalocyanine dye. We then investigated the potential application of the IRD-alpha CD206 probe to near-infrared fluorescence (NIRF) imaging and photoimmunotherapy (PIT) of tumors resistant to treatment with the kinase inhibitor sorafenib. Sorafenib treatment had no effect on tumor growth in a 4T1 mouse model of breast cancer, but induced M2 macrophage polarization in tumors. M2 macrophage recruitment by sorafenib-treated 4T1 tumors was noninvasively visualized by in vivo NIRF imaging of IRD-alpha CD206. Small-animal single-photon emission computed tomography (SPECT)/CT and intratumoral micro distribution analysis indicated TAM-specific localization of the IRD-alpha CD206 probe in 4T1 tumors after several rounds of sorafenib treatment. Upon light irradiation, IRD-alpha CD206 suppressed the growth of sorafenib-resistant tumors. In vivo CT imaging and ex vivo histological analysis confirmed the inhibition of lung metastasis in mice by IRD-alpha CD206 PIT. These results demonstrate the utility of the IRD-alpha CD206 probe for TAM-targeted diagnostic imaging and treatment of tumors that are resistant to conventional therapeutics. (C) 2016 Elsevier Ltd. All rights reserved.