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      1. Author :
        He, T.; Xue, Z.; Lu, K.; Valdivia y Alvarado, M.; Wong, K. K.; Xie, W.; Wong, S. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Comput Med Imaging Graph
      6. Products :
      7. Volume :
        36
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States, with more than half of the cancers are located peripherally. Computed tomography (CT) has been utilized in the last decade to detect early peripheral lung cancer. However, due to the high false diagnosis rate of CT, further biopsy is often necessary to confirm cancerous cases. This renders intervention for peripheral lung nodules (especially for small peripheral lung cancer) difficult and time-consuming, and it is highly desirable to develop new, on-the-spot earlier lung cancer diagnosis and treatment strategies. PURPOSE: The objective of this study is to develop a minimally invasive multimodality image-guided (MIMIG) intervention system to detect lesions, confirm small peripheral lung cancer, and potentially guide on-the-spot treatment at an early stage. Accurate image guidance and real-time optical imaging of nodules are thus the key techniques to be explored in this work. METHODS: The MIMIG system uses CT images and electromagnetic (EM) tracking to help interventional radiologists target the lesion efficiently. After targeting the lesion, a fiber-optic probe coupled with optical molecular imaging contrast agents is used to confirm the existence of cancerous tissues on-site at microscopic resolution. Using the software developed, pulmonary vessels, airways, and nodules can be segmented and visualized for surgical planning; the segmented results are then transformed onto the intra-procedural CT for interventional guidance using EM tracking. Endomicroscopy through a fiber-optic probe is then performed to visualize tumor tissues. Experiments using IntegriSense 680 fluorescent contrast agent labeling alphavbeta3 integrin were carried out for rabbit lung cancer models. Confirmed cancers could then be treated on-the-spot using radio-frequency ablation (RFA). RESULTS: The prototype system is evaluated using the rabbit VX2 lung cancer model to evaluate the targeting accuracy, guidance efficiency, and performance of molecular imaging. Using this system, we achieved an average targeting accuracy of 3.04 mm, and the IntegriSense signals within the VX2 tumors were found to be at least two-fold higher than those of normal tissues. The results demonstrate great potential for applying the system in human trials in the future if an optical molecular imaging agent is approved by the Food and Drug Administration (FDA). CONCLUSIONS: The MIMIG system was developed for on-the-spot interventional diagnosis of peripheral lung tumors by combining image-guidance and molecular imaging. The system can be potentially applied to human trials on diagnosing and treating earlier stage lung cancer. For current clinical applications, where a biopsy is unavoidable, the MIMIG system without contrast agents could be used for biopsy guidance to improve the accuracy and efficiency.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22483054
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10364
      1. Author :
        Zhang, X.; Bloch, S.; Akers, W.; Achilefu, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Curr Protoc Cytom
      6. Products :
      7. Volume :
        Chapter 12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Cell Line, Tumor; Diagnostic Imaging/*methods; Fluorescent Dyes/chemistry/metabolism; Humans; Mice; Molecular Probes/*diagnostic use; Nanoparticles/chemistry; Quantum Dots; Spectroscopy, Near-Infrared/*methods
      12. Abstract :
        Cellular and tissue imaging in the near-infrared (NIR) wavelengths between 700 and 900 nm is advantageous for in vivo imaging because of the low absorption of biological molecules in this region. This unit presents protocols for small animal imaging using planar and fluorescence lifetime imaging techniques. Included is an overview of NIR fluorescence imaging of cells and small animals using NIR organic fluorophores, nanoparticles, and multimodal imaging probes. The development, advantages, and application of NIR fluorescent probes that have been used for in vivo imaging are also summarized. The use of NIR agents in conjunction with visible dyes and considerations in selecting imaging agents are discussed. We conclude with practical considerations for the use of these dyes in cell and small animal imaging applications.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22470154
      14. Call Number :
        PKI @ kd.modi @ 24
      15. Serial :
        10386
      1. Author :
        G. Blum
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Current Opinion in Drug Discovery Development
      6. Products :
      7. Volume :
        10
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Biology; Cancer
      11. Keywords :
        Proteases; pathology; biological markers; fluorescence imaging reagents; in vivo imaging; fluorescence molecular tomography; FMT
      12. Abstract :
        Proteases play pivotal roles in the normal function of cells. In addition, the expression and activity of proteases are significantly upregulated in several pathologies, including cancer, arthritis and atherosclerosis, and hence they can be considered to be biological markers for these pathologies. The hydrolyzing activity of proteases has been used to generate a variety of fluorescent imaging reagents, the design and utility of which are reviewed here. The use of imaging reagents to visualize protease activity allows for improved detection of various pathologies as well as the ability to monitor the efficacy of therapies in vivo and provide molecular information regarding the nature of the pathology.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18729022
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4475
      1. Author :
        Okuda, Tomoyuki; Kawaguchi, Yasuhisa; Okamoto, Hirokazu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Current topics in medicinal chemistry
      6. Products :
      7. Volume :
        9
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; Gene Silencing; PC-3M-luc; Peptides; Proteins; RNA Interference; Transfection
      12. Abstract :
        RNA interference (RNAi) is an attractive phenomenon for practical use that specifically inhibits gene expression and is carried out by small double-stranded RNAs (dsRNAs) including small interfering RNA (siRNA) or short hairpin RNA (shRNA). In addition, RNAi is of great interest for clinical use to cure refractory diseases related to the expression of a specific gene. To achieve gene silencing in the body, a sufficient amount of dsRNA must be delivered and internalized into target cells. However, dsRNAs have a large molecular weight and net negative charge, which limits their membrane-permeating ability. Moreover, dsRNAs are rapidly degraded by endonucleses in the body. Therefore, for the efficient delivery of dsRNAs, many approaches based on drug delivery systems have been carried out. In this review, we focus on recent reports about the application of functional peptides and proteins designed for the efficient delivery of dsRNAs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19860710
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8962
      1. Author :
        Adachi, T.; Kawakami, E.; Ishimaru, N.; Ochiya, T.; Hayashi, Y.; Ohuchi, H.; Tanihara, M.; Tanaka, E.; Noji, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Dev Growth Differ
      6. Products :
      7. Volume :
        52
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, Animals; Base Sequence; Cell Line, Tumor; Collagen/*chemistry; DNA Primers; *Gene Silencing; Mice; RNA, Small Interfering/*administration & dosage/*chemistry; Reverse Transcriptase Polymerase Chain Reaction
      12. Abstract :
        Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro-Hyp-Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long-term gene silencing in vivo. We found that the SYCOL-mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti-luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL-based non-viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20874713
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10352
      1. Author :
        Hardy, Jonathan; Chu, Pauline; Contag, Christopher H
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Disease models & mechanisms
      6. Products :
      7. Volume :
        2
      8. Issue :
        1-2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Bone Marrow; Bone Marrow Cells; Disease Models, Animal; Female; Host-Pathogen Interactions; Humans; Knee Joint; Listeria monocytogenes; Listeriosis; Mice; Mice, Inbred BALB C; Mutation; pXen-5; Tibia
      12. Abstract :
        Murine listeriosis is one of the most comprehensive and well-studied models of infection, and Listeria monocytogenes has provided seminal information regarding bacterial pathogenesis. However, many aspects of the mouse model remain poorly understood, including carrier states and chronic colonization which represent important features of the spectrum of host-pathogen interaction. Bone marrow has recently been shown to harbor L. monocytogenes, which spreads from this location to the central nervous system. Bone could, therefore, be an important chronic reservoir, but this infection is difficult to study because it involves only a few bacteria and the extent of infection cannot be assessed until after the animal is sacrificed. We employed in vivo bioluminescence imaging to localize L. monocytogenes bone infections over time in live mice, revealing that the bacteria grow in discrete foci. These lesions can persist in many locations in the legs of mice and are not accompanied by a histological indication such as granuloma or a neutrophil infiltratate. We demonstrate that highly attenuated hly mutants, which have defective intracellular replication, are capable of prolonged focal infection of the bone marrow for periods of up to several weeks. These results support the recently proposed hypothesis that the bone marrow is a unique niche for L. monocytogenes.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19132117
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9018
      1. Author :
        Katharina Jannasch, Jeannine Missbach-Guentner and Frauke Alves
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        N/A
      5. Publication :
        Drug Discovery Today: Disease Models
      6. Products :
      7. Volume :
        6
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        Drug Discovery
      11. Keywords :
        FMT; ProSense; in vivo imaging
      12. Abstract :
        The incidence of asthma is increasing throughout the world. Animal models are crucial for understanding the pathophysiology of asthma and for developing new therapies. Novel imaging approaches will be a powerful tool for studying asthma in animal models. This review will give a short overview of different imaging techniques that are currently used and will focus on new developments in visualization of asthma that might be used in animals as well as being translated to humans.
      13. URL :
        http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B75D8-4Y5GVHG-1&_user=10&_coverDate=02%2F28%2F2010&_rdoc=1&_fmt=high&_orig=browse&_origin=browse&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=58c3195065086c72b7aa74f13df11
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4533
      1. Author :
        Tremoleda, J. L.; Khalil, M.; Gompels, L. L.; Wylezinska-Arridge, M.; Vincent, T.; Gsell, W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        EJNMMI Res
      6. Products :
      7. Volume :
        1
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense
      12. Abstract :
        Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22214535
      14. Call Number :
        PKI @ kd.modi @ 15
      15. Serial :
        10477
      1. Author :
        Shan, Liang; Wang, Songping; Korotcov, Alexandru; Sridhar, Rajagopalan; Wang, Paul C
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Ethnicity & disease
      6. Products :
      7. Volume :
        18
      8. Issue :
        2 Suppl 2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Breast Neoplasms; Disease Models, Animal; Humans; Luciferases; Luminescent Measurements; Lung Neoplasms; Mammary Neoplasms, Animal; MDA-MB-231-D3H1 cells; Mice; Mice, Nude; Tumor Cells, Cultured
      12. Abstract :
        INTRODUCTION Convenient animal models are needed to study the progression and treatment of human tumors in vivo. Luciferase-based bioluminescent imaging (BLI) enables researchers to monitor tumors noninvasively and is sensitive to subtle changes in tumors. METHODS Three human breast cancer models in nude mice were established by using luciferase-expressing MDA-MB-231-luc cells. They were subcutaneous xenografts (n = 8), mammary gland xenografts (n = 5), and lung metastases (n = 3). The tumors were imaged in live mice by using a highly sensitive BLI system. The relationship between the intensity of bioluminescence from the tumor was analyzed with respect to tumor volume. Bioluminescent signals from lung metastases were studied to determine the threshold of detectability. RESULTS Tumors growing in the mice's backs and mammary gland fat pads were imaged dynamically after administration of D-luciferin. The bioluminescent intensity from the tumors gradually increased and then decreased in a one-hour span. The time to reach maximum signal intensity differed significantly among tumors and was independent of tumor volume and unrelated to maximum signal intensity. A significant correlation was observed between tumor volume and maximum signal intensity in tumors from both sites. Lung metastatic lesions of .3-.5 mm in diameter were clearly detectable through the entire animal imaging process. CONCLUSION The animal models established with luciferase-expressing cancer cells in combination with BLI provide a system for rapid, noninvasive, and quantitative analysis of tumor biomass and metastasis. This biosystem simplifies in vivo monitoring of tumors and will be useful for noninvasive investigation of tumor growth and response to therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18646323
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8991
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